Neutropenia as an adverse event following vaccination : results from randomized clinical trials in healthy adults and systematic review

Background : In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology : We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings : Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions : It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events

Peroxisomes in intestinal and gallbladder epithelial cells of the stickleback, Gasterosteus aculeatus L. (Teleostei)

The occurrence of microbodies in the epithelial cells of the intestine and gallbladder of the stickleback, Gasterosteus aculeatus L., is described. In the intestine the organelles are predominantly located in the apical and perinuclear zone of the cells and may contain small crystalline cores. In gallbladder epithelial cells the microbodies are distributed randomly. The latter organdies are characterized by the presence of large crystalloids. Cytochemical and biochemical experiments show that catalase and D-amino acid oxidase are main matrix components of the microbodies in both the intestinal and gallbladder epithelia. These organelles therefore are considered peroxisomes. In addition, in intestinal mucosa but not in gallbladder epithelium a low activity of palmitoyl CoA oxidase was detected biochemically. Urate oxidase and L-α hydroxy acid oxidase activities could not be demonstrated.

The magnitude of postconvulsive leukocytosis mirrors the severity of periconvulsive respiratory compromise : a single center retrospective study

Background: Generalized epileptic convulsions frequently exhibit transient respiratory symptoms and non-infectious leukocytosis. While these peri-ictal effects appear to arise independently from one another, the possibility that they stem from a common ictal pathophysiological response has yet to be explored. We aimed to investigate whether peri-ictal respiratory symptoms and postictal leukocytosis coexist. Methods: We performed a single center retrospective chart review of 446 patients brought to our emergency department between January 1, 2017 and August 23, 2018 for the care of generalized epileptic convulsions with or without status epilepticus. We included 152 patients who were stratified based on the presence (PeCRC+) or absence (PeCRC-) of overt periconvulsive respiratory compromise (PeCRC). In addition, patients were stratified based on the presence or absence of postconvulsive leukocytosis (PoCL), defined as an initial postconvulsive white blood cell (WBC) count ≥ 11,000 cells/mm3. Triage vital signs, and chest x ray (CXR) abnormalities were also examined. Results: Overt PeCRC was observed in 31.6% of patients, 43% of whom required emergent endotracheal intubations. PoCL was observed in 37.5% of patients, and was more likely to occur in PeCRC+ than in PeCRC- patients (79.2 vs. 18.2%; OR = 17.0; 95% CI = 7.2-40.9; p < 0.001). Notably, the magnitude of PoCL was proportional to the severity of PeCRC, as the postconvulsive WBC count demonstrated a negative correlation with triage hemoglobin oxygen saturation (R = -0.22; p < 0.01; CI = -0.48 to -0.07). Moreover, a receiver operating characteristic analysis of the WBC count's performance as predictor of endotracheal intubation reached a significant area under the curve value of 0.81 (95% CI = 0.71-0.90; p < 0.001). Finally, PeCRC+ patients demonstrated frequent CXR abnormalities, and their postconvulsive WBC counts correlated directly with triage heart rate (R = 0.53; p < 0.001). Conclusion: Our data support the existence of an ictal pathophysiological response, which induces proportional degrees of PoCL and PeCRC. We suggest this response is at least partially propelled by systemic catecholamines

