Improvement of lung preservation - From experiment to clinical practice

Background. Reperfusion injury represents a severe early complication following lung transplantation. Among the pathogenetic factors, the high potassium content of Euro-Collins(R) solution is discussed. Material and Methods: In a pig model of orthotopic left-sided lung transplantation we investigated the effect of Euro-Collins solution (EC: n=6) versus low potassium dextran (LPD: Perfadex(R): n = 6). Sham-operated (n = 6) animals served as control. Transplant function, cellular energy metabolism and endothelial morphology served as parameters. In a clinical investigation, 124 patients were evaluated following single (EC: n = 31; LPD n = 37) or double (EC: n = 17; LPD n = 39) lung transplantation, whose organs where preserved with EC (n = 48) or LPD (n = 76). Duration of ischemia, duration of ventilation and stay on ICU were registered. Primary transplant function was evaluated according to AaDO(2) values. Cause of early death (30 days) was declared. Results: Experimental results: After flush with EC and 18 h ischemia, a reduction of tissue ATP content (p < 0.01 vs inital value and LPD) was noted. Endothelial damage after ischemia was severe (p < 0.05 vs control), paO(2) was significantly decreased. Clinical results: In the LPD group, duration of ischemia was longer for the grafts transplanted first (SLTx and DLTx: p = 0.0009) as well as second (2. organ DLTx: p = 0.045). Primary transplant function was improved (day 0: SLTx: p = 0.0015; DLTx: p = 0.0095, both vs EC). Duration of ventilation and stay on ICU were shorter (n.s.). Reperfusion injury-associated death was reduced from 8% (EC) to 0 (LPD). Conclusion: In experimental lung preservation, LPD lead to an improved graft function. These results were confirmed in clinical lung transplantation. Clinical lung preservation, therefore, should be carried out by use of LPD. Copyright (C) 2002 S. Karger AG, Basel

A stable, oligosymptomatic malaria focus in Thailand

Blood from most of the 250 residents of a nonmigratory farming village in south-eastern Thailand was visually examined for malaria parasites monthly for 2 years. Nearly 97% of the population had at least one (median = 5) patent Plasmodium falciparum infection per year; 72% had one due to P. vivax (median = 1). This contrasted with a slide positivity rate of 17% calculated from 12 months of passive case detection before the study began. Children 1-9 years old had the highest mean monthly prevalence (51%) and highest geometric mean density (10/500 white blood cells) of P. falciparum. Fewer than half the expected number of mixed infections were found but these were more common at high densities of P. falciparum. Individuals over 19 years old comprised 52% of the population but accounted for only 18% of P. vivax and 32% of P. falciparum gametocytaemias. Fever rates were marginally higher in those below 10 years old (8%) but occurred with equal frequency in those with patent infections or negative. The spleen rate (89% stage 1) was 24% in those under 15 years old and 7% in those older. No malaria mortality was seen. P. falciparum cases treated for 10 d with quinine + tetracycline (QT) cleared the infection as often as those given one dose of mefloquine + sulfadoxine + pyrimethamine (MSP); both treatments reduced densities in cases not cured. Apparently unsupervised compliance was no better with MSP than with QT. The role played by hyperendemic, cryptic foci in Asian epidemics of malaria may have been underestimate

Quantitative EEG (QEEG) Measures Differentiate Parkinson`s Disease Patients from Healthy Controls

Objectives: To find out which Quantitative EEG (QEEG) parameters could best distinguish patients with Parkinson's disease (PD) with and without Mild Cognitive Impairment from healthy individuals and to find an optimal method for feature selection. Background: Certain QEEG parameters have been seen to be associated with dementia in Parkinson's and Alzheimer's disease. Studies have also shown some parameters to be dependent on the stage of the disease. We wanted to investigate the differences in high-resolution QEEG measures between groups of PD patients and healthy individuals, and come up with a small subset of features that could accurately distinguish between the two groups. Methods: High-resolution 256-channel EEG were recorded in 50 PD patients (age 68.8 ± 7.0 year; female/male 17/33) and 41 healthy controls (age 71.1 ± 7.7 year; female/male 20/22). Data was processed to calculate the relative power in alpha, theta, delta, beta frequency bands across the different regions of the brain. Median, peak frequencies were also obtained and alpha1/theta ratios were calculated. Machine learning methods were applied to the data and compared. Additionally, penalized Logistic regression using LASSO was applied to the data in R and a subset of best-performing features was obtained. Results: Random Forest and LASSO were found to be optimal methods for feature selection. A group of six measures selected by LASSO was seen to have the most effect in differentiating healthy individuals from PD patients. The most important variables were the theta power in temporal left region and the alpha1/theta ratio in the central left region. Conclusion: The penalized regression method applied was helpful in selecting a small group of features from a dataset that had high multicollinearity. Keywords: Parkinson's disease, QEEG, cognitive decline, Parkinson's disease dementia, neurodegenerative disorders, machine learnin

