COVID-19 with severe acute respiratory distress in a pregnant woman leading to preterm caesarean section: A case report.

We report the case of a 25-year-old pregnant woman, parity one, at 34 + 2 weeks of gestation, with a body mass index of 41 kg/m2 but no other comorbidities. There was a family history of COVID-19 among her one-year-old son, husband, brother, father and mother. She was admitted with chest pain and a nasopharyngeal swap positive for COVID-19. Due to the severity of the infection, a multidisciplinary team of anaesthesiologists, intensivists, obstetricians, neonatologists, and infectious disease specialists recommended delivery by caesarean section at 35 + 0 weeks of gestation, with combined spinal and epidural anaesthesia. Three days after delivery, the patient developed severe acute respiratory distress syndrome (ARDS) and was intubated for 25 days. The neonate was observed in the neonatal intensive care unit and no vertical transmission occurred. This case highlights the importance of the timing of delivery, the need for extended postpartum observation and a beneficial effect of inhaled nitric oxide after delivery for women with COVID-19.

Identification of a novel mutation in the factor VIII gene causing severe haemophilia A.

BACKGROUND: Deficiency in coagulation factor VIII encoded by F8 results in the X-linked recessive bleeding disorder haemophilia A (HEMA). Here we describe the identification of a novel variant in the factor VIII gene, F8, in an adult male patient with severe haemophilia A. CASE PRESENTATION: The patient was diagnosed in early childhood and subsequently co-infected with Hepatitis C and HIV acquired during early blood transfusion for haemophilia in the 1980ies. The identified F8 deletion, c.5411_5413delTCT, p.F1804del lies within a conserved part of the molecule, is predicted by bioinformatic software to be deleterious by the loss of Phenylalanine, and has not been previously described in any database. CONCLUSION: This novel F8 deletion as a cause of haemophilia A did not result in generation of inhibitory antibodies to Factor VIII treatment and may have impact on (prenatal) diagnosis, genetic counselling, and treatment decisions in the affected family as well as in other families diagnosed with this F8 mutation. Finally, this novel mutation should be included in the panel of known genetic variants in F8 when searching for the genetic etiology in patients suspected of HEMA.

The challenge of discriminating between HIV-1, HIV-2 and HIV-1/2 dual infections.

OBJECTIVES: Discrimination between HIV-1 and HIV-2 is important to ensure appropriate antiretroviral treatment (ART) and epidemiological surveillance. However, serological tests have shown frequent mistyping when applied in the field. We evaluated two confirmatory tests, INNO-LIA HIV I/II Score and ImmunoComb HIV 1/2 BiSpot, for HIV type discriminatory capacity. METHODS: Samples from 239 ART-naïve HIV-infected patients from the Bissau HIV Cohort in Guinea-Bissau were selected retrospectively based on the initial HIV typing performed in Bissau, ensuring a broad representation of HIV types. INNO-LIA results were interpreted by the newest software algorithm, and three independent observers read the ImmunoComb results. HIV-1/HIV-2 RNA and DNA were measured for confirmation. RESULTS: INNO-LIA results showed 123 HIV-1 positive samples, 69 HIV-2 positive and 47 HIV-1/2 dually reactive. There was agreement between INNO-LIA and HIV-1/HIV-2 RNA and DNA detection, although not all HIV-1/2 dually reactive samples could be confirmed by the nucleic acid results. Overall, the observers found that the ImmunoComb results differed from the INNO-LIA results, with agreements of 90.4, 91.2 and 92.5%, respectively, for HIV-1, HIV-2 and HIV-1/2. The combined kappa-score for agreement between the three observers was 0.955 (z-score 35.1; P < 0.01). Of the HIV-2 mono-reactive samples (INNO-LIA), the three observers interpreted 24.6-31.9% as HIV-1/2 dually infected by ImmunoComb. None of these samples had detectable HIV-1 RNA or DNA. CONCLUSIONS: There was accordance between INNO-LIA calls and nucleic acid results, whereas ImmunoComb overestimated the number of HIV-1/2 dually infected patients. Confirmatory typing is needed for patients diagnosed with HIV-1/2 dual infection by ImmunoComb.

