A logistic regression model including DNA status and morphology of spermatozoa for prediction of fertilization in vitro

To determine predictive values of routine semen analysis, sperm morphology evaluation using strict criteria and DNA status for in-vitro fertilization (IVF), 66 consecutive couples undergoing IVF in a university hospital IVF programme were prospectively investigated. Semen samples from 66 men were evaluated by routine semen analysis, morphology evaluation using strict criteria and acridine orange staining for determination of DNA status. A new technique is described for acridine orange scoring which consisted of evaluation of two smears per case, with and without heat treatment. Resistance to heat-provoked denaturation was determined by the difference between two evaluations. A logistic regression model was built and receiver operating characteristic curves were constructed to determine the threshold values and to compare diagnostic properties. Morphology evaluation using strict criteria and concentration of progressively motile spermatozoa were found to be the principal parameters determining the sperm fertilizing capacity in vitro. The logistic regression model composed of morphology evaluation using strict criteria and acridine orange score had a powerful diagnostic capability for prediction of fertilization in vitro.      

ECG-synchronized cardiac MR imaging: method and evaluation

An electrocardiographic (ECG) sensing and gating device compatible with a 0.35-tesla (T) magnetic resonance (MR) imager has been developed and used to produce 802 MR images of the heart in 30 patients. The instrument consists of an isolated acquisition module, an electrically floating preamplifier, and a monitor gating module. Two spin-echo images were acquired for each of five, 0.7-cm thick, transaxial sections from the base to the apex of the heart during each ECG-synchronized imaging run. Image quality was assessed in a blind study by two investigators, on a scale from 0 to 3, as diagnostic [2-3] or nondiagnostic [0-1]. There was agreement in 91.4% of their assessments of diagnostic images (68.1% of the images studied). Resolution of heart anatomy on the MR images was adversely affected by prolonged spin-echo time delay, imaging in late diastole, image acquisition at the cardiac apex, irregular triggering, and artifacts. The synchronization of gradient pulses to the ECG at 0.35 T appears safe for patients, permits diagnostic resolution of images, allows image acquisition at distinct points during the cardiac cycle, and enables monitoring of patients during imaging.     

Emotional demands at work and risk of hospital-treated depressive disorder in up to 1.6 million Danish employees: a prospective nationwide register-based cohort study

ObjectivePrevious studies on effects of emotional demands on depression have relied on self-reported exposure data and lacked control for potential confounding by pre-employment risk factors for depression. This study used a register-based design to examine the risk of hospital-treated depressive disorder in relation to occupational levels of emotional demands at work, furthermore addressing the role of risk factors for depression before workforce entry.MethodsWe analyzed data from two Danish register-based cohorts – Job Exposure Matrix Analyses of Psychosocial Factors and Healthy Ageing in Denmark (JEMPAD, N= 1 665 798) (17) and Danish Work Life Course Cohort (DaWCo, N=939 411), which link assessments of emotional demands by job exposure matrices to records of hospital-treated depressive disorder among employees aged 15–59 years at baseline (average follow up: 9.7 years in JEMPAD, 7.3 years in DaWCo). Potential confounders comprised sociodemographics, job control, work-related violence and physical demands at work. In DaWCo, we followed individuals from their entry into the workforce, and also included data on risk factors for depression before workforce entry (eg, parental income, education, and psychiatric diagnoses).ResultsEmployees in occupations with high emotional demands had an increased risk of hospital-treated depressive disorder with confounder-adjusted hazard ratios of 1.32 [95% confidence interval (CI) 1.24‒1.41] and 1.19 (95% CI 1.09‒1.30) in JEMPAD and DaWCO, respectively. This association remained after controlling for risk factors before workforce entry.ConclusionsThis study suggests that employees in occupations with high emotional demands are at increased risk of hospital-treated depressive disorder. This increased risk was neither attributable to reporting bias nor explained by the included risk factors for depression recorded before workforce entry.     

Survival after out-of-hospital cardiac arrest,Viet Nam: multicentre prospective cohort study

ObjectiveTo investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.MethodsWe did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.FindingsOf 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54–9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03–8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33–12.74).ConclusionImprovements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.     

2-chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia

A number of effective treatments are available for patients with hairy cell leukemia (HCL). 2-Chlorodeoxyadenosine (2-CdA) induces more than 80% complete responses, but is associated with profound suppression of CD4+ lymphocyte counts. However, the duration of each is uncertain. We have analyzed a previously reported cohort of 40 patients who had responded to 2-CdA. Eight patients (20%) have relapsed at a median of 16 months (range, 3 to 23 months). The remaining 32 patients were observed for a median of 30 months (range, 7 to 43 months). No patients have died. At 3 years, the actuarial disease-free survival rate is 77% (95% confidence interval, 70% to 84%). The median CD4+ lymphocyte count before therapy was 743/microL (range, 58 to 2,201/microL). The median CD4+ nadir after treatment was 139/microL (range, 25 to 580/microL). There was a single opportunistic infection and no second malignancies observed. Although there was evidence of some improvement in CD4+ lymphocyte counts on sequential testing, CD4+ counts remained significantly lower than baseline (P < .0001) at a median of 23 months after therapy (median, 237/microL; range, 25 to 514/microL), and were also lower than baseline (P < .002) in those patients with more than 1 year of follow-up (median, 27 months; range, 13 to 42 months). The median time to reach an absolute CD4+ lymphocyte count of 365/microL, the lower limit of the normal range, was 40 months. Although responses to 2-CdA are durable in the majority of patients with HCL, the uncertain long-term consequences of the observed CD4+ lymphocytopenia suggest caution in the broad application of this therapy.     

