Diabetic myonecrosis complicated by emphysematous pyomyositis and abscess caused by Escherichia coli: a case report.

BACKGROUND: Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging. CASE PRESENTATION: We describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3-4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case. CONCLUSIONS: Identifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.

Superspreading of SARS-CoV-2 Omicron BA.2.23 among vaccinated Finnish adults: symptomatic COVID-19 only contracted by those without recent infection.

An outbreak of SARS-CoV-2 was confirmed after an academic party in Helsinki, Finland, in 2022. All 70 guests were requested to fill in follow-up questionnaires; serologic analyses and whole-genome sequencing (WGS) were conducted when possible.Of those participating - all but one with ≥3 vaccine doses - 21/53 (40%) had test-confirmed symptomatic COVID-19: 7% of those with earlier episodes and 76% of those without. Half (11/21) were febrile, but none needed hospitalisation. WGS revealed subvariant BA.2.23.Compared to vaccination alone, our data suggest remarkable protection by hybrid immunity against symptomatic infection, particularly in instances of recent infections with homologous variants.

Safety and immunogenicity of ETVAX®, an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa.

BACKGROUND: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies. METHODS: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX® or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence. RESULTS: The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX® recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of ≥2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX® recipients (93%) responded to either LTB or O78. CONCLUSIONS: This Phase 2b trial is the largest on ETVAX® undertaken amongst travellers to date. ETVAX® showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.

Clinical characteristics and evaluation of the incidence of cryptococcosis in Finland 2004-2018.

BACKGROUND: Cryptococcosis is one of the major causes of mortality among HIV patients worldwide. Though most often associated with late stage HIV infection/AIDS, a significant number of cases occur in other immunocompromised patients such as solid organ transplant recipients and patients with hematological malignancies. Immunocompromised patients are a heterogeneous group and their number increases constantly. Since little is known about the incidence and the clinical features of cryptococcosis in Northern Europe, our aim was to investigate the clinical characteristics of cryptococcosis patients in Finland. METHODS: We retrospectively reviewed the laboratory confirmed cryptococcosis cases in Finland during 2004-2018. Only those who were treated for cryptococcosis were included in the study. Initial laboratory findings and medical records were also collected. RESULTS: A total of 22 patients with cryptococcosis were included in our study. The annual incidence of cryptococcosis was 0.03 cases per 100,000 population. Ten patients were HIV-positive and 12 out of 22 were HIV-negative. Hematological malignancy was the most common underlying condition among HIV-negative patients. CONCLUSIONS: To our knowledge, this is the first study of the clinical presentation and incidence of cryptococcosis in Finland. We demonstrate that invasive cryptococcal infection occurs not only in HIV/AIDS patients or otherwise immunocompromised patients but also in immunocompetent individuals. Even though cryptococcosis is extremely rare in Finland, its recognition is important since the prognosis depends on rapid diagnostics and early antifungal therapy.

A randomized, controlled trial comparing the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccination to a repeated dose 13-valent pneumococcal conjugate vaccination in adult liver transplant recipients.

BACKGROUND: Solid organ transplant (SOT) patients are at significant risk for invasive pneumococcal disease. The optimal pneumococcal vaccination strategy for SOT patients is not known. METHODS: The potential adult liver transplant recipients were randomised into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before the transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before the transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, e.g. before and after the second PCV13 (visits V3,V4). RESULTS: Out of 47 patients, 19 (PCV13 arm) and 17 (PPV23 arm) received a liver transplant and all these patients completed the study (36/47, 76,6%). Each vaccine schedule elicited a good immune response. At V2, the geometric mean concentrations (GMCs) of antibodies for serotypes 6A, 7F and 23F, and the geometric mean titers (GMT́s) of OPA for serotypes 4, 6A, 6B and 23F were significantly higher for PCV13, but the proportions of patients reaching OPA cut-off ≥ 8 or ELISA cut-off ≥ 1.0 µg/ml did not differ between the arms. At V3 the antibody concentrations and the OPA had declined to baseline in both arms. The second PCV13 vaccination elicited an immune response. There was no difference in adverse events. No vaccine-related allograft rejection was detected. CONCLUSIONS: The immunogenicity of PPV23 and PCV13 was comparable in this patient material, but the seroresponses waned after transplantation. The second dose of PCV13 restored the immune responses and was well tolerated.

