Nawracające zapalenie opłucnej jako wiodący objaw rodzinnej gorączki śródziemnomorskiej

Familial Mediterranean Fever (FMF) is a disease with an autosomal recessive inheritance affecting inhabitants of the Mediterranean Sea basin area. It is the most prevalent fever-inflammatory syndrome manifested by fever episodes, serositis and rash. The symptoms regress spontaneously and between recurrent attacks of fever the child is healthy. Amyloidosis is the most serious complication. A case of a 8 year-old boy, a son of Armenian immigrants, with recurrent pleuritis is presented.     

Exposure density and neighborhood disparities in COVID-19 infection risk

Although there is increasing awareness of disparities in COVID-19 infection risk among vulnerable communities, the effect of behavioral interventions at the scale of individual neighborhoods has not been fully studied. We develop a method to quantify neighborhood activity behaviors at high spatial and temporal resolutions and test whether, and to what extent, behavioral responses to social-distancing policies vary with socioeconomic and demographic characteristics. We define exposure density (Exρ) as a measure of both the localized volume of activity in a defined area and the proportion of activity occurring in distinct land-use types. Using detailed neighborhood data for New York City, we quantify neighborhood exposure density using anonymized smartphone geolocation data over a 3-mo period covering more than 12 million unique devices and rasterize granular land-use information to contextualize observed activity. Next, we analyze disparities in community social distancing by estimating variations in neighborhood activity by land-use type before and after a mandated stay-at-home order. Finally, we evaluate the effects of localized demographic, socioeconomic, and built-environment density characteristics on infection rates and deaths in order to identify disparities in health outcomes related to exposure risk. Our findings demonstrate distinct behavioral patterns across neighborhoods after the stay-at-home order and that these variations in exposure density had a direct and measurable impact on the risk of infection. Notably, we find that an additional 10% reduction in exposure density city-wide could have saved between 1,849 and 4,068 lives during the study period, predominantly in lower-income and minority communities.

