Remote patient monitoring for chronic heart failure in France: When an innovative funding program (ETAPES) meets an innovative solution (Satelia® Cardio).

Introduction: Remote patient monitoring (RPM) is a telehealth activity to collect and analyze patient health or medical data. Its use has expanded in the past decade and has improved medical outcomes and care management of non-communicable chronic diseases. However, implementation of RPM into routine clinical activities has been limited. The objective of this study was to describe the French funding program for RPM (known as ETAPES) and one of the RPM solution providers (Satelia®) dedicated to chronic heart failure (CHF). Methods: A descriptive assessment of both the ETAPES funding program and Satelia® RPM solution was conducted. Data were collected from official legal documents and information that was publicly available online from the French Ministry of Health. Results and Discussion: ETAPES was formally created in 2016 based on previous legislation pertaining to the national health insurance funding strategy. However, it only started to operate in 2018. Patients with CHF were only eligible if they were at medium or high risk of re-hospitalization with a New York Heart Association (NYHA) score superior or equal to two and a BNP>100 pg/ml or NT pro BNP>1000 pg/ml. Medical monitoring was supported through the therapeutic education of a patient on the RPM model of care with a minimum of three training sessions during the first six months. The use of Satelia® Cardio is noteworthy since it relies only on symptomatic monitoring through which the patient manually reports their information by answering a simple questionnaire on a regular basis and does not rely on any connected devices. Conclusion: Innovative funding programs and solutions for RPM need real-world evaluation in the future.

New markers in predicting the severity of acute pancreatitis in the emergency department: Immature granulocyte count and percentage.

BACKGROUND: Acute pancreatitis (AP) may vary in severity, from mild, self-limiting pancreatic inflammation to rapidly progressive life-threatening clinical course. If the severity of AP can be predicted early and treated quickly, it may lead to a decrease in morbidity and mortality rates. There?fore, we aimed to investigate the clinical utility of immature granulocyte count (IGC) and IGC percentage (IG%) in showing the severity of AP in this study. METHODS: Two hundred and twenty-seven patients who were admitted to our emergency department and diagnosed with AP between March 1 and September 30, 2019, were included in the study. The patients were divided into two groups as mild and severe AP (MAP and SAP) according to the severity of the disease. Demographic characteristics of the patients, disease etiology, disease severity, and inflammation markers [white blood cell count (WBC), IGC, IG%, neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP)] were recorded. Differences between the groups were statistically analyzed. RESULTS: Of the patients included in the study, 183 (80.7%) were in the MAP group and 44 (19.3%) were in the SAP group. The mean WBC, NLR, CRP, IGC, and IG% levels were significantly higher in the SAP group compared to the MAP group. The power of IGC and IG% in predicting SAP was higher than other inflammation markers (WBC, NLR, and CRP) [(AUC for IGC: 0.902; sensitivity: 78.2%; specificity: 92.8%); (AUC for IG%: 0.843; sensitivity: 72.7%; specificity: 84.6%)]. CONCLUSION: IGC and IG% show the severity of AP more effectively than WBC, NLR, and CRP, which are traditional inflammation markers.

[Genotyping of Toxoplasma gondii strains from immunocompromised patients]. / Génotypage de souches de Toxoplasma gondii chez des patients immunodéprimés.

The genotypes of Toxoplasma gondii strains isolated from HIV and non-HIV immunocompromised patients with cerebral and extracerebral toxoplasmosis were determined and compared to those of strains isolated from non-immunocompromised patients in order to identify the possible relationships between parasite genotype and morbidity of toxoplasmosis. One hundred and ten strains of T. gondii were obtained, either by cell culture (n = 73), brain biopsy (n = 17) or mouse inoculation (n = 20). Ninety strains isolated from immunocompromised patients (74 HIV+ and 16 non-HIV patients) were compared to 20 strains isolated from immunocompetent patients (17 cases of congenital toxoplasmosis, and three cases of primary acquired infection). Genotyping was performed by PCR/RFLP on locus SAG2, and T. gondii strains were classified as Type I, II or III. Ninety out of 110 strains were successfully genotyped, including 20 strains that had been maintained in mice, 69/73 strains maintained in cell cultures, but only 1/17 strains from formalin-fixed paraffin-embedded brain biopsies. 76.7% of the strains in the study population were of type II, 15.6% were type I and 7.7% were type III. The distribution of strain genotypes in immunocompromised and non-immunocompromised patients was comparable: 14.1% and 21% for type I, 76.1% and 79% for type II and 9.8% and 0% for type III, respectively; no correlation could be established between genotype and clinical presentation, i.e., cerebral or extracerebral toxoplasmosis. These results suggest that the type of infecting parasitic strain does not predominantly influence the pathogenesis of toxoplasmosis in immunocompromised patients and fully supports the need for specific prophylaxis in patients infected by T. gondii, regardless of the strain genotype.

Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis.

