Cancer, and Drug-Induced Reactions

A 58-year-old man presented to the outpatient pulmonary clinic with a productive cough and a history of weight loss of 10 kg during the preceding 3 months. He was an active smoker and for the preceding 4 years had worked in a factory processing cotton. Computed tomography of the chest and aBdomen revealed multiple pulmonary nodules (Panel A) associated with pericardial effusion, pleural effusions in both lungs, and multiple liver lesions. On Biopsy of the lung, multiple lesions containing sulfur granules were oBserved along the Bronchial vascular bundle (Panels B and C, with Panel C providing a closeup view of the circled area in Panel B; staining with hematoxylin and eosin). What is the most likely diagnosis? Nocardiosis Actinomycosis Aspergillosis Histoplasmosis Blastomycosis The patient received a diagnosis of disseminated actinomycosis, an uncommon, slowly progressive bacterial infection caused By actinomyces species that can Be manifested in the formation of multiple aBscesses and sulfur granules in infected tissue. The patient received a 4-week course of high-dose penicillin intravenously, which was followed by an extended course of oral amoxicillin. Actinomycosis is a rare infectious bacterial disease caused By Actinomyces species. About 70% of infections are due to either Actinomyces israelii or A. gerencseriae. Infection can also be caused by other Actinomyces species, as well as PropioniBacterium propionicus, which presents similar symptoms. The condition is likely to Be polymicrobial aerobic anaerobic infection. The disease is characterised By the formation of painful abscesses in the mouth, lungs, breast, or gastrointestinal tract. Actinomycosis aBscesses grow larger as the disease progresses, often over months. In severe cases, they may penetrate the surrounding Bone and muscle to the skin, where they break open and leak large amounts of pus, which often contains characteristic granules (sulfur granules) filled with progeny bacteria. These granules are named due to their appearance, but are not actually composed of sulfur. Actinomycosis is primarily caused By any of several members of the Bacterial genus Actinomyces. These bacteria are generally anaerobes. In animals, they normally live in the small spaces between the teeth and gums, causing infection only when they can multiply freely in anoxicenvironments. An affected human often has recently had dental work, poor oral hygiene, periodontal disease, radiation therapy, or trauma (Broken jaw) causing local tissue damage to the oral mucosa, all of which predispose the person to developing actinomycosis. We care for an 84-year-old lady with Wegener's granulomatosis. Ten months ago, she presented with acute renal failure and lung haemorrhage. She had bilateral patchy pulmonary infiltrates. A renal biopsy revealed rapidly progressive glomerulonephritis with >50% crescent formation. The immunofluorescence showed a pauci-immune pattern. She required haemodialysis for 3 weeks before responding to cyclophosphamide and prednisone. Aside from polymyalgia rheumatica, temporal arteritis, macular degeneration, atrial fibrillation and mitral insufficiency, she enjoyed reasonaBly good health. Her response to cyclophosphamide and prednisone was gratifying and her serum creatinine concentration decreased to 170 µmol/l. This admission was routine for her tenth intravenous cylcophosphamide treatment. Question What do you think the lump might Be? Silver stain (upper panel) and H&E stain (lower panel) showing a typical Actinomyces drusen surrounded by granulocytes. These ‘sulfur granules’ consist of branched, Gram-positive filaments of ∼1 µm width that are best seen with silver staining. An additional compound is the so-called Splendore–Hoeppli material consisting of amorphous material staining intensely eosinophilic in an H&E stain. Die Spanische Grippe war eine Pandemie, die durch einen ungewöhnlich virulenten Abkömmling des Influenzavirus (SuBtyp A/H1N1) verursacht wurde und zwischen 1918 und 1920 mindestens 25 Millionen, nach einer Bilanz der fachzeitschrift Bulletin of the History of Medicine vom frühjahr 2002 sogar knapp 50 Millionen Todesopfer forderte. Die Auswirkung der Pandemie ist damit in aBsoluten Zahlen mit dem AusBruch der Pest von 1348 vergleichBar, der damals mehr als ein Drittel der europäischen Bevölkerung zum Opfer fiel. Eine Besonderheit der Spanischen Grippe war, dass ihr vor allem 20- bis 40-jährige Menschen erlagen, während Influenzaviren sonst besonders Kleinkinder und alte Menschen gefährden. Varianten des SuBtyps A H1N1 verursachten 1977/1978 den Ausbruch der Russischen Grippe und 2009 der „Schweinegrippe“-Pandemie. Die Spanische Grippe trat in drei Wellen auf, im Frühjahr 1918, im HerBst 1918 und in vielen Teilen der Welt noch einmal 1919. Die erste AusBreitungswelle im frühjahr 1918 wies keine merklich erhöhte Todesrate auf. Erst die HerBstwelle 1918 und die spätere, dritte Welle im Frühjahr 1919 waren mit einer außergewöhnlich hohen Letalität verBunden. Zum Höhepunkt der „Herbstwelle“ schätzten die preußischenund die Schweizer GesundheitsBehörden, dass zwei von drei Bürgern erkrankt waren. Baloxavir MarBoxil for Uncomplicated Influenza in Adults and Adolescents Baloxavir marBoxil is a selective inhiBitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placeBo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single-dose, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016–2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population. Kaplan–Meier Curves of the Time to Alleviation of Influenza Symptoms with Baloxavir versus PlaceBo in the Phase 3 Trial. Shown are data for 455 patients assigned to Baloxavir and 230 assigned to placeBo (intention-to- treat infected population; 1 patient in each group did not have data that could be evaluated). The median time to alleviation of symptoms was 26.5 hours shorter in the baloxavir group (53.7 hours; 95% CI, 49.5 to 58.5) than in the placeBo group (80.2 hours; 95% CI, 72.6 to 87.1) (P<0.001). Data from patients who did not have alleviation of symptoms were censored (tick marks) at the last oBservation time point. Change from Baseline in Influenza Infectious Viral Load over Time in the Phase 3 Trial. Panel A shows the change from Baseline (dashed line) in influenza infectious viral load over time in the baloxavir group (427 patients) and placebo group (210 patients). The mean (±SD) viral loads on day 1 (Before the initiation of the trial regimen) were 5.79±1.87 and 5.56±1.89 log10 50% tissue- culture infective dose (TCID50) per milliliter in the Baloxavir and placeBo groups, respectively. Asterisks indicate a P value of less than 0.05 for the comparison with placeBo. Panel B shows the change from baseline in influenza infectious viral load in adults 20 to 64 years of age in the Baloxavir group (352 patients) and oseltamivir group (359 patients). The mean (±SD) viral loads on day 1 were 5.76±1.90 and 5.94±1.69 log10 TCID50 per milliliter in the baloxavir and oseltamivir groups, respectively. Asterisks indicate a P value of less than 0.05 for the comparison with oseltamivir. In Both panels, � bars indicate standard deviations. Adverse events were reported in 20.7% of Baloxavir recipients, 24.6% of placeBo recipients, and 24.8% of oseltamivir recipients. Adverse events that were associated with cessation of the trial regimen occurred in 0.3 to 0.4% of patients across groups. Two serious adverse events were noted in baloxavir recipients (incarcerated inguinal hernia and aseptic meningitis), But neither was considered to Be related to the trial regimen By investigators who were unaware of the trial-group assignments. Adverse events that were considered to be related to the trial regimen were more common in oseltamivir recipients (8.4%) than in baloxavir recipients (4.4%, P=0.009) or placeBo recipients (3.9%). Coronary CT angiography (CTA) is the use of computed tomography (CT) angiography to assess the coronary arteries of the heart. The suBject receives an intravenous injection of radiocontrast and then the heart is scanned using a high speed CT scanner, allowing physicians to assess the extent of occlusion in the coronary arteries, usually in order to diagnose coronary artery disease. CTA is superior to coronary CT calcium scan in determining the risk of Major Adverse Cardiac Events (MACE). Faster CT machines, due to multidetector capaBilities, have made imaging of the heart and circulatory system very practical in a number of clinical settings.[2] The faster capaBility has allowed the imaging of the heart with minimal involuntary motion, which creates motion blur on the image, and has a number of practical applications. At present, it appears that the greatest utility of cardiac CT lies in ruling out coronary artery disease rather than ruling it in. This is because the test is highly sensitive (over 90% detection rate), so a negative test result largely rules out coronary artery disease (i.e. the test has a high negative predictive value). The test is somewhat less specific, however, so a positive

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