The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia: a prospective study in kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. METHODS: This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. RESULTS: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)). CONCLUSIONS: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.

BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor. METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound. RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred. CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).

Daily activity performance in congenital and childhood forms of myotonic dystrophy type 1: a population-based study.

AIMS: To identify and describe the profile characterizing motor and process skills during daily activity performance in individuals with congenital and childhood forms of myotonic dystrophy type 1 (DM1) and to investigate differences in performance between subgroups. METHOD: Sixty participants (34 males, 26 females, mean age=17y 8mo, SD=6y 0mo, range 5y 8mo-29y 0mo) were divided into severe congenital (n=9), mild congenital (n=20), and childhood (n=31) DM1 subgroups. Daily activity performance was evaluated using a standardized observational instrument: the Assessment of Motor and Process Skills. RESULTS: Deficits in performance were more pronounced in process than motor skills. Performance more than 2 SDs below age-specific norms was seen in 65% of participants for process skills and 33% of participants for motor skills. The cut-off scores indicated a potential need for assistance in daily activities for 79% of participants older than 18 years of age (n=28) due to deficient process skills. INTERPRETATION: Extensive deficits in daily activity performance were found in congenital and childhood forms of DM1, mainly owing to deficient process skills. Such skills impact on the ability to perform daily activities and could explain dependency in individuals with DM1. Process skills should be considered when evaluating daily activity performance. WHAT THIS PAPER ADDS: Young people with myotonic dystrophy type 1 show deficits in motor and process skills when performing daily activities, compared with normative data. Deficits in process skills were more pronounced than deficits in motor skills.

Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients.

Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG-degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single-center, open-label ascending-dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 [n = 3]; 0.25 mg/kg ×1 [n = 3], or 0.25 mg/kg ×2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti-HLA was abolished. IdeS also cleaved the IgG-type B cell receptor on CD19+ memory B cells. Anti-IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA-B7), detected by complement-dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg ×2) and when the HLA-incompatible donor (HLA-B7+ ) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.

Ventriculostomy-related infections in subarachnoid hemorrhage patients-a retrospective study of incidence, etiology, and antimicrobial therapy.

BACKGROUND: This study was performed to investigate the incidence and etiology of ventriculostomy-related infections (VRIs) in patients with subarachnoid hemorrhage (SAH) and to assess adherence to local clinical guidelines regarding empirical antimicrobial therapy and diagnostic routines. METHODS: A total of 191 consecutive SAH patients treated in the neuro-intensive care unit of Uppsala University Hospital between 2010 and 2013 were included retrospectively. Information regarding cerebrospinal fluid samples, bacterial cultures, ventriculostomy treatment, patient characteristics, and antibiotic treatment were collected from electronic patient records. RESULTS: Eleven patients developed VRI, resulting in an incidence of 5.8% per patient, 5.4% per ventriculostomy catheter, and 4.1 per 1000 catheter days. Coagulase-negative staphylococci caused nine cases of VRI and Klebsiella pneumoniae and Staphylococcus aureus caused one each. Empirical VRI therapy was initiated on 97 occasions in 81 subjects (42.4%). Out of the 11 patients with VRI, four did not receive empirical antibiotic therapy before the positive culture result. The clinical actions performed after analysis of CSF samples were in line with the action suggested by the local guidelines in 307 out of 592 cases (51.9%). CONCLUSIONS: The incidence of VRI in our cohort was comparable to what has previously been reported. Coagulase-negative staphylococci was the most common agent. Our study demonstrates the difficulty in diagnosing VRI in SAH patients. Improved adherence to clinical guidelines could to some extent reduce the use of empirical antibiotic treatment, but better diagnostic methods and routines are needed.

Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study (.).

OBJECTIVE: It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease. MATERIALS AND METHODS: In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry. RESULTS: Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA. CONCLUSIONS: Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.

Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy.

BACKGROUND: Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. METHODS: Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. RESULTS: The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. CONCLUSIONS: Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors. CLINICAL TRIALS REGISTRATION: NCT00031486.

Diagnosis of external ventricular drainage related infections with real-time 16S PCR and third-generation 16S sequencing.

OBJECTIVE: Investigate the performance of real-time 16S PCR and third-generation 16S sequencing in the diagnosis of external ventricular drain related infections (EVDRI). METHODS: Subjects with suspected EVDRI were prospectively included at Uppsala University Hospital. Subjects were included into three groups: subjects with negative CSF culture with and without antibiotic treatment and subjects with positive CSF culture, respectively. CSF was analysed with real-time 16S PCR and third-generation 16S sequencing. Real-time 16S PCR positivity/negativity and number of 16S sequence reads were compared between groups. For culture positive subjects, species identification in third-generation sequencing and routine culture was compared. RESULTS: 84 subjects were included. There were 18, 44 and 22 subjects in the three groups. Real-time PCR was positive in 17 of 22 subjects in the culture positive group and negative in 61 of the 62 subjects in the two culture negative groups. The sensitivity and specificity for real-time 16S PCR compared to culture was estimated to 77% and 98%, respectively. Species identification in 16S sequencing and culture was concordant in 20 of 22 subjects. The number of 16S sequence reads were significantly higher in the culture positive group than in both culture negative groups (p < 0.001). There was no significant difference in number of 16S sequences between the two culture negative groups. CONCLUSIONS: Real-time 16S PCR predict culture results with sufficient reliability. Third-generation 16S sequencing could enhance sensitivity and species identification in diagnostics of EVD-related infections. False negative culture results appear to be uncommon in patients with suspected EVDRI.

Clinical outcome with low-dose valacyclovir in high-risk renal transplant recipients: a 10-year experience.

BACKGROUND: Cytomegalovirus (CMV) remains an important pathogen in transplant patients, and valacyclovir (VACV) prophylaxis 8 g/day has been used in high-risk CMV-seromismatched [D+/R-] renal transplant patients to decrease CMV disease. Neurotoxic adverse effects have limited its use, and the aim of the present study was to retrospectively evaluate low-dose VACV prophylaxis, 3 g/day for 90 days after transplantation, in 102 D+/R- renal transplant patients. METHODS: We compared patient and graft survival rates up to 5 years after transplantation with the data from the Collaborative Transplant Study Group (CTS) database. The incidence of CMV disease, rejection and neurotoxic adverse effects was analyzed up to 1 year after transplantation. RESULTS: The patient and graft survival rates up to 5 years were comparable with those derived from the CTS. CMV disease was diagnosed in 25% of the patients and 2% developed tissue-invasive CMV disease. The rejection frequency was 22% and neurotoxic adverse effects were seen in 2% of the patients. CONCLUSIONS: Low-dose VACV prophylaxis (3 g/day) for 90 days post-transplantation results in high patient and graft survival rates and reduces the incidence of CMV disease. Neurotoxic adverse effects are minimal. We believe that low-dose VACV prophylaxis should be considered to form one of the arms in future prospective comparison studies for the prevention of CMV disease in the high-risk D+/R- population of renal transplant patients.

Intervention with hand orthosis: experience from boys with Duchenne muscular dystrophy and their parents.

PURPOSE: To identify and describe possible ways of experiencing an intervention with hand orthoses in a study group including boys with Duchenne muscular dystrophy (DMD) and their parents. To capture the experiences of the persons directly involved as well as their family members. MATERIAL AND METHODS: Eight boys with DMD (aged 8-21; median age 17.7) and five of their parents were interviewed immediately post-intervention. Additionally, follow-up interviews were later performed with five boys and three parents. RESULTS: Ten categories of intervention experiences emerged and were allocated to three aspects: "Prerequisites in the treatment situation", "The intervention makes a difference" and "Instilling hope for the future". The requirements for intervention success include co-operation with parents and hand orthoses with a good fit. Maintained or increased joint mobility, reduced pain and improved occupational performance were experienced. CONCLUSION: The boys and parents perceived that the intervention with hand orthoses could counteract the deterioration of the boys' hands. This instilled hope of preserving occupational performance throughout life. They also considered that a good hand-orthosis fit, appropriate adjustments to daily routines and good co-operation with the people around them were important for the intervention to be and remain successful.

Preserving the ability to perform activities with the hands is of paramount importance for boys with Duchenne muscular dystrophy and their parents.Intervention with hand orthoses counteracts deterioration of the hands.Successful treatment with hand orthoses requires that specific prerequisites in the treatment situation are met, that the treatment makes a difference for activity performance and that it instils hope for the future when it comes to performing meaningful activities.

Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of Kidney Transplant Recipients.

BACKGROUND BK virus (BKV) infection after kidney transplantation leads to BKV-associated nephropathy (BKVAN) in up to 10% of recipients, and is associated with an increased risk of allograft dysfunction or loss. The objective of this study was to estimate the incidence of BKVAN and to analyze whether enhanced induction is associated with an increased risk of BKVAN, possibly justifying more intensive surveillance. MATERIAL AND METHODS This was a single-center retrospective cohort study. All patients who underwent kidney transplantation or simultaneous pancreas and kidney transplantation at the Uppsala University Hospital in Sweden between 2005 and 2014 were included, a period when BKV screening was not yet implemented. The effect of enhanced induction, defined as treatment with thymoglobulin, rituximab, and/or eculizumab, often in combination with IVIg and glycosorb, immunoadsorption and/or plasmapheresis/apheresis, was analyzed in a multivariable Cox proportional hazards model together with sex, age, cytomegalovirus mismatch (donor+/recipient-) and rejection treatment as co-predictors. Further, the effects of BKVAN on graft survival was analyzed in a univariable Cox proportional hazards model. RESULTS In total 44 of 928 (4.7%) patients developed a biopsy-verified BKVAN 4.8 (1.5-34.2) months after transplantation. Male sex was identified as a risk factor (HR 2.02, P=0.04) but not enhanced induction. Patients with BKVAN experienced a significantly higher risk of graft loss (HR 4.37, P<0.001). CONCLUSIONS Male sex, but not enhanced induction, was found to be a risk factor for BKVAN development after kidney transplantation. BKVAN is associated with an increased risk of graft loss.

Radical reduction of cephalosporin use at a tertiary hospital after educational antibiotic intervention during an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

OBJECTIVES: During an outbreak of extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae at our hospital, we performed an educational antibiotic intervention aimed at reducing prescriptions of second- and third-generation cephalosporins and preventing increased use of fluoroquinolones and carbapenems. In this report, we describe the implementation strategy used and evaluate the intervention effect according to Cochrane recommendations. METHODS: New recommendations for empirical intravenous antibiotic treatment were communicated to prescribers throughout the hospital by infectious diseases physicians working with Strama (the Swedish strategic programme against antibiotic resistance). No restrictive measures were used. The intervention effect was analysed with interrupted time series (ITS) regression analysis of local and national monthly antibiotic sales data. RESULTS: A radical immediate and sustained reduction was demonstrated for the cephalosporins targeted in the intervention, whereas consumption of piperacillin/tazobactam and penicillin G increased substantially. Fluoroquinolone and carbapenem use was essentially unchanged. The ESBL outbreak subsided and no increased resistance to piperacillin/tazobactam was detected in K. pneumoniae, Escherichia coli or Pseudomonas aeruginosa blood isolates during the 2.5 year follow-up. CONCLUSIONS: Our study clearly demonstrates that an educational intervention can have an immediate and profound effect on antibiotic prescription patterns at a large tertiary hospital. ITS regression analysis of local and national antibiotic sales data was valuable to readily assess the immediate and sustained effects of the intervention.

CMV-specific T-cell immunity, viral load, and clinical outcome in seropositive renal transplant recipients: a pilot study.

BACKGROUND: Cytomegalovirus (CMV) infection is still the leading opportunistic infection following solid organ transplantation. The aim of this prospective study of renal transplant recipients was to evaluate the dynamics of CMV-specific T-cells, viral load, and clinical symptoms of CMV infection. METHODS: Levels of tetramer-selected CD8(+) T-cells (TetraCD8), CMV-specific interferon-gamma producing CD8(+) T-cells (IFNgammaCD8), and CD4(+) T-cells (IFNgammaCD4), measured using major histocompatibility complex-tetramer and cytokine flow cytometry techniques, and CMV DNA were monitored monthly in 17 CMV-seropositive patients up to one yr (median 12 months, range 3-12) after transplantation and correlated to clinical outcome. RESULTS: CMV DNAemia was detected in 94% of the patients, but only one patient developed CMV disease. CMV DNAemia >1 million copies/mL was seen in asymptomatic patients. CMV-specific T-cells decreased rapidly after transplantation. TetraCD8 and IFNgammaCD8 regenerated within three months, whereas IFNgammaCD4 recovery was impaired up to one yr after transplantation. The proportion of IFNgammaCD4 at two months post-transplantation as compared with baseline, correlated strongly with the magnitude of the CMV DNAemia. CONCLUSIONS: Monitoring the reduction of IFNgammaCD4 compared with baseline during the first months after transplantation could be considered in predicting risk for high-grade CMV DNAemia and in deciding strategic approaches for pre-emptive and prophylactic therapy.

Severe group A streptococcal infections in Uppsala County, Sweden: clinical and molecular characterization of a case cluster from 2006 to 2007.

This study describes a recent cluster of 30 patients (median age 52 years) with serious group A streptococcal (GAS) infections in Uppsala County, Sweden, from December 2006 to May 2007. Patients hospitalized with a severe GAS infection, i.e. cases with either invasive GAS (iGAS) disease or patients with a positive non-sterile site culture/rapid antigen test for GAS and clinically considered as having a critical disease, were included in the study. Common clinical presentations were skin and soft tissue infections (53%) and pneumonia (17%). Eight patients (27%) were diagnosed with streptococcal toxic shock syndrome. In 40% of the cases no relevant underlying disease was reported. Among the 16 patients with soft tissue infections, the upper chest, neck or upper arm area was frequently affected and the infection was associated with severe pain. Among the 20 collected isolates, the T1/emm1 type dominated (80%). The majority (86%) of 7 analysed acute sera lacked neutralizing activity against superantigens produced by the patients' own infecting isolate. The study underscores the association between T1/emm1 and outbreaks of serious GAS infections. This highlights the importance of surveillance for prompt identification of more aggressive isolates in the community, thereby increasing awareness among healthcare professionals of these life-threatening infections.

Management of BK-virus infection - Swedish recommendations.

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.

Evaluation of hand orthoses in Duchenne muscular dystrophy.

PURPOSE: The purpose of this study was to evaluate whether treatment of boys with Duchenne muscular dystrophy using hand orthoses could benefit joint mobility, grip strength, or fine motor function. METHOD: Eight boys with Duchenne muscular dystrophy were provided with individually customised rest orthoses. The results were analysed using single-subject design. The study included a baseline and an intervention phase. A follow-up examination was also performed. RESULTS: Boys with less than 50° passive wrist extension mobility were included. Wrist extension of the dominant hand increased in four and was maintained in four. Wrist extension in the non-dominant hand increased in five, was maintained in two and decreased in one. Thumb abduction in the dominant hand increased in six and two remained stable. In the non-dominant hand five increased and three remained stable. Grip strength and fine motor function showed also positive results. CONCLUSIONS: This study indicates that the use of hand orthoses in Duchenne muscular dystrophy can delay development of contractures and improve passive wrist extension and thumb abduction. Hand orthoses can therefore be recommended for boys who start to develop contractures in the long finger flexors. Due to small sample size further studies are needed to confirm this result. Implications for rehabilitation Evaluation of hand orthoses in Duchenne muscular dystrophy. Preserved hand function is of uttermost importance for performance of activities in the late stages of Duchenne muscular dystrophy. Contractures of long finger flexors affect hand function and limit performance of daily activities. Hand orthoses can delay development of contractures and preserve hand function and give prerequisites for independence. The occupational therapists should measure wrist joint mobility regularly to be able to find the right time for intervention with hand orthoses in this progressive disorder.

Decreased HHV-6 IgG in Alzheimer's Disease.

Human herpesviruses have previously been implicated in the pathogenesis of Alzheimer's disease (AD) but whether they are causal, facilitating, or confounding factors is yet to be established. A total of 50 AD subjects and 52 non-demented (ND) controls were analyzed in a multiplex assay for IgG reactivity toward herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6). The HHV-6 IgG reactivity was significantly lower in AD subjects compared to ND controls, whereas there were no differences in HSV, VZV, or CMV antibody levels between the groups. Analysis of peripheral blood mononuclear cells with a subtype-specific HHV-6 PCR revealed no signs of reactivation, as AD and ND subjects presented with comparable HHV-6 DNA levels in PBMCs, and all positive samples were of subtype B. Whether HHV-6 is a factor in AD remains to be elucidated in future studies.