IGF-I antisense gene therapy has been applied successfully to animal models of glioma, hepatoma and teratocarcinoma. The antisense strategy has shown that tumor cells transfected with vectors encoding IGF-I antisense RNA lose tumorigenicity, become immunogenic and are associated with tumor specific immune response involving CD8+ lymphocytes. An IGF-I triple helix approach to gene therapy for glioma was recently described. The approach we have taken is to establish parameters of change using the IGF-I triple helix strategy. PCC-3 embryonal carcinoma cells derived from murine teratocarcinoma which express IGF-I were used as a model. The cells were transfected with vector which encodes an oligoribonucleotide that forms RNA-IGF-I DNA triple-helix structure. The triple-helix stops the production of IGF-I. Cells transfected in this manner underwent changes in phenotype and an increase in MHC-I and B-7 cell surface molecules. They also showed enhancement in the production of apoptotic cells (60-70%). The "triple helix" transfected cells lost the ability to induce tumor when injected subcutaneously in syngeneic 129 Sv mice. When co-transfected in vitro with expression vectors encoding both MHC-I and B-7 cDNA in antisense orientation, the "triple-helix" transfected cells were down-regulated in expression of MHC-I and B-7 and the number of apoptotic cells was significantly decreased. Injection of the doubly co-transfected cells into 129 Sv mice was associated with induction of teratocarcinoma. Comparison between antisense and triple-helix transfected cells strategies showed similar immunogenic and apoptotic changes. The findings suggest that triple-helix technology may offer a new clinical approach to treatement of tumors expressing IGF-I.

Report of a fatal case of dengue infection with hepatitis: demonstration of dengue antigens in hepatocytes and liver apoptosis.

A fatal case of dengue (DEN) infection associated with a spleen rupture and with hepatitis is reported here. Microscopic studies showed numerous areas of spleen rupture with hematomas and revealed necrotic foci in liver samples obtained at autopsy. Although hepatitis was reported in several cases of DEN fever, the mechanism of liver injury remains poorly understood. In this case, immunohistochemistry showed that DEN viral antigens were mostly detected in hepatocytes surrounding the necrotic foci. By in situ detection of DNA fragmentation, apoptotic hepatocytes were found to be colocated with DEN virus-infected hepatocytes. These findings suggest that hepatocytes are the major sites of DEN virus replication in the liver and that DEN virus induces apoptosis of hepatocytes in vivo.

Detection and localization by in situ molecular biology techniques and immunohistochemistry of hepatitis C virus in livers of chronically infected patients.

Hepatitis C virus (HCV) detection in the livers of chronically infected patients remains a debatable issue. We used immunohistochemistry, in situ hybridization (ISH) alone or after microwave heating with FITC-labeled probes, RT-PCR with unlabeled primers followed by ISH (RT-PCR-ISH), and in situ RT-PCR with FITC-labeled primers (in situ RT-PCRd) to localize the virus in 38 liver biopsy specimens from 21 chronically infected HCV patients treated with interferon-alpha (IFN-alpha). Biopsies were taken at the beginning and end of IFN-alpha treatment and 1 year later. Results were compared with that of HCV-PCR in serum. RT-PCR-ISH and in situ RT-PCRd showed HCV signal in all liver biopsies even in responders with seronegative HCV PCR. This signal was intranuclear, diffuse, or peripheral, in hepatocytes, bile ductule cells, and lymphocytes. Cytoplasmic signals were occasionally observed. Whereas the percentage of labeled hepatocytes remained constant, the number of labeled lymphoid follicles decreased after INF-alpha therapy. Immunohistochemistry resulted in the same pattern of positivity but it was weaker and inconstant. This study indicates the persistency of HCV latency in IFN-alpha responders 1 year after IFN-alpha treatment cessation, a finding that certainly deserves confirmation.

Improved detection of human papillomavirus infection in genital intraepithelial neoplasia in human immunodeficiency virus positive (HIV +) women by polymerase chain reaction-in situ hybridization.

The prevalence of genital human papillomavirus (HPV) infection was evaluated in 30 consecutive human immunodeficiency virus (HIV) + women by polymerase chain reaction (PCR)-in situ hybridization (ISH) on paraffin-embedded tissue sections and compared with that found with standard ISH. Biopsies were removed from normal or neoplastic areas in the cervix, vagina, and vulva, and ISH was performed with biotinylated or fluorescein isothiocyanate genomic DNA probes. One probe was used for HPV screening and others for HPV typing (types 6, 11, 16, 18, 31, and 33). Sequences were amplified by the "hot-start" PCR method and followed by standard ISH. Among the 30 HIV + women, 90% scored HPV + in one or several locations by PCR-ISH, whereas only 67% were positive by ISH. Oncogenic HPV types were found in 63% by PCR-ISH and in only 43% by ISH. The same HPV types detected by standard ISH were also recognized by PCR-ISH, but with the latter the signal was amplified. Moreover, some HPV types were found with PCR-ISH but not by ISH. We conclude that PCR-ISH is a valuable and sensitive method for specific detection of HPV.

[In situ gene amplification on tissue sections (in situ PCR). A new technique for pathologists]. / L'amplification génique in situ sur coupes tissulaires (PCR-in situ).

In situ polymerase chain reaction is a recent technique which combines the sensitivity of PCR reaction to intracellular localization of genomic sequences with the same specificity as in situ hybridization. This reaction is based on the in situ annealing and polymerisation of oligonucleotides complementary to nucleotides located at each side of the target DNA sequence to amplify. We describe the Hot Start PCR (DNA) and the Hot Start PCR after reverse transcription step (RNA). It allows to amplify some nucleic sequences to a high level, becoming easier to detect. The vizualisation can be realized by direct in situ PCR, the product obtained being directly identifiable by incorporation of labeled nucleotides or primers, or preferentially by indirect in situ PCR. In this case, the amplification is followed by in situ hybridization with labeled probes. This last procedure is more specific. Numerous controls are essential at each step of the technique for validating results.