Vaccination recommendations for adult patients with autoimmune inflammatory rheumatic diseases

BACKGROUND: The number of individuals with autoimmune inflammatory rheumatic diseases (AIIRDs) treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and, in particular, biological therapies is also rising. The immunosuppressants, as well as the AIIRD itself, increase the risk of infection in this population. Thus, preventing infections by means of vaccination is of utmost importance. New Swiss vaccination recommendations for AIIRD patients were initiated by the Swiss Federal Office of Public Health and prepared by a working group of the Federal Commission for Vaccination Issues as well as by consultation of international experts. METHODS: A literature search was performed in electronic databases (Cochrane, Medline, PubMed, Embase). In addition, unpublished literature was identified through a targeted website search of relevant organisations and international conferences dealing with vaccination, infectious diseases and rheumatology. RESULTS: Although data are scarce, the following main points were retrieved from the literature. Inactivated vaccines are safe, but their immunogenicity may be reduced in AIIRD patients, especially if they are under immunosuppressive therapy. Rituximab and abatacept appear to reduce significantly immune responses after vaccination. Live vaccines are generally contraindicated under immunosuppressive therapy owing to safety concerns. Specific exceptions, as well as time intervals for the administration of live vaccines after interruption of an immunosuppressive therapy, have been formulated in this article. CONCLUSION: More evidence regarding the immunogenicity and safety of vaccinations in AIIRD patients under various therapies is needed. Vaccination recommendations should be updated on a regular basis, as more scientific data will become available

Brolucizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: Ophthalmology and Diabetology Treatment Aspects.

Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events

The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

BACKGROUND: The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. METHODS: Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. RESULTS: In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were 1 case per 100,000 visits to consider targeted malaria prophylaxis recommendations to minimize use of chemoprophylaxis for low risk exposure during visits to S-E Asia. Policy needs to be adjusted regularly to reflect the changing risk

Immunogenicity and safety of yellow fever vaccination for 102 HIV-infected patients

BACKGROUND: Yellow fever vaccine (17DV) has been investigated incompletely in human immunodeficiency virus (HIV)-infected patients, and adequate immunogenicity and safety are of concern in this population. METHODS: In the Swiss HIV Cohort Study, we identified 102 patients who received 17DV while they were HIV infected. We analyzed neutralization titers (NTs) after 17DV administration using the plaque reduction neutralization test. NTs of 1:>or=10 were defined as reactive, and those of 1:<10 were defined as nonreactive, which was considered to be nonprotective. The results were compared with data for HIV-uninfected individuals. Serious adverse events were defined as hospitalization or death within 6 weeks after receipt of 17DV. RESULTS: At the time of 17DV administration, the median CD4 cell count was 537 cells/mm(3) (range, 11-1730 cells/mm(3)), and the HIV RNA level was undetectable in 41 of 102 HIV-infected patients. During the first year after vaccination, fewer HIV-infected patients (65 [83%] of 78; P = .01) than HIV-uninfected patients revealed reactive NTs, and their NTs were significantly lower (P < .001) than in HIV-uninfected individuals. Eleven patients with initially reactive NTs lost these reactive NTs <or= 5 years after vaccination. Higher NTs during the first year after vaccination were associated with undetectable HIV RNA levels, increasing CD4 cell count, and female sex. We found no serious adverse events after 17DV administration among HIV-infected patients. CONCLUSION: Compared with HIV-uninfected individuals, HIV-infected patients respond to 17DV with lower reactive NTs, more often demonstrate nonprotective NTs, and may experience a more rapid decline in NTs during follow-up. Vaccination with 17DV appears to be safe in HIV-infected individuals who have high CD4 cell counts, although rate of serious adverse events of up to 3% cannot be exclude

The Chronic Diseases Clinic of Ifakara (CDCI)- establishing a model clinic for chronic care delivery in rural sub-Saharan Africa

The rollout of antiretroviral drugs in sub-Saharan Africa to address the huge health impact of the HIV pandemic has been one of the largest projects undertaken in medical history and is an unprecedented medical success story. However, the path has been and still is characterized by many far reaching implementational challenges. Here, we report on the building and maintaining of a role model clinic in Ifakara, rural Southwestern Tanzania, within a collaborative project to support HIV services within the national program, training for staff and integrated research to better understand local needs and improve patients' outcomes