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- Dalianis, Tina, et al.
(author)
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Management of BK-virus infection - Swedish recommendations
- 2019
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In: Infectious Diseases. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 51:7, s. 479-484
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Research review (peer-reviewed)abstract
- BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.
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- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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- Remberger, Mats, et al.
(author)
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Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
- 2011
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
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Journal article (peer-reviewed)abstract
- We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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- Swartling, Lisa, et al.
(author)
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The Importance of Secretor-Status in Norovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation
- 2022
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In: Viruses. - : MDPI. - 1999-4915. ; 14:7
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Journal article (peer-reviewed)abstract
- Background. Human secretor-status is a strong susceptibility factor for norovirus infection in immunocompetent people. The predominant norovirus genotype GII.4 almost exclusively infects secretors and is also associated with more severe symptoms. However, it is not known to what extent this also applies to immunocompromised individuals. Our objective was to determine the importance of secretor-status and norovirus genotype for the susceptibility and/or the clinical course of norovirus infection in allogeneic hematopoietic stem cell transplant (HCT) patients. Methods: This was a retrospective study of 89 HCT patients diagnosed with norovirus infection. Secretor-status and norovirus genotype were determined using stored extracted DNA or blood (n = 89) and fecal samples (n = 22), respectively. Results: Seven of eighty-nine (8%) of the patients were secretor-negative, a small proportion compared to the expected rate of at least 20% non-secretors in the general Swedish population. Among the genotyped samples, norovirus genotype GII.4 was predominant (n = 12) and only detected in secretor-positive individuals. Patients with norovirus GII.4 had a median symptom duration of 36 (3-681) days compared to 15 (1-94) days in patients infected with other norovirus genotypes (n = 10, p = 0.1). Conclusions: The results suggest that secretor-status affects the susceptibility to norovirus infection even when the immune system is severely compromised. The norovirus genotype may also be a risk factor for chronic norovirus symptoms in immunocompromised patients.
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| 8. |
- Swartling, Lisa
(author)
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Viral gastrointestinal infections in allogeneic hematopoietic stem cell transplant patients
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Gastrointestinal symptoms, and elevated liver enzymes, are common after HSCT, often due to drug toxicity, graft-versus-host disease (GVHD) or infections. It is essential to distinguish between GVHD and infection, since both conditions may progress to lethal disease, but require opposite strategies for the immunosuppressive treatment. Several of the viral gastrointestinal infections are easily transmitted and can cause outbreaks in health care facilities. In this thesis I studied viral gastrointestinal infections in HSCT patients, with focus on human adenovirus (HAdV), norovirus and hepatitis E virus (HEV), addressing transmission within health care, clinical importance, risk factors for severe/prolonged disease and the importance of secretor-status. In paper I we analyzed an outbreak of HAdV at the Center for Allogeneic Hematopoietic Stem Cell transplantation (CAST), Karolinska University Hospital. We identified nine patients with HAdV A31. Hygiene measures were implemented, but the outbreak continued for a prolonged time. High strain on the staff during the early part of the outbreak, possible contamination of the facilities of the ward, and unidentified cases with sparse symptoms, may have contributed to the prolonged outbreak. The clinical consequences were significant, although no patient developed severe HAdV disease. Paper II was a retrospective study of the clinical importance, and risk factors for long-term symptoms, in 63 HSCT patients with norovirus infection. In paper III, we analyzed if secretor-status influenced the clinical course of norovirus infection in 89 HSCT patients with norovirus infection, of whom 63 also had been included in paper II. we found chronic symptoms of norovirus (>30 days) in 18/89 (20%) of the patients. Severe combined immunodeficiency (SCID) diagnosis was associated with chronic norovirus symptoms in both paper II and III, which may be due to the delayed immune reconstitution in many of these patients. The number of secretor-negative patients was low compared to the general population, indicating that secretor-negative genotype may protect against norovirus even when the patient is severely immunocompromised. Paper IV was a retrospective study of the frequency and clinical importance of HEV infection in a cohort of 236 HSCT recipients. HEV RNA was detected in 8/236 (3.4%) patients 6 months after HSCT. We found that elevated alanine aminotransferase (ALT) at six months after HSCT was associated with HEV infection. Spontaneous clearance was common, but one patient died of multiorgan failure where HEV infection may have contributed. In conclusion, we found that an outbreak of HAdV can be difficult to control and may have serious consequences. Norovirus causes chronic symptoms (> 30 days) in 20% of HSCT patients, and SCID as indication for HSCT is associated with a chronic course of norovirus infection. We found that problems discriminating symptoms of HAdV, or norovirus, from symptoms of gastrointestinal GVHD, are a significant clinical challenge. HEV infection is an infrequent, but potentially severe, differential diagnosis in patients with elevated ALT six months after HSCT.
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