As of December 17, 2020, there have been 73 million cases of COVID-19 in more than 200 countries, and 1.6 million people have lost their lives to the disease (1). The COVID-19 pandemic is considered the most severe public health crisis since the 1918 flu pandemic due to its transmission and infection characteristics (2–5). Social distancing (also referred to as physical distancing) has been shown to be an effective behavioral nonpharmaceutical intervention to reduce the transmission rate of COVID-19 (3–7). Social distancing reduces the probability of contacts between individuals who might be infected, resulting in reduced exposure risk (7, 8). Governments have implemented a range of social-distancing policies, including travel bans, restrictions on gatherings, school closures, nonessential business closures, and restaurant restrictions. In particularly hard-hit locations, mandatory “stay-at-home” orders have been issued to limit or avoid unnecessary close contacts outside of the home (7–9).Studies have found that social-distancing measures help to prevent transmission of the virus and reduce the reproduction (R₀) number (5–7, 10–14). These practices help to avoid overwhelming hospital intensive care units and healthcare systems, control doubling time of infections, and ultimately save lives (5, 8, 14, 15). Although not without potentially significant hardship to individuals and communities, social distancing is an important public health tool to flatten the epidemic curve and support longer-term economic and public health benefits (3, 15–17).However, the impact of, and response to, stay-at-home orders and social-distancing guidelines is not uniform across neighborhoods and communities (18, 19). In order to maximize the positive effects of social distancing, individuals need to change their typical behavior, often dramatically (3, 20). Despite government-mandated social-distancing policies (such as New York State’s PAUSE order), socio-behavioral responses vary across neighborhoods, further contributing to disparities in risk of infection (4, 7, 21). Disparities in social-distancing practices—namely, geographic or population subgroup differences in adopting behavior changes in response to the same policy context—may stem from varying levels of awareness, perception, or belief in the severity of the virus threat; differences in social and cultural norms; or the ability of households and communities to alter normal activity patterns given economic constraints or other existing responsibilities (7, 20–23). For example, lower-income households typically do not have the option to work from home, and going to a place of work (often in essential services) is unavoidable, meaning higher risk of exposure to COVID-19 for themselves, as well as their families and communities (7, 24). Within specific neighborhoods, norms can also be reinforcing; if large numbers of residents are essential workers and not socially distancing, other residents may have similar behavioral responses (20).A growing number of outbreaks are occurring in densely populated areas (25), with disproportionate impacts on lower-income and predominantly minority communities (18, 26–28). Measuring and understanding social distancing and behavior change across neighborhoods can provide critical insight into the design and implementation of more effective—and equitable—public health policy. Given the potential heterogeneity in localized responses to social-distancing recommendations, quantifying local patterns of activity represents an emerging tool to understand and eventually reduce local exposure risk and limit community outbreaks (7, 29, 30). Although there has been increasing awareness of the troubling disparities in infection rates and outcomes in vulnerable communities, the effectiveness of behavioral interventions at the scale of individual neighborhoods has not been fully studied. Often, studies that do attempt to observe effects at higher spatial resolutions rely on simulations or are limited to relatively coarse areal units (e.g., county or state) due to data availability and computational constraints (31–34). Absent a more complete understanding of neighborhood activity patterns in response to nonpharmaceutical interventions, disaggregating built-environment, behavioral, and social determinants of health in the context of COVID-19 remains a challenge.We develop a method to quantify neighborhood activity at high spatial and temporal resolutions to test whether—and to what extent—behavioral responses to social-distancing policies vary with socioeconomic, demographic, and built-environment characteristics. We define exposure density (Exρ) as a measure of both the localized volume of activity in a defined area and the proportion of activity occurring in nonresidential and outdoor land uses, areas that can be associated with an increased risk of exposure to others that may be infected. We utilize this approach to capture community inflows/outflows of people as a result of the pandemic and changes in mobility behavior for those that remain.Our focus is on New York City (NYC), the first epicenter of the pandemic in the United States, where a statewide stay-at-home order (NY on PAUSE) was introduced on March 22, 2020. By June 30, 2020, NYC had more than 212,000 confirmed cases of COVID-19, accounting for 8% of the nationwide total, resulting in at least 18,492 confirmed deaths and 4,604 probable deaths (35). Our methodology proceeds in three steps. First, we develop a generalizable method for assessing neighborhood activity levels using smartphone geolocation data over a 3-mo period (February, March, and April) covering more than 12 million unique devices within the Greater New York area, together with land-use classifications at 1-m grid resolution. Second, we measure and analyze disparities in community social distancing by estimating variations in neighborhood activity and associated patterns in community characteristics before and after the stay-at-home order. Finally, we evaluate the effect of exposure density on COVID-19 infection rates associated with localized demographic, socioeconomic, and built-environment characteristics in order to identify disparities in health outcomes related to mobility behavior. Our findings provide insight into the timely evaluation of the effectiveness of social distancing at the scale of individual neighborhoods and support a more equitable allocation of resources to vulnerable and at-risk communities.     

In hospital observation of patients with acute coronary syndrome without ST elevation and multivessels coronary artery disease treated with early invasive strategy. Comparison of results of percutaneous coronary intervention and coronary artery by-pass grafting

Acute coronary syndromes (ACS) without persistent ST-segment elevation are the main cause of hospitalization, morbidity and mortality. The objective of this study was to compare clinical and angiographic parameters as well as in-hospital results of treating 307 consecutive patients with ACS without persistent ST-segment elevation with either PCI or CABG. Inclusion criteria were: rest angina within the last 24 hours, ST-segment depression (> 0.5 mm), T-wave inversion (> 1 mm) in at least two leads, positive serum cardiac markers. PCI was performed in 75.9% of patients and 24.1% of patients underwent CABG. Both groups did not differ as to age, sex, history of diabetes, arterial hypertension, heart failure, smoking and ejection fraction. Positive troponin was significantly more frequent in the PCI group. 51% of PCI patients and 80% of CABG patients had complete revascularization (p = 0.00001). Independent predictors of in-hospital death in the CABG group were: inability to determine culprit vessel during coronary angiography due to lesions' severity (OR 13.65; 95% CI 9.40-15.20; p = 0.007) and heart failure (OR 15.58; 95% CI 12.29-18.01; p = 0.003). In the PCI group these independent predictors were: Braunwald's IIIC unstable angina (OR 5.48; 95% CI 3.10-7.17; p = 0.04) and diabetes (OR 2.22; 95% CI 1.07-3.90; p = 0.003). In-hospital mortality rate was significantly higher in the CABG group (8.1% vs 1.7% p < 0.01). Patients with multivessel coronary artery disease and ACS without ST-segment elevation treated with PCI have better in-hospital outcome than patients assigned to CABG, but the rate of complete revascularization is lower.     