Causes of iron overload in blood donors - a clinical study.

BACKGROUND AND OBJECTIVES: Despite the obligate iron loss from blood donation, some donors present with hyperferritinaemia that can result from a wide range of acute and chronic conditions including hereditary haemochromatosis (HH). The objective of our study was to investigate the causes of hyperferritinaemia in the blood donor population and explore the value of extensive HH mutational analyses. MATERIALS AND METHODS: Forty-nine consecutive donors (f = 6, m = 43) were included prospectively from the Capital Regional Blood Center. Inclusion criteria were a single ferritin value >1000 µg/l or repeated hyperferritinaemia with at least one value >500 µg/l. All donors were questioned about their medical history and underwent a physical examination, biochemical investigations and next-generation sequencing of HH-related genes, including the HFE gene, the haemojuvelin gene (HFE2/HJV), the hepcidin gene (HAMP), the ferroportin 1 gene (SLC40A1) and the transferrin receptor 2 gene (TFR2). RESULTS: Forty of 49 donors were mutation positive with a combined 69 mutations, 54 of which were located in the HFE gene. There were 11 mutations in the TFR2 gene, two mutations in the HFE2 gene and two mutations in the HAMP gene. Only four donors had apparent alternative causes of hyperferritinaemia. CONCLUSION: HH-related mutations were the most frequent cause of hyperferritinaemia in a Danish blood donor population, and it appears that several different HH-genotypes can contribute to hyperferritinaemia. HH screening in blood donors with high ferritin levels could be warranted. HH-related iron overload should not in itself result in donor ineligibility.

Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark: A nationwide cohort study.

Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC), and surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C, and data from national health registries and patient charts were obtained. Tumour stage was based on Barcelona-Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stages 0-3. We included 1075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4988 person years (PY), 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4-1.5] in 2002-2003 to 2.9/100 PY [2.4-3.4] in 2012-2013. One-year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP ≥ 20 ng mL-1 was 17%. Twenty-three (21%) patients were diagnosed with early-stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early-stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal, and most patients were diagnosed with advanced HCC with a poor prognosis.

IgE antibodies to alpha-gal in the general adult population: relationship with tick bites, atopy, and cat ownership.

BACKGROUND: The carbohydrate alpha-gal epitope is present in many animal proteins, including those of red meat and animal immunoglobulins, such as cat IgA. Systemic anaphylaxis to the alpha-gal epitope has recently been described. OBJECTIVE: To investigate and compare the prevalence of alpha-gal-specific (s)IgE and its associated factors in the general adult population from two separated (Northern and Southern) European regions (Denmark and Spain, respectively). METHODS: Cross-sectional study of 2297 and 444 randomly selected adults from 11 municipalities in Denmark and one in Spain. Alpha-gal sIgE was assessed by ImmunoCAP to bovine thyroglobulin. Additional assessments included a panel of skin prick test (SPT) to common aeroallergens and epidemiological factors, including the history of tick bites in the Danish series. RESULTS: The prevalence of positive (≥ 0.1 kUA /L) sIgE to alpha-gal was 5.5% and 8.1% in the Danish and Spanish series, respectively. The prevalence of sIgE ≥ 0.35 kUA /L was 1.8% and 2.2% in Denmark and Spain, respectively. Alpha-gal sIgE positivity was associated with pet ownership in both series and, particularly, cat ownership (data available in the Danish series). Alpha-gal sIgE positivity was associated with atopy (SPT positivity) in both series, although it was not associated with SPT positivity to cat or dog dander. Alpha-gal sIgE positivity was strongly associated with a history of tick bites. CONCLUSIONS AND CLINICAL RELEVANCE: The prevalence of alpha-gal sIgE antibodies in these general adult European populations is similarly low. The presence of alpha-gal sIgE antibodies is associated with a history of tick bites, atopy, and cat ownership.