Posttransfusion purpura following bone marrow transplantation

BACKGROUND : Thrombocytopenia is a major cause of morbidity and hospital expense following bone marrow transplantation. Platelet transfusions in these patients are frequently complicated by the recipient's development of antibodies to HLA class I antigens. When these patients become refractory to the transfusion of HLA-matched platelets, the recipient's platelet antigen phenotype must be determined, to ensure that donor platelets will be phenotypically compatible. Cases of alloimmunization to HPA-1a and HPA-1b resulting in refractoriness to transfused platelets and the subsequent development of a posttransfusion purpura-like syndrome are reported. CASE REPORTS: In the first case, a 43-year-old woman with Stage IV infiltrating ductal breast cancer presented to the hospital for a transplant of autologous peripheral blood stem cells. After the transplant, her platelet count remained less than 10 × 10⁹ per L, despite daily platelet transfusions, including HLA-matched platelets. Fourteen days following the transplant, her serum was found to contain anti-HPA-1a. Initially, the patient was refractory to the transfusion of HPA-1a-negative platelets, but after treatment with intravenous immunoglobulin, she had transient increases in posttransfusion platelet counts. She was also treated with a staphylococcal protein A immunoadsorption column and has not had any such subsequent refractoriness. Her genotype has been found, by use of allele-specific oligonucleotide hybridization with white cell DNA, to be HPA-1b/1b. The second case involved a 32-year-old woman with chronic myelogenous leukemia who received an unrelated-donor marrow transplant. Three years later, her CML recurred, and she was treated with interferon-alpha. Four months afterward, she experienced interferon-alpha-induced thrombocytopenia and the interferon therapy was discontinued. She received 12 platelet transfusions in 20 days, but none was effective. Antibodies specific for HLA antigens and HPA-1b were detected, and three HLA-matched, HPA-1b-negative apheresis platelet components were given, but without effect. Two days after treatment with methylprednisolone (1 g intravenously) and prednisone (2 mg/kg/day orally), her platelet count was 26 × 10⁹ per L, and after 8 more days, it was 102 × 10⁹ per L, without further transfusions. She was found to be homozygous for HPA-1a (HPA-1a/1a). CONCLUSION : Anti-HPA- 1a and anti-HPA-1b can cause refractoriness to platelet transfusions in bone marrow transplant patients. Testing for platelet-specific antibodies should be considered in all patients who are refractory to HLA-matched platelets.     

False-negative serological HLA-B27 typing results may be due to altered antigenic epitopes and can be detected by polymerase chain reaction

Serological typing with the microlymphocytotoxicity test (MLCT) and flow cytometry (FC) using HLA-B27 antisera is commonly used for the determination of HLA-B27. However, in some patients tested more than once, negative results have turned out to be positive at following investigations. We retested by polymerase chain reaction (PCR) samples from 20 randomly selected patients with reactive arthritis or Reiter's syndrome who had now been followed for 20 yr. Ten of the patients were originally tested to be HLA-B27 positive and 10 HLA-B27 negative by the MLCT. All 10 serologically HLA-B27 positive individuals were also positive in the PCR. However, 2/10 patients interpreted as being HLA- B27 negative were positive by PCR. At this time, the same two patients were also positive in the routine MLCT and FC using four different monoclonal antibodies against HLA-B27. PCR is superior to serological techniques to determine HLA-B27 positivity unequivocally, since it is based on the detection of HLA-B27 gene sequences.      

Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ara-C and recombinant human granulocyte-macrophage colony- stimulating factor

We administered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) (120 micrograms/m2/d by continuous intravenous [IV] infusion) to 12 patients with newly diagnosed acute myeloid leukemia (AML) at relatively high risk of early death during remission induction. GM-CSF began 3 days after completion of induction chemotherapy (ara-C 1.5 g/m2 d x 4 days by continuous IV infusion after a 3 g/m2 bolus). Rates of fatal infection (42%), pneumonia and/or sepsis (83%), and CR (50%) did not differ significantly (P less than .05) from those observed after administration of the identical chemotherapy without GM-CSF to 53 historical controls with newly diagnosed AML at similarly high risk of early death. There were no significant differences between the GM-CSF-treated and the historical groups in the time required to reach neutrophil counts of 500 or 1,000/microL after administration of chemotherapy. Four patients died of infection before they could have benefited from the earliest recovery of neutrophil count observed in patients who entered CR. Growth of leukemia after GM-CSF administration was observed in only 1 of the 8 patients who survived long enough for response to induction therapy to be fully evaluated. This observation suggests that it might be safe to undertake larger, randomized studies, perhaps using earlier administration of GM-CSF, to definitively determine the role of GM-CSF added to chemotherapy in patients with newly diagnosed AML.