initial clinical evaluation
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Author(s):  
Hao Xie ◽  
Junjia Liu ◽  
Diego M. Alem Glison ◽  
Jason B. Fleming

Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for their application in the management of both solid and hematologic malignancies. Since its initial discovery, the technology of targeted protein degradation, especially in the form of PROTACs, has had significant advances. A number of PROTACs have entered a late stage of preclinical development. Several of them are either in phase 1/2 clinical trials or approaching approval for initial clinical evaluation. This article discusses the preclinical and clinical findings of PROTACs of clinically relevant protein targets in cancer.


2020 ◽  
Vol 40 (4) ◽  
pp. 1378-1390
Author(s):  
Dominik Spinczyk ◽  
Marcin Stronczek ◽  
Aleksandra Badura ◽  
Piotr Sperka ◽  
Dorota Krywalska ◽  
...  

2020 ◽  
Vol 20 (3) ◽  
pp. 899-903
Author(s):  
Lucas Ribeiro dos Santos ◽  
Márcio Luís Duarte ◽  
Élcio Roberto Duarte ◽  
Felipe Nunes Figueiras

Abstract Introduction: polyorchidism is an unusual pathology, about 200 cases in the world literature. Case report: we reported a case of polyorchidism in a 16-year-old male patient diagnosed by ultrasound and confirmed by magnetic resonance imaging. Discussion: most of the cases presented, there is a supernumerary testis, but there are reports on more than three, up to five testicles with supranumerical gonads on both sides of the scrotum. The diagnosis is usually performed in late puberty, incidentally, with a painless scrotal mass or at the emergency room, presenting a testicular torsion of the whole hemiscrotum or supernumerary testisalone, and the differential diagnosis should be made with epididymal cyst and spermatocele, besides other extra-testicular masses (hydroceles, varicoceles, lipomas, tumors.) and para-testicular masses (hernias, scrotal calculi). After the initial clinical evaluation, ultrasound is the first line subsidiary exam. Magnetic Resonance Imaging is very helpful, just in case the ultrasound diagnosis is uncertain. The supernumerary testishave the same Magnetic Resonance Imaging characteristics as the normal testes (intermediate signal intensity on T1- weighted images and high signal intensity on T2-weighted images).


Author(s):  
George Cholankeril ◽  
Alexander Podboy ◽  
Vasiliki Irene Aivaliotis ◽  
Edward A. Pham ◽  
Sean Spencer ◽  
...  

AbstractBackgroundHigh rates of concurrent gastrointestinal manifestations have been noted in patients with COVID-19, however the association between these digestive manifestations and need for hospitalization has not been established.MethodsFollowing expedited approval from our Institutional Review Board, we analyzed retrospectively collected data from consecutive patients with confirmed COVID-19 based on a positive polymerase chain reaction testing at our institution from March 03, 2020 to April 7, 2020. Baseline demographic, clinical, laboratory and patient-reported symptom data were collected at presentation in the emergency room. Multivariable logistic regression analyses were performed to evaluate the association between hospitalization and presence of gastrointestinal symptoms.ResultsDuring this study period, we identified 207 consecutive patients with confirmed COVID-19. 34.5% noted concurrent gastrointestinal symptoms; of which 90% of gastrointestinal symptoms were mild. In a multivariate regression model controlled for demographics and disease severity, an increased risk for hospitalization was noted in patients with any gastrointestinal symptom (adjusted OR 4.84 95% CI: 1.68-13.94]. Diarrhea was associated with a seven-fold higher likelihood for hospitalization (adjusted OR=7.58, 95% CI: 2.49-20.02, P <0.001) and nausea or vomiting had a four times higher odds. (adjusted OR 4.39, 95% CI: 1.61-11.4, P = 0.005).ConclusionWe demonstrate that a significant portion of COVID19 patients have concurrent mild gastrointestinal symptoms and that the presence of these digestive symptoms is associated with a need for hospitalization. With the current focus on streamlining triaging efforts, first responders and frontline providers should consider assessing for digestive symptoms in their initial clinical evaluation and decision-making.


2019 ◽  
Vol 7 (3_suppl) ◽  
pp. 2325967119S0013
Author(s):  
Julie C. Wilson ◽  
Morgan N. Potter ◽  
Michael W. Kirkwood ◽  
Pamela E. Wilson ◽  
Aaron Provance ◽  
...  

Background: Historically, exercise has been discouraged while patients are experiencing concussion symptoms. However, recent evidence suggests that exercise soon after concussion is not detrimental and may be beneficial to recovery. Few studies have assessed the impact of early exercise in pediatric sport-related concussion. Therefore, the purpose of our investigation was to evaluate if clinical characteristics vary between patients who engaged in early exercise post-injury relative to patients who had not resumed physical activity at initial clinical evaluation. Methods: We conducted an analysis of data collected from a prospective clinical registry of pediatric patients with concussion. Included subjects were evaluated in a pediatric sports medicine concussion clinic between January 1, 2015 and August 31, 2017, less than 19 years of age and evaluated within 20 days of a sport-related concussion. The independent variable was whether or not the patient reported participating in early exercise, defined as exercise occurring since the injury and prior to initial clinical evaluation. Type of exercise was classified by corresponding stage of the return to play protocol. Other variables were collected from routine clinical evaluation including: demographics, injury details, medical history form (pre-injury history of attention deficit/hyperactivity disorder, learning disability, anxiety, depression, and migraine/headaches), the Health and Behavior Inventory (HBI) symptom frequency questionnaire, and a set of balance, vestibular, and oculomotor function tests [Balance Error Scoring System (BESS), Romberg, tandem gait, gaze stability, and near point of convergence]. We performed univariable comparisons of demographic and medical history variables between the early exercise and no exercise groups using Mann-Whitney U and Fisher’s exact tests. Variables that demonstrated potential significance between groups (defined as p < 0.20) were included as covariates in subsequent multivariable models. In order to identify the clinical variables that were associated with early exercise, we constructed a series of regression models where exercise (yes vs. no) was the predictor variable and clinical measures were the outcome variables. Linear regression models were used with continuous outcome variables (e.g. number of BESS errors), while logistic regression models were used with binary outcome variables (e.g. presence of current headache or not). Results: We examined data from 575 pediatric patients: 69 reported engaging in early exercise and 506 did not report exercising (Table 1). The no exercise group was seen approximately 4 days earlier post-injury than the early exercise group, had longer symptom resolution times (median= 16 [interquartile range (IQR)= 8-24] vs. 10.5 [IQR= 4-17] days; p= 0.02), and had a higher proportion of participants with pre-injury history of migraine/headaches. The majority (65%) of the early exercise group indicated participation in light aerobic activity prior to the initial clinical evaluation, with a minority reporting participation in more rigorous exercise (Table 2). The exercise group consisted of a lower proportion of individuals experiencing a headache and exhibiting an abnormal Romberg test during the initial evaluation (Table 3). In addition, the early exercise group had fewer median BESS errors than the no exercise group for testing in single leg and tandem stance on a firm surface (Table 3). Patients in the early exercise group and their parents reported significantly lower HBI scores than the no exercise group (Figure 1). When controlling for pre-existing headache history and time from injury until clinical evaluation, several factors were associated with early exercise (Table 5). Patients who engaged in early exercise after concussion were less likely to report current headache and also recorded lower self- and parent-reported HBI scores. They also demonstrated fewer BESS errors in single leg stance firm, tandem stance firm, and tandem stance foam conditions. Conclusions: The impact of early exercise following concussion is an emerging area of research, and to date, few studies have examined this in pediatric patients with sport-related concussion. In our study, patients who did not engage in early exercise had greater odds of headache, worse postural stability, and higher patient- and parent-symptom rating at initial clinical evaluation. Given our study design, we cannot determine if patients engaged in early exercise due to lower symptom burden and higher functioning at the time of assessment, or whether early exercise actually positively affects clinical characteristics. However, our results suggest that early exercise is associated with better post-injury outcomes, and not universally detrimental in pediatric sport-related concussion. Future research, including prospective randomized controlled trials, is needed to determine the causal relationship between exercise and pediatric concussion outcomes. TABLES/FIGURES [Table: see text]


2018 ◽  
Vol 13 ◽  
pp. S117
Author(s):  
Nathalya Fernanda Rossi ◽  
Marcela Castelli Malandrin ◽  
Gabriela Minari ◽  
Thais Maria Pinto E Souza ◽  
Francisco Lázaro Pereira de Sousa ◽  
...  

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