Decreased ATP-sensitive K(+) current density during chronic human atrial fibrillation

Chronic atrial fibrillation (AF) is associated with shortening of action potential duration (APD), which involves modified activity of atrial ion currents. However, little is known about the activity of ATP-sensitive K(+) channels (I(K,ATP)) during chronic AF. An AF-related increase in the activity of I(K,ATP) would reduce APD and could contribute to initiation and/or perpetuation of AF. Here, we studied the activity of I(K,ATP) in atrial myocytes from patients with sinus rhythm (SR) and chronic AF. Human atrial myocytes were isolated from atrial tissue obtained from patients undergoing open-heart surgery. Inward rectifier currents were measured with the whole-cell patch-clamp technique by applying a depolarizing ramp pulse (1245 ms) from -100 to +40 mV (0.5 Hz). I(K,ATP) was activated with the I(K,ATP) channel opener rilmakalim. The inward rectifier I(K1) and I(K,ATP) were identified by their sensitivity to 1 mM Ba(2+). Density of I(K1) did not differ between cells from patients with AF (at -100 mV: -14.8 +/- 1.3 pA/pF, n = 38/10 (cells/patients)) and SR (-13.8 +/- 1.5 pA/pF, n = 33/16). In both types of cells, rilmakalim stimulated I(K,ATP) (defined as rilmakalim-inducible current) in a concentration-dependent manner (0.3-10 microM). However, maximum activation of I(K,ATP) with 10 microM rilmakalim was smaller in AF than in SR cells (at -100 mV: -5.3 +/- 0.8 pA/pF, n = 22/7 vs. -11.2 +/- 2.9 pA/pF, n = 19/9; at +40 mV: +9.6 +/- 2.1 pA/pF, n = 22/7 vs. +23.7 +/- 3.4 pA/pF, n = 19/9 for AF and SR, respectively; P < 0.05). Only aortic valve disease and pulmonary hypertension were found to be independent contributors to I(K,ATP) current density. We provide evidence that chronic AF is associated with a downregulation of ATP-sensitive K(+) currents. These changes may provide an additional molecular mechanism for electrical remodeling in chronic AF.     

Concurrent DNA Copy‐Number Alterations and Mutations in Genes Related to Maintenance of Genome Stability in Uninvolved Mammary Glandular Tissue from Breast Cancer Patients

Somatic mosaicism for DNA copy‐number alterations (SMC‐CNAs) is defined as gain or loss of chromosomal segments in somatic cells within a single organism. As cells harboring SMC‐CNAs can undergo clonal expansion, it has been proposed that SMC‐CNAs may contribute to the predisposition of these cells to genetic disease including cancer. Herein, the gross genomic alterations (>500 kbp) were characterized in uninvolved mammary glandular tissue from 59 breast cancer patients and matched samples of primary tumors and lymph node metastases. Array‐based comparative genomic hybridization showed 10% (6/59) of patients harbored one to 359 large SMC‐CNAs (mean: 1,328 kbp; median: 961 kbp) in a substantial portion of glandular tissue cells, distal from the primary tumor site. SMC‐CNAs were partially recurrent in tumors, albeit with considerable contribution of stochastic SMC‐CNAs indicating genomic destabilization. Targeted resequencing of 301 known predisposition and somatic driver loci revealed mutations and rare variants in genes related to maintenance of genomic integrity: BRCA1 (p.Gln1756Profs*74, p.Arg504Cys), BRCA2 (p.Asn3124Ile), NCOR1 (p.Pro1570Glnfs*45), PALB2 (p.Ser500Pro), and TP53 (p.Arg306*). Co‐occurrence of gross SMC‐CNAs along with point mutations or rare variants in genes responsible for safeguarding genomic integrity highlights the temporal and spatial neoplastic potential of uninvolved glandular tissue in breast cancer patients.