Occurrence Of Severe Infections Research Articles

Impact of COVID-19 Vaccination in Thailand: Averted Deaths and Severe Infections Across Age Groups

The COVID-19 pandemic has underscored the pivotal role of vaccines in mitigating the devastating impact of the virus. In Thailand, the vaccination campaign against SARS-CoV-2 began on 28 February 2021, initially prioritizing healthcare professionals before expanding into a nationwide effort on 7 June 2021. This study employs a mathematical model of COVID-19 transmission with vaccination to analyze the impact of Thailand’s COVID-19 vaccination program from 1 March 2021 to 31 December 2022. We specifically assess the potential loss of lives and occurrence of severe infections across various age groups in a hypothetical scenario where vaccines were not administered. By fitting our model with officially reported COVID-19 death data, our analysis reveals that vaccination efforts prevented a total of 300,234 deaths (95% confidence interval: 295,938–304,349) and averted 1.60 million severe COVID-19 infections (95% confidence interval: 1.54–1.65 million). Notably, the elderly population over 80 years old benefited the most from vaccination, with an estimated 84,518 lives saved, constituting 4.28% of this age group. Furthermore, individuals aged between 70 and 74 years experienced the highest reduction in severe infections, with vaccination potentially preventing 8.35% of this age bracket from developing severe COVID-19.

Intrapartum antibiotic exposure and infectious diseases in childhood – a population-based cohort study

Intrapartum antibiotics are used to prevent group B streptococcus disease in newborn infants. We hypothesised that intrapartum antibiotic exposure is associated with the occurrence of childhood infectious diseases because it influences the development of the gut microbiome. The cohort for this population-based study comprised vaginally delivered children born in Northern Finland in 2007-2018. We used structured electronic medical records linked to comprehensive national registers. Primary outcome was the number of infectious disease episodes leading to an emergency room visit, outpatient hospital visit, or hospitalisation from birth until five years of age. Analyses were performed on 9733 children (48.8% girls) exposed to intrapartum antibiotics and on 35,842 unexposed children (49.9% girls). Exposure to intrapartum antibiotics was associated with increased risk of any infectious disease episode at the ages 7-28 days (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.10-1.54) and 1-2 years (aIRR 1.10, 95% CI 1.02-1.18). The occurrence of urinary tract infections was associated with the exposure to intrapartum antibiotics whereas the occurrence of severe infections caused by pathogens susceptible to penicillin was reversely associated with the exposure to intrapartum antibiotics. Maternal intrapartum antibiotics were associated with the occurrence of infectious diseases in the offspring. The observed associations appeared to depend on bacterial pathogens and their antimicrobial susceptibility to penicillin. Pediatric Research Foundation, Alma och K.A. Snellman Foundation, Orion Research Foundation, Päivikki and Sakari Sohlberg Foundation, Finnish Medical Foundation, Academy of Finland, Finland.

Hypogammaglobulinemia and severe infections in Multiple Sclerosis patients on anti-CD20 agents: a multicentre study

BackgroundHypogammaglobulinemia (HG) is a known side effect of treatment with anti-CD20 monoclonal antibodies, and it is associated with the risk of infections. ObjectivesAim of this retrospective multicentre study was to assess the frequency of HG in Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder patients treated with Ocrelizumab or Rituximab and its association with the occurrence of severe infections (SI). Furthermore, predictors of HG and SI were sought. MethodsWe included 556 patients (190M, 366F, mean age: 47 years) with a mean follow-up of 28 months (range 12-90 months). ResultsIgG HG occurred in 20% and IgM HG in 34% of patients. At multivariable analysis, the risk of IgG HG was influenced by an older age (≥50 years) (OR 1.64, 95%CI: 1.06-2.54, p=0.027), and by the number of treatment cycles (OR: 1.20, 95%CI: 1.09-1.33, p<0.001).A total of 25 SI occurred (100 person-years rate: 1.8), with a disease phenotype other than relapsing-remitting (OR 1.50, 95%CI: 1.02-2.20; p=0.039) and IgG HG (OR 2.65, 95%CI: 1.15-6.12; p=0.022) increasing its risk. ConclusionsIgG and IgM HG occurred in a considerable proportion of patients. IgG HG increased the risk of SI, which were, nevertheless, relatively infrequent. Our results highlight the importance of monitoring immunoglobulin levels during treatment with anti-CD20 agents, to personalize treatment strategies.

