Kongenitalna malformacija dišnih putova

Kongenitalna malfomacija dišnih putova (CPAM) rijetka je i izazovna bolest, još uvijek nepoznatih patogenetskih mehanizama i etiologije. Predstavlja hamartomatoznu displastičnu razvojnu malformaciju pluća koja najčešće zahvaća jedan plućni režanj, dok je rjeđe zahvaćeno više režnjeva ili je tvorba bilateralna. Ne postoji spolna predispozicija za ovu malformaciju. CPAM je podijeljena u pet tipova od kojih je tip II najčešće udružen s drugim komorbiditetima. Klinički tijek bolesti je varijabilan, te uključuje asimptomatsku prezentaciju sve do životno ugrožavajućih stanja, poput fetalnog hidropsa ili zatajenja respiracije u novorođenčeta. Poznato je da tvorba može regredirati u zadnjem tromjesečju trudnoće, no regresija je obično nepotpuna. Djeca s CPAM-om rađaju se obično kao normotermna novorođenčad, uredne porođajne težine. Sumnja na ovu malformaciju postavlja se antenatalnim ultrazvučnim pregledom u drugom tromjesečju trudnoće (anomaly scan), a potvrđuje se postnatalno kompjuteriziranom tomografijom. Konačna dijagnoza potvrđuje se postoperativno patohistološkom analizom. Liječenje obuhvaća prenatalne i postnatalne postupke koji ponajprije ovise o kliničkom statusu fetusa i majke, simptomatologiji novorođenčeta ili starijeg djeteta, te o procjeni rizika za maligne bolesti. Najvažnija indikacija za antenatalnu intervenciju je hidrops fetusa ili rizik za njegov razvoj. Postnatalno liječenje može biti ekspektativno ili kirurško (hitno ili elektivno). Za simptomatsku djecu mišljenja su usuglašena u smjeru rane operacije, no još uvijek ne postoji algoritam profilaktičkog liječenja djece koja su asimptomatska. U svakom slučaju, dugotrajni rizik za infekcije i maligne alteracije nadmašuje kratkotrajni rizik od operacije, te je preporučena operacija takvih promjena u prvim godinama života, no međutim, točna dob nije definirana. Komplikacije svih postupaka javljaju se u nezanemarivom postotku, a smrtni je ishod rijedak

Malignant transformation of germ cell tumor with teratomatous component into advanced retroperitoneal sarcoma - case report and literature review

Background: A late-relapse germ cell tumor (GCT) might contain malignant non-germ cell tumor cells, known as „somatic-type malignancy” (SM). Development of secondary SM is extremely rare and occurs in only 1% of patients with GCT. Case study: We present the case of a 42-year-old patient who developed retroperitoneal tumor with duodenal and right colon involvement 6 years after he underwent left orchidectomy for stage IIC mixed GCT (95% seminoma, 5% teratoma). Since the tumor markers for germline tumor were normal, another type of tumor was highly suspected, most likely a malignant alteration of the residual teratoma. Tumor was completely removed and pathological report suggested undifferentiated sarcoma. Conclusion: R0 resection and postoperative patient follow-up by the protocol for at least 6 years after orhidectomy is the key to successful treatment of GCT. Malignant tumor transformations are rare, but still possible so clinicians should be aware of the importance of frequent and adequate patient monitoring

Challenges in assessing exposure and vulnerability to natural hazards in large cities: the case study of Arequipa near the Misti volcano, south Peru

Assessing risk of potential natural catastrophes in cities remains challenging, in particular as we need to elaborate quantitative criteria for exposure and vulnerability. Statistical and probabilistic methods have been applied to Arequipa, one of the most vulnerable Latin America cities. The second largest city of Peru is highly exposed to natural hazards: earthquakes, eruptions from the historically active El Misti volcano, rain-triggered flash floods and mass flows together with landslides from the Río Chili canyon walls. First, we propose a long-term probabilistic multi-hazard assessment for the Misti composite cone located 17 km from Arequipa. Second, we examine criteria for delineating areas prone to mass flow hazards and characterizing multiple sources of vulnerability forthe city. Third, a statistical methodology to better estimate damage probability for buildings is proposed

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania, as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens

Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation

IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21lowCD38low). Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all cause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008±2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. Results 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/ HDL-Cholesterol: 8.94, 15.09, 6.92. Conclusions In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers