Seasonality of serum prostate-specific antigen levels: a population-based study

OBJECTIVE: The measurement of PSA serum levels is central to all early detection programs for prostate cancer. Although individual PSA values were known to fluctuate in the short and long term, the influence of insolation and seasons on PSA had not been addressed to date. To assert the relationship between total and free PSA and meteorological data in 8644 participants (55-70 years) in the French arm of the ERSPC study. METHODS: Blood sample was taken at the local laboratory after informed consent and frozen sera were sent for central testing of total and free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat with Hybritech reagents. Monthly meteorological data -- insolation, daily temperatures and rain precipitations -- were obtained from the local branches of the National Meteorology Agency. RESULTS: Total PSA -- but not free PSA -- was correlated with insolation, that is the monthly accrual in hours of sunshine during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI: 0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and percent-free PSA (free PSA divided by the total PSA). Interdependence between total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such relationship was even more evident in summer when the tested participants more often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the year, resulting in 23% more chances of being referred for biopsies (Odds ratio 1.23, 95%CI: 1.10-1.40). CONCLUSIONS: Total PSA was shown to be strongly associated with insolation and seasons while the percent-free PSA was not influenced.     

Real-Time Genomics for Tracking Severe Acute Respiratory Syndrome Coronavirus 2 Border Incursions after Virus Elimination,New Zealand

Since severe acute respiratory syndrome coronavirus 2 was first eliminated in New Zealand in May 2020, a total of 13 known coronavirus disease (COVID-19) community outbreaks have occurred, 2 of which led health officials to issue stay-at-home orders. These outbreaks originated at the border via isolating returnees, airline workers, and cargo vessels. Because a public health system was informed by real-time viral genomic sequencing and complete genomes typically were available within 12 hours of community-based positive COVID-19 test results, every outbreak was well-contained. A total of 225 community cases resulted in 3 deaths. Real-time genomics were essential for establishing links between cases when epidemiologic data could not do so and for identifying when concurrent outbreaks had different origins.     

Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias

AIMS: In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial. METHODS AND RESULTS: The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27 (95% CI 0.88-1.85) for death or spontaneous MI. CONCLUSION: The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies.     

Sofa dermatitis

Furniture components can cause contact allergies. In the last years several cases of eczema after sofa contact have been reported. Typically the skin lesions develop on the back, the buttocks, the dorsal aspects of the thighs and arms and are often very resistant to topical corticoid therapy. Dimethylfumarate (DMF) is postulated to be the causative agent for this Type IV hypersensitivity reaction. DMF is an antimicrobial substance, which is used in asian upholstered furniture industry amongst others. We report the case of a 65‐year old patient with generalised severely itching maculopapular, partly eczematous skin lesions on the buttocks, back, abdomen and arms. The resistance to therapy, several relapses after discharge from hospital as well as the detailed history lead us to the tentative diagnosis. The sofa dermatitis was proven by positive patch testing with furniture material and dimethylfumarate.     

Molecular diversity of Glanzmann thrombasthenia in southern India: new insights into mRNA splicing and structure-function correlations of alphaIIbbeta3 integrin (ITGA2B, ITGB3)

The molecular basis of Glanzmann thrombasthenia (GT) was studied in 40 families from southern India. Of 23 identified mutations (13 in the alphaIIb (ITGA2B) gene and 10 in the beta3 (ITGB3) gene), 20 were novel and three were described previously. Three mutations in the beta3 gene-p.Leu143Trp (Leu117Trp), p.Tyr307Stop (Tyr281Stop), and p.Arg119Gln (Arg93Gln)-were detected in 12, three, and two families, respectively, with definite founder effects observed for the first two mutations. Alternative splicing was predicted in silico for the normal variant and a missense variant of the beta3 gene, and for 10/11 frameshift or nonsense mutations in alphaIIb or beta3. The prediction was confirmed experimentally for a c.2898_2902dupCCCCT mutation in exon 28 of the alphaIIb gene that induced exon skipping. Seven out of nine missense mutations substituted highly conserved amino acids buried in the proteins' cores, predicting structural abnormalities. Among these, a beta3 substitution, p.Cys39Gly (Cys13Gly) was found to cause intracellular degradation of the beta3 subunit, in contrast to previous findings that mutations at Cys435, the partner of Cys13 in a disulfide bond, cause constitutive activation of alphaIIbbeta3. The two patients with a beta3 Arg93Gln mutation had normal clot retraction, consistent with a recent finding that this substitution is associated with normal surface expression of alphaIIbbeta3. In conclusion, this study demonstrates that a variety of mutations account for GT in southern Indian patients, provides new insights into mRNA splicing, and highlights the role of specific amino acids in structure-function correlations of alphaIIbbeta3.     

Distribution of ENG and ACVRL1 (ALK1) mutations in French HHT patients

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease characterized by arteriovenous malformations and resulting from mutations in two major genes: ENG and ACVRL1. The aim of the present study was to estimate the prevalence of the mutations of ENG and ACVRL1 in HHT, based on the largest series of patients reported so far, recruited through a national network. We previously reported the first mutation screening of both genes, in French HHT patients, using heteroduplex analysis. This previous study, bringing 60 novel mutations, provided a significant improvement to the knowledge of molecular pathology in HHT. However, 32% (n=48) of the patients with a confirmed clinical diagnosis remained without mutation. In these patients, we performed an extensive molecular analysis that included the sequencing of the whole coding sequence, the search for large rearrangements, and screening of the potential 5' regulatory regions. Additionally, due to the lack of large pedigrees suitable for linkage analysis, and since SMAD4 germline mutations have been reported in families with combined HHT and juvenile polyposis, we screened this gene and five other genes involved in the TGF-beta/BMP pathway in the patients without mutation of ENG or ACVRL1. Only a novel SMAD1 non-conservative substitution was found in one patient, changing a poorly conserved methionine to an isoleucin. Twenty-three mutations were found in ACVRL1 and 8 in ENG (including a duplication of exons 4 to 8 and deletions of exons 1 to 3 and 9 to 14). Our results, combined with our previous data, increase the mutation rate to 88% (n=119/136) in French patients with a confirmed clinical diagnosis. Our results also emphasize the higher prevalence of large insertions/deletions in ENG and the predominance of ACVRL1 over ENG mutations.     

Rationale for establishing regional ST-elevation myocardial infarction receiving center (SRC) networks

Recent developments have provided a unique opportunity for the organization of regional ST-elevation myocardial infarction (STEMI) receiving center (SRC) networks. Because cumulative evidence has demonstrated that rapid primary percutaneous coronary intervention (PCI) is the most effective reperfusion strategy for acute STEMI, the development of integrated SRC networks could extend the benefits of primary PCI to a much larger segment of the US population. Factors that favor the development of regional SRC networks include results from recently published clinical trials, insight into contemporary STEMI treatment patterns from observational registries, experience with the nation's current trauma system, and technological advances. In addition, the 2004 American College of Cardiology/American Heart Association STEMI guidelines have specified that optimal "first medical contact-to-balloon" times should be <90 minutes, so a clear benchmark for timely reperfusion has been established. Achievement of this benchmark will require improvements in the current process of care as well as increased multidisciplinary cooperation between emergency medical services, emergency medicine physicians, and cardiologists. Two types of regional SRC networks have already begun to evolve in role-model cities, including prehospital cardiac triage and interhospital transfer. Regional coordination of SRC networks is needed to ensure quality monitoring and to delineate the ideal reperfusion strategy for a given community based on available resources and expertise.