Combination treatment with telitacicept, mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy: A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A (IgA) antibody production by inhibiting the activity of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby decreasing IgA deposition in the glomeruli and local inflammatory response. This ultimately protects the kidneys from damage. This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy. CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment. Pathologically, she exhibited focal proliferative glomerulonephritis. Treatment with angiotensin II receptor blocker, hormones, and mycophenolate mofetil did not lead to a significant improvement in her condition. However, upon the addition of telitacicept, the patient’s renal function recovered and her proteinuria rapidly reduced. Hormones were swiftly tapered and discontinued, with no occurrence of severe infections or related complications. CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

Rational use of immunoglobulins (IVIgs and SCIgs) in secondary antibody deficiencies.

Immunoglobulins for intravenous use (IVIgs) and subcutaneous use (SCIgs) can prevent recurrent and severe infections in patients with secondary antibody deficiencies that are frequently linked to haematological/oncological malignancies as well as other clinical conditions and their respective treatments. Even so, as IVIgs and SCIgs are costly and their supply is limited, their clinical use must be optimised. The aim of this position paper is to provide structured practical guidance on the optimal use of IVIgs and SCIgs in secondary antibody deficiencies, particularly in haematological and oncological practice. The authors agree that the occurrence of severe infections is a prerequisite for the use of IVIgs. Serum IgG levels in general as well as IgG subclass levels can be additional indicators of whether a patient could benefit from IVIgs. Responsiveness to vaccines can help to identify immunodeficiency. Patients with chronic lymphocytic leukaemia or multiple myeloma who are receiving respective treatment, especially B-cell depletion therapy, but also some patients with autoimmune diseases are prone to antibody deficiencies and need IVIgs. For the optimal use of IVIgs and to maximise their potential benefit, the indication must be individually assessed for each patient. As a primary treatment goal, the authors define a sufficient prophylaxis of severe infections, which can be supported by normalising IgG levels. If the initiated treatment is insufficient or linked to intolerable adverse reactions, switching the product within the class of IVIgs or changing to a different batch of the same product can be considered. Pausing treatment can also be considered if there are no infections, which happens more frequently in summer, but treatment needs to be resumed once infections return. These structured recommendations for IVIg treatment in patients with secondary antibody deficiency may provide guidance for clinical practice and therefore help to allocate IVIgs to those who will benefit the most, without overusing valuable resources.

Clinical Presentation, Pathological Spectrum, and Outcomes of Alcoholic Cirrhosis-Related Immunoglobulin A Nephropathy

BackgroundIgA nephropathy associated with cirrhosis is frequent but often overlooked as largely considered silent. Until now, little has been known about their presentation and outcomes. MethodsWe conducted a retrospective multicenter study on patients with kidney biopsy-proven cirrhosis-related IgA nephropathy (cirrhosis-IgAN), diagnosed between 2009 and 2022. We mixed them up with 83 primary IgA nephropathy (pIgAN) diagnosed during the same period, using a partitioning clustering approach, to determine common clinicopathological profiles. ResultsAll the 46 patients with cirrhosis-related IgA nephropathy had an excessive alcoholic consumption. Clinical presentation was severe with acute kidney injury (AKI) in 79%, alternative causes of AKI was found in 62% of cases. Three clinicopathological clusters were identified: one represented chronic involvement, the second could be assimilated to mild disease, and the third corresponded to a MPGN pattern and was associated with heavy proteinuria and intrinsic AKI (without alternative causes). While the two first were equally distributed between pIgAN and cirrhosis-IgAN, the third was more frequent in patients with cirrhosis. The cumulative mortality rate in cirrhosis-IgAN was 26% and 46% at 1-year and 3-years. Steroid exposure and moderate/severe AKI were associated with higher mortality and steroid exposure was associated with the occurrence of severe infection. ConclusionOur results suggest that high AKI incidence is related to extrinsic causes in most cases but can also be driven by IgA-dominant MPGN in a subset of patients. Steroid use was associated with infectious disease and mortality. Further studies are needed to clarify the place of immunosuppressive treatment in cirrhosis-IgAN patients.

Analysis of surgical site infection and tumour-specific survival rate in patients with renal cell carcinoma after laparoscopic radical nephrectomy.

Surgical site infections (SSIs) may pose a significant risk to patients undergoing surgery. This study aims to explore the risk factors for SSIs in patients undergoing laparoscopic radical nephrectomy for renal cell carcinoma and the impact of infection on tumour-specific survival (CSS) after nephrectomy for renal cell carcinoma. To explore the risk factors for SSIs in patients undergoing laparoscopic radical nephrectomy for renal cell carcinoma and the impact of infection on tumour-specific survival (CSS) after nephrectomy for renal cell carcinoma. A retrospective analysis was conducted on 400 patients in our hospital from June 2021 to June 2023. This study divided patients into two groups: those with SSI and those without SSI. Collect general data and information related to the operating room. Clearly defined inclusion and exclusion criteria. Select surgical time, laminar mobile operating room use, and intraoperative hypothermia as observation indicators. Perform statistical analysis using SPSS 25.0 software, including univariate, multivariate, and survival analyses of wound-infected and uninfected patients. Out of 400 patients, 328 had no SSIs, 166 died during follow-up, 72 had SSIs, and 30 died during follow-up. There was no statistically significant difference (p > 0.05) in comparing primary data between individuals without SSIs and those with SSIs. There were statistically significant differences (p < 0.05) in surgical time, nonlaminar flow operating room use, and intraoperative hypothermia. The postoperative survival time of SSI patients with a tumour diameter of 7.0-9.9 cm was significantly longer than that of SSI patients, and the difference was statistically significant (p < 0.05). The occurrence of severe infection in patients with other tumour diameters did not affect postoperative survival, and the difference was not statistically significant (p > 0.05). After multiple factor analysis, it was found that severe infection can prolong the postoperative survival of patients with tumour diameter exceeding 7 cm (HR = 0.749, p < 0.05). This study identified nonlaminar flow operating rooms, prolonged surgical time, and intraoperative hypothermia as significant risk factors for SSIs. After nephrectomy for renal cell carcinoma patients with a tumour diameter of 7-9.9 μ m, perioperative infection can prolong their survival. However, it has no significant effect on patients with other tumour diameters.

Diagnosis of Malnutrition According to GLIM Criteria Predicts Complications and 6-Month Survival in Cancer Outpatients.

Background and Aims: Malnutrition is a condition that has a great impact on oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity, and reduced tolerance to chemotherapy, among other complications. The recently developed GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. We aimed to evaluate the performance of these new criteria for the prediction of complications and mortality in patients with cancer. Methods: This work is a prospective, single-center study. All outpatients under active treatment for head and neck, upper gastrointestinal, and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival based on GLIM diagnoses of malnutrition. Results: We enrolled 165 outpatients, 46.66% of whom were malnourished. During the 6-month follow-ups, patients with malnutrition (46.7%, according to GLIM criteria) had a ~3-fold increased risk of hospital admission (p < 0.001) and occurrence of severe infection (considered as those requiring hospitalization, intravenous antibiotics, and/or drainage by interventional procedures) (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for higher doses of opioids (both p < 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). The 6-month survival of malnourished patients was significantly lower (p = 0.023) than in non-malnourished patients. Conclusions: Diagnoses of malnutrition according to the GLIM criteria in oncology patients undergoing active treatment predict increased complications and worse survival at 6-month follow-ups, making them a useful tool for assessing the nutritional status of oncology patients.

Diagnosis of malnutrition according to glim criteria predicts complications and six-month survival in cancer outpatients.

e24093 Background: Malnutrition is a condition with great impact in oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity and reduced tolerance to chemotherapy, among other complications. The recent GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. Due to the few studies that assess the predictive capacity of these new criteria, we aimed to evaluate their performance for the prediction of complications and mortality in patients with cancer. Methods: Prospective, single-centre study. All outpatients under active treatment for head and neck, upper gastrointestinal and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival, based on GLIM diagnosis of malnutrition. Results: We enrolled 165 outpatients 46.66% malnutrition. During 6-month follow-up, patients with malnutrition (46.7%, according to GLIM criteria) had an ̃3-fold increased risk of hospital admission (p &lt; 0.001) and the occurrence of severe infections (considered as such those requiring hospitalization, intravenous antibiotics and/or drainage by interventional procedure) during follow-up (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for a higher dose of opioids (both p &lt; 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). 6-month survival of malnourished patients was significantly lower (p = 0.023) than non-malnourished patients. Conclusions: Diagnosis of malnutrition according to GLIM criteria in oncology patients on active treatment predicts increased complications and worse survival at 6-month follow-up, making them a useful tool to assess the nutritional status of oncology patients.[Table: see text]

IgA Vasculitis With Henoch-Schönlein Purpura as an Immune Complication Associated With Left Ventricle Assist Device Insertion.

