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1.
J Arthroplasty ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38703925

RESUMO

INTRODUCTION: Periprosthetic joint infection (PJI) can be a serious complication of total knee arthroplasty (TKA). A method believed to decrease the incidence of PJI is antibiotic laden bone cement (ALBC). Current clinical practice guidelines do not recommend ALBC in primary TKA. The purpose of this study was to compare ALBC to plain cement (PC) in preventing PJI in primary TKA. METHODS: This retrospective analysis included 109,242 Medicare patients in the American Joint Replacement Registry who underwent a cemented primary TKA from January 2017 to March 2021, and had at least one year of follow-up. Patients who received ALBC were compared to patients who received PC. Demographic and case-specific variables such as age, sex, race, body mass index (BMI), Charlson Comorbidity Index (CCI), anesthesia type, and operative time were used to create propensity scores. A logistic regression was run to predict the probability of receiving ALBC. Also, a multivariate model was run on the full unstratified population, using the same covariates as were used to create the propensity model. The primary outcome was differences in PJI rates. RESULTS: Logistic regression analysis showed that a higher preoperative diagnosis of osteoarthritis, higher CCI, higher BMI, women, race, and anesthesia requirements increased a patient's probability of receiving ALBC. In the full unstratified multivariate model, ALBC did not show a statistically significant difference in risk of revision for infection compared to PC. DISCUSSION/CONCLUSION: The use of ALBC in primary TKA has not been shown to be more efficacious in preventing PJI within the population of Medicare patients in the United States. However, this study is limited given it is a retrospective database study that may inherently have biases and the large dataset has a potential for overpowering the findings.

2.
Appl Spectrosc ; 78(5): 456-476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38439705

RESUMO

Here, Raman spectroscopy is used to develop a univariate partial least squares (PLS) calibration capable of quantifying geochemistry in synthetic and natural silicate glass samples. The calibration yields eight oxide-specific models that allow predictions of silicon dioxide (SiO2), sodium oxide (Na2O), potassium oxide (K2O), calcium oxide (CaO), titanium dioxide (TiO2), aluminum oxide (Al2O3), ferrous oxide (FeOT), and magnesium oxide (MgO) (wt%) in glasses spanning a wide range of compositions, while also providing correlation-coefficient matrices that highlight the importance of specific Raman channels in the regression of a particular oxide. The PLS suite is trained on 48 of the 69 total glasses, and tested against 21 validation samples (i.e., held out of training). Trends in root mean square error of calibration (RMSEC), root mean square error of cross-validation (RMSECV), and root mean square error of prediction (RMSEP) model accuracy metrics are investigated to uncover the efficacy of utilizing multivariate analysis for such Raman data and are contextualized against recently produced strategies. The technique yields an average root mean of calibration (∼2.4 wt%), cross-validation (∼ 2.9 wt%), prediction (∼ 2.6 wt%), and normalized variance (∼ 28%). Raman band positional shifts are also mapped against underlying chemical variations; with major influences arising primarily as a function of overall oxidation state and silica concentration: via ferric cation (Fe3+)/ferrous cation (Fe2+) ratios and SiO2 (wt%). The algorithm is further validated preliminarily against a separate external set of 11 natural basaltic glasses to unravel the limitations of the synthetic models on natural samples, and to determine the suitability of "universal" Raman-model applications in scenarios where prior chemical contextualization of the target sample is possible. This study represents the first time Raman spectra of amorphous silicates have been paired with PLS, offering a foundation for future improvements utilizing these systems.

3.
Disabil Rehabil ; : 1-14, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353245

RESUMO

PURPOSE: Hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are multisystem conditions marked by dysfunctional connective tissue. This feasibility study evaluated a 9-week integrative medicine program in this population. METHODS: Using a single-arm study design, adults with HSD or EDS were given recommendations for an anti-inflammatory Mediterranean diet and self-management with additional behavioral and psychosocial support. Preliminary data on feasibility based on recruitment and retention, adherence to the diet, mobile app tracking, changes to perceived well-being via health outcomes, and satisfaction with care were obtained. RESULTS: Thirteen participants were enrolled within a 4-month timeframe. Eight participants completed the study. Three participants met dietary tracking requirement in at least 4 of 8 intervention weeks and met the macronutrient requirements in at least half of the weeks tracked. No decreases in VAS pain scores after 5 and 9 weeks were noted; however, 62.5% (n = 5) of participants had decreased pain at 9 weeks, compared to baseline. There were significant improvements (p<.05) in six of twelve measurements of satisfaction with care at the end of the intervention. CONCLUSION: This study provides a foundation for future research on patient experience and introduces a novel treatment paradigm focused on nutrition and self-management.Trial Registration: National Institutes of Health clinicaltrials.gov; identifier: NCT04734041. IMPLICATIONS FOR REHABILITATION: Lifestyle and dietary interventions are relatively safe and well tolerated in the hypermobility spectrum disorder (HSD) and Ehlers-Danlos disorder (EDS) population.Participants in our 9-week integrative medicine program actively engaged in self-management of their condition and showed promising adherence to dietary and tracking requirements.Effective treatment of the intricacies and dynamics of these highly variable and clinically heterogeneous disorders may require a network of healthcare providers, integrative healthcare, as well as behavioral and psychosocial support.Dietary tracking through mobile apps might help promote self-efficacy and adherence to dietary changes.Symptom tracking might be an effective way for patients to track changes to their health and could provide valuable information for health professionals engaged in managing the disorders.

4.
Contemp Clin Trials ; 131: 107273, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37380021

RESUMO

BACKGROUND: Oxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. METHODS: Patients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.


Assuntos
Acupressão , Terapia por Acupuntura , Antineoplásicos , Neoplasias Gastrointestinais , Neoplasias Pancreáticas , Doenças do Sistema Nervoso Periférico , Humanos , Oxaliplatina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Viabilidade , Antineoplásicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/etiologia , Crioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
5.
Artigo em Inglês | MEDLINE | ID: mdl-37205179

RESUMO

Invasive aspergillosis is a known complication in patients with hematologic malignancies. Tracheopleural fistulas are very rare and reported in immunocompromised adults. We present a case of invasive pulmonary aspergillosis with tracheopleural fistula in a pediatric patient with a history of rhabdomyosarcoma and macrophage activation syndrome. This case highlights the importance of recognizing life-threatening fungal infections and coordinating surgical subspecialities for patient care.

6.
Alcohol Clin Exp Res (Hoboken) ; 47(7): 1271-1282, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37208964

RESUMO

BACKGROUND: Alcohol is a carcinogen and its intake prior to developing cancer and throughout its duration exacerbates cancer cachexia in rodent models. However, the effects on cancer cachexia of stopping alcohol prior to tumor establishment are unknown. METHODS: Male and female mice consumed either a nonalcohol control liquid diet (CON) or a 20% ethanol (kcal/day) liquid diet (EtOH) for 6 weeks. All mice then consumed a control diet and mice in the cancer groups were inoculated with C26 colon cancer cells. Gastrocnemius muscles were collected and analyzed after ~2 weeks. RESULTS: Skeletal muscle weight and male epididymal and female perigonadal fat mass were reduced more by the combination of cancer and prior EtOH than either exposure alone in both males and females. In males, protein synthesis was reduced by 30% following alcohol exposure, while no reductions were observed in female mice. AMPK Thr172 phosphorylation was increased in both male and female EtOH-Cancer groups, while Akt Thr308 phosphorylation was reduced only among males in EtOH-Cancer mice. Substrates in the mTORC1 pathway were reduced by cancer in both males and females, but prior alcohol intake only reduced phosphorylation of 4E-BP1 Ser65 and rpS6 Ser240/244 to a greater extent in male, but not female, mice. Autophagic and proteasomal signaling were largely unaffected by prior alcohol intake in cancer mice, despite a greater increase in Murf1 mRNA in both sexes. CONCLUSIONS: Prior alcohol consumption accelerates or worsens the onset of certain aspects of cancer cachexia in a sex-dependent manner, with males being more sensitive to these exposures, even with abstinence from alcohol prior to tumor initiation.

7.
Mol Cell Endocrinol ; 566-567: 111914, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36958649

RESUMO

OBJECTIVE: To determine whether alcohol consumed within the meal influences the feeding induced increase in mTORC1 signaling. METHODS: Alcohol provided in the liquid diet was consumed by alcohol naïve, fasted, C57BL/6Hsd female mice and gastrocnemius was collected 1hr after the refeeding. Subsequent experiments determined the extent to which changes in mTORC1 signaling persisted across the day. RESULTS: Compared with control mice, protein synthesis, mTORC1 (Ser2448), 4EBP1 (Ser65), S6K1 (Thr389), rpS6 (Ser240/244), Akt (Thr308), and ULK1 (Ser757) were lower in EtOH. Similar suppressive patterns were observed in the hours following consumption of alcohol containing food throughout the dark cycle. Higher peak blood alcohol concentrations induced by intraperitoneal injection of alcohol extended the time and magnitude of mTORC1 pathway suppression. CONCLUSION: Alcohol administered as part of the meal results in lower skeletal muscle mTORC1 signaling while subsequent models show that alcohol may influence this pathway across the day.


Assuntos
Consumo de Bebidas Alcoólicas , Serina-Treonina Quinases TOR , Camundongos , Feminino , Animais , Serina-Treonina Quinases TOR/metabolismo , Fosforilação , Camundongos Endogâmicos C57BL , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Etanol/farmacologia , Etanol/metabolismo , Refeições , Músculo Esquelético/metabolismo
8.
Disabil Rehabil ; 45(21): 3549-3559, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36222285

RESUMO

PURPOSE: Hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS) are frequently underdiagnosed, contributing to patient dissatisfaction in the healthcare system. This study evaluated the health service utilization, care, and subjective experiences of living with chronic illness among adults with HSD and EDS in the United States and Canada. METHODS: This was an anonymous, web-based, cross-sectional healthcare survey. The survey obtained basic demographic information, the Patient Assessment of Chronic Illness Care (PACIC+), as well as responses to questions on the use of healthcare and integrative medicine. RESULTS: A total of 353 surveys were received. The most common complementary therapies used were physical therapy (82%), massage (68%), yoga (58%), chiropractic (48%), and meditation (43%). Mean (SD) summary PACIC and PACIC 5 As scores were 2.16 (0.77) and 2.25 (0.83), respectively. Across all PACIC domains, mean scores of individuals whose typical doctor visit was 30 min or at least an hour were significantly higher than those of individuals who indicated typical visits of 15 min (all p < 0.0001 by one-way ANOVA). There was widespread agreement on the importance of patient-provider relationship and trust, physicians' understanding of the individual's complete medical history, and prioritization of physical and emotional safety (>95% agree or strongly agree to each). CONCLUSION: Individuals with HSD or EDS report low satisfaction with chronic illness care and commonly seek out complementary and self-administered therapies, likely in an attempt to manage symptoms. Respondents reported a desire for greater time and attention from physicians. Results from this study could educate the healthcare community to improve support mechanisms for HSD and EDS populations.IMPLICATIONS FOR REHABILITATIONPatients with hypermobility spectrum disorders (HSD) or Ehlers-Danlos syndromes (EDS) express a desire for patient-centered care and peer support from other individuals with HSD or EDS.Individuals with HSD or EDS have typically seen multiple doctors for their condition and their satisfaction with chronic care, as measured by the Patient Assessment of Chronic Illness Care (PACIC+), is low.The use of various complementary and integrative health treatments, as well as specialized diets, is common in this population, and might be beneficial for symptom management.Healthcare delivery for HSD and EDS may require a multidisciplinary healthcare team, as complementary and self-care modalities are typically used in addition to physical therapy, pain medication, and other conventional care.


Assuntos
Síndrome de Ehlers-Danlos , Instabilidade Articular , Adulto , Humanos , Estudos Transversais , Dor , Doença Crônica , Síndrome de Ehlers-Danlos/diagnóstico , Avaliação de Resultados da Assistência ao Paciente , Instabilidade Articular/terapia , Instabilidade Articular/psicologia
9.
Case Rep Hematol ; 2022: 3641474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330223

RESUMO

A 49-year-old male with no past medical history presented with acute-onset painful mucosal erosions along with flaccid bullae on his trunk, scalp, and intertriginous areas. The patient initially underwent a skin biopsy which demonstrated suprabasilar acantholysis and lichenoid interface dermatitis. This was followed by a computed tomography scan which identified a large abdominal lymph node. Core needle biopsy of this node demonstrated follicular lymphoma. Lastly, indirect immunofluorescence (IIF) in rat bladder was positive (titer 1 : 10,240). This finding confirmed the diagnosis of paraneoplastic pemphigus (PNP) in the setting of follicular lymphoma. The patient's cutaneous disease was treated with a combination of intravenous immunoglobulin and methylprednisolone, along with intravenous rituximab, with a resolution of his cutaneous symptoms. His lymphoma was treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), with an interval decrease in his tumor burden. PNP is an autoimmune-mediated mucocutaneous disease associated with underlying neoplasm, most commonly non-Hodgkin lymphoma or chronic lymphocytic leukemia. Affected patients develop variable autoantibodies to antigens on keratinocytes and the basement membrane zone. Severe intractable stomatitis is characteristic, in addition to polymorphous cutaneous eruptions including bullae and erosions. Mortality rates can reach up to 90% due to malignancy, sepsis, or bronchiolitis obliterans, an irreversible and often lethal cause of pulmonary insufficiency. We highlight PNP manifesting in a patient with lymphoma, who responded well to the skin- and malignancy-directed treatments. PNP is an exceedingly rare diagnosis that should be considered in a patient with intractable stomatitis.

10.
Trials ; 23(1): 885, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273173

RESUMO

BACKGROUND: Xanthohumol (XN), a bioactive flavonoid from Humulus lupulus with anti-inflammatory properties, has potential benefits for patients with Crohn's disease (CD), a type of inflammatory bowel disease. We recently completed and published results of a placebo-controlled phase I clinical trial demonstrating the safety and tolerability of 24 mg XN daily for 8 weeks. The present study aims to evaluate the safety and tolerability of the same dose of XN adults with clinically active CD in a placebo-controlled phase II clinical trial. Additional aims will assess the impact of XN on inflammatory biomarkers, platelet function, CD clinical activity, and stool microbial composition. The metabolism of XN will also be evaluated. This article provides a model protocol for consideration in investigations of XN or other natural products in disease states. METHODS: A triple-masked, randomized, placebo-controlled trial will be conducted in adults with clinically active CD. Participants (n ≤ 32) will be randomized to either 24 mg encapsulated XN per day or placebo and followed for 8 weeks. Throughout the trial, participants will be queried for adverse events. Biomarkers of clinical safety, blood and stool markers of inflammation, platelet function, Crohn's Disease Activity Index score, stool microbial composition, and XN metabolite profiles in blood, urine, and stool will be assessed every 2 weeks. DISCUSSION: We describe the protocol for a phase II clinical trial that evaluates the safety and tolerability of XN in adults with active CD, as well as evaluate metabolism and mechanisms that are relevant to CD and other diseases with underlying inflammation and/or gut permeability. The effects of XN on inflammatory biomarkers, platelet function, the microbiota, and multi-omics biomarkers measured in this phase II trial of adults with CD will be compared to the effects of XN in healthy adults in our previous phase I trial. The results of the study will advance the evidence guiding the use of XN in patients with CD. TRIAL REGISTRATION: ClinialTrials.gov NCT04590508. Registered on October 19, 2020.


Assuntos
Produtos Biológicos , Doença de Crohn , Microbiota , Adulto , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Flavonoides/efeitos adversos , Biomarcadores , Inflamação , Produtos Biológicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como Assunto
11.
J Integr Complement Med ; 28(1): 36-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35085022

RESUMO

Introduction: As the COVID-19 pandemic continues to impact workforces in the United States, the Acupuncture and Telehealth Survey was released to assess the acupuncture profession's use of telehealth and workforce response to a changing regulatory landscape. Methods: An online cross-sectional survey of licensed acupuncturists in the United States was conducted in May 2020 for 4 weeks. Novel online recruitment strategies were successfully implemented including social media pages, digital media marketing, and webinar presentations. Statistical analyses were used to ascertain varying impacts on acupuncturists with telehealth training, and the use of online health care platforms, stratified by age, and history of licensure. Results: One thousand forty-five respondents from 46 states completed the survey. The majority of respondents noted a significant reduction in working hours regardless of telehealth training history (mean -18.7 h/week, p < 0.001, 95% confidence interval [-19.5 to -18.0]); however, acupuncturists managing patients online reported a lesser magnitude of impact (mean -17.3, p = 0.004). Respondents noted stress, immune support, and pain as the most common conditions managed through telehealth. Acupuncturists using telehealth primarily educated patients on nutrition- or herbal-based therapies and acupressure techniques, similar to acupuncturists managing suspected or confirmed COVID-19 cases. Although only 21% of acupuncturists reported receiving telehealth training, 38% were providing telehealth, and 13% were considering it in the future with concerns for quality patient care. Discussion: Acupuncturists' working hours were significantly reduced during the COVID-19 pandemic although many pivoted to a variety of online health care techniques and profession-specific modalities for continued patient care. This effect could be minimized by the use of telehealth platforms, necessitating adequate training on telehealth in the acupuncture profession.


Assuntos
Terapia por Acupuntura , COVID-19 , Telemedicina , Estudos Transversais , Humanos , Internet , Pandemias , SARS-CoV-2 , Estados Unidos
12.
Spine (Phila Pa 1976) ; 47(9): 672-679, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35066538

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess readmission rates and risk factors for 30-day and 90-day readmission after elective lumbar decompression at a single institution. SUMMARY OF BACKGROUND DATA: Hospital readmission is an undesirable aspect of interventional treatment. Studies evaluating readmissions after elective lumbar decompression typically analyze national databases, and therefore have several drawbacks inherent to their macroscopic nature that limit their clinical utility. METHODS: Patients undergoing primary one- to four-level lumbar decompression surgery were retrospectively identified. Demographic, surgical, and readmission data within "30-days" (0-30 days) and "90-days" (31-90 days) postoperatively were extracted from electronic medical records. Patients were categorized into four groups: (1) no readmission, (2) readmission during the 30-day or 90-day postoperative period, (3) complication related to surgery, and (4) Emergency Department (ED)/Observational (OBs)/Urgent (UC) care. RESULTS: A total of 2635 patients were included. Seventy-six (2.9%) were readmitted at some point within the 30- (2.3%) or 90-day (0.3%) postoperative periods. Patients in the pooled readmitted group were older (63.1 yr, P  < 0.001), had a higher American Society of Anesthesiologists (ASA) grade (31.2% with ASA of 3, P = 0.03), and more often had liver disease (8.1%, P = 0.004) or rheumatoid arthritis (12.0%, P = 0.02) than other cohorts. A greater proportion of 90-day readmissions and complications had surgical-related diagnoses or a diagnosis of recurrent disc herniation than 30-day readmissions and complications (66.7% vs. 44.5%, P = 0.04 and 33.3% vs. 5.5%, P < 0.001, respectively). Age (Odds ratio [OR]: 1.02, P = 0.01), current smoking status (OR: 2.38, P < 0.001), longer length of stay (OR: 1.14, P < 0.001), and a history of renal failure (OR: 2.59, P = 0.03) were independently associated with readmission or complication. CONCLUSION: Increased age, current smoking status, hospital length of stay, and a history of renal failure were found to be significant independent predictors of inpatient readmission or complication after lumbar decompression.


Assuntos
Readmissão do Paciente , Insuficiência Renal , Descompressão/efeitos adversos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
14.
J Clin Med ; 10(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34575330

RESUMO

Neutrophil-lymphocyte ratio (NLR) is a biomarker of the systemic inflammatory response. The objective of this systematic scoping review was to examine the literature on NLR and inflammatory bowel disease (IBD). PubMed, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Specialized Register, DOAJ, PDQT, Biosis Citation Index, Scopus, and Web of Science were systematically searched. A total of 2621 citations yielding 62 primary studies were synthesized under four categories: distinguishing patients with IBD from controls, disease activity differentiation, clinical outcome prediction, and association of NLR with other IBD biomarkers. Thirty-eight studies employed receiver operating characteristic (ROC) curve analysis to generate optimal NLR cutpoints for applications including disease activity differentiation and prediction of response to treatment. Among the most promising findings, NLR may have utility for clinical and endoscopic disease activity differentiation and prediction of loss of response to infliximab (IFX). Overall findings suggest NLR may be a promising IBD biomarker. Assessment of NLR is non-invasive, low cost, and widely accessible given NLR is easily calculated from blood count data routinely and serially monitored in patients with IBD. Further research is justified to elucidate how evaluation of NLR in research and clinical practice would directly impact the quality and cost of care for patients living with IBD.

15.
Mol Nutr Food Res ; 65(8): e2001170, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33629812

RESUMO

SCOPE: Xanthohumol, a prenylflavonoid from hops, has been extensively studied preclinically but has undergone limited research in human subjects. A triple-masked, placebo-controlled phase I clinical trial was conducted to examine the safety and tolerability of xanthohumol. METHODS AND RESULTS: Thirty healthy volunteers were randomized to 24 mg day-1 xanthohumol (99.8% pure) or placebo for eight weeks. Comprehensive metabolic panels, complete blood counts, body weight, vital signs, and health-related quality of life questionnaires were assessed every two weeks. Participants were interviewed for adverse events (AEs) throughout the trial. Thirteen of 14 (93%) and 14 of 16 (88%) participants completed the trial in the placebo and xanthohumol groups, respectively. There were no withdrawals due to AEs. There were no clinically relevant, between-group differences in laboratory biomarkers, body weight, vital signs, or health-related quality of life. There were no severe or FDA-defined serious AEs, but non-serious AEs are documented in both the placebo (n = 42) and xanthohumol (n = 58) groups. CONCLUSION: Over an eight-week period, 24 mg daily xanthohumol was safe and well-tolerated by healthy adults.


Assuntos
Flavonoides/efeitos adversos , Flavonoides/farmacologia , Propiofenonas/efeitos adversos , Propiofenonas/farmacologia , Adulto , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Placebos , Qualidade de Vida
17.
Trials ; 21(1): 835, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028396

RESUMO

BACKGROUND: Natural products may provide a source for the discovery and development of adjunctive pharmacological interventions to modulate the inflammatory pathways contributing to chronic disease. Xanthohumol, a flavonoid from the hops plant (Humulus lupulus), has antioxidant and anti-inflammatory properties and may act as a prebiotic to the intestinal microbiota. Xanthohumol is not currently approved as a drug by the US Food and Drug Administration (FDA), but is available as a dietary supplement and ingredient in medical foods. To formally test the safety of xanthohumol, a phase I clinical trial ("XMaS") was designed and approved under an Investigational New Drug application to the US FDA. The main objective is to examine the clinical safety and subjective tolerability of xanthohumol in healthy adults compared to placebo. Additional aims are to monitor biomarkers related to inflammation, gut permeability, bile acid metabolism, routes, and in vivo products of xanthohumol metabolism, and to evaluate xanthohumol's impact on gut microbial composition. METHODS: The safety and tolerability of xanthohumol in healthy adults will be evaluated in a triple-masked, randomized, placebo-controlled trial. Participants will be randomized to either 24 mg/day of xanthohumol or placebo for 8 weeks. Blood cell counts, hepatic and renal function tests, electrolytes, and self-reported health-related quality of life measures will be collected every 2 weeks. Participants will be queried for adverse events throughout the trial. Xanthohumol metabolites in blood, urine, and stool will be measured. Biomarkers to be evaluated include plasma tumor necrosis factor-alpha, various interleukins, soluble CD14, lipopolysaccharide-binding protein, fecal calprotectin, and bile acids to assess impact on inflammatory and gut permeability-related mechanisms in vivo. Stool samples will be analyzed to determine effects on the gut microbiome. DISCUSSION: This phase I clinical trial of xanthohumol will assess safety and tolerability in healthy adults, collect extensive biomarker data for assessment of potential mechanism(s), and provide comparison data necessary for future phase II trials in chronic disease(s). The design and robustness of the planned safety and mechanistic evaluations planned provide a model for drug discovery pursuits from natural products. TRIAL REGISTRATION: ClinicalTrials.gov NCT03735420 . Registered on November 8, 2018.


Assuntos
Microbiota , Propiofenonas , Flavonoides/efeitos adversos , Propiofenonas/efeitos adversos , Qualidade de Vida , Estados Unidos
18.
Artigo em Inglês | MEDLINE | ID: mdl-32476704

RESUMO

Kidney biopsies are currently performed using preoperative imaging to identify the lesion of interest and intraoperative imaging used to guide the biopsy needle to the tissue of interest. Often, these are not the same modalities forcing the physician to perform a mental cross-modality fusion of the preoperative and intraoperative scans. This limits the accuracy and reproducibility of the biopsy procedure. In this study, we developed an augmented reality system to display holographic representations of lesions superimposed on a phantom. This system allows the integration of preoperative CT scans with intraoperative ultrasound scans to better determine the lesion's real-time location. An automated deformable registration algorithm was used to increase the accuracy of the holographic lesion locations, and a magnetic tracking system was developed to provide guidance for the biopsy procedure. Our method achieved a targeting accuracy of 2.9 ± 1.5 mm in a renal phantom study.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32476707

RESUMO

We developed a reliable and repeatable process to create hyper-realistic, kidney phantoms with tunable image visibility under ultrasound (US) and CT imaging modalities. A methodology was defined to create phantoms that could be produced for renal biopsy evaluation. The final complex kidney phantom was devised containing critical structures of a kidney: kidney cortex, medulla, and ureter. Simultaneously, some lesions were integrated into the phantom to mimic the presence of tumors during biopsy. The phantoms were created and scanned by ultrasound and CT scanners to verify the visibility of the complex internal structures and to observe the interactions between material properties. The result was a successful advancement in knowledge of materials with ideal acoustic and impedance properties to replicate human organs for the field of image-guided interventions.

20.
Ir Med J ; 111(7): 789, 2018 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-30520616

RESUMO

Introduction Quick, painless, cheap and reliable, the sweat test remains the gold standard diagnostic test for cystic fibrosis. We aimed to describe the pattern of testing in Ireland over a calendar year. Methods Information on sweat test practices was requested from each centre between 1st January 2011 and 31st December 2011, and the number of positive, negative, equivocal, and insufficient samples was recorded. Results In 2011 there were 2555 sweat tests performed in 15 centres, ranging from 35 to over 450 tests per centre. 35 (1.4%) were in the diagnostic range. The overall quantity not sufficient (QNS) rate was 10.3% (range 0-28.3%). Testing was performed across a wide age range (2.5 weeks to 75 years). The mean sweat chloride value was 16.5 mmol/L (SD 16.1 mmol/L). Discussion Our study demonstrates a high number of sweat tests performed in Ireland with significant variation in sweat testing practices across 15 different sites.

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