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1.
World Neurosurg ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38968995

RESUMO

BACKGROUND: Brainstem tumors represent ∼10% of pediatric brain tumors, ∼80% of these are diffuse midline glioma (DMG). Given invariably poor prognosis in DMG, there continues to be immense variation worldwide in performing biopsy of these lesions. Several contemporary studies in recent years have provided new data to elucidate the safety profile of biopsy and an updated meta-analysis is thus indicated. METHODS: We found 29 studies of pediatric brainstem biopsy in the last 20 years (2003-2023, 1002 children). We applied meta-analysis of proportions using a random-effects model to generate point estimates, confidence intervals, and measures of heterogeneity. RESULTS: 87% of procedures were stereotactic needle biopsies (of these, 62% with a frame, 14% without frame, and 24% robotic.) Biopsy resulted in a histological diagnosis ("technical yield") in 96.8% of cases (95% CI 95.4-98.2). Temporary complications were seen in 6% (95 CI 4-8), with the most common neurological complications being 1) cranial nerve dysfunction, 2) worsening or new ataxia, and 3) limb weakness. Permanent complications (excluding death) were seen in 1% (95% CI 0.5-2), most commonly including cranial nerve dysfunction and limb weakness. 5 deaths were reported in the entire pooled cohort of 1002 children (0.5%). CONCLUSIONS: When counseling families on the merits of brainstem biopsy in children, it is reasonable to state that permanent morbidity is rare (<2%). If biopsy is performed specifically to facilitate enrollment in clinical trials requiring a molecular diagnosis, the risks of biopsy outlined here should be weighed against potential benefits of trial enrollment.

2.
Transpl Infect Dis ; : e14318, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38946207

RESUMO

BACKGROUND: The goal was to determine trends in immunosuppression use and its impact on cytomegalovirus (CMV) outcomes over the past 10 years. METHODS: This was a single-center longitudinal cohort study of adult kidney recipients transplanted between Jan 2012 and June 2021. Baseline and follow-up data were gathered via chart abstraction and analyzed using univariate and multivariate analyses. RESULTS: Of 2392 kidney transplants conducted, 131 patients did not meet inclusion criteria. The mean age was 52 years, 41% were female, 57% were black, and 19% were CMV high-risk. The use of rabbit anti-thymocyte globulin (RATG) induction (odds ratio [OR] 1.6, 1.3-2.1), tacrolimus (FK) level >8 ng/mL (OR 1.1, 1.09-1.11), CMV D+/R- rates (OR 1.06, 1.02-1.10), white blood cell count <3000 (OR 1.22, 1.18-1.26) and valganciclovir prophylaxis (OR 1.7, 1.6-1.9) have significantly increased over the past 10 years.  Rejection rates (OR 0.86, 0.82-0.91) and BK viremia >2000 (OR 0.91, 0.91-0.98) have decreased. RATG induction (adjusted hazard ratio [aHR] 1.35, 1.2-1.5), FK >8 ng/mL (aHR 3.5, 3.2-3.9), Belatacept conversion (aHR 2.5, 2.1-3.1), and rejection (aHR 1.8, 1.6-2.0) were significant risk factors for developing CMV infection, while mycophenolate mofetil <1500 mg (aHR 0.52, 0.47-0.59), mammalian target of rapamycin inhibitor (mTORi) conversion (0.77, 0.56-0.89), cyclosporine-A conversion (aHR 0.68, 0.56-0.84) were associated with lower risk of CMV infection. CONCLUSION: Increasing use of potent immunosuppression coupled with higher CMV D+/R- F rates may be driving higher rates of CMV infection. Cyclosporine and mTORi conversion appears to be protective against CMV.  A more individualized immunosuppression regimen based on infection risk merits consideration.

3.
ACG Case Rep J ; 11(7): e01431, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39006049

RESUMO

Immune checkpoint inhibitors (ICIs) are important immunotherapeutic tools with known potential for adverse events (immune-related adverse events [irAEs]) in the gastrointestinal system. Although ICI-induced colitis and diarrhea are well documented, irAEs localized to the stomach are less frequently described. The management of most irAEs is suspension of ICI therapy and immune suppression. In rare cases of ICI-induced gastritis, treatment strategies of immune suppression have been scarcely described. To our knowledge, there have been no reported cases of severe ICI-induced gastritis leading to fistula formation. This case report describes a patient with isolated ICI-induced gastritis leading to an ulcer with gastrocolic fistula and his treatment course.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38928969