Endothelial dysfunction, increased inflammation, and activated coagulation in HIV-infected patients improve after initiation of highly active antiretroviral therapy.

OBJECTIVES: Endothelial dysfunction and inflammation have been demonstrated to be markers of cardiovascular risk. We investigated the effects of HIV infection per se and the antiretroviral treatment prescribed on the levels of risk factors of cardiovascular disease. METHODS: This was a prospective study of 20 treatment-naïve, nonsmoking, HIV-positive patients examined before and after 3 months of treatment with a protease inhibitor (PI)-containing regimen followed by 3 months of treatment with nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing therapy. Parameters of inflammation, endothelial function and coagulation were examined. The results were compared with those for an age- and gender-matched, nonsmoking, healthy control group. RESULTS: Compared with controls, treatment-naïve HIV-infected patients exhibited endothelial dysfunction [flow-mediated dilation (FMD) 108 vs. 111% for HIV-infected vs. control groups, respectively; P < 0.05] and activation [von Willebrand factor 2.0 vs. 0.9 U/l; soluble intercellular adhesion molecule (sICAM) 313 vs. 211 ng/L, respectively; P < 0.01]. Inflammation [C-reactive protein (CRP) 24 vs. 8.6 nmol/L; fibrinogen 9.4 vs. 8.6 µmol/L, respectively; P < 0.05] and coagulation/fibrinolysis (D-dimers 0.55 vs. 0.23 µg/mL, respectively; P < 0.01) were increased. Initiating therapy resulted in normalization of FMD and a significant decrease in endothelial activation and CRP. CONCLUSION: Endothelial dysfunction together with increased inflammation and coagulation were more prevalent in untreated HIV-infected patients compared with controls. These cardiovascular risk factors improved with treatment, although not all parameters normalized after 6 months.

Automated image analysis of Euglena gracilis Klebs (Euglenophyta) for measuring sublethal effects of three model contaminants.

The short-term impacts of atrazine (herbicide), tributyltin (organometal) and copper on the behaviour of Euglena gracilis Klebs (Euglenophyta) were assessed. First, the ECOTOX automated image analysis system was used, which measured swimming velocity, cell shape, percentage of cells swimming upwards, and randomness of swimming. Next, visual observation by microscopy was used to measure percentage of cell motility and cell shape. Behavioural changes can be used as an indicator of stress in less than 24 h, potentially making them suitable for inclusion in early-warning systems for water quality. Findings indicate that E. gracilis is a very sensitive organism to copper, showing inhibition of motility with visual observation at 0.8 µmol/L within 1 h. The image analysis system was in general less sensitive than visual observation for detecting behavioural changes after incubation in copper. In contrast, after exposure to organic contaminants atrazine and tributyltin, the ECOTOX system detected small changes in the number of cells swimming upwards (antigravitactic behaviour) at higher concentrations.

In situ transmission electron microscopy of light-induced photocatalytic reactions.

Transmission electron microscopy (TEM) makes it possible to obtain insight into the structure, composition and reactivity of photocatalysts, which are of fundamental interest for sustainable energy research. Such insight can be used for further material optimization. Here, we combine conventional TEM analysis of photocatalysts with environmental TEM (ETEM) and photoactivation using light. Two novel types of TEM specimen holder that enable in situ illumination are developed to study light-induced phenomena in photoactive materials, systems and photocatalysts at the nanoscale under working conditions. The technological development of the holders is described and two representative photo-induced phenomena are studied: the photodegradation of Cu2O and the photodeposition of Pt onto a GaN:ZnO photocatalyst.

Previously unrecognized advanced liver disease unveiled by transient elastography in patients with Haemophilia and chronic hepatitis C.

