Prophylactic Treatment Strategies Research Articles

Invasive aspergillosis in liver transplant recipients in the current era

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA.

P440 Myenteric plexitis and active inflammation at surgical margins are high-risk predictors for postoperative clinical recurrence of Crohn’s disease

Abstract Background Preventing postoperative recurrence is an important issue for clinical management of Crohn’s disease (CD). Identification of practical risk factors and an effective prophylactic treatment strategy has been desired for the prevention of postoperative recurrence. Although some of the clinical risk factors have been applied to select candidates for prophylactic treatments, these attempts have not fully prevented postoperative recurrence. In this study, we investigate the histological features at resected margins which predicted postoperative recurrence, and whether the initiation of prophylactic treatments could prevent postoperative recurrence in these cases. Methods We retrospectively reviewed the clinical recurrence rate in CD patients who underwent intestinal resection between January 2019 and December 2021. Clinical recurrence was defined by combination of serological, radiographic, and endoscopic findings or treatment escalation. To assess the histological risk factors for postoperative recurrence, resection margins of the surgical specimens were evaluated for the presence of myenteric plexitis, granulomas, and active inflammation. Each histological feature was evaluated from Grade 0 to 3. We also examined the ability of prophylactic treatments to prevent postoperative recurrence stratified with histological findings related to clinical recurrence rates. Results Of the 141 patients included in this study, 61.9% had plexitis (grade 3:Inflammatory cells at myenteric plexus, 10&amp;gt;HPF) at the proximal margin and 13.5% had active inflammation (grade 3: erosion or ulcer) at the distal margin. Log rank test identified the presence of plexitis (Grade3) (HR:1.84, 95%CI [1.05-3.22], p=0.029) at the proximal margin and active inflammation (Grade3) at the distal margin (HR:1.29, 95%CI [1.05-1.58], p=0.012) as possible risks of clinical recurrence (Figure). Multivariate analysis confirmed that the presence of plexitis (Grade3) at the proximal margin (HR 1.82, 95% CI 1.04-3.21, P=0.038) and active inflammation (Grade 3) at the distal margin (HR 2.31, 95% CI 1.18-4.46, P=0.013) were associated with postoperative clinical recurrence. Prophylactic use of immunomodulators (IM) and biologics did not show a significant reduction of clinical recurrence compared to treatment without IM and/or biologics in patient with histological risk factors (Table). Conclusion Our results indicate that the presence of plexitis in the proximal margin and active inflammation in the distal margin of the resected intestine are risk factors for postoperative recurrence. In these cases, initiation of prophylactic treatments with biologics and/or IM may not prevent the clinical recurrence.

Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing

BackgroundSome of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. Our goal was to provide a step-by-step methodological protocol for creating an alternative standardized, more economical, and transferable pre-clinical animal research model of excisional full-thickness wound healing following a simulated autologous tissue transfer which includes the primary ischemia, reperfusion, and secondary ischemia events with the latter mimicking flap salvage procedure.ResultsUnlike in the most frequently used classical unilateral McFarlane’s caudally based dorsal random pattern skin flap model, in the herein described bilateral epigastric fasciocutaneous advancement flap (BEFAF) model, one flap heals under normal and a contralateral flap—under perturbed conditions or both flaps heal under conditions that vary by one within-subjects factor. We discuss the advantages and limitations of the proposed experimental approach and, as a part of model validation, provide the examples of its use in laboratory rat (Rattus norvegicus) axial pattern flap healing studies. ConclusionsThis technically challenging but feasible reconstructive surgery model eliminates inter-subject variability, while concomitantly minimizing the number of animals needed to achieve adequate statistical power. BEFAFs may be used to investigate the spatiotemporal cellular and molecular responses to complex tissue injury, interventions simulating clinically relevant flap complications (e.g., vascular thrombosis) as well as prophylactic, therapeutic or surgical treatment (e.g., flap delay) strategies in the presence or absence of confounding risk factors (e.g., substance abuse, irradiation, diabetes) or favorable wound-healing promoting activities (e.g., exercise). Detailed visual instructions in BEFAF protocol may serve as an aid for teaching medical or academic researchers basic vascular microsurgery techniques that focus on precision, tremor management and magnification.Graphical

Effects of compound prebiotics as prophylactic and therapeutic supplementation in a mouse model of acute colitis.

