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MSD manual: professional model.
tosis patients.Purpose of review The purpose of this review is to summarize the current understanding of germline mutations as they contribute to leukemia development and progression. We also discuss how these new insights may help improve clinical management of germline mutations associated with leukemia. Recent findings Germline mutations may represent important initial mutations in the development of leukemia where interaction with somatic mutations provide further hits in leukemic progression. In addition, germline mutations may also contribute to leukemogenesis by impacting bone marrow stem-cell microenvironment and immune cell development and function. Summary Leukemia is characterized by the clonal expansion of malignant cells secondary to somatic or germline mutations in a variety of genes. Gemcitabine Understanding somatic mutations that drive leukemogenesis has drastically improved our knowledge of leukemia biology and led to novel therapeutic strategies. Advances have also been made in identifying germline mutations that may affect leukemic development and progression. This review will discuss the biological and clinical relationship of germline mutations with clonal hematopoiesis, bone marrow microenvironment, and immunity in the progression of leukemia.Purpose of review Dipeptidyl peptidase 4 (DPP4) is a serine protease with diverse regulatory functions in healthy and diseased cells. Much remains unknown about the mechanisms and targets of DPP4. Here we discuss new studies exploring DPP4-mediated cellular regulation, provide an updated list of potential targets of DPP4, and discuss clinical implications of each. Recent findings Recent studies have sought enhanced efficacy of targeting DPP4's role in regulating hematopoietic stem and progenitor cells for improved clinical application. Further studies have identified DPP4 functions in different cellular compartments and have proposed ways to target this protein in malignancy. These findings, together with an expanded list of putative extracellular, cell surface, and intracellular DPP4 targets, provide insight into new DPP4-mediated cell regulation. Summary DPP4 posttranslationally modifies proteins and peptides with essential roles in hematopoietic cell regulation, stem cell transplantation, and malignancy. Targets include secreted signaling factors and may include membrane proteins and transcription factors critical for different hematopoietic functions. Knowing these targets and functions can provide insight into new regulatory roles for DPP4 that may be targeted to enhance transplantation, treat disease, and better understand different regulatory pathways of hematopoiesis.Objective Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesized that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multiomics data. Summary background data Observational cohort study. n = 57 for the discovery cohort (clinical, transcriptomics, proteomics, and metabolomics data) and n = 312 for the validation cohort (clinical and metabolomics data). Methods We integrated coincident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated 4 different metrics for patient similarity using unbiased mathematical, biological, and clinical measures of internal and external validity.We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS). Results Our results identify 4 distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that 2 endotypes in AP recapitulate disease endotypes previously reported in ARDS. Conclusions Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalizable patterns exist in diverse presentations of critical illness.Supplemental Digital Content is available in the textPurpose of review Examine recent evidence of randomized controlled trials and meta-analyses regarding the effect of maternal vitamin D status and supplementation over obstetrical and offspring outcomes. Recent findings Maternal serum 25-hydroxyvitamin [25(OH)D] progressively declines during pregnancy because of fetal physiological demands and adjustments. Vitamin D supplementation during pregnancy in women with low vitamin D status may improve fetal growth and reduce the risks for small-for-gestational-age, preeclampsia, preterm birth, and gestational diabetes. Mothers with sufficient vitamin D levels have offsprings with less enamel defects and less attention deficit and hyperactive disorders and autism. All pregnant women should be supplemented with 600 IU/day of vitamin D3. We discuss evidence indicating that higher vitamin D doses (1000-4000 IU/day) may be convenient to achieve better maternal and infant outcomes. Low maternal vitamin D status during pregnancy may be associated in infants with a higher risk for lower bone mineral content, enamel defects and attention deficit hyperactive disorder. Summary Recent evidence from vitamin D intervention studies and meta-analyses of a large number of studies support vitamin D supplementation during pregnancy to improve maternal, fetal and, immediate and later offspring health.Purpose of review The purpose of this publication is to review the currently available and most up-to-date information regarding the pathogenesis, diagnosis, and treatment of pelvic congestion syndrome. Recent findings The diagnosis of pelvic congestion syndrome is difficult to make; however, it should remain on the differential for chronic pelvic pain. The most recent available research seems to favour endovascular treatment with interventional radiology over surgical management, with high success rate and low occurrence of complications. Summary High-level evidence on the diagnosis and management of pelvic congestion syndrome is lacking. Only a small number of randomized controlled trials exist. More high-quality research is needed, particularly involving practicing obstetrician and gynecologists as the majority of these patients, and the clinical outcomes of any interventions implemented for pelvic congestion syndrome are ultimately managed by OB/GYN providers.Purpose of review Uterine leiomyomas are a common condition estimated to affect 70-80% of reproductive-aged women. An evolving body of evidence continues to guide our understanding of various surgical and interventional treatment options, such as uterine artery embolization (UAE). This article provides an updated review of novel findings regarding UAE. Recent findings Despite an abundance of observational studies and several small randomized controlled trials, large scale long-term comparative efficacy studies are lacking. Although short-term outcomes continue to be favorable, recent trials show reoperation rate of up to 35% in 10 years and may raise some concerns regarding ovarian reserve, fertility and pregnancy outcomes. Summary UAE remains a safe and effective alternative to surgery in the management of leiomyomas. A deeper investigation into understanding this treatment's optimal use in various patient populations is needed.Not availble.In the year 1527, following the invasion of Italy by Landsknechts, who were headed by Georg von Frundsberg, the bubonic plague appeared in the country. These soldiers were part of an army that Charles V sent to invade Italy in order to subjugate the Italian states which had adhered to the League of Cognac. In Bologna during the year 1527 believers held a procession from the Sanctuary of the Madonna del Soccorso, through the city, as far as the Church of San Rocco. The reason for this practice was linked with the plague epidemic. After some cases of plague observed in the Borgo di San Pietro district the miracle of the interruption of the epidemics, thanks to the intervention of Our Lady, was narrated by the faithfuls. Later, after several decades, it was reported by several authors from Bologna, who were not witnesses to the facts, that the epidemic had involved 12,000 out of a total population of around 60,000 inhabitants at that time. We re-evaluated this situation starting from the demographic data concerny charitable activities to aid the inhabitants of Bologna, during a difficult historical period, namely the Protestant Reformation, and contributed to strengthen the faith of Catholic believers.The choice of Dedeagatch as the place where the station of the Adrianoupolis-Constantinople railway line was to be built was the reason for the foundation of the Greek city of Alexandroupolis (originally under the Ottoman government). The population grew in its early years mainly due to the settlement by railway and construction workers. Meanwhile, poverty, poor hygiene and environmental conditions led to a series of epidemics and various sporadic cases of infections such as malaria, typhoid fever, scarlet fever and tubercolosis, infections which marked the early history of Alexandroupolis. The first documented death due to typhoid fever in the area, namely that of the Italian civilian Giuseppe Bigheti, is mentioned in the paper.Neurocysticercosis (NCC) is a global health problem. In more developed countries, NCC is mainly a disease affecting immigrants. In developing countries, NCC is the most common parasitic disease of the nervous system and the main cause of acquired epilepsy. NCC is also an unrecognized cause of strokes and could account for 4%-12% of strokes. Here, I report a case of a 58-year-old woman who presented to the emergency department (ED) with severe headache, vomiting, and sudden loss of consciousness. Multiple NCC and Fisher grade 4 aneurysmal subarachnoid hemorrhage (SAH) were demonstrated by neuroimaging. This patient evolved favorably with albendazole and corticosteroids. This case exemplifies that NCC must be considered in the differential diagnosis of stroke in younger and middle-aged patients, especially if they do not have classical cardiovascular risk factors and come from endemic regions for cysticercosis.Invasive pulmonary aspergillosis (IPA) is a life-threatening condition that usually occurs in immunocompromised hosts. However, according to recent reports it can affect immunocompetent hosts with severe influenza infection due to viral-dependent disruption of respiratory immune defenses. We present the case of a 61-year-old Caucasian man admitted to the Emergency Department with respiratory failure and fever, who was diagnosed with H1N1 influenza and IPA. Because of his poor general conditions, he was treated with a double antifungal scheme, although this lies outside the suggested treatment guidelines. This choice turned out to be extremely effective. He was discharged after one month and his clinical conditions showed rapid improvement, with nearly complete normalization of the radiological pattern in three months. IPA remains a life-threatening condition, even in immunocompetent hosts, and should therefore always be suspected; if necessary, a combined treatment should rapidly be started. We report this case as the interest in influenza-associated IPA is high, both due to the clinical severity of this condition, which is treatable if identified early, and the emerging importance of respiratory infections caused by viruses belonging to the SARS family, such as SARS-CoV-2.
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