The impact of donor policies in Europe: a steady increase, but not everywhere

<p>Abstract</p> <p>Background</p> <p>Transplantable organs are scarce everywhere. Therefore, countries have developed policies to support the efficient use of potential donors. Nevertheless, the shortage of organs remains. Were these policies in vain? The aim of this study is to assess the impact of donor policies on donor procurement in 10 Western European countries from 1995 to 2005.</p> <p>Method</p> <p>To assess the impact of the donor policies we studied the conversion of potential donors into effectuated donors. 80% of the donors died from CVAs or a (traffic) accident. We considered these mortality rates to be a good proxy for potential donors. Here we call the conversion of potential donors into actual donors 'the donor efficiency rate by proxy'.</p> <p>Results</p> <p>The mortality rates for CVA and (traffic) accidents have decreased in the countries under study. At the same time, in most countries the donor efficiency rates have steadily increased. The variance in donor efficiency rates between countries has also increased from 1995 to 2005. Four countries introduced a new consent system or changed their existing system, without (visible) long-term effects.</p> <p>Conclusion</p> <p>The overall increase in donor efficiency means that the efforts to improve donor policies have paid off. However, substantial differences between countries were found. The success of donor policies in terms of the number of absolute donors is blurred by the success of policies on traffic safety and CVA treatment. It remains unclear which specific policy measures are responsible for the increase in donor efficiency rates. This increase is not related to having a presumed consent system. Furthermore, an analysis of countries that introduced a new consent system or changed their system showed no effect on donor efficiency.</p

Integrated nanomechanical motion detection by means of optical evanescent wave coupling - art. no. 64640E

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H5N1 Influenza Vaccine Formulated with AS03A Induces Strong Cross-Reactive and Polyfunctional CD4 T-Cell Responses

Objective Adjuvantation of an H5N1 split-virion influenza vaccine with AS03(A) substantially reduces the antigen dose required to produce a putatively protective humoral response and promotes cross-clade neutralizing responses. We determined the effect of adjuvantation on antibody persistence and B- and T-cell-mediated immune responses. Methods Two vaccinations with a split-virion A/Vietnam/1194/2004 (H5N1, clade 1) vaccine containing 3.75-30 mu g hemagglutinin and formulated with or without adjuvant were administered to groups of 50 volunteers aged 18-60 years. Results Adjuvantation of the vaccine led to better persistence of neutralizing and hemagglutination-inhibiting antibodies and higher frequencies of antigen-specific memory B cells. Cross-reactive and polyfunctional H5N1-specific CD4 T cells were detected at baseline and were amplified by vaccination. Expansion of CD4 T cells was enhanced by adjuvantation. Conclusion Formulation of the H5N1 vaccine with AS03(A) enhances antibody persistence and induces stronger T- and B-cell responses. The cross-clade T-cell immunity indicates that the adjuvanted vaccine primes individuals to respond to either infection and/or subsequent vaccination with strains drifted from the primary vaccine strain

Implementing preoperative Botulinum toxin A and progressive pneumoperitoneum through the use of an algorithm in giant ventral hernia repair

Background Repair of large ventral hernias with loss of domain can be facilitated by preoperative Botulinum toxin A (BTA) injections and preoperative progressive pneumoperitoneum (PPP). The aim of this study is to evaluate the outcomes of ventral hernioplasty using a standardized algorithm, including component separation techniques, preoperative BTA and PPP. Methods All patients between June 2014 and August 2018 with giant hernias (either primary or incisional) of more than 12 cm width were treated according to a previously developed standardized algorithm. Retrospective data analysis from a prospectively collected dataset was performed. The primary outcome was closure of the anterior fascia. Secondary outcomes included complications related to the preoperative treatment, postoperative complications, and recurrences. Results Twenty-three patients were included. Median age was 65 years (range 28-77) and median BMI was 31.4 (range 22.7-38.0 kg/m(2)). The median loss of domain was 29% (range 12-226%). For the primary and secondary endpoints, 22 patients were analyzed. Primary closure of the anterior fascia was possible in 82% of all patients. After a median follow-up of 19.5 months (range 10-60 months), 3 patients (14%) developed a hernia recurrence and 16 patients (73%) developed 23 surgical site occurrences, most of which were surgical site infections (54.5%). Conclusion Our algorithm using both anterior or posterior component separation, together with preoperative BTA injections and PPP, achieved an acceptable fascial closure rate. Further studies are needed to explore the individual potential of BTA injections and PPP, and to research whether these methods can prevent the need for component separation, as postoperative wound morbidity remains high in our study