Compound prebiotics (CP) have been explored in modulation of intestinal microbiota and remission of inflammatory responses in the acute colitis (AC). Yet, research on the roles of simultaneous prophylactic and therapeutic CP intervention in relation to AC remains lacking. Here, CP were pre-fed to examine preventive effects. CP, CP combined with mesalazine (5-aminosalicylic acid) (CPM), and mesalazine were used to evaluate therapeutic effects on the dextran sulfate sodium (DSS)-induced AC. Results showed that prophylactic CP and therapeutic CPM alleviated AC, evidenced by variations of body weight, colon length, spleen index, disease activity index score, histological score, and intestinal mucosa. Ruminococcus and Bifidobacterium were detected in significant abundance in the prophylactic CP and therapeutic CPM groups, respectively. Phylogenetic ecological network analysis revealed that therapeutic CPM probably had the strongest coupling between microbes in changing intestinal microbiota to influence treatment. However, changes in short-chain fatty acids (SCFAs) seemed to have no persuasive results, probably due to reduced SCFA level in feces and variability in transit, absorption, and utilization. Furthermore, therapeutic CP exerted higher value in terms of observed species and Shannon diversity, as well as a more concentrated distribution by principal coordinates analysis. Together, the favorable roles of CP in colitis provide directions for prebiotics in designing effective prophylactic functional diets and treatment strategies. KEY POINTS: • Prebiotics as prophylactic intervention effectively inhibited acute colitis. • Prebiotics as prophylactic and therapeutic interventions had distinct effects on gut microbiota. • Prebiotics combined with drug intervention had higher efficacy in treating acute colitis.

Risk assessment and prophylactic treatment strategies for central nervous system relapse of diffuse large B-cell lymphoma

Rituximab treatment significantly improved the outcomes of diffuse large B-cell lymphoma (DLBCL). A central nervous system (CNS) relapse remains a serious and fatal event for patients with DLBCL; therefore, the clinical question of the optimal treatment regimen for reducing the risk of CNS relapse remains unknown. The CNS-International Prognostic Index was identified as a predictive model for CNS relapse. No factors can completely predict CNS relapse although several reports regarding high-risk factors for CNS relapse have been reported. In practice, intrathecal methotrexate (MTX) and high-dose MTX therapy have been used for CNS prophylaxis. Unfortunately, evidence of the optimal therapy for CNS prophylaxis in patients with DLBCL remains lacking. This study aimed to review CNS relapse assessment and discuss study results with clinical impacts on CNS prophylaxis treatment strategies in DLBCL.

Pharmacokinetics of a FDA-labeled dose of diclazuril administered orally once weekly to adult horses

Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (ProtazilTM) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five individual diclazuril doses were administered at weekly intervals to 8 adult horses. Blood was collected via venipuncture immediately before (trough concentration) and 10 hours after (peak concentration) each diclazuril administration. Following the fifth dose, additional blood samples were collected every 24 hours after the peak blood collection for 7 days. All plasma samples were analyzed by high-pressure liquid chromatography. The pharmacokinetic analysis was performed using a nonlinear mixed effects model. The mean population-derived peak concentration was 264 ng/mL and the mean terminal half-life was 3.6 days. Thus, the oral administration of an FDA-labeled dose of diclazuril to healthy horses once a week was able to produce steady-state plasma drug concentrations known to inhibit S. neurona in vitro.

Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People's Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

Assessing the effectiveness of prophylactic treatment strategies for sheep scab

Ovine psoroptic mange (sheep scab) is a condition caused by a hypersensitivity response to the ectoparasitic mite, Psoroptes ovis. It is an animal welfare concern and causes extensive economic losses to the sheep industry worldwide. More effective scab management is required to limit increases in infection prevalence, particularly given growing concerns over acaricide resistance. Here, a stochastic metapopulation model is used to explore the effectiveness of a range of prophylactic acaricide treatment strategies in comparison to no intervention. Over a simulated one-year period, movement control, based on the prophylactic treatment of animals being moved in sales, followed by farm biosecurity of bought in animals, was shown to be the most effective at reducing scab risk and more cost-effective than no intervention. Localised targeting of prophylaxis in areas of high scab prevalence was more effective than using prophylaxis at random, however, this localised effect declined post-treatment because of the import of infected animals. The analysis highlights the role of the movement of infected animals in maintaining high levels of scab infection and the importance of reducing this route of transmission to allow localised management to be effective.

Effect of individualized treatment strategy on postoperative nausea and vomiting in gynaecological laparoscopic surgery: a double-blind, randomized, controlled trial

BackgroundPostoperative nausea and vomiting (PONV) have always been a concern of clinicians and may increase medical costs for patients. Consensus guidelines recommend using multiple antiemetics with different mechanisms as prophylaxis in patients at high risk of PONV. Individualized risk scores for nausea and vomiting and individualized treatment strategies are feasible. This study evaluated the effect of individualized treatment strategies on postoperative nausea and vomiting after laparoscopic gynaecological operations.MethodsThis was a double-blind, randomized, controlled trial. A total of 119 adult patients who underwent gynaecological laparoscopic surgery under general anaesthesia were randomly divided into an individualized treatment group or a control group, with the individualized treatment group receiving individualized prevention according to a preoperative risk score of nausea and vomiting and the control group receiving no individualized prevention. Vomiting, retching, nausea, and use of rescue medication were all recorded for 24 h after the operation. The primary outcome variable was complete response, defined as no emesis or the use of rescue medication 24 h postoperatively.ResultsThe complete response rate was higher in the individualized treatment group (56.7%) than in the control group (23.7%) (95% CI, 0.01–0.27; P < 0.001). The incidences of emesis (18.3% vs. 44.1%, P = 0.002) were significantly lower in the individualized treatment group than in the control group. There were no differences in any nausea (26.7% vs. 33.9%, P = 0.391) or rescue medication use (6.7% vs. 8.5%, P = 0.743). Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently in the individualized treatment group than in the control group.ConclusionIn conclusion, this single-centre, double-blind, randomized study suggests that an individualized PONV prophylactic treatment strategy based on the number of PONV risk factors could be a safe and effective regimen to reduce the incidence of PONV in adult patients undergoing laparoscopic gynaecological surgery.

CE: Diagnosing and Managing Migraine.

Roughly 90% of the U.S. population will develop a headache within their lifetime, and headache disorders account for more disability-adjusted life-years than all other neurologic disorders combined. Among primary headache disorders, the two most common are tension-type headache and migraine, with migraine identified as the most disabling. Here, the authors describe the importance of differentiating primary and secondary headache disorders and discuss the pathophysiology; clinical assessment; and outpatient management of the debilitating migraine headache, summarizing both acute and prophylactic treatment strategies that can substantially reduce associated disability.

Current osteomyelitis mouse models, a systematic review.

Osteomyelitis is an inflammatory bone disease caused by an infecting microorganism leading to a gradual bone loss. Due to the difficulty in studying osteomyelitis directly in patients, animal models allow researchers to investigate the pathogenesis of the infection and the development of novel prophylactic, anti-inflammatory and antimicrobial treatment strategies. This review is specifically focused on the in vivo mouse osteomyelitis studies available in literature. Thus, a systematic search on Web of Science and PubMed was conducted using the query "(infection) AND (mice OR mouse OR murine) AND (model OR models) AND (arthroplasty OR fracture OR (internal fixator) OR (internal fixation OR prosthesis OR implant OR osteomyelitis)". After critical assessment of the studies according to the inclusion and exclusion criteria, 135 studies were included in the detailed analysis. Based on the model characteristics, the studies were classified into five subject groups: haematogenous osteomyelitis, post-traumatic osteomyelitis, bone-implant-related infection, peri-prosthetic joint infection, fracture-related infection. In addition, the characteristics of the mice used, such as inbred strain, age or gender, the characteristics of the pathogens used, the inoculation methods, the type of anaesthesia and analgesia used during surgery and the procedures for evaluating the pathogenicity of the infecting micro-organism were described. Overall, the mouse is an excellent first step in vivo model to study the pathogenesis, inflammation and healing process of osteomyelitis and to evaluate novel prophylaxis and treatment strategies.

Hospital costs of delayed gastric emptying following pancreatoduodenectomy and the financial headroom for novel prophylactic treatment strategies

Hospital costs of delayed gastric emptying following pancreatoduodenectomy and the financial headroom for novel prophylactic treatment strategies

Relationship Between Prolonged Intraocular Inflammation and Macular Edema After Cataract Surgery.

PurposeTo assess whether aqueous flare is related to an increased risk of pseudophakic cystoid macular edema (PCME) following uneventful cataract surgery in nondiabetic and diabetic patients.MethodsA post hoc analysis of five consecutive randomized clinical trials in the Department of Ophthalmology, Kymenlaakso Central Hospital, Finland. Aqueous flare levels were recorded in 448 eyes of 448 patients before surgery, and after the course of topical anti-inflammatory treatment 28 days and three months after cataract surgery.ResultsAqueous flare increase of <50%, ≥50%, ≥100%, and ≥200% associated in central subfield macular thickness (CSMT) increase across the groups at 28 days and three months after surgery. Increase of aqueous flare ≥100% compared to those with <100% was associated with increased CSMT (P = 0.022 at 28 days, and P = 0.027 at three months). At three months, macular thickening (at least 10% CSMT increase) was observed in 12.7% compared to 4.6% of eyes when using a cutoff value of 100% increase in aqueous flare (P = 0.033). Although diabetic patients presented higher aqueous flare levels at baseline compared to nondiabetic patients (12.9 ± 11.8 vs. 9.8 ± 8.2 photon units/ms P < 0.001), the postoperative levels illustrated a similar profile in aqueous flare increase between the two groups.ConclusionsAt 28 days, aqueous flare increase was associated with macular thickening. A 100% cutoff value could potentially be used when studying anti-inflammatory efficacy of different treatment protocols. Flare values exceeding this cutoff value could be considered as an indication for extending anti-inflammatory therapy.Translational RelevanceA 100% increase in aqueous flare at 28 days after cataract surgery from baseline predicted macular thickening up to three months postoperatively. Identifying a correlation between increased aqueous flare levels and pseudophakic cystoid macular edema may allow recognition of the most vulnerable patients, development of prophylactic treatment strategies and reduction of the number and severity of postoperative complications.

Hospital costs of delayed gastric emptying following pancreatoduodenectomy and the financial headroom for novel prophylactic treatment strategies.

Delayed gastric emptying (DGE) is one of the most common complications following pancreatoduodenectomy (PD). In-hospital costs of DGE are unknown as well as the financial headroom for novel prophylactic treatments. This retrospective study aims to estimate the hospital costs of DGE and model the financial headroom per patient for new prophylactic treatment strategies within budget. Retrospective analysis of a single-center prospective database including patients after PD (2010-2017). In-hospital costs for clinically relevant DGE (ISGPS grade B/C) were calculated by comparing patient groups with and without DGE or other complications. The financial headroom per patient was modelled for potential reductions (0-100%) of empirical DGE baseline risks (15-30%). Overall, DGE was present in 156 (26.9%) of 581 patients after PD. Costs for patients with isolated DGE (n=90) were €10,295 higher than for patients without complications (n=333). Costs for patients with other complications including DGE (n=66) were €9008 higher than for patients with other complications without DGE (n=92). The financial headroom for a novel prophylactic treatment per patient undergoing PD was €975 per 10% absolute decrease of DGE risk. Hospital costs of DGE after PD are substantial. The financial headroom per patient for new DGE prophylactic treatments can be easily calculated via www.pancreascalculator.com.

In Silico Assessment of SARS-CoV-2 Mutations with Relevancy to Prophylactic and Monoclonal-Based Treatment Strategies

Abstract The ongoing pandemic caused by SARS-CoV-2 has inflicted significant disease burden worldwide. Several vaccines are now in use that are based on the virus’s highly immunogenic spike “S” protein, which mediates infection of host cells. However, since the emergence of the reference strain in 2019, the virus has underdone &amp;gt;40,000 nucleotide mutations, many of which have resulted in deletions or amino acid substitutions in the S protein. Most mutations appear to be random, while others deviate from expected outcomes. Indeed, some non-random mutations appear to confer resistance to either innate or adaptive immune functions while other enhance transmissibility. Although the consequences of these mutations are largely unknown, there is concern for the ability of select mutations to detract from the protection conferred by prophylaxis strategies and interventional therapies. We have therefore selected &amp;gt;50 whole genome-length mutant strain from 3 relatively closed populations to compare against widely circulating strains of concern and the reference strain so that we could assess differences in mutation events within the context of distinct population immunogenetics. For each strain we have biochemically characterized potentially critical mutations, assessed the randomness of each mutation, and assessed key mutations occurring in the S, M, E and N proteins for their ability to influence innate or adaptive immune recognition using bioinformatic platforms. The results of this study further our understanding for how these mutations influence population-based immunity to the virus, including biomedical interventions, as well as help explain the selection pressures and external events that are driving this genetic diversification.

Silk-elastinlike copolymers enhance bioaccumulation of semisynthetic glycosaminoglycan ethers for prevention of radiation induced proctitis

Radiation-induced proctitis (RIP) is a debilitating adverse event that occurs commonly during lower abdominal radiotherapy. The lack of prophylactic treatment strategies leads to diminished patient quality of life, disruption of radiotherapy schedules, and limitation of radiotherapy efficacy due to dose-limiting toxicities. Semisynthetic glycosaminoglycan ethers (SAGE) demonstrate protective effects from RIP. However, low residence time in the rectal tissue limits their utility. We investigated controlled delivery of GM-0111, a SAGE analogue with demonstrated efficacy against RIP, using a series of temperature-responsive polymers to compare how distinct phase change behaviors, mechanical properties and release kinetics influence rectal bioaccumulation. Poly(lactic acid)-co-(glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid)-co-(glycolic acid) copolymers underwent macroscopic phase separation, expelling >50% of drug during gelation. Poloxamer compositions released GM-0111 cargo within 1 h, while silk-elastinlike copolymers (SELPs) enabled controlled release over a period of 12 h. Bioaccumulation was evaluated using fluorescence imaging and confocal microscopy. SELP-415K, a SELP analogue with 4 silk units, 15 elastin units, and one elastin unit with lysine residues in the monomer repeats, resulted in the highest rectal bioaccumulation. SELP-415K GM-0111 compositions were then used to provide localized protection from radiation induced tissue damage in a murine model of RIP. Rectal delivery of SAGE using SELP-415K significantly reduced behavioral pain responses, and reduced animal mass loss compared to irradiated controls or treatment with traditional delivery approaches. Histological scoring showed RIP injury was ameliorated for animals treated with GM-0111 delivered by SELP-415K. The enhanced bioaccumulation provided by thermoresponsive SELPs via a liquid to semisolid transition improved rectal delivery of GM-0111 to mice and radioprotection in a RIP model.

Synthetic Phenolic Glycolipids for Application in Diagnostic Tests for Leprosy.

Point‐of‐care (POC) diagnostic tests for the rapid detection of individuals infected with Mycobacterium leprae, the causative pathogen of leprosy, represent efficient tools to guide therapeutic and prophylactic treatment strategies in leprosy control programs, thus positively contributing to clinical outcome and reducing transmission of this infectious disease. Levels of antibodies directed against the M. leprae‐specific phenolic glycolipid I (PGL−I) closely correlate with an individual's bacterial load and a higher risk of developing leprosy. We describe herein the assembly of a set of PGL glycans carrying the characteristic phenol aglycon and featuring different methylation patterns. The PGL trisaccharides were applied to construct neoglycoproteins that were used to detect anti‐PGL IgM antibodies in leprosy patients. ELISAs and quantitative lateral‐flow assays based on up‐converting nanoparticles (UCP‐LFAs) showed that the generated PGL−I and PGL‐II trisaccharide neoglycoconjugates can be applied for the detection of anti M. leprae IgM antibodies in POC tests.

Hospital costs of delayed gastric emptying following pancreatoduodenectomy and the financial headroom for novel prophylactic treatment strategies

Introduction: Delayed gastric emptying (DGE) is one of the most common complications following pancreatoduodenectomy (PD). In-hospital costs of DGE are unknown as well as the financial headroom for novel prophylactic treatments. This retrospective study aims to estimate the hospital costs of DGE and model the financial headroom per patient for new prophylactic treatment strategies within budget.

Assessment of two prophylactic fluid strategies in aneurysmal subarachnoid hemorrhage: A randomized trial.

ObjectiveTo compare the effect of two prophylactic euvolemic fluid strategy regimens on the incidence of cerebral vasospasm and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH).MethodsNinety-six patients with a basal intravenous intake of 15 mL/kg/day of Ringer’s lactate solution were included, and an additional 15 to 50 mL/kg/day Ringer’s lactate (RL-group) or hydroxyethyl starch 130/0.4 solution (HES-group) was administered to maintain the targeted mean arterial pressure. The primary end point was the occurrence of cerebral vasospasm during the first 14 days. The secondary end points were case fatality, Barthel’s index, and Glasgow Outcome Scores (GOS) at 30 days after SAH.ResultsCerebral vasospasm developed in 42 patients (43.7%), and nine of these events were severe. The vasospasm rate among the RL- and HES-based groups was 25/48 and 17/48, respectively. For the secondary endpoint, four patients (4%) died by the end of follow-up (two in each group). Unfavorable outcome cases were not different in the RL and HES groups (9 vs. 14, respectively). There was no difference between the Barthel’s scores at 30 days between the two groups.ConclusionsUsing starches in a prophylactic treatment strategy in aneurysmal SAH in not supported by the study.The trial was registered at Clinicaltrials.gov under the number NCT02064075

Assessing Anti-HCMV Cell Mediated Immune Responses in Transplant Recipients and Healthy Controls Using a Novel Functional Assay.

HCMV infection, reinfection or reactivation occurs in 60% of untreated solid organ transplant (SOT) recipients. Current clinical approaches to HCMV management include pre-emptive and prophylactic antiviral treatment strategies. The introduction of immune monitoring to better stratify patients at risk of viraemia and HCMV mediated disease could improve clinical management. Current approaches quantify T cell IFNγ responses specific for predominantly IE and pp65 proteins ex vivo, as a proxy for functional control of HCMV in vivo. However, these approaches have only a limited predictive ability. We measured the IFNγ T cell responses to an expanded panel of overlapping peptide pools specific for immunodominant HCMV proteins IE1/2, pp65, pp71, gB, UL144, and US3 in a cohort of D+R– kidney transplant recipients in a longitudinal analysis. Even with this increased antigen diversity, the results show that while all patients had detectable T cell responses, this did not correlate with control of HCMV replication in some. We wished to develop an assay that could directly measure anti-HCMV cell-mediated immunity. We evaluated three approaches, stimulation of PBMC with (i) whole HCMV lysate or (ii) a defined panel of immunodominant HCMV peptides, or (iii) fully autologous infected cells co-cultured with PBMC or isolated CD8+ T cells or NK cells. Stimulation with HCMV lysate often generated non-specific antiviral responses while stimulation with immunodominant HCMV peptide pools produced responses which were not necessarily antiviral despite strong IFNγ production. We demonstrated that IFNγ was only a minor component of secreted antiviral activity. Finally, we used an antiviral assay system to measure the effect of whole PBMC, and isolated CD8+ T cells and NK cells to control HCMV in infected autologous dermal fibroblasts. The results show that both PBMC and especially CD8+ T cells from HCMV seropositive donors have highly specific antiviral activity against HCMV. In addition, we were able to show that NK cells were also antiviral, but the level of this control was highly variable between donors and not dependant on HCMV seropositivity. Using this approach, we show that non-viraemic D+R+ SOT recipients had significant and specific antiviral activity against HCMV.