RESUMO

Marital relationships offer health benefits, including a lower risk of cardiovascular disease (CVD). However, quality of the relationship matters; ambivalent behaviors may increase CVD risk by affecting blunted nocturnal blood pressure (BP) dipping. This study tracked daytime and nocturnal SBP and DBP in 180 normotensive individuals (90 couples; participant mean age 25.04; 91.58% white) over a 24 h period using ambulatory blood pressure monitors to explore the impact of martial quality. Results showed that perceptions of spousal ambivalence were associated with blunted nocturnal BP dipping. Perceptions of one's own behavior as ambivalent also showed blunted nocturnal dipping. When in an ambivalent relationship, a gender interaction was found such that women were most likely to have blunted SBP dipping, but men were more likely to have blunted nocturnal DBP dipping. Overall, this study found an association between ambivalence and BP dipping, thus uncovering one virtually unexplored pathway by which marital relationships may have adverse effects on health.


Assuntos
Pressão Sanguínea , Casamento , Humanos , Masculino , Feminino , Adulto , Pressão Sanguínea/fisiologia , Casamento/psicologia , Adulto Jovem , Monitorização Ambulatorial da Pressão Arterial , Sono/fisiologia , Ritmo Circadiano/fisiologia , Cônjuges/psicologia
5.
Horm Res Paediatr ; : 1-12, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38663372

RESUMO

Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at T-cell marker CD3, is the first medication approved by the FDA to delay progression from stage 2 to stage 3 type 1 diabetes. To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance on the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions. We present considerations on all aspects of teplizumab administration, utilizing evidence where possible and providing a spectrum of expert opinions on unknown aspects. We discuss patient selection and prescreening, highlighting the safety and considerations for monitoring and treatment of side effects. We propose a schedule of events, a protocol for administration, and discuss practice management aspects. We advocate for the need for further long-term systematic surveillance studies to continue evaluating the efficacy and safety of teplizumab.

6.
J Family Med Prim Care ; 13(2): 498-504, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38605757

RESUMO

Background: The healthcare managers need to develop the managerial skills and use it for better healthcare delivery. A manager requires leadership skill to empower employees and motivate them to work in an efficient manner to achieve organizational goal. Motivating employees/subordinates and developing positive attitude toward them is one of the crucial skills that the leader needs to develop. The way health team works as a unit affects the outcome and needs good leader. With this background, the current study tends to explore the managerial skills of middle-level managers. Objectives: 1. To assess the leadership and team management skills of middle-level managers and 2. To find out motivational factors used by managers. Materials and Methods: A cross-sectional study was conducted among district-level healthcare managers and medical officers. Data collection was performed via semistructured and scale-based questionnaire and analyzed using Microsoft office excel. Results: 60% of managers had participative leadership style. Team work skills were fair enough among the managers. 53% of medical officers were freshly appointed with experience of less than one year. The middle-level managers used appreciation of work (41.8%) as major motivator of the team. Conclusions: The middle-level healthcare managers have good leadership quality as well as teamwork skills. Appreciation of work is commonly used motivator.

7.
J Am Soc Echocardiogr ; 37(2): 119-170, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309834

RESUMO

Echocardiography is a fundamental component of pediatric cardiology, and appropriate indications have been established for its use in the setting of suspected, congenital, or acquired heart disease in children. Since the publication of guidelines for pediatric transthoracic echocardiography in 2006 and 2010, advances in knowledge and technology have expanded the scope of practice beyond the use of traditional modalities such as two-dimensional, M-mode, and Doppler echocardiography to evaluate the cardiac segmental structures and their function. Adjunct modalities such as contrast, three-dimensional, and speckle-tracking echocardiography are now used routinely at many pediatric centers. Guidelines and recommendations for the use of traditional and newer adjunct modalities in children are described in detail in this document. In addition, suggested protocols related to standard operations, infection control, sedation, and quality assurance and improvement are included to provide an organizational structure for centers performing pediatric transthoracic echocardiograms.


Assuntos
Cardiologia , Cardiopatias , Criança , Humanos , Estados Unidos , Ecocardiografia/métodos , Ecocardiografia Doppler/métodos
8.
Clin Ther ; 46(1): e1-e6, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37880055

RESUMO

INTRODUCTION: Significant progress has been made in the management of patients with acute coronary syndrome (ACS) during the past few decades. However, the role of direct oral anticoagulants (DOACs) in post-ACS prophylactic therapy remains unknown. This study aims to assess the efficacy and safety of DOACs plus antiplatelet treatment (APT) after ACS. METHODS: A systematic literature search was conducted to identify randomized clinical trials comparing DOACs plus APT with APT alone after ACS. The primary efficacy end points were cardiovascular mortality, myocardial infarction, all-cause mortality, and stroke and systemic embolization (SSE). The primary safety end point was major bleeding. The random-effects model was used to calculate relative risk (RR) and corresponding 95% CIs. RESULTS: Nine trials with a total of 53,869 patients were identified, with 33,011 (61.2%) in the DOACs plus APT group and 20,858 (38.8%) in the APT alone group. The use of DOACs did not decrease the risk of cardiovascular death (RR = 0.87; 95% CI, 0.75-1.01; P = 0.08; I2 = 0%) or myocardial infarction (RR = 0.90; 95% CI, 0.80-1.02; P = 0.10; I2 = 6%). However, the risk of SSE was significantly lower in patients who received DOACs plus APT compared with APT alone (RR = 0.67; 95% CI, 0.50-0.90; P = 0.008). Moreover, all-cause mortality was significantly lower in the DOACs plus APT group (RR = 0.83; 95% CI, 0.71-98; P = 0.03; I2 = 0%). However, the risk of major bleeding was significantly higher in patients treated with DOACs plus APT compared with APT alone (RR = 2.53; 95% CI, 1.96-3.26; P < 0.01; I2 = 0%), as was the risk of nonmajor bleeding (RR = 2.27; 95% CI, 1.51-3.41; P < 0.01). IMPLICATIONS: DOACs plus APT for the prevention of left ventricular thrombus in patients with ACS were associated with a lower risk of SSE and all-cause mortality but increased the risk of major and nonmajor bleeding. The benefits and risks of this approach should be weighed based on a patient's individual clinical characteristics.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Anticoagulantes/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/complicações , Acidente Vascular Cerebral/prevenção & controle , Hemorragia/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Administração Oral
9.
BMJ Glob Health ; 8(12)2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38114236

RESUMO

Event-based surveillance (EBS) can be implemented in most settings for the detection of potential health threats by recognition and immediate reporting of predefined signals. Such a system complements existing case-based and sentinel surveillance systems. With the emergence of the COVID-19 pandemic in early 2020, the Kenya Ministry of Health (MOH) modified and expanded an EBS system in both community and health facility settings for the reporting of COVID-19-related signals. Using an electronic reporting tool, m-Dharura, MOH recorded 8790 signals reported, with 3002 (34.2%) verified as events, across both community and health facility sites from March 2020 to June 2021. A subsequent evaluation found that the EBS system was flexible enough to incorporate the addition of COVID-19-related signals during a pandemic and maintain high rates of reporting from participants. Inadequate resources for follow-up investigations to reported events, lack of supportive supervision for some community health volunteers and lack of data system interoperability were identified as challenges to be addressed as the EBS system in Kenya continues to expand to additional jurisdictions.


Assuntos
COVID-19 , Pandemias , Humanos , Quênia/epidemiologia , COVID-19/epidemiologia , Saúde Pública
10.
Clin Transplant ; 37(12): e15149, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37788162

RESUMO

Outcomes analyzing conversion from IR-tacrolimus (IR) to LCP-tacrolimus (LCP) in obesity are limited. This was a retrospective longitudinal cohort study of patients converted from IR to LCP from June 2019 to October 2020. Primary outcomes were conversion ratios for weight-based dose at a steady-state therapeutic level and identification of appropriate dosing weight. Other outcomes included tacrolimus coefficient of variation (CV), time in therapeutic range (TITR), adverse events, infections, donor specific antibodies (DSAs), and acute rejection. A total of 292 patients were included; 156 and 136 patients with a BMI < 30 and BMI ≥ 30 kg/m2 , respectively. Baseline characteristics were similar, except for pancreas transplant, diabetes, and HLA mismatch. IR to LCP conversion ratio ranged from .73 to .79. Mean LCP dose was similar (.08 vs. .07 mg/kg/day for BMI < 30 and BMI ≥ 30 kg/m2 , respectively); there was a significant difference in IR and LCP mg/kg dosing at steady state with TBW (.11 mg/kg vs.09 mg/kg and .08 mg/kg vs. .06 mg/kg, respectively). The most appropriate dosing weight was adjusted body weight (AdjBW), consistent across IR and LCP steady-state doses, and might yield more accurate steady-state dosing requirements. In multivariable modeling, BMI was a significant predictor of steady state mg/kg dosing at therapeutic goal for total body weight (TBW), but not ideal body weight (IBW) or AdjBW.


Assuntos
Transplante de Rim , Tacrolimo , Humanos , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Estudos Longitudinais , Preparações de Ação Retardada , Esquema de Medicação , Obesidade/tratamento farmacológico , Obesidade/cirurgia , Obesidade/etiologia , Transplantados , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia
11.
Curr Probl Cardiol ; 48(10): 101879, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37343774

RESUMO

The influence of body mass index (BMI) on Transcatheter Aortic Valve Replacement (TAVR) outcomes has been the focus of several previous studies. In this study, we examined the relationship between BMI and various clinical outcomes following TAVR procedures. A comprehensive analysis was conducted using a large cohort of patients who underwent TAVR. In this study, we identified patients who underwent Transcatheter aortic valve replacement (TAVR) in the year 2020. Procedure Classification System (ICD-10-PCS) codes were used to identify TAVR cases. The weighted final study sample included 77319 TAVR hospitalizations. Patients were categorized into 5 groups based on their Body Mass Index (BMI. Our findings revealed that there was no significant difference in in-hospital mortality among different BMI groups when compared to patients with a normal BMI (20 to 24.9). patients with a BMI of 25 or higher demonstrated a statistically significant shorter duration of hospitalization compared to those with a normal BMI. patients with a BMI ranging between 30 and 39.9 exhibited decreased hospitalization costs when compared to patients with a normal BMI. Moreover, our study revealed a decrease in atrial fibrillation, acute heart failure and acute kidney injury complications following TAVR in patients with above-normal BMI. Despite similar in-hospital mortality across BMI groups, having a BMI of 25 or greater is associated with improved immediate outcomes following TAVR. These benefits in overweight and obese patients are consistent with findings described in recent literature. Further studies are warranted to explore the underlying mechanisms and potential implications of these associations, as well as to optimize patient selection and management strategies for TAVR procedures.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Humanos , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Índice de Massa Corporal , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
12.
Chem Sci ; 14(18): 4724-4734, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37181774

RESUMO

DFT-Calculations predict that a low-valent complex (BDI)Mg-Ca(BDI) with bulky ß-diketiminate (BDI) ligands is thermodynamically stable. It was attempted to isolate such a complex by salt-metathesis between [(DIPePBDI*)Mg-Na+]2 and [(DIPePBDI)CaI]2 (DIPePBDI = HC[C(Me)N-DIPeP]2; DIPePBDI* = HC[C(tBu)N-DIPeP]2; DIPeP = 2,6-CH(Et)2-phenyl). Whereas in alkane solvents no reaction was observed, salt-metathesis in C6H6 led to immediate C-H activation of benzene to give (DIPePBDI*)MgPh and (DIPePBDI)CaH, the latter crystallizing as a THF-solvated dimer [(DIPePBDI)CaH·THF]2. Calculations suggest reduction and insertion of benzene in the Mg-Ca bond. The activation enthalpy for the subsequent decomposition of C6H62- into Ph- and H- is only 14.4 kcal mol-1. Repeating this reaction in the presence of naphthalene or anthracene led to heterobimetallic complexes in which naphthalene2- or anthracene2- anions are sandwiched between (DIPePBDI*)Mg+ and (DIPePBDI)Ca+ cations. These complexes slowly decompose to their homometallic counterparts and further decomposition products. Complexes in which naphthalene2- or anthracene2- anions are sandwiched between two (DIPePBDI)Ca+ cations were isolated. The low-valent complex (DIPePBDI*)Mg-Ca(DIPePBDI) could not be isolated due to its high reactivity. There is, however, strong evidence that this heterobimetallic compound is a fleeting intermediate.

13.
J Am Pharm Assoc (2003) ; 63(4): 1203-1210, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37164264

RESUMO

BACKGROUND: Before the coronavirus disease 2019 (COVID-19) pandemic, 20% of the adult population in the United States experienced mental illness annually. Since the COVID-19 pandemic, 93% of countries have reported disruptions to mental health services. The demand for services is high whereas infrastructure and qualified professionals are appallingly low. Health care in the correctional setting is unique, where mental illness prevalence is double than that in the community. The intersection of policies and procedures and the beneficence plus nonmaleficence responsibility of health care professionals is exceptionally complex. Studies have shown the potential benefits of pharmacists following patients in chronic care psychiatry visits. OBJECTIVES: An inpatient psychiatric pharmacy clinic was launched to fill gaps to provide safe and up-to-date patient-centric services for more than 240 extremely psychiatrically ill inmate patients at the Federal Correctional Center Butner (FCC Butner), a Federal Bureau of Prisons medical center. METHODS: The inpatient psychiatric pharmacist practiced independently under a collaborative practice agreement and completed mental health clinical visits for a revolving portion of 240 inpatient mental health inmate patients at FCC Butner. The pharmacist provided ancillary services including completing movement disorder testing, monitoring narrow therapeutic index medication laboratory test results, and executing an antipsychotic psychoeducation meeting with other health care departments and inmate patients. RESULTS: Notably, 74% of patients monitored in the specialty program experienced stable or improved symptoms of depression, schizophrenia, and bipolar disorder. Adverse effects, particularly psychiatric-related movement disorders, were also more closely managed. Finally, 43% of the total inmate patient population who previously declined psychiatric medication treatment consented to begin treatment after participation in a pilot antipsychotic psychoeducation meeting. CONCLUSION: The inpatient psychiatric pharmacy program at FCC Butner is a dynamic program that has bolstered the facility's health care mission. The services detailed in this article can be applied to other correctional environments that have a medical outpatient or inpatient presence.


Assuntos
Antipsicóticos , COVID-19 , Transtornos Mentais , Farmácia , Adulto , Humanos , Estados Unidos , Prisões , Pandemias , Antipsicóticos/efeitos adversos , Transtornos Mentais/tratamento farmacológico , COVID-19/epidemiologia , Farmacêuticos
14.
JAMA Surg ; 158(6): 618-624, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37017945

RESUMO

Importance: Opioid use following kidney transplant is associated with an increased risk of graft loss and mortality. Opioid minimization strategies and protocols have shown reductions in short-term opioid use after kidney transplant. Objective: To evaluate the long-term outcomes associated with an opioid minimization protocol following kidney transplant. Design, Setting, and Participants: This single-center quality improvement study evaluated postoperative and long-term opioid use before and after the implementation of a multidisciplinary, multimodal pain regimen and education process in adult kidney graft recipients from August 1, 2017, through June 30, 2020. Patient data were collected from a retrospective chart review. Exposures: Preprotocol and postprotocol implementation use of opioids. Main Outcomes and Measures: Between November 7 and 23, 2022, opioid use before and after protocol implementation was evaluated up to 1 year after transplant using multivariable linear and logistic regression. Results: A total of 743 patients were included, with 245 patients in the preprotocol group (39.2% female and 60.8% male; mean [SD] age, 52.8 [13.1 years]) vs 498 in the postprotocol group (45.4% female and 54.6% male; mean [SD] age, 52.4 [12.9 years]). The total morphine milligram equivalents (MME) in the 1-year follow-up in the preprotocol group was 1203.7 vs 581.9 in the postprotocol group. In the postprotocol group, 313 patients (62.9%) had 0 MME in the 1-year follow-up vs 7 (2.9%) in the preprotocol group (odds ratio [OR], 57.52; 95% CI, 26.55-124.65). Patients in the postprotocol group had 99% lower odds of filling more than 100 MME in the 1-year follow-up (adjusted OR, 0.01; 95% CI, 0.01-0.02; P < .001). Opioid-naive patients postprotocol were one-half as likely to become long-term opioid users vs preprotocol (OR, 0.44; 95% CI, 0.20-0.98; P = .04). Conclusions and Relevance: The study's findings show a significant reduction in opioid use in kidney graft recipients associated with the implementation of a multimodal opioid-sparing pain protocol.


Assuntos
Transplante de Rim , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Analgésicos Opioides/uso terapêutico , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle
15.
Pharmacogenet Genomics ; 33(3): 59-65, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36877088

RESUMO

OBJECTIVES: LCP tac has a recommended starting dose of 0.14 mg/kg/day in kidney transplant. The goal of this study was to assess the influence of CYP3A5 on perioperative LCP tac dosing and monitoring. METHODS: This was a prospective observational cohort study of adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele). RESULTS: In this study, 120 were screened, 90 were contacted and 52 provided consent; 50 had genotype results, and 22 patients expressed CYP3A5*1. African Americans (AA) comprised 37.5% of nonexpressors versus 81.8% of expressors (P = 0.001). Initial LCP tac dose was similar between CYP3A5 groups (0.145 vs. 0.137 mg/kg/day; P = 0.161), whereas steady state dose was higher in expressors (0.150 vs. 0.117 mg/kg/day; P = 0.026). CYP3A5*1 expressors had significantly more tac trough concentrations of less than 6 ng/ml and significantly fewer tac trough concentrations of more than 14 ng/ml. Providers were significantly more likely to under-adjust LCP tac by 10 and 20% in CYP3A5 expressors versus nonexpressors (P < 0.03). In sequential modeling, CYP3A5 genotype status explained the LCP tac dosing requirements significantly more than AA race. CONCLUSION: CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers.


Assuntos
Citocromo P-450 CYP3A , Transplante de Rim , Tacrolimo , Adulto , Humanos , Citocromo P-450 CYP3A/genética , Genótipo , Estudos Prospectivos , Tacrolimo/administração & dosagem
16.
Int J Pediatr Otorhinolaryngol ; 167: 111497, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36893584

RESUMO

Management of tongue venous malformations can be challenging in the pediatric population due to their heterogeneity in presentation, extent of involvement and functional compromise. It is important to recognize the value of various treatment options in order to guide management of each patient in an individualized fashion. Here we describe a series of patients with tongue venous malformations that are managed using diverse modalities to illustrate the relative benefits and risks of each technique. The challenges of venous malformation treatment can be mitigated by tailoring the approach to each individual patient and malformation. This case series also emphasizes the need and importance of working in the setting of a multidisciplinary vascular anomalies team.


Assuntos
Embolização Terapêutica , Malformações Vasculares , Criança , Humanos , Embolização Terapêutica/métodos , Escleroterapia/métodos , Língua , Malformações Vasculares/diagnóstico , Malformações Vasculares/terapia , Veias/anormalidades
17.
Ann Am Thorac Soc ; 20(7): 1029-1037, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36912897

RESUMO

Rationale: Increased cardiovascular risk in obstructive sleep apnea (OSA) persists after continuous positive airway pressure (CPAP) and alternative therapies are needed. Impaired endothelial protection against complement is a cholesterol-dependent process that initiates endothelial inflammation in OSA, which increases cardiovascular risk. Objectives: To investigate directly whether lowering cholesterol improves endothelial protection against complement and its proinflammatory effects in OSA. Methods: Newly diagnosed patients with OSA (n = 87) and OSA-free controls (n = 32) participated. Endothelial cells and blood were collected at baseline, after 4 weeks of CPAP therapy, and again after 4 weeks of 10 mg atorvastatin versus placebo using a randomized, double-blind, parallel-group design. Primary outcome was the proportion of a complement inhibitor, CD59, on the endothelial cell plasma membrane in OSA patients after 4 weeks of statins versus placebo. Secondary outcomes were complement deposition on endothelial cells and circulating levels of its downstream proinflammatory factor, angiopoietin-2, after statins versus placebo. Results: Baseline expression of CD59 was lower, whereas complement deposition on endothelial cells and levels of angiopoietin-2 were greater, in patients with OSA compared with controls. CPAP did not affect expression of CD59 or complement deposition on endothelial cells in patients with OSA, regardless of adherence. Compared with placebo, statins increased expression of endothelial complement protector CD59 and lowered complement deposition in patients with OSA. Good CPAP adherence was associated with increased angiopoietin-2 levels, which was reversed by statins. Conclusions: Statins restore endothelial protection against complement and reduce its downstream proinflammatory effects, suggesting a potential approach to reduce residual cardiovascular risk after CPAP in patients with OSA. Clinical trial registered with www.clinicaltrials.gov (NCT03122639).


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Apneia Obstrutiva do Sono , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Angiopoietina-2 , Células Endoteliais , Colesterol , Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia
18.
Nutrients ; 15(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36839254

RESUMO

Inflammatory bowel disease (IBD) is a chronic disorder thought to be caused by enteric inflammation in a genetically susceptible host. Although the pathogenesis of IBD is largely unknown, it is widely accepted that dietary components play an important role. Human and animal-based studies have explored the role of various dietary components such as meat, artificial sweeteners and food additives in causing enteric inflammation. Several diets have also been studied in patients with IBD, specifically their role in the induction or maintenance of remission. The most well-studied of these include exclusive enteral nutrition and specific carbohydrate diet. A diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), typically prescribed for patients with irritable bowel syndrome, has also been studied in a specific subgroup of patients with IBD. In this review, we describe the current evidence on how various dietary components can induce enteric and colonic inflammation, and the clinical-epidemiological evidence exploring their role in predisposing to or protecting against the development of IBD. We also discuss several special diets and how they affect clinical outcomes in IBD patients. Based on the available evidence, we provide guidance for patients and clinicians managing IBD regarding the best practice in dietary modifications.


Assuntos
Doenças Inflamatórias Intestinais , Animais , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Dieta/efeitos adversos , Oligossacarídeos/efeitos adversos , Dissacarídeos/efeitos adversos , Inflamação/induzido quimicamente , Monossacarídeos/efeitos adversos
19.
Clin Transplant ; 37(5): e14941, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36809653

RESUMO

BACKGROUND: The influence of converting to once daily, extended-release LCP-Tacrolimus (Tac) for those with high tacrolimus variability in kidney transplant recipients (KTRs) is not well-studied. METHODS: Single-center, retrospective cohort study of adult KTRs converted from Tac immediate release to LCP-Tac 1-2 years post-transplant. Primary measures were Tac variability, using the coefficient of variation (CV) and time in therapeutic range (TTR), as well as clinical outcomes (rejection, infections, graft loss, death). RESULTS: A total of 193 KTRs included with a follow-up of 3.2 ± .7 years and 1.3 ± .3 years since LCP-Tac conversion. Mean age was 52 ± 13 years; 70% were African American, 39% were female, 16% living donor and 12% donor after cardiac death (DCD). In the overall cohort, tac CV was 29.5% before conversion, which increased to 33.4% after LCP-Tac (p = .008). In those with Tac CV >30% (n = 86), conversion to LCP-Tac reduced variability (40.6% vs. 35.5%; p = .019) and for those with Tac CV >30% and nonadherence or med errors (n = 16), LCP-Tac conversion substantially reduced Tac CV (43.4% vs. 29.9%; p = .026). TTR significantly improved for those with Tac CV >30% with (52.4% vs. 82.8%; p = .027) or without nonadherence or med errors (64.8% vs. 73.2%; p = .005). CMV, BK, and overall infections were significantly higher prior to LCP-Tac conversion. In the overall cohort, 3% had rejection before conversion and 2% after (p = NS). At end of follow-up, graft and patient survival were 94% and 96%, respectively. CONCLUSIONS: In those with high Tac CV, conversion to LCP-Tac is associated with a significant reduction in variability and improvement in TTR, particularly in those with nonadherence or medication errors.


Assuntos
Transplante de Rim , Tacrolimo , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Transplantados , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-36752701

RESUMO

Summary: Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism triggered by precipitants that increase the activity of the sodium-potassium pump in the skeletal muscle. In our case study, a previously healthy 34-year-old male presented to the emergency department with new onset thyrotoxicosis, secondary to Graves' disease. Given the severity of his triiodothyronine (T3) thyrotoxicosis, he was admitted and started on a high dose of beta-blocker, thioamides, and intravenous hydrocortisone. On the second day of his hospitalization, he developed acute flaccid paralysis of his lower extremities. Subsequent stroke workup was negative, and his electrolytes revealed severe hypokalemia and hyperglycemia consistent with TPP. He was treated with potassium and had a complete recovery of his paralysis and hypokalemia within hours. The patient has not had any recurrence since this singular episode in the hospital. This case highlights the scenario where the treatment of hyperthyroidism with high-dose corticosteroids to reduce the conversion of thyroxine to T3 inadvertently resulted in TPP. Clinicians should be aware of this potentially rare but serious consequence of using steroids to manage hyperthyroidism. Learning points: High-dose steroids used to treat hyperthyroidism in hospitalized patients may rarely precipitate thyrotoxic periodic paralysis (TPP) by inducing hypokalemia and hyperglycemia. TPP should be included in the differential diagnosis for acute flaccid paralysis in hospitalized patients with hyperthyroidism. Since TPP is associated with trans-cellular shifts in potassium instead of total body potassium depletion, conservative repletion of potassium is recommended to avoid rebound hyperkalemia.

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