Before the introduction of viral inactivation procedures and viral screening of plasma-products, haemophiliacs were at high risk of infection with HCV. Those who acquired HCV infection in the 1980s, and are still alive today, may have developed significant liver fibrosis or cirrhosis. However, liver biopsy has not routinely been utilized in the evaluation of haemophiliacs with HCV in Denmark. The aim of this study was to investigate the prevalence of significant fibrosis/cirrhosis among haemophiliacs as evaluated by transient elastography (TE). Cross-sectional investigation of adult patients with haemophilia A or B. TE with liver stiffness measurements (LSM) ≥ 8 kPa were repeated after 4-6 weeks. Significant fibrosis and cirrhosis was defined as measurements ≥ 8 kPa or ≥ 12 kPa respectively. Among 307 patients with haemophilia A or B registered at the two Haemophilia centres, 141(46%) participate in this study. Forty (28.4%) had chronic hepatitis C, 33 (23.4%) past hepatitis C and 68 (48.2%) had never been infected, at screening LSM ≥ 8 kPa were found in 45.7%, 24.7% and 4.6% respectively. Among patients with chronic hepatitis C significant fibrosis was confirmed in 17.1% and cirrhosis in 2.9% by repeated LSM ≥ 8 and ≥ 12 kPa respectively. The median TE-value in never HCV-infected haemophiliacs was comparable with what has been found in healthy non-haemophiliacs. In Danish haemophiliacs where liver biopsy has not routinely been used for assessing severity of liver fibrosis, LSM identified advanced liver disease in one-fifth of cases that had not been recognized during clinical follow-up.

Mortality in HIV-infected injection drug users with active vs cleared hepatitis C virus-infection: a population-based cohort study.

Acute hepatitis C virus (HCV) infection may lead to chronic HCV-infection with detectable HCV RNA or to spontaneous clearance with no HCV RNA, but detectable HCV antibodies. It is unknown whether HCV RNA status is associated with mortality in HIV-infected injection drug users (IDUs). We conducted a nationwide population-based cohort study to examine the impact of HCV RNA status on overall and cause-specific mortality in HIV-infected IDUs. We computed cumulative mortality and used Cox Regression to estimate mortality rate ratios (MRR). We identified 392 HIV-infected patients of whom 284 (72%) had chronic HCV-infection (HCV RNA positive patients) and 108 (28%) had cleared the HCV-infection (HCV RNA negative patients). During 1286 person-years of observation (PYR), 157 persons died (MR = 122/1000 PYR, 95% CI: 104-143). The estimated 5-year probabilities of survival were 0.58 (95% CI: 0.51-0.65) in the chronically HCV-infected and 0.52 (95% CI: 0.40-0.63) in the cleared HCV group. Chronic HCV-infection was not associated with overall mortality: MRR 0.85, 95% CI: 0.59-1.21. In HIV-infected Danish IDUs, chronic HCV-infection is not associated with increased mortality compared to patients who have cleared the infection.

Corticosteroid injections, eccentric decline squat training and heavy slow resistance training in patellar tendinopathy.

A randomized-controlled single-blind trial was conducted to investigate the clinical, structural and functional effects of peritendinous corticosteroid injections (CORT), eccentric decline squat training (ECC) and heavy slow resistance training (HSR) in patellar tendinopathy. Thirty-nine male patients were randomized to CORT, ECC or HSR for 12 weeks. We assessed function and symptoms (VISA-p questionnaire), tendon pain during activity (VAS), treatment satisfaction, tendon swelling, tendon vascularization, tendon mechanical properties and collagen crosslink properties. Assessments were made at 0 weeks, 12 weeks and at follow-up (half-year). All groups improved in VISA-p and VAS from 0 to 12 weeks (P<0.05). VISA-p and VAS improvements were maintained at follow-up in ECC and HSR but deteriorated in CORT (P<0.05). In CORT and HSR, tendon swelling decreased (-13+/-9% and -12+/-13%, P<0.05) and so did vascularization (-52+/-49% and -45+/-23%, P<0.01) at 12 weeks. Tendon mechanical properties were similar in healthy and injured tendons and were unaffected by treatment. HSR yielded an elevated collagen network turnover. At the half-year follow-up, treatment satisfaction differed between groups, with HSR being most satisfied. Conclusively, CORT has good short-term but poor long-term clinical effects, in patellar tendinopathy. HSR has good short- and long-term clinical effects accompanied by pathology improvement and increased collagen turnover.

Predictors of antiviral treatment initiation in hepatitis C virus-infected patients: a Danish cohort study.

Predictive factors for initiation of antiviral therapy in chronically infected hepatitis C virus (HCV) patients are not fully elucidated. The aim of this study was to determine predictive factors for initiation of treatment with standard or pegylated interferon either alone or combined with ribavirin. A Danish cohort of individuals chronically infected with HCV was used and observation time was calculated from the date of inclusion in the cohort to date of death, last clinical observation, 1 January 2007, or start of HCV antiviral treatment in treatment-naïve patients. Kaplan-Meier survival analysis was used to construct time to event curves. Cox regression was used to determine the incidence rate ratios as estimates of relative risk (RR) and 95% confidence intervals (CI). A total of 1780 patients were enrolled in the study. The cumulative chance of treatment initiation over 5 years was 33.0%. We found several strong predictors of treatment initiation: elevated alanine aminotransferase [>2 times upper limit (RR = 2.17, 95% CI 1.64-2.87), >3 times upper limit (RR = 3.64, 95% CI 2.75-4.81)], genotype 2 or 3 (RR = 1.86, 95% CI 1.49-2.31) and HIV co-infection (RR = 0.28, 95% CI 0.15-0.53). To our knowledge, this study is the first to estimate factors predicting initiation of antiviral treatment in patients with chronic HCV infection on a nationwide scale. We found that several of the factors predicting initiation of antiviral treatment correlate with factors known to predict a better response to treatment and factors known to increase the progression of liver disease.

Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative comparison in plasma virus RNA versus CD45RO+T cell proviral DNA.

BACKGROUND: Viral populations defined by 103K/N and 184M/V as linked or single mutations in the HIV-1 reverse transcriptase gene were investigated in plasma samples and compared with previous findings in the CD45RO(+)T cell compartment. OBJECTIVE: To develop an ARMS assay for plasma virions and to investigate the expression of resistance mutations (103N and 184V) and dynamic interactions between proviral DNA and plasma virions. STUDY DESIGN: A clinical cross-sectional study, including 11 patients on lamivudine efavirenz and/or nevirapine therapy. The viral populations were determined by an assay based on real-time PCR and amplification refractory mutation system (ARMS). RESULTS: The 103N and 184V mutations were not detected in patients with stable low viremia. Patients previously exposed to mono or dual therapy often carried minor viral populations of either one or both mutations in plasma. The viral population with linked mutations (103N and 184V) was detected in two patients after more than 2 years of non-NNRTI HAART. CONCLUSION: The ARMS assay is useful for detecting viral quasi-species containing efavirenz and lamivudine resistant mutations in plasma virions and in proviral DNA. Data suggest an unequal distribution of linked-mutation populations in plasma and CD45RO(+)T cells. Furthermore, the linked 103N-184V mutation may be more fit than the single 184V mutation and this linked population emerges rapidly under inadequate drug pressure.

Fluoropolymer-coated dacron versus PTFE grafts for femorofemoral crossover bypass: randomised trial.

OBJECTIVES: To investigate whether patency of a thin walled 8 mm fluoropassivated Dacron graft was similar to that of a standard 8mm PTFE graft for femorofemoral crossover bypass surgery. DESIGN: A randomised multicentre clinical trial comparing two vascular grafts with participation of 10 departments of vascular surgery in Denmark, Sweden and Norway. PATIENTS AND METHODS: 198 patients were randomised to PTFE (n=107) or fluoropolymer-coated Dacron grafts (n=91), 63% underwent surgery for claudication, 27% for ischaemic rest pain and 10% for tissue loss. The median follow-up time was 24 months (IQR 19-26 months). RESULTS: The primary patency rate of the two grafts was similar (log rank test: p=0.35). The primary patency rates (95% CI) for coated Dacron and PTFE grafts were 92% (86-98) and 94% (89-99) at 12 months and 87% (74-95) and 93% (87-99) at 24 months, respectively. CONCLUSION: In patients with unilateral iliac artery disease not amenable to angioplasty, the femoral-femoral bypass is durable and effective. No difference in patency was found between the two graft materials (fluoropolymer coated Dacron and PTFE).

