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2.
Mod Pathol ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526875

RESUMO

The response of human epidermal growth factor receptor2 (HER2)- positive breast cancer (BC) patients to anti-HER2 targeted therapy is significant. However, the response is not uniform and a proportion of HER2-positive patients do not respond. This study aims to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive BC patients. The study group comprised 500 BC patients treated with neoadjuvant chemotherapy (NACT) and/or neoadjuvant anti-HER2 therapy and surgery who had tumours that were 3+ or 2+ with HER2 immunohistochemistry (IHC). HER2 IHC 2+ tumours were classified into five groups by fluorescence in situ hybridisation (FISH) according to the 2018 ASCO/CAP guidelines of which Groups 1, 2 and 3 were considered HER2 amplified. Pathological complete response (pCR) was more frequent in HER2 IHC 3+ tumours than in HER2 IHC 2+/HER2 amplified tumours, when either in receipt of NACT alone (38% versus 13%; p = 0.22) or neoadjuvant anti-HER2 therapy (52% versus 20%; p < 0.001). Multivariate logistic regression analysis showed that HER2 IHC 3+ and histological grade 3 were independent predictors of pCR following neoadjuvant anti-HER2 therapy. In the HER2 IHC 2+/HER2 amplified tumours or ASCO/CAP FISH Group 1 alone, ER-negativity was an independent predictor of pCR following NACT and/or neoadjuvant anti-HER2 therapy. In the current study, 22% of HER2-positive tumours became HER2-negative by IHC and FISH following neoadjuvant treatment, the majority (74%) HER2 IHC 2+/HER2 amplified tumours. Repeat HER2 testing after neoadjuvant treatment should therefore be considered.

4.
Orbit ; : 1-9, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588671

RESUMO

Purpose: The purpose of this study is to report the safety and outcomes of optic nerve sheath fenestration (ONSF) performed via superomedial eyelid crease approach. Methods: A retrospective chart review was performed on patients undergoing superomedial eyelid crease ONSF at a single institution between 2014-2019. Data obtained included preoperative visual acuity (VA), mean deviation (MD) on visual field (VF), papilledema grade, intraoperative time, estimated blood loss, intraoperative complications and optic nerve sheath biopsy results. Postoperative month 6 (POM6) data collected included VA, MD, papilledema grade, and lid contour. Outcome measures included overall change in VA, MD, and papilledema grade at POM6. Statistical analysis was performed using STATA version 16 statistical software. Data analysis was done comparing all patients pre- and postoperatively. Additional subgroup analysis was performed on patients undergoing ONSF for IIH vs other indications, and on the contralateral unoperated eye. Results: A total of 31 eyes of 24 patients were identified, four of whom were excluded due to being lost to follow-up. At POM6, improvement was seen in VA (p<0.001) across all groups. There was improvement in POM6 median papilledema grade and MD, but these did not reach statistical significance. Additional subgroup analysis on patients with IIH showed statistically significant improvement in POM 6 VA (p=0.009), papilledema (p=0.009) and MD (p<0.001), as well as VA improvement in the contralateral unoperated eye (p<0.001). Conclusions: Superomedial eyelid crease approach for ONSF is a safe and effective surgery in IIH and other conditions of excess pressure within the optic nerve sheath.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33571653

RESUMO

INTRODUCTION: In bilateral shoulder arthroplasty patients, it is unclear what features are responsible for the timing of their contralateral shoulder arthroplasty. This study hypothesized that patient factors (age, gender, hand dominance), disease factors (diagnosis, radiographic severity of contralateral shoulder), and surgical factors (type of arthroplasty) impact timing to contralateral surgery. METHODS: A retrospective review of 332 patients treated with bilateral anatomic (TSA) or reverse (RSA) shoulder arthroplasty (172 TSA/TSA, 107 RSA/RSA, or 53 TSA/RSA) were divided into groups depending on the interval timing between arthroplasty surgeries: group 1 - 142 (≤1 year), group 2 - 62 (1-2 years), and group 3 - 128 (≥2 years). Preoperative factors were analyzed to determine associations between different time groups, including age, gender, hand dominance, diagnosis, radiographic severity of contralateral shoulder, and type of surgery. Bilateral diagnoses included: 211 Osteoarthritis (OA), 36 cuff tear arthropathy (CTA), 13 inflammatory arthritis, 12 massive cuff tears without OA, and 4 avascular necrosis. RESULTS: OA patients had their contralateral shoulder arthroplasty sooner than CTA patients (p=0.035). OA patients with arthritic changes on contralateral radiographs prior to the first arthroplasty had their contralateral arthroplasty sooner than those without contralateral radiographs (p<0.0001). Patients who had TSA first had their contralateral arthroplasty sooner than patients who had RSA (p=0.037). DISCUSSION: This study confirmed our hypothesis identifying preoperative variables associated with different time intervals between arthroplasties. The preoperative factors associated with the highest likelihood of having contralateral shoulder arthroplasty within one year included: OA, radiographic bilateral shoulder disease, and TSA for the first surgery. LEVEL OF EVIDENCE: Level II; Retrospective Design; Prognosis Study.

6.
Vaccine ; 39(9): 1428-1434, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33541794

RESUMO

BACKGROUND: DTaP-IPV-Hib-HepB is a fully-liquid, hexavalent combination vaccine (Vaxelis™) approved for vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive disease due to Haemophilus influenzae type b (Hib). Hib capsular polysaccharide, polyribosylribitol phosphate (PRP), is conjugated to Neisseria meningitidis outer membrane protein complex (OMPC). Safety and immunogenicity of DTaP-IPV-Hib-HepB were evaluated in 6 Phase III clinical studies including > 5,200 children. Studies included vaccination schedules in the United States (2, 4, 6 months of age) and Europe (2, 3, 4, 12 months of age and 2,4,11-12 months of age). METHODS: Data pertaining to anti-PRP responses of DTaP-IPV-Hib-Hep B compared to control vaccines from 5 Phase III studies are summarized. RESULTS: Post-infant series, the percentage of participants that achieved protective antibody thresholds for PRP (anti-PRP titer ≥ 0.15 µg/mL and ≥ 1.0 µg/mL, respectively) were higher in DTaP-IPV-Hib-HepB recipients compared to recipients who received control vaccines. A high level of protective responses (96.6% at ≥ 0.15 µg/mL [95% CI:94.8, 97.9%]; 72.9% at ≥ 1.0 µg/mL [95% CI:69.2,76.4%]) were seen post-dose 2 of the 2 + 1 vaccination schedule and met superiority criteria over comparator, p-value < 0.001. In the same schedule, prior to administration of the toddler dose (in the second year of life), anti-PRP titers were higher in DTaP-IPV-Hib-HepB recipients (91.4% at ≥ 0.15 µg/mL; 46.8% at ≥ 1.0 µg/mL) as compared to recipients who received control vaccines (63.4% at ≥ 0.15 µg/mL; 17.1% at ≥ 1.0 µg/mL). One-month post-toddler dose, high levels of anti-PRP titers were achieved in both DTaP-IPV-Hib-HepB recipients (99.8% at ≥ 0.15 µg/mL; 96.6% at ≥ 1.0 µg/mL) and recipients who received control vaccines (99.5% at ≥ 0.15 µg/mL; 94.9% at ≥ 1.0 µg/mL). CONCLUSIONS: These results support that DTaP-IPV-Hib-HepB induces a robust and sustained early Hib response. During the high-risk period for Hib disease after the infant vaccine and prior to the toddler dose; >90% of recipients maintained superior protective anti-PRP levels compared to control.

7.
Breast Cancer Res ; 23(1): 22, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588869

RESUMO

BACKGROUND: The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS. METHODS: Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23-75 years from the Generations Study. RESULTS: The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio (E/O) at the highest risk decile :0.97 (95 % CI 0.51 - 1.86) for women younger than 50 years and 1.09 (0.66 - 1.80) for women 50 years or older. Adding reproductive/lifestyle factors and PRS to the BOADICEA model improved discrimination modestly in younger women (area under the curve (AUC) 69.7 % vs. 69.1%) and substantially in older women (AUC 64.6 % vs. 56.8%). The Tyrer-Cuzick model with PRS showed evidence of overestimation at the highest risk decile: E/O = 1.54(0.81 - 2.92) for younger and 1.73 (1.03 - 2.90) for older women. CONCLUSION: The extended BOADICEA model identified women in a European-ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. With the increasing availability of PRS, these analyses can inform choice of risk models incorporating PRS for risk stratified breast cancer prevention among women of European ancestry.

9.
Biomol NMR Assign ; 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33486616

RESUMO

Human thymidylate synthase (hTS) is a 72 kDa homodimeric enzyme responsible for the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), making it the sole source of de novo dTMP in human cells. As a result, hTS is an attractive anti-cancer therapeutic target. Additionally, hTS is known to possess a number of interesting biophysical features, including adoption of active and inactive conformations, positively cooperative substrate binding, half-the-sites activity, and interacting with its own mRNA. The physical mechanisms underlying these properties, and how they may be leveraged to guide therapeutic development, are yet to be fully explored. Here, as a preface to detailed NMR characterization, we present backbone amide and ILVM methyl resonance assignments for hTS in apo and dUMP bound forms. In addition, we present backbone amide resonance assignments for hTS bound to a substrate analog and the native cofactor.

14.
Toxins (Basel) ; 13(2)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494380

RESUMO

The purpose of this study was to determine and compare the effects between injecting botulinum toxin A (BTX-A) transconjunctivally into the palpebral lobe and transcutaneously into the orbital lobe of the lacrimal gland in patients with epiphora due to lacrimal outflow obstruction. This randomized controlled study included 53 eyes of 31 patients with unilateral or bilateral epiphora. Patients were randomly allocated to receive an injection of BTX-A (3 units) either transconjunctivally (n = 15, 25 eyes) or transcutaneously (n = 16, 28 eyes). For objective assessments, the tear meniscus height and Schirmer's I test with topical anesthesia were measured at baseline and after 2, 6, 12, and 24 weeks of follow-up. Subjective evaluations were performed using the Munk score. After BTX-A injection, patients in both groups experienced significant objective and subjective reductions in tearing at all follow-up times compared to pre-injection (success rate 86.8%), and the effect lasted for a mean duration of 5.63 months. The two delivery routes showed similar clinical effectiveness for a single injected dose of BTX-A. In conclusion, injecting BTX-A via either a transconjunctival or transcutaneous route helps to reduce normal tear production and results in significant improvements in the symptoms in patients with epiphora.

15.
Heart Fail Rev ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495937

RESUMO

Obesity is a growing worldwide epidemic with significant economic burden that carries with it impacts on every physiologic system including the cardiovascular system. Specifically, the risk of heart failure has been shown to increase dramatically in obese individuals. The purpose of this review is to provide background on the individual burdens of heart failure and obesity, followed by exploring proposed physiologic mechanisms that interconnect these conditions, and furthermore introduce treatment strategies for weight loss focusing on bariatric surgery. Review of the existing literature on patients with obesity and heart failure who have undergone bariatric surgery is presented, compared, and contrasted.

16.
Urology ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33412222

RESUMO

OBJECTIVE: To determine whether a postoperative prescription for opioids affects parental assessment of pain control following pediatric circumcision. METHODS: This postoperative survey assessed the parental assessment of pain control in 199 patients, ages<18 years undergoing circumcision. This study was conducted at a quaternary care children's hospital in Houston, Texas from December 2018 to January 2020. Postoperative pain regimens included acetaminophen and ibuprofen or combination hydrocodone/acetaminophen in addition to ibuprofen for postoperative analgesia based on the surgical preference. The primary study outcome was identification of the proportion of parents rating their child's analgesia following pediatric circumcision as poor or inadequate based on the postoperative analgesic regimen. RESULTS: Of the 502 surveys sent, the response rate was 40% (199/502) of those who received the survey email, and 64% (199/308) for those who opened the email. Between the opioid and nonopioid groups, there was no difference in, race/ethnicity (Caucasian; 28% vs 37%; P = .43) or insurance status (insured; 51% vs 45%; P = .44). The proportion of parents who rated their child's pain as poor or inadequately controlled following circumcision was relatively rare:5.5% and 1.1% in the nonopioid and opioid groups, respectively. Parents rating their child's pain as excellent with regards to pain control following circumcision were 61% and 53% in the nonopioids and opioid groups, respectively. CONCLUSION: The results of this study indicate that nonopioid analgesic regimens following pediatric circumcision were not associated with decreased parental satisfaction or an increasing assessment of poor or inadequately controlled pain. Limiting opioid exposure following pediatric circumcision is feasible and does not result in worse parental satisfaction with the analgesic plan.

17.
PLoS One ; 16(1): e0245840, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481930

RESUMO

OBJECTIVES: We aimed to derive and validate a triage tool, based on clinical assessment alone, for predicting adverse outcome in acutely ill adults with suspected COVID-19 infection. METHODS: We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. The primary outcome was death or organ support (respiratory, cardiovascular, or renal) by record review at 30 days. We split the cohort into derivation and validation sets, developed a clinical score based on the coefficients from multivariable analysis using the derivation set, and the estimated discriminant performance using the validation set. RESULTS: We analysed 11773 derivation and 9118 validation cases. Multivariable analysis identified that age, sex, respiratory rate, systolic blood pressure, oxygen saturation/inspired oxygen ratio, performance status, consciousness, history of renal impairment, and respiratory distress were retained in analyses restricted to the ten or fewer predictors. We used findings from multivariable analysis and clinical judgement to develop a score based on the NEWS2 score, age, sex, and performance status. This had a c-statistic of 0.80 (95% confidence interval 0.79-0.81) in the validation cohort and predicted adverse outcome with sensitivity 0.98 (0.97-0.98) and specificity 0.34 (0.34-0.35) for scores above four points. CONCLUSION: A clinical score based on NEWS2, age, sex, and performance status predicts adverse outcome with good discrimination in adults with suspected COVID-19 and can be used to support decision-making in emergency care. REGISTRATION: ISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533.


Assuntos
/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , /patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Reino Unido/epidemiologia
18.
19.
Int Neurourol J ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33504125

RESUMO

Purpose: The objective of this study was to investigate the change in near visual function after the administration of oral silodosin to patients with lower urinary tract symptom (LUTS). Methods: This prospective study included treatment naïve patients who were scheduled to start treatment with silodosin for LUTS. A comprehensive ophthalmological evaluation including the near vision and the automated pupillometry was performed at baseline and after 3 months of silodosin treatment. For subjective assessment of near visual ability and satisfaction, a Near Activity Visual Questionnaire-10 (NAVQ-10) was also used at the same time (higher scores indicating worse quality). Results: Of 23 patients enrolled in this study, 15 continued with silodosin (8mg once daily) treatment for 3 months and completed a follow-up evaluation. The mean age of participants was 60.4±8.4 years. Distant visual acuity and spherical error were unchanged after silodosin treatment. However, near vision acuity (logMAR) was improved after treatment (right, 0.47±0.36 vs. 0.38±0.39, p=0.018; left, 0.41±0.37 vs. 0.31±0.34, p=0.068; both, 0.27±0.26 vs. 0.21±0.27, p=0.043). Pupil size under room light decreased significantly in both eyes (right, 3.77±0.60 vs. 3.16±0.58, p=0.001; left, 3.72±0.80 vs. 3.21±0.75, p=0.002). The Rasch scale at NAVQ-10 improved from 54.7±9.9 to 48.5±11.2 (p=0.004). Conclusions: This preliminary study demonstrated that highly selective alpha-1A adrenergic receptor antagonists such as silodosin improve near visual acuity and quality in patients with LUTS/BPH. Decrease in pupil size caused by inhibition of adrenergic alpha 1 mediated contraction of iris dilator muscle is a possible mechanism underlying improved near vision.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33492072

RESUMO

PURPOSE: To describe an unusual case of unilateral, endogenous endophthalmitis in an otherwise healthy, term neonate. METHODS: A 3-week-old otherwise healthy, term male infant was referred to St. Louis Children's Hospital for a second opinion of presumed panuveitis of the right eye. PATIENTS: Single male infant. RESULTS: Diffusion weighted magnetic resonance imaging (MRI) demonstrating purulent intraocular contents facilitated the diagnosis of endophthalmitis. Examination of surgical vitreous samples by staining and cytology demonstrated Gram-positive bacterial cocci in short chains, thereby confirming endophthalmitis. Polymerase chain reaction testing of vitreous fluid identified Streptococcus agalactiae, despite an unremarkable systemic workup and a negative pre-partum maternal Group B streptococcal screen. CONCLUSIONS: Endogenous endophthalmitis is a rare but devastating cause of vision loss in otherwise healthy, term neonates. Prompt diagnosis may be facilitated by MRI imaging and diagnostic vitreous biopsy.

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