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1.
J Clin Transl Sci ; 8(1): e63, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655451

RESUMO

Background: Impaired motor and cognitive function can make travel cumbersome for People with Parkinson's disease (PwPD). Over 50% of PwPD cared for at the University of Arkansas for Medical Sciences (UAMS) Movement Disorders Clinic reside over 30 miles from Little Rock. Improving access to clinical care for PwPD is needed. Objective: To explore the feasibility of remote clinic-to-clinic telehealth research visits for evaluation of multi-modal function in PwPD. Methods: PwPD residing within 30 miles of a UAMS Regional health center were enrolled and clinic-to-clinic telehealth visits were performed. Motor and non-motor disease assessments were administered and quantified. Results were compared to participants who performed at-home telehealth visits using the same protocols during the height of the COVID pandemic. Results: Compared to the at-home telehealth visit group (n = 50), the participants from regional centers (n = 13) had similar age and disease duration, but greater disease severity with higher total Unified Parkinson's disease rating scale scores (Z = -2.218, p = 0.027) and lower Montreal Cognitive Assessment scores (Z = -3.350, p < 0.001). Regional center participants had lower incomes (Pearson's chi = 21.3, p < 0.001), higher costs to attend visits (Pearson's chi = 16.1, p = 0.003), and lived in more socioeconomically disadvantaged neighborhoods (Z = -3.120, p = 0.002). Prior research participation was lower in the regional center group (Pearson's chi = 4.5, p = 0.034) but both groups indicated interest in future research participation. Conclusions: Regional center research visits in PwPD in medically underserved areas are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.

2.
Microbiol Spectr ; 12(1): e0314723, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38059629

RESUMO

IMPORTANCE: Because biofilm formation is such a problematic feature of Staphylococcus aureus infections, much effort has been put into identifying biofilm inhibitors. However, the results observed with these compounds are often reported in isolation, and the methods used to assess biofilm formation vary between labs, making it impossible to assess relative efficacy and prioritize among these putative inhibitors for further study. The studies we report address this issue by directly comparing putative biofilm inhibitors using a consistent in vitro assay. This assay was previously shown to maximize biofilm formation, and the results observed with this assay have been proven to be relevant in vivo. Of the 19 compounds compared using this method, many had no impact on biofilm formation under these conditions. Indeed, only one proved effective at limiting biofilm formation without also inhibiting growth.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Antibacterianos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Biofilmes , Projetos de Pesquisa , Testes de Sensibilidade Microbiana
3.
Anticancer Res ; 44(1): 151-155, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38160002

RESUMO

BACKGROUND/AIM: Opioids are a common treatment for cancer-related pain and information is limited on the rates of opioid use for cervical cancer patients. This study aimed to analyze outpatient opioid use and various predictors among patients with cervical cancer at a tertiary academic medical center. PATIENTS AND METHODS: Data from patients with cervical cancer receiving treatment at a single institution, from August 2019 to July 2022, were retrospectively collected. Women with unrelated chronic opioid use or opioid use associated with acute inpatient stays were excluded. Charts were reviewed for patient demographics, disease characteristics, treatment characteristics, disease outcomes, and opioid prescriptions. The primary endpoint was duration of opioid use ≥6 months. Pearson's chi-squared testing, Welch's two-sample t-testing and Fisher's exact testing were used to determine predictors of opioid use ≥6 months. RESULTS: In total, 108 patients with cervical cancer (76.1%) of the 142 that received treatment were prescribed opioids. In women who were prescribed outpatient opioids, the median duration of opioid use was 69 days (interquartile range=5-359 days). In total, 40 (37.0%) had prescriptions for ≥180 days and 27 (25.0%) had prescriptions ≥365 days. On bivariate analysis, lower stage and receipt of surgery were associated with opioid use duration <6 months. Age, race, histology, substance/tobacco/alcohol use, depression/anxiety, and the receipt of brachytherapy/radiation were not associated with length of opioid prescriptions. CONCLUSION: This study demonstrated that 37% of patients with cervical cancer were using opioids for cancer-related pain longer than 6 months. Higher stage was associated with opioid use duration ≥6 months.


Assuntos
Dor do Câncer , Transtornos Relacionados ao Uso de Substâncias , Neoplasias do Colo do Útero , Humanos , Feminino , Analgésicos Opioides/efeitos adversos , Estudos Retrospectivos , Dor do Câncer/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Centros Médicos Acadêmicos , Padrões de Prática Médica , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia
4.
Sci Rep ; 13(1): 22784, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123606

RESUMO

Upper-limb bradykinesia occurs early in Parkinson's disease (PD) and bradykinesia is required for diagnosis. Our goal was to develop, implement and validate a game "walking" a frog through a maze using bimanual, alternating finger-tapping movements to provide a salient, objective, and remotely monitorable method of tracking disease progression and response to therapy in PD. Twenty-five people with PD and 16 people without PD participated. Responses on 5 different mazes were quantified and compared to spatiotemporal gait parameters and standard disease metrics in these participants. Intertap interval (ITI) on maze 2 & 3, which included turns, was strongly inversely related to stride-length and stride-velocity and directly related to motor UPDRS scores. Levodopa decreased ITI, except in maze 4. PD participants with freezing of gait had longer ITI on all mazes. The responses quantified on maze 2 & 3 were related to disease severity and gait stride-length, were levodopa responsive, and were worse in people with freezing of gait, suggesting that these mazes could be used to quantify motor dysfunction in PD. Programming our frog-in-maze game onto a remotely distributable platform could provide a tool to monitor disease progression and therapeutic response in people with PD, including during clinical trials.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Levodopa/farmacologia , Levodopa/uso terapêutico , Hipocinesia , Movimento , Extremidade Superior , Marcha/fisiologia , Progressão da Doença
5.
Thyroid ; 33(9): 1045-1054, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37279296

RESUMO

Background: The frequency and factors associated with thyroid hormone replacement therapy among patients with subclinical hypothyroidism (SCH) remain uncertain. Methods: In this electronic health records-based observational cohort study, we included adults diagnosed with SCH from four academic centers (the United States and Mexico) from January 1, 2016, to December 31, 2018. We aimed to identify the determinants of thyroid hormone replacement therapy for SCH and the frequency of treated SCH. Results: A total of 796 patients (65.2% women) had SCH, and 165 (20.7%) were treated with thyroid hormone replacement therapy. The treated group was younger [51.0 (standard deviation {SD} 18.3) vs. 55.3 (SD 18.2) years, p = 0.008] and had a higher proportion of women (72.7% vs. 63.2%, p = 0.03) compared with the untreated group. Only 46.7% of patients in the treated group and 65.6% in the untreated group had confirmatory thyroid function tests (TFTs) before the decision to start thyroid hormone replacement therapy was made. There was no difference in the frequency of thyroid autoimmunity evaluation, but a positive thyroid autoimmunity test was more frequent in the treated group compared with the untreated group (48.2% vs. 20.3%, p < 0.001). In a multivariable logistic regression model, female sex (odds ratio [OR] = 1.71 [CI 1.13-2.59], p = 0.01) and index thyrotropin (TSH) level (OR = 1.97 [CI 1.56-2.49], p < 0.001 for every SD [2.75 mIU/L] change) were associated with higher odds of treatment. Conclusions: Among patients with SCH, female sex and index TSH level were associated with higher odds of treatment. Moreover, in our population, the decision to treat or not to treat SCH was often based on only one set of abnormal TFTs, and thyroid autoimmunity assessment was underused.


Assuntos
Registros Eletrônicos de Saúde , Hipotireoidismo , Adulto , Feminino , Humanos , Masculino , Hipotireoidismo/diagnóstico , Tireotropina/uso terapêutico , Terapia de Reposição Hormonal , Tiroxina/uso terapêutico
6.
Radiat Res ; 200(2): 107-115, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37327124

RESUMO

Historically, animal numbers have most often been in the hundreds for experiments designed to estimate the dose reduction factor (DRF) of a radiation countermeasure treatment compared to a control treatment. Before 2010, researchers had to rely on previous experience, both from others and their own, to determine the number of animals needed for a DRF experiment. In 2010, a formal sample size formula was developed by Kodell et al. This theoretical work showed that sample sizes for realistic, yet hypothetical, DRF experiments could be less than a hundred animals and still have sufficient power to detect clinically meaningful DRF values. However, researchers have been slow to use the formula for their DRF experiments, whether from ignorance to its existence or hesitancy to depart from "tried and true" sample sizes. Here, we adapt the sample size formula to better fit usual DRF experiments, and, importantly, we provide real experimental evidence from two independent DRF experiments that sample sizes smaller than what have typically been used can still statistically detect clinically meaningful DRF values. In addition, we update a literature review of DRF experiments which can be used to inform future DRF experiments, provide answers to questions that researchers have asked when considering sample size calculations rather than solely relying on previous experience, whether their own or others', and, in the supplementary material, provide R code implementing the formula, along with several exercises to familiarize the user with the adapted formula.


Assuntos
Tamanho da Amostra , Animais , Estudos de Viabilidade
7.
Sex Med Rev ; 11(3): 278-290, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-36941207

RESUMO

INTRODUCTION: Penile amputation causes severe physical and psychosocial distress. Microsurgical implementation in penile replantation is presumed to be superior to surgical repair. This assumption has been difficult to verify. OBJECTIVES: The purpose of this study was threefold: (1) to produce an updated review of penile replantation, substantiated by the largest sample size to date; (2) to appraise the comparative value of the novel PENIS Score and propose the PACKAGE Checklist, a guide for standardization of future case reports and reviews; and (3) to improve confusing terminology and recommend the standardization of vocabulary. METHODS: A literature review assessed 432 full-text case reports in 20 languages and identified 123 microsurgical and 40 surgical cases of penile replantation. The novel PENIS Score stratified penile amputations based on 5 criteria: position along the shaft, extension through the penis, neurovascular repair, ischemia time and type, and severed edge condition and contamination. For the outcome measurements, a Kendall tau coefficient evaluated the association between each PENIS criterion for short-term postoperative complications and 3 outcome measures: erection, urination, and sensation. RESULTS: Less than half of surgical reports on penile replantation are sufficiently detailed to complete all PENIS Score criteria. The viability of microsurgical and surgical replantation was equivalent at 92% and 94%, respectively. A statistically significant correlation was found between microsurgical repair and the return of sensation but not with nerve repair. Return of sensation with nerve repair was 51%, and microsurgical replantation without nerve repair was 42%; both were significantly higher than the 14% for surgical replantation. Preservation of a skin bridge was associated with a 40% reduction in severe postoperative complications. CONCLUSION: Microsurgical replantation is superior in return of sensation, with or without nerve repair. Implementing the PACKAGE Checklist and PENIS Score will help inform case reports and reviews.


Assuntos
Amputação Traumática , Microcirurgia , Masculino , Humanos , Lista de Checagem , Amputação Traumática/cirurgia , Amputação Traumática/psicologia , Reimplante , Pênis/cirurgia , Complicações Pós-Operatórias/cirurgia
8.
Cureus ; 15(1): e34190, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36843727

RESUMO

Purpose The healthcare system across the world was forced to implement new policies, guidelines, and procedures due to the coronavirus disease 2019 (COVID-19) pandemic, which led many patients to make an impossible choice about their health. For various reasons, many patients chose to remain at home and delay any interaction at medical facilities to protect themselves or others from the virus. Patients managing chronic diseases faced unprecedented challenges during this period, and the long-term effects on these patient populations remain unclear. Oncology patients, specifically those diagnosed with head and neck cancers, require prompt diagnosis and initiation of treatment for better outcomes. While the overall impact of how the pandemic has affected oncology patients is unknown, this retrospective study examined how the staging of head and neck tumors at our institution has been impacted since the beginning of the pandemic. Methods Available patient data (from August 1, 2019, through June 28, 2021) were collected from medical records and compared to determine statistical significance. Patients were categorized into a Pre-pandemic group, Pandemic group, and Vaccine-approved group, and patient and treatment characteristics were analyzed to look for patterns. The pre-pandemic period was defined as the period from August 1, 2019, to March 16, 2020, the pandemic period was defined as the period from March 17, 2020, to December 31, 2020, and the vaccine-approved period was defined as the period from January 1, 2021, to June 28, 2021.  Results Fisher's exact tests were used to compare tumor, node, metastasis (TNM) staging distributions between the three groups. In the Pre-pandemic group, out of 67 patients, 33 patients (55.0%) were diagnosed with a T stage of 0-2 and 27 patients (45.0%) were diagnosed with a T stage of 3-4. In the Pandemic and Vaccine-approved groups, out of 139 patients, 50 patients (39.1%) were diagnosed with a T stage of 0-2 and 78 patients (60.9%) were diagnosed with a T stage of 3-4; these differences were statistically significant (P-value = 0.0426). The Pre-pandemic group had 25 patients (41.7%) diagnosed with a group stage of 0-2 and 35 patients (58.3%) diagnosed with a group stage of 3-4. The Pandemic and Vaccine-approved groups had 36 patients (28.1%) diagnosed with a group stage of 0-2 and 92 patients (71.9%) diagnosed with a group stage of 3-4; these results trended to statistically significant (P-value = 0.0688). Conclusions Our findings suggest that there have been a higher number of patients with head and neck cancer diagnosed with a T stage of 3 or 4 since the start of the COVID-19 pandemic. The effects of the COVID-19 pandemic are ongoing and will need further evaluation to determine the overall effects on oncology patients. Increased morbidity and mortality rates may be a potential result in the years to come.

9.
J Ren Nutr ; 33(3): 499-502, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36736470

RESUMO

OBJECTIVE: Studies have shown that low or high serum bicarbonate levels (reflecting metabolic acidosis or alkalosis) are associated with increased all-cause mortality rates in moderate and advanced chronic kidney disease (CKD) cases. Correction of presumed acidosis using sodium bicarbonate, targeting serum levels around 22 mmol/L, has proven to be beneficial in delaying the progression of the disease and provided mortality benefit. A similar prognostic association may exist between uncorrected metabolic acidosis in chronic liver disease. Correcting it with sodium-containing salts may require more interventions due to increased sodium/fluid load. In patients with liver failure, a naturally alkalotic state, where sodium load is a concern, the impact of this intervention is unclear. DESIGN: This study aims to generate proof of concept through a retrospective chart review in individuals with CKD-related metabolic acidosis and liver cirrhosis. RESULT: Our analysis revealed a statistically significant association between the need for paracentesis and bicarbonate therapy. Our study has multiple drawbacks, including a retrospective chart review and limitation of data due to single-center patients. CONCLUSION: We extrapolate that lowering bicarbonate targets in other clinical scenarios like liver failure, pregnancy, and cardiac failure may be prudent and will lead to a lower sodium load.


Assuntos
Acidose , Hepatopatias , Falência Hepática , Insuficiência Renal Crônica , Humanos , Bicarbonatos , Estudos Retrospectivos , Acidose/complicações , Acidose/tratamento farmacológico , Doença Crônica , Sódio , Hepatopatias/complicações , Rim , Falência Hepática/complicações
10.
Am J Emerg Med ; 63: 44-49, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36327748

RESUMO

OBJECTIVES: The objective of this study is to identify predictors of airway compromise among patients presenting to the emergency department with angioedema in order to develop and validate a risk score to augment clinician gestalt regarding need for intubation. METHODS: Retrospective chart review of emergency department patients with a diagnosis of angioedema. After data extraction they were randomly divided into a training and test set. The training set was used to identify factors associated with intubation and to develop a model and risk score to predict intubation. The model and risk score were then applied to the test set. RESULTS: A total of 594 patients were included. Past medical history of hypertension, presence of shortness of breath, drooling, and anterior tongue or pharyngeal swelling were independent predictors included in our final model and risk score. The Area Under the Curve for the Receiver Operator Characteristic curve was 87.55% (83.42%-91.69%) for the training set and 86.1% (77.62%-94.60%) for the test set. CONCLUSIONS: A simple scoring algorithm may aid in predicting angioedema patients at high and low risk for intubation. External validation of this score is necessary before wide-spread adoption of this decision aid.


Assuntos
Angioedema , Intubação Intratraqueal , Humanos , Serviço Hospitalar de Emergência , Estudos Retrospectivos , Tratamento de Emergência
11.
Lab Med ; 53(6): 623-628, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-35771890

RESUMO

IMPORTANCE: Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. OBJECTIVE: Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Our study aims to determine the safety and efficacy of treating hospitalized COVID-19 patients with 2 units of COVID-19 convalescent plasma (CCP). METHOD: This was a retrospective study of Arkansas patients treated with CCP using the (US) Food and Drug Administration (FDA) emergency Investigational New Drug (eIND) mechanism from April 9, 2020, through August 9, 2020. It was a multicenter, statewide study in a low-resource setting, which are areas that lack funding for health care cost coverage on various levels including individual, family, or social. Adult patients (n = 165, volunteer sample) in Arkansas who were hospitalized with severe or life-threatening acute COVID-19 disease as defined by the FDA criteria were transfused with 2 units of CCP (250 mL/unit) using the FDA eIND mechanism. The primary outcome was 7- and 30-day mortality after the second unit of CCP. RESULTS: Unadjusted mortality was 12.1% at 7 days and 23.0% at 30 days. The unadjusted mortality was reduced to 7.7% if the first CCP unit was transfused on the date of diagnosis, 8.7% if transfused within 3 days of diagnosis, and 32.0% if transfused at or after 4 or more days of diagnosis. The risk of death was higher in patients that received low, negative, or missing titer CCP units in comparison to those that received higher titer units. CONCLUSION: The provision of 2 units of CCP was associated with a reduction in mortality in patients treated with high titer units within 3 days of COVID-19 diagnosis. Given the results, CCP is a viable, low-cost therapy in resource-constrained states and countries.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/terapia , SARS-CoV-2 , Estudos Retrospectivos , Teste para COVID-19 , Soroterapia para COVID-19
12.
J Clin Med ; 11(6)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35329966

RESUMO

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. Although outpatient ASCT has been shown to be safe and feasible, the procedure is overall rare with most patients in the US undergoing inpatient ASCT. Furthermore, hospitalization rates for patients that undergo outpatient ASCT remain high. Adequate markers that predict hospitalization during outpatient ASCT are lacking, yet would be of great clinical value to select patients that are suited to outpatient ASCT. In this study we aimed to elucidate differences between planned outpatient and inpatient ASCT and further evaluated clinical characteristics that are significantly associated with hospitalization during planned outpatient hospitalization. Factors that were significantly associated with a planned inpatient ASCT included an advanced MM disease stage, worse performance status as well as non-Caucasian race, while low albumin levels and female gender were significantly associated with hospitalization during outpatient ASCT. The results of this analysis provide crucial knowledge of factors that are associated with planned inpatient ASCT and hospitalization during outpatient ASCT and could guide the treating physician in decision-making and further facilitate outpatient transplantation.

13.
Sci Rep ; 12(1): 4180, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264705

RESUMO

Movement amplitude setting is affected early in Parkinson's disease (PD), clinically manifesting as bradykinesia. Our objective was to determine if amplitude setting of upper limb bimanual movements and bipedal gait are similarly modulated in PD. 27 PD and 24 control participants were enrolled. Participants performed a bimanual anti-phase finger tapping task wearing gloves with joint angular sensors, and an instrumented gait assessment. Participants performed normal and fast paced assessments to vary motor load. PD participants were evaluated OFF (PD-OFF) and ON (PD-ON) levodopa. PD-OFF participants had smaller tap amplitude, and greater tap amplitude variability than controls in the more affected hands (all p < 0.05). Tap amplitude and stride length (p = 0.030) were correlated in PD-OFF. Tap amplitude was also correlated with motor UPDRS (p < 0.005) and bradykinesia motor (p < 0.05) and ADL (p < 0.005) UPDRS subscores. The relative amount of improvement in tap amplitude and stride length with levodopa was correlated. In PD, upper limb and gait amplitude setting are similarly scaled with motor demand and dopamine supplementation. This suggests these automated motor functions are subserved by common functional networks.


Assuntos
Doença de Parkinson , Dopamina , Marcha/fisiologia , Humanos , Hipocinesia , Levodopa/farmacologia , Levodopa/uso terapêutico
14.
J Surg Oncol ; 125(8): 1211-1217, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35195923

RESUMO

OBJECTIVE: To investigate a possible link between breast and thyroid cancer. METHODS: A multicenter retrospective review of patients in the electronic medical records of six Accrual to Clinical Trial (ACT) institutions with both breast cancer and thyroid carcinoma. Each center queried its data using a predefined data dictionary. Information on thyroid and breast cancer included dates of diagnosis, histology, and patient demographics. RESULTS: A random-effects model was used. There were 4.24 million women's records screened, 44 605 with breast cancer and 11 846 with thyroid cancer. The relative risks observed at each institution ranged from 0.49 to 13.47. The combined risk ratio (RR) estimate was 1.77 (95% confidence interval: 0.50-5.18). CONCLUSION: There was no association between the risk of developing thyroid cancer and being a breast cancer survivor compared to no history of breast cancer, but the range of relative risks among the participating institutions was wide. Our findings warrant further study of more institutions with larger sample size. Additionally, further analysis of the significance of regional RR differences may be enlightening.


Assuntos
Neoplasias da Mama , Neoplasias da Glândula Tireoide , Neoplasias da Mama/tratamento farmacológico , Coleta de Dados , Feminino , Humanos , Risco , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/terapia
15.
Pediatr Transplant ; 26(4): e14231, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35043516

RESUMO

BACKGROUND: Echocardiographic markers of ACR are essential for early recognition and management. The literature's primary focus has been on the LV with little attention given to the RV. This study aimed to investigate echocardiographic right ventricular indices in the detection of ACR and to evaluate their utility as prognostic indicators of graft integrity. METHODS: We performed a retrospective chart review of children with biopsy-proven ACR following orthotopic heart transplant and an echocardiogram within 24 h of biopsy. Selected echocardiographic markers were compared at baseline, during ACR, and at follow-up. RESULTS: Forty-eight patients (56% male) had a total of 84 ACR episodes. Decrease in RV FAC (mean - 17.1%, p < .001) and TAPSE (mean - 8.9%, p < .001) with increase in left ventricular posterior wall thickness in diastole and systole (LVPWTd) (mean + 9.0%, p = .012) and LVPWTs (mean + 8.3%, p = .016) were found during ACR. Interestingly, these parameters improved following the episode of rejection. Additionally, these markers were compared after recovery between children with and without graft failure. RV dysfunction (FAC and TAPSE) and changes in LV posterior wall thickness were not found to have prognostic significance for graft integrity in children with heart transplantation. CONCLUSIONS: RV echocardiographic functional parameters should be considered as valuable adjuncts in rejection surveillance. Further, the presence of RV dysfunction does not have prognostic significance for graft integrity but is reversible as ongoing damage was not detectable by such.


Assuntos
Transplante de Coração , Disfunção Ventricular Direita , Criança , Ecocardiografia , Feminino , Rejeição de Enxerto/diagnóstico , Humanos , Masculino , Estudos Retrospectivos , Disfunção Ventricular Direita/diagnóstico , Função Ventricular Direita
16.
Hepatol Commun ; 6(2): 361-373, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34558847

RESUMO

Current guidelines recommend restricting acetaminophen (APAP) use in patients with cirrhosis, but evidence to support that recommendation is lacking. Prior studies focused on pharmacokinetics (PK) of APAP in cirrhosis but did not rigorously examine clinical outcomes, sensitive biomarkers of liver damage, or serum APAP-protein adducts, which are a specific marker of toxic bioactivation. Hence, the goal of this pilot study was to test the effects of regularly scheduled APAP dosing in a well-defined compensated cirrhosis group compared to control subjects without cirrhosis, using the abovementioned outcomes. After a 2-week washout, 12 subjects with and 12 subjects without cirrhosis received 650 mg APAP twice per day (1.3 g/day) for 4 days, followed by 650 mg on the morning of day 5. Patients were assessed in-person at study initiation (day 1) and on days 3 and 5. APAP-protein adducts and both conventional (alanine aminotransferase) and sensitive (glutamate dehydrogenase [GLDH], full-length keratin 18 [K18], and total high-mobility group box 1 protein) biomarkers of liver injury were measured in serum on the mornings of days 1, 3, and 5, with detailed PK analysis of APAP, metabolites, and APAP-protein adducts throughout day 5. No subject experienced adverse clinical outcomes. GLDH and K18 were significantly different at baseline but did not change in either group during APAP administration. In contrast, clearance of APAP-protein adducts was dramatically delayed in the cirrhosis group. Minor differences for other APAP metabolites were also detected. Conclusion: Short-term administration of low-dose APAP (650 mg twice per day, <1 week) is likely safe in patients with compensated cirrhosis. These data provide a foundation for future studies to test higher doses, longer treatment, and subjects who are decompensated, especially in light of the remarkably delayed adduct clearance in subjects with cirrhosis.


Assuntos
Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Cirrose Hepática/tratamento farmacológico , Acetaminofen/sangue , Adulto , Alanina Transaminase/sangue , Analgésicos não Narcóticos/sangue , Biomarcadores/sangue , Esquema de Medicação , Feminino , Glutamato Desidrogenase/sangue , Proteína HMGB1/sangue , Humanos , Queratina-18/sangue , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Adulto Jovem
17.
Front Immunol ; 12: 645299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659195

RESUMO

Advances in high-throughput sequencing have revolutionized the manner with which we can study T cell responses. We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion. By performing bulk T cell receptor (TCR) ß deep sequencing of peripheral blood mononuclear cells before and after 4 vaccinations, 70 putatively vaccine-specific clonotypes were identified for being significantly increased using a beta-binomial model. In order to verify the vaccine-specificity of these clonotypes, T cells with specificity to a region, HPV 16 E6 91-115, previously identified to be vaccine-induced using an interferon-γ enzyme-linked immunospot assay, were sorted and analyzed using single-cell RNA-seq and TCR sequencing. HPV specificity in 60 of the 70 clonotypes identified to be vaccine-specific was demonstrated. TCR ß bulk sequencing of the cervical liquid-based cytology samples and cervical formalin-fixed paraffin-embedded samples before and after 4 vaccinations demonstrated the presence of these HPV-specific T cells in the cervix. Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells not only in the periphery but also in the cervix. Such an approach should be useful as a novel approach to assess vaccine-specific responses in various anatomical areas.


Assuntos
Vacinas Anticâncer/uso terapêutico , Papillomavirus Humano 16/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Vacinas contra Papillomavirus/uso terapêutico , Lesões Intraepiteliais Escamosas/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ensaios Clínicos Fase I como Assunto , Feminino , Genes Codificadores dos Receptores de Linfócitos T , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno , Humanos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/virologia , Gradação de Tumores , RNA-Seq , Indução de Remissão , Lesões Intraepiteliais Escamosas/imunologia , Lesões Intraepiteliais Escamosas/patologia , Lesões Intraepiteliais Escamosas/virologia , Linfócitos T/imunologia , Linfócitos T/virologia , Fatores de Tempo , Resultado do Tratamento , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
18.
Aerosp Med Hum Perform ; 92(4): 240-247, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33752787

RESUMO

INTRODUCTION: U.S. Air Force Special Operations Command (AFSOC) female aircrew represent a small group of military personnel in challenging high-risk, high-demand professions. Personality characteristics may play a key role in distinguishing those women who pursue a career as a special operations aircrew member and succeed in this pursuit. Having access to normative personality data can potentially support psychologists in assessing AFSOC female aircrew and subsequently making informed recommendations to leadership.METHODS: A total of 586 AFSOC aircrew trainees58 (9.9%) women and 528 (90.1%) mencompleted a series of computer-based psychological tests to assess cognitive ability and personality traits.RESULTS: Results indicated significant differences between female AFSOC aircrew and female civilians on four of the five NEO Personality Inventory domains: Neuroticism (M 74.9 vs. M 87.1), Extraversion (M 123.7 vs. M 112.8), Openness to Experience (M 122.6 vs. M 111.0), and Conscientiousness (M 136.0 vs. M 120.6), respectively. The comparison between female AFSOC aircrew and male AFSOC aircrew revealed significant differences across three of the five domains: Neuroticism (M 74.9 vs. M 65.1), Openness to Experience (M 122.6 vs. M 115.0), and Agreeableness (M 119.6 vs. M 112.7), respectively.DISCUSSION: Implications for assessment and interpretation of psychological testing are discussed. This paper provides a unique perspective and insight into those who pursue and excel in this career field. Identifying specific personality traits in our AFSOC female aircrew allows for tailored care and support when evaluating readiness in special operations aircrew for optimizing performance.Chappelle W, Shadle AH, Martinez RN, Reardon LE, Goodman T, Spencer H, Thompson W. Personality traits that distinguish special operations female aircrew. Aerosp Med Hum Perform. 2021; 92(4):240247.


Assuntos
Militares , Personalidade , Feminino , Humanos , Masculino , Ocupações , Inventário de Personalidade
19.
Otolaryngol Head Neck Surg ; 165(3): 387-397, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33461421

RESUMO

OBJECTIVE: Variants of primary hyperparathyroidism (pHPT), described as normocalcemic (NC) and normohormonal (NH), can confuse the diagnosis of classic pHPT. DATA SOURCES: A MEDLINE search was performed for variants of pHPT using the PubMed database (last queried October 2019). REVIEW METHODS: The search was restricted to articles published after 1960 that were specific to humans. Studies were included in our analysis if laboratory values and incidence of end-organ involvement were reported for NCpHPT and NHpHPT variants. The search returned 189 articles; 27 additional studies were identified and included for a total of 216. Non-English-language studies were excluded. Abstracts were screened, full-text articles were then assessed, and 82 articles were excluded. Data were pooled using a random-effects model in studies that compared NC or NH pHPT to classic pHPT. Comparative laboratory values are presented. CONCLUSION: This analysis compares NCpHPT and NHpHPT to classic pHPT. Nephrolithiasis was 21.7% (NCpHPT), 15.9% (classic pHPT), and 25.4% (NHpHPT). Decreased bone mineral density was 49.7% (NCpHPT), 39.7% (classic pHPT), and 40.3% (NHpHPT). Fractures in the NCpHPT group were not significantly different from the classic pHPT. Hypertension in the NCpHPT group was significantly less than classic pHPT (odds ratio, 0.59; 95% CI, 0.40-0.88). IMPLICATIONS FOR CLINICAL PRACTICE: This information may serve to inform clinicians of the laboratory subtleties of these variants that are being seen with greater frequency in contemporary practice.


Assuntos
Cálcio/sangue , Hiperparatireoidismo Primário/classificação , Hormônio Paratireóideo/sangue , Biomarcadores/sangue , Densidade Óssea , Fraturas Ósseas/etiologia , Humanos , Hipertensão/etiologia
20.
Infect Immun ; 89(4)2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33468580

RESUMO

Mutation of purR was previously shown to enhance the virulence of Staphylococcus aureus in a murine sepsis model, and this cannot be fully explained by increased expression of genes within the purine biosynthesis pathway. Rather, the increased production of specific S. aureus virulence factors, including alpha toxin and the fibronectin-binding proteins, was shown to play an important role. Mutation of purR was also shown previously to result in increased abundance of SarA. Here, we demonstrate by transposon sequencing that mutation of purR in the USA300 strain LAC increases fitness in a biofilm while mutation of sarA has the opposite effect. Therefore, we assessed the impact of sarA on reported purR-associated phenotypes by characterizing isogenic purR, sarA, and sarA/purR mutants. The results confirmed that mutation of purR results in increased abundance of alpha toxin, protein A, the fibronectin-binding proteins, and SarA, decreased production of extracellular proteases, an increased capacity to form a biofilm, and increased virulence in an osteomyelitis model. Mutation of sarA had the opposite effects on all of these phenotypes and, other than bacterial burdens in the bone, all of the phenotypes of sarA/purR mutants were comparable to those of sarA mutants. Limiting the production of extracellular proteases reversed all of the phenotypes of sarA mutants and most of those of sarA/purR mutants. We conclude that a critical component defining the virulence of a purR mutant is the enhanced production of SarA, which limits protease production to an extent that promotes the accumulation of critical S. aureus virulence factors.


Assuntos
Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Endopeptidases/biossíntese , Mutação , Proteínas Repressoras/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Transativadores/biossíntese , Fatores de Virulência/genética , Animais , Biofilmes/crescimento & desenvolvimento , Elementos de DNA Transponíveis , Suscetibilidade a Doenças , Espaço Extracelular , Regulação Bacteriana da Expressão Gênica , Camundongos , Osteomielite/microbiologia , Staphylococcus aureus/patogenicidade , Virulência/genética
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