The impact of CMV on the respiratory burst of macrophages in response to Pneumocystis carinii.

Infection of human monocyte-derived macrophages with CMV decreased the respiratory burst when cells were stimulated with opsonized zymosan or Pneumocystis carinii (P. carinii). Such an effect, though smaller, was also seen with heat-inactivated CMV, but only when triggered by zymosan. The effect was most pronounced in cells obtained from CMV antibody-negative donors. Dexamethasone further reduced the respiratory burst, both in uninfected and CMV-infected cells. Interferon-gamma increased the response in uninfected cells and, to a lesser extend, in cells treated with heat-inactivated CMV, whereas no effect was seen with infective CMV. No overt productive infection or cytopathology could be detected, however, the monocytes incubated with infective but also heat-inactivated CMV formed clusters, a phenomenon that was equally pronounced in cultures from CMV antibody positive and negative-donors. These results might help explain the worse prognosis of P. carinii pneumonia in patients coinfected with CMV and receiving dexamethasone.

[Zoonoses among immigrants]. / Zoonoser blandt indvandrere.

During the last ten years Denmark has received an increasing number of immigrants, especially from the Balkans, the Middle East, and Somalia. Some of these may suffer from the zoonoses occurring in their country of origin. But apart from echinococcosis, zoonoses in these immigrants do not seem to pose a quantitatively greater problem than in Danes who have visited these areas. However it is important to have a knowledge of the symptoms and mode of transmission of zoonoses occurring in areas where the immigrants come from.

Viremia in chronic hepatitis C patients evaluated by the Amplicor RT-PCR, a nested RT-PCR, and transaminase levels.

A commercially available kit, Amplicor, was compared with a locally developed nested reverse-transcriptase (RT) PCR for qualitative detection of HCV-RNA. Sixty-one serum samples from sixty-one patients with liver disease, and 60 samples from 60 hemophiliacs without symptoms, but known to have been heavily exposed to hepatitis C virus, were investigated. There was a high degree of concordance between the two diagnostic tests (97%), the Amplicor kit being slightly more sensitive than the in-house PCR, when evaluated using serial dilutions of samples showing discrepant results. The relationship between viremia and abnormal ALT levels was studied in the two groups of patients. Among those with chronic liver disease, 8.3% of patients with viremia had normal ALT levels, whereas transaminases were normal in 20% of hemophiliacs with viremia. This points to ALT as being a poor marker of ongoing viral replication.

Alpha interferon therapy in Danish haemophiliac patients with chronic hepatitis C: results of a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment.

Following a survey among all Danish haemophiliac patients 49 HIV-negative patients with chronic hepatitis C were offered enrollment in a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment. Dose modifications and treatment discontinuation were based upon changes in transaminase levels. Forty-seven patients enrolled received 3 MU of alpha interferon thrice weekly (TIW) for 3 months. Twenty-six nonresponders had their dose increased to 6 MU TIW for an additional 3 months, while 21 responding patients continued on 3 MU TIW. At 6 months, 25 patients with a complete or a partial biochemical response were randomly allocated to either a fixed dose regimen (13 patients) (3 or 6 MU thrice weekly) or an individualized dose regimen (12 patients) tapering interferon dose from 3 or 6 MU by one-third every 2 months if transaminases were persistently normal. The remaining 22 biochemical nonresponders were followed for an additional 6 months without further treatment. After 12 months of treatment, 18 patients (38%) had a virological response, irrespective of regimen, and seven patients (16%) had a sustained virological and biochemical response after 6 months of follow up. Overall, the individualized treatment regimen did not seem to offer any advantage over the fixed dose regimen. The response to alpha interferon treatment in Danish haemophiliac patients with chronic hepatitis C immediately after treatment is comparable to that obtained in previous studies among nonhaemophiliacs. However, a sustained virological and biochemical response was seen in only 16% of treatment patients.