The implantation of left ventricular assist devices (LVADs) in patients with end-stage heart failure can be associated with some forms of immune dysregulation and systemic inflammatory response. These abnormalities may be related to impaired T-lymphocyte-dependent immunity and B-lymphocyte hyper-reactivity and may lead to the development of autoimmune processes and the occurrence of severe infections. We present here the first observation of a peculiar immune complication associated with the implantation of an LVAD, characterized by an IgA vasculitis clinically manifested as Henoch-Schönlein purpura. The vasculitis was biologically associated with a significant increase of the plasma levels of C-X-C motif chemokine ligand (CXCL)13, a CXC motif chemokine produced by follicular dendritic cells, which targets CXCR5, a receptor primarily expressed by B lymphocytes, to promote their chemotaxis and expansion. Spontaneous resolution of the vasculitis occurred over time, concomitantly to a decrease of CXCL13 expression. These findings suggest that CXCL13 might be an interesting biomarker to detect auto-antigen sampling and the risk of secondary immune complications following LVAD implantation.

OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

OP0098 POLYPHARMACY IS ASSOCIATED WITH A POORER TREATMENT RESPONSE AND INCREASED RISK OF ADVERSE EVENTS IN EARLY RHEUMATOID ARTHRITIS

Association between body mass index and severe infection in older adults with microscopic polyangiitis: a retrospective cohort in Japan

BackgroundAlthough previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that older adults with AAV and a low BMI would be at a higher risk of infection. We therefore investigated the association between underweight status at AAV diagnosis and subsequent occurrence of severe infection in older adults with AAV.MethodsThis single-center retrospective cohort study included 93 consecutive older adults with microscopic polyangiitis (MPA) treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models. The cumulative probability of the development of the first severe infection was calculated using the Kaplan-Meier method and the log-rank test. The level of statistical significance was set at P < 0.05.ResultsDuring the median follow-up period of 19 (6–53) months, 29 (31.2%) patients developed at least one severe infection. Older age (adjusted hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.14–3.52, per 10 years; P = 0.016), low BMI (< 18.5 kg/m2 compared with normal BMI [18.5–23.0 kg/m2], adjusted HR = 2.63, 95% CI: 1.11–6.19; P = 0.027), and use of methylprednisolone pulse therapy (adjusted HR = 2.48, 95% CI: 1.07–5.76; P = 0.034) were found to be significant predictors of severe infection.ConclusionsLow BMI was associated with a higher risk of severe infection in older adults with MPA, suggesting that careful management may be required to prevent this complication in this vulnerable group. Further studies are needed to elucidate the optimal treatment strategy for these patients.

Predicting and comparing postoperative infections in different stratification following PCNL based on nomograms

To discuss the mechanisms of infection complications in different degrees after percutaneous nephrolithotomy (PCNL) through predicting and comparing post-PCNL infections based on nomograms, a retrospective cohort study was conducted among 969 cases who underwent PCNL from Dec 5, 2016 to Dec 25, 2017 in Kunming, Yunnan Province. We examined clinical features, urine routine, blood routine, blood biochemistry, imaging studies and operative information and recorded the examination results before surgery for univariate and multivariate logistic regression. We applied receiver operating characteristic curves, calibration curves, accuracy, specificity, sensitivity, positive predictive value and negative predictive value to evaluate and compare the models. Nomograms were used to visualize the different degrees of postoperative infection complications. The risk scores of the three groups were compared by diabetes mellitus distribution. Our results suggest that the more severe the infection is, the more accurate the model predicts and that the occurrence of severe infection mostly is related to the patients' homeostasis. Hence, we developed an online post-PCNL sepsis dynamic nomogram which can achieve visualization and dynamically predict the incidence of sepsis in postoperative patients.

Late Steroid Withdrawal Following AB0-Incompatible Renal Transplantation

BackgroundCurrent evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. MethodsSteroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W). For comparison, we analyzed 19 patients who remained on triple immunosuppression including steroids (group M). Minimum follow-up was 24 months following transplantation and 12 months after steroid withdrawal. ResultsBaseline characteristics, including observation times, were not different between groups W and M. Graft survival was 100% in group W compared with 84% (16/19) in group M (P = .15). In group M, 1 patient experienced graft failure because of suspected antibody-mediated rejection (ABMR) following temporary cessation of mycophenolate treatment after a diagnosis of cryptococcal pneumonia. Two patients died with functioning graft because of sepsis. In group W, we observed 1 episode of ABMR following steroid withdrawal. At the end of follow-up, estimated glomerular filtration rates (eGFR) were 54 (19–91) versus 60 (15–85) mL/min/1.73 m2 in group W versus M, respectively (P = .67). ConclusionsLate steroid withdrawal following AB0i transplantation is feasible at a moderate risk of rejection. We recommend close monitoring of renal function and HLA antibodies during and after steroid withdrawal. On the other hand, the occurrence of severe infections causing death and graft loss in patients on triple maintenance immunosuppression including steroids should remind us to consider the overall immunosuppressive burden.

Parenteral nutrition associated cholestasis

Parenteral nutrition (PN) is life saving for many preterm infants and other neonates with severe illness, but prolonged use of PN can lead to intrahepatic cholestasis, referred to as parenteral nutrition–associated cholestasis (PNAC). It is defined as direct bilirubin greater than 2.0 mg/dL persistent for at least 2 consecutive tests duringthe administration of PN, not associated with other known causes of cholestasis [1-3]. With the increasing survival of preterm infants and neonates requiring intensive care, PNAC has become a more common clinical challenge. The incidence of PNAC varywidely depending on the population studied, with high incidencein populations carrying several risk factors for PNAC. It increases with duration of PN and ranges from 10% to 85% in infants [4-8]. A multifactorial aetiology has been proposed for the development of PNAC. Recognized risk factors for PNAC include low birth weight, low gestational age, necrotizing enterocolitis, intestinal malformations, and intestinal surgery. A further risk factor is the occurrence ofsevere infections, due to the requirement for central line for infusion of PN, and bacterial overgrowth caused by enteralstarvation and immature immune function[9-13]. However, exposure to PN is demonstratedas the main factor in the development of PNAC. Intravenous hyper-alimentationhas been implicated, such as thetotal caloric overload, the quality of aminoacid solutions, the cumulative amount and the quality of lipid infusion, the presence of excessivealuminium in the PN solution, and the high manganese intake with PN [1,14-17]. Ursodeoxycholic acid, cyclic PN, light protection for PN, tapering the soybean-based lipid emulsion, and antibiotics to decontaminate bacterial overgrowth are used to treat PNAC [18-21]. In recent years, increasing attention has been paid to the lipid content in PN. It has been found that fish oil–containing lipid emulsions could be useful in infants to reverse PNAC for whom enteral feeding is intolerable. However, no evidence supports the use of fish oil–containing lipid emulsions to prevent PNAC in neonates, including preterm infants [22]. Enteral feeding remains the best strategy to reverse and prevent PNAC, with as little as 10% of caloric intake showing beneficial effects [5,22].

ATG induction in renal transplant recipients: Long-term hazard of severe infection is associated with long-term functional T cell impairment but not the ATG-induced CD4 cell decline

Background and methodsWe showed previously that rabbit ATG induction induces a strong decrease of CD4+ T cells together with impaired in vitro IL-2 secretion up to 1year post-transplant. To further characterize long-term immunological effects of ATG induction 2 and 5years post-transplant, we used sensitive intracellular cytokine analysis in the same prospective study of 84 renal transplant recipients (ATG, n=44). ResultsA significantly increased frequency of severe infectious disease (HR=2.0, p=0.027) as well as suppressed T cell functions were found within 2years after ATG induction but not beyond (logistic regression (logreg): CD4 cell IL-10 responses, p=0.064; T cell proliferation, p=0.038). Impaired T cell proliferation at 2years was associated with occurrence of severe infection (p=0.017). Importantly, a strong and persistent decrease of CD4 cell counts (p<0.0005 at 5years) was independently associated with ATG induction (logreg p=0.002) but not related to functional CD4 cell impairment (helper activity/cytokine production) or an increased risk of infection. ConclusionsSevere infection up to 2years after ATG induction was associated with impaired T cell proliferative capacity but not with the profound decline in CD4 cell counts that occurred after ATG induction and persisted up to 5years.

Is Renal Allograft Dysfunction a Risk Factor for Severe Infection in Kidney Transplant Recipients?

The ANTICIPE study is a cross-sectional, multicenter, French study. The aim of this study was to describe clinical and biological parameters observed in a cohort of 1446 stable renal transplant recipients, according to the stage of chronic kidney disease. Severe infection was defined as an infection necessitating ≥7 days of hospital stay. We observed a negative correlation between declining glomerular filtration rate and occurrence of severe infection (P < .0001). In multivariate analysis, severe infection was associated with age, female gender, chronic kidney disease stage (Kidney Disease Outcomes Quality Initiative classification), and number of acute rejection episodes. Our study suggested that renal allograft function is a predictor not only of cardiac death and cardiovascular complications, but also of severe infections.

M-ficolin levels are associated with the occurrence of severe infections in patients with haematological cancer undergoing chemotherapy

The pattern recognition molecules H-ficolin, L-ficolin and M-ficolin bind to micro-organisms. They activate the lectin pathway of complement through mannan-binding lectin (MBL)-associated serine proteases (MASPs). Association between low MBL levels and infections in patients undergoing chemotherapy for haematological diseases has been observed previously. We now examine for MASP-2, MASP-3 and ficolin levels. We assessed the concentration of lectin pathway molecules as risk factors for infection in patients with haematological malignancy undergoing chemotherapy. Samples taken before the initiation of chemotherapy covering 117 chemotherapy cycles in 105 patients were available. MASPs and ficolins were measured by time-resolved immunoflourometric assays and the levels related to parameters of infections. End-points included febrile neutropenia, documented infections, bacteraemia or severe infections. Lower M-ficolin concentrations were found in patients who developed a severe infection: median 0·27 µg/ml compared to 0·47 µg/ml in patients who did not develop a severe infection (P = 0·01). Conversely, MASP-2 was higher in these patients: median 0·53 µg/ml compared to 0·37 µg/ml, respectively (P = 0·008). When considering M-ficolin levels below 0·36 µg/ml as deficient, the time to development of severe infection was shorter in the M-ficolin deficient group: the hazard ratio was 2·60 (95% confidence interval: 1·23-5·49). No associations were revealed between infections and H-ficolin, L-ficolin or MASP-3. Patients with low M-ficolin are more likely to develop severe infections, whereas MASP-2 showed the opposite.

Thymus and immune reconstitution after allogeneic hematopoietic stem cell transplantation in humans: never say never again

Assessment of the host immune status is becoming a key issue in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the long-term follow-up of these patients, severe post-transplant infections, relapse or secondary malignancies may be directly related to persistent immune defects. In allo-HSCT, T-cell differentiation of donor progenitors within the recipient thymus is required to generate naive recent T-cell emigrants (RTE). These cells account for a durable T-cell reconstitution, generating a diverse T-cell receptor (TCR) repertoire and robust response to infections. It is now possible to quantify the production of RTE by measuring thymic T-cell receptor excision circles or 'TREC' which are small circular DNA produced during the recombination of the genomic segments encoding the TCR alpha chain. Here we discuss the role of thymic function in allo-HSCT. The pre-transplant recipient thymic function correlates with clinical outcome in terms of survival and occurrence of severe infections. Post-transplant, TREC analysis showed that the thymus is a sensitive target to the allogeneic acute graft-versus-host disease (GvHD) reaction but is also prone to recovery in young adult patients. In all, thymus is a key player for the quality of immune reconstitution and clinical outcome after allo-HSCT. Thymic tissue is plastic and it is a future challenge to halt or reverse thymic GVHD therapeutically by acting at the level of T-cell progenitors generation, thymic homing and/or epithelial thymic tissue preservation.

Rituximab for Patients With Refractory Mucous Membrane Pemphigoid

Mucous membrane pemphigoid (MMP) still represents a potentially life- and sight-threatening disease. In a subset of patients with severe MMP, conventional immunosuppressants are ineffective or contraindicated. Twenty-five patients with severe refractory MMP, including 5 with mucous membrane-dominant epidermolysis bullosa acquisita, received 1 or 2 cycles of rituximab (375 mg/m(2) weekly for 4 weeks). Twenty-one of the patients were receiving concomitant therapy with dapsone and/or sulfasalazine therapy, which was maintained during rituximab cycles. Complete responses in all affected sites (ocular and/or extraocular) were obtained in 17 patients (68%) by a median time of 12 weeks after the first cycle, and 5 additional patients responded completely after a second cycle, yielding an 88% complete response rate. In all but 1 of the 10 patients with ocular lesions, their eyes became noninflammatory within a mean of 10 weeks. Among the 3 patients (12%) who developed severe infectious complications, 2 (8%) died; they had been receiving concomitant conventional immunosuppressants and high-dose corticosteroids and were hypogammaglobulinemic. Treatment with immunosuppressants was discontinued for all other patients, and no other infection was observed. Ten patients experienced relapse after a mean of 4 (range, 1-16) months after achieving complete responses. Rituximab appears to have rapid and dramatic efficacy in patients with severe, refractory MMP. The occurrence of severe infections in patients receiving concomitant conventional immunosuppressants supports using rituximab without other immunosuppressants. Controlled prospective studies are warranted to define an optimal treatment protocol.