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IDH1 and IDH2 Mutations as Novel Therapeutic Targets in Acute Myeloid Leukemia (AML): Current Perspectives
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Angelo Paci, Mael Heiblig, Christophe Willekens, Sophie Broutin, Mehdi Touat, Virginie Penard-Lacronique, Stéphane de Bottona
Finally and importantly, ivosidenib was very well tolerated (up to 1200 mg per day). Among all patients enrolled (n = 258), the most common all-grade adverse events were diarrhea (33%), leukocytosis (30%), nausea (30%), fatigue (29%), febrile neutropenia (25%), dyspnea (24%), anemia (23%), QT prolongation (23%), peripheral edema (22%), pyrexia (21%), and decreased appetite (20%). All-grade and grade > 3 DS was noted in 11% and 5% of patients, respectively. When safety was assessed in 179 patients with R/R AML treated with ivosidenib at a dose of 500 mg daily. A treatment-emergent AE was experienced by 99% of patients and the event was grade 3% for 79%. The most common grade 3 treatment-emergent adverse reactions (ARs) were DS (13%), QTc prolongation (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Two patients (<1%) had Guillain-Barre syndrome that could not be attributed to a cause other than ivosidenib (DiNardo et al., 2018; Norsworthy et al., 2019).
Angiogenesis Treatment with CD13 Targeting Nanomedicines
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Madhu Gupta, Ramesh K. Goyal, Vikas Sharma
A novel metalloenzyme inhibitor, CHR–2797 which has potential to convert into a pharmacologically active acid product (CHR–79888) inside cells. It is a potent inhibitor of a number of intracellular aminopeptidases and shows their antineoplastic property against a range of tumor cell lines in vitro and in vivo (Krige et al., 2008). CHR–2797 is orally bioavailable agent, and in combination with paclitaxel it can be employed as undergoing phase Ib clinical investigation in the treatment of solid tumors (van Herpen et al., 2010). According to the reported phase I trial with accelerated titration design, 40 patients were selected with advanced solid tumors. CHR–2797 was taken once a time daily, but it showed toxicities such as fatigue, diarrhea, peripheral edema, nausea, dizziness, and constipation. One patient prompted partial response in case of renal cell carcinoma, and four patients had stable disease for >6 months (Reid et al., 2009). Tosedostat is currently in a registration study in patients with relapsed/refractory acute Macleod leukemia.
Clinical Effects of Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
All 10 patients clearly had their vasculitis reproduced on at least three separate occasions. Usually, there was a sequential progression of symptoms of color change of the hands, feet, nose, and skin followed by pulse alteration, periorbitol and peripheral edema, and petechial and/or spontaneous bruising. It is evident by the data shown in Table 2.18 that many different susceptibilities existed in each patient. Also, it was observed that some individual incitants would produce only portions, while others would produce all the patient's original signs and symptoms. These reactions were further substantiated by the benign asymptomatic course after ingestion or inhalation of nonreactive foods and food odors plus the reproducibility of signs by retesting of reacting foods. Ninety-five percent of the reactions that occurred within the first 4 hours started within the first 5 minutes after ingestion, leaving no doubt in the minds of observing personnel and patients that there was a cause–effect relationship. The severe reactions lasted up to 48 hours with lesser effects lasting up to 5 days. The moderate reactions lasted 4–8 hours while the mild ones were terminated within a 4-hour period. One hundred percent of the associated signs and symptoms were reproduced (Table 2.21).
Hypersensitivity pneumonitis in a slaughterhouse worker: A case report
Published in Archives of Environmental & Occupational Health, 2022
Elena Vasileiou, Paschalis Ntolios, Paschalis Steiropoulos, Theodoros Constantinidis, Evangelia Nena
A 60-year old, white/Caucasian, male presented to the Respiratory Outpatient Unit of our Institution, with progressively worsening dyspnea and nonproductive cough over the preceding 6 months. On presentation, the patient was alert, oriented and tempo-spatially collaborative. He was hydrated and afebrile, with a respiratory rate of 20 breaths per minute, blood pressure 135/75 mmHg and hemoglobin oxygen saturation (SaO2) 95% while breathing room air. Pulmonary auscultation revealed bilateral, fine “Velcro” crackles while the cardiac auscultation and abdominal examination were normal. He had no palpable lymphadenopathy or peripheral edema, and rest of physical examination was normal. His medical history included only a number of episodes of flu-like symptoms that subsided without specific treatment in the past. A detailed occupational history was obtained, where he mentioned that he has been working in a sheep/goat slaughterhouse for the last 25 years. He did not have a pet and he did not report any hobbies or contact with animals in his free time, although he lived in a rural setting with his elderly mother. He was nonsmoker but reported a moderate consumption of alcohol.
Physiological principles of Starling-like control of rotary ventricular assist devices
Published in Expert Review of Medical Devices, 2020
Andrew F. Stephens, Shaun D. Gregory, Aidan J.C. Burrell, Silvana Marasco, Dion Stub, Robert F. Salamonsen
Summarily, the Starling curve functionally relates ventricular output to ventricular pressure (preload), while the venous return line indicates how the venous return also varies with venous pressure and vascular tone. In the steady-state, the venous return must equal the ventricular output otherwise volume shifts will occur between the arterial and venous pools, which, in the native heart, may cause either pulmonary or peripheral edema depending on the nature of the problem. Ventricular output can be identified by the intersection of the Starling curve and venous return line (dotted horizontal lines, Figure 3: left and right). This relationship then forms the basis of the SLC. Functionally relating preload and ventricular output suffers the limitation that a single rigid equation which cannot describe the wide variety of cardiac states observed in humans. Therefore, physiologists expanded the model to incorporate families of Starling control lines which are controlled by neural and hormonal factors extrinsic to the heart [27].
Should we overcome the resistance to bioelectrical impedance in heart failure?
Published in Expert Review of Medical Devices, 2020
Stephen J. Hankinson, Charles H. Williams, Van-Khue Ton, Stephen S. Gottlieb, Charles C. Hong
BIVA, while limited to observational studies, may be useful to screen for peripheral edema in the ambulatory setting, aid with monitoring volume removal, and improve diagnostic accuracy of acute HF with inconclusive BNP levels (e.g. obesity). Considering observational studies are inherently limited by selection and confounding biases, observational findings should be viewed as hypothesis generating rather than definitive [67]. Therefore, RCTs are needed to evaluate BIVA-guided medical management in patients with acute and chronic HF. Leg BI, while not extensively studied in HF, has the potential to act as a surrogate for BIVA in assessing peripheral edema. Therefore, BIVA and LI may be useful as simple, noninvasive methods to screen for peripheral edema in outpatients with HF, particularly when clinicians are unable to detect peripheral edema on physical exam. Bioreactance, while validated in septic shock, has not been validated in cardiogenic shock; however, future observational studies and RCTs could investigate bioreactance-guided medical management of HF.