A randomized, controlled trial comparing the immunogenecity and safety of a 23-valent pneumococcal polysaccharide vaccination to a repeated dose 13-valent pneumococcal conjugate vaccination in kidney transplant recipients.

BACKGROUND: The risk of invasive pneumococcal disease is significant among solid organ transplant (SOT) recipients. The optimal pneumococcal vaccination strategy for SOT patients is not known. METHODS: The potential kidney transplant recipients in dialysis were randomized into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, for example, before and after the second PCV13 (visits V3,V4). RESULTS: Out of 133 participants, 48 (PCV13 arm) and 46 (PPV23 arm) received a kidney transplant, and 37 + 37 in both arms completed the study. After the first vaccination, the geometric mean concentrations (GMCs) in the PCV13 arm were significantly higher for 9/13 serotypes and the OPA geometric mean titers (GMTs) were significantly higher for 4/13 serotypes. At V3, the antibody levels had declined but OPA remained significantly higher for 7/13 (PCV13) vs 4/13 (PPV23) serotypes. At V4, the GMCs for 9/13 serotypes and the GMTs for 12/13 serotypes were significantly higher in the PCV13 arm. The GMCs but not GMTs were lower than at V2. There was no difference in adverse effects. No vaccine-related allograft rejection was detected. CONCLUSIONS: The immunogenicity of PCV13 was better in dialysis patients, and revaccination with PCV13 was immunogenic and safe.

Low-dose valganciclovir prohylaxis is efficacious and safe in cytomegalovirus seropositive heart transplant recipients with anti-thymocyte globulin.

BACKGROUND: Cytomegalovirus (CMV) remains an important pathogen in solid organ transplant patients. OBJECTIVE: We executed a hybrid prophylactic and pre-emptive valganciclovir (VGCV) prophylaxis to prevent CMV infection in heart transplant patients with anti-thymocyte globulin (ATG) induction and retrospectively evaluated the efficacy and safety of this regimen. METHODS: Hundred adult heart transplant patients between 2004 and 2010 were included. Recipients with CMV serostatus D+/R- received VGCV 900 mg OD for 6 months and 94.2% (81/86) of R+ recipients received a low-dose 450 mg OD for 3 months. Blood CMV was monitored until 3 months after cessation of the prophylaxis. RESULTS: All patients accomplished the prophylaxis. The overall incidence of CMV disease was 4% (4/100) and it was more frequent in D+/R- patients (P = .001). Three of eighty-six (3.5%) of R+ patients had CMV infection (one CMV disease) while on prophylaxis, 2/3 were still on the original significantly reduced renal dose though. There was one late CMV disease in both D+/R- and R+ groups. Ganciclovir/VGCV treatment was successful in all patients. CONCLUSIONS: The hybrid strategy with low-dose VGCV in R+ patients with ATG was efficient and safe. The good treatment results indicate that the regimen did not lead to a clinically relevant resistance. Optimal renal dosage is essential throughout prophylaxis.

Immunosuppression Adversely Affects TST but Not IGRAs in Patients with Psoriasis or Inflammatory Musculoskeletal Diseases.

The performance of the interferon gamma release assays (IGRAs) and tuberculin skin test (TST) was reviewed retrospectively in patients with psoriasis, inflammatory musculoskeletal diseases, or miscellaneous inflammatory conditions. The study was carried out over a 22-month period using 109 records of patients with psoriasis (n = 21), musculoskeletal disease (n = 74), or other inflammatory conditions (n = 14). Forty-four (48%) of 109 patients were on immunosuppressive therapy and 38/109 (35%) on systemic glucocorticoid therapy. The agreement between the IGRAs was substantial (κ = 0.71) whilst that between the IGRAs and TST was low (κ = 0.32). Logistic regression models revealed that IGRAs associated with risk factors for latent tuberculosis infection better than TST. TST was influenced by age, BCG vaccination, sex, and glucocorticoid therapy. We found that IGRAs performed equally well with low level of indeterminate results (1-2%). IGRAs were superior to TST because the latter was influenced by BCG-vaccination status and immunosuppressive therapy.