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Navigating antibiotics at the end of life is a challenge for infectious disease (ID) physicians who remain deeply committed to providing patient-centered care and engaging in shared decision making. ID physicians, who often see patients in both inpatient and outpatient settings and maintain continuity of care for patients with refractory or recurrent infections, are ideally situated to provide guidance that aligns with patients' goals and values. Complex communication skills, including navigating difficult emotions around end-of-life care, can be used to better direct shared decision making and assist with antibiotic stewardship.
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Médicos , Assistência Terminal , Humanos , Antibacterianos/uso terapêutico , Morte , Tomada de Decisões , Pacientes Internados , Assistência Terminal/psicologiaRESUMO
Prior studies showed that mice deficient in the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in synthesis of the thiol antioxidant glutathione (GSH), have decreased ovarian GSH concentrations, chronic ovarian oxidative stress, poor oocyte quality resulting in early preimplantation embryonic mortality and decreased litter size, and accelerated age-related decline in ovarian follicle numbers. Global deficiency of the catalytic subunit of this enzyme, Gclc, is embryonic lethal. We tested the hypothesis that granulosa cell- or oocyte-specific deletion of Gclc recapitulates the female reproductive phenotype of global Gclm deficiency. We deleted Gclc in granulosa cells or oocytes of growing follicles using Gclc floxed transgenic mice paired with Amhr2-Cre or Zp3-Cre alleles respectively. We discovered that granulosa cell-specific deletion of Gclc in Amhr2Cre;Gclc(f/-) mice recapitulates the decreased litter size observed in Gclm-/- mice, but does not recapitulate the accelerated age-related decline in ovarian follicles observed in Gclm-/- mice. In addition to having lower GSH concentrations in granulosa cells, Amhr2Cre;Gclc(f/-) mice also had decreased GSH concentrations in oocytes. By contrast, oocyte-specific deletion of Gclc in Zp3Cre;Gclc(f/-) mice did not affect litter size or accelerate the age-related decline in follicle numbers, and these mice did not have decreased oocyte GSH concentrations, consistent with transport of GSH between cells via gap junctions. The results suggest that GSH deficiency at earlier stages of follicle development may be required to generate the accelerated follicle depletion phenotype observed in global Gclm null mice.
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Multiple regulated neutrophil cell death programs contribute to host defense against infections. However, despite expressing all necessary inflammasome components, neutrophils are thought to be generally defective in Caspase-1-dependent pyroptosis. By screening different bacterial species, we found that several Pseudomonas aeruginosa (P. aeruginosa) strains trigger Caspase-1-dependent pyroptosis in human and murine neutrophils. Notably, deletion of Exotoxins U or S in P. aeruginosa enhanced neutrophil death to Caspase-1-dependent pyroptosis, suggesting that these exotoxins interfere with this pathway. Mechanistically, P. aeruginosa Flagellin activates the NLRC4 inflammasome, which supports Caspase-1-driven interleukin (IL)-1ß secretion and Gasdermin D (GSDMD)-dependent neutrophil pyroptosis. Furthermore, P. aeruginosa-induced GSDMD activation triggers Calcium-dependent and Peptidyl Arginine Deaminase-4-driven histone citrullination and translocation of neutrophil DNA into the cell cytosol without inducing extracellular Neutrophil Extracellular Traps. Finally, we show that neutrophil Caspase-1 contributes to IL-1ß production and susceptibility to pyroptosis-inducing P. aeruginosa strains in vivo. Overall, we demonstrate that neutrophils are not universally resistant for Caspase-1-dependent pyroptosis.
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Inflamassomos , Piroptose , Animais , Proteínas Reguladoras de Apoptose/genética , Caspase 1/metabolismo , Exotoxinas/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/microbiologia , Pseudomonas aeruginosa/metabolismoRESUMO
BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. CONCLUSION: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.
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Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine preclinical model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or posttraumatic OA, on either a chow or high-fat diet, despite similar body weight and the presence of systemic inflammation. These findings indicate that adipose tissue itself plays a critical role in the pathophysiology of OA. Susceptibility to posttraumatic OA was reintroduced into LD mice using implantation of a small adipose tissue depot derived from wild-type animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a mediator of joint degeneration.
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Tecido Adiposo/metabolismo , Lipodistrofia/metabolismo , Osteoartrite do Joelho/metabolismo , Tecido Adiposo/fisiopatologia , Tecido Adiposo/transplante , Adiposidade , Animais , Peso Corporal , Cartilagem/patologia , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças/complicações , Suscetibilidade a Doenças/metabolismo , Feminino , Fibroblastos/metabolismo , Hiperplasia/complicações , Inflamação/metabolismo , Lipodistrofia/diagnóstico por imagem , Lipodistrofia/genética , Lipodistrofia/fisiopatologia , Locomoção , Masculino , Camundongos , Força Muscular , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/prevenção & controle , Dor/complicações , Comunicação Parácrina/fisiologiaRESUMO
INTRODUCTION: While benzodiazepines (BZD) are the standard of care therapy for the management alcohol withdrawal syndrome (AWS), phenobarbital (PHB) is often used as an alternative agent. The objective of this study is to assess the use of PHB therapy for the management of AWS in trauma-surgical intensive care unit (TSCU) patients. MATERIALS AND METHODS: This is an institutional review board-approved single-center, retrospective study conducted at a large academic medical center. Patients aged ≥ 18 y admitted to the TSCU receiving PHB therapy for primary management of AWS were included. The primary outcome evaluated was the incidence of AWS-related complications (AWSRC) defined as severe agitation, delirium tremens, or seizures following initiation of PHB. Secondary outcomes included the incidence of oversedation and duration of mechanical ventilation. RESULTS: Sixty patients were included in this study. AWSRC following initiation of PHB occurred in 65% of patients. Median time to initiation of PHB (42 versus 18 h, P = 0.001) and rates of oversedation (79.5% versus 28.6%, P < 0.001) were significantly greater among patients who experienced AWSRC compared to those who did not. Univariate analysis revealed use of BZD therapy for ≥ 24 h prior to PHB initiation, time from hospital admission to PHB initiation ≥ 24 h, presence of AWS symptoms at baseline, and baseline MINDS score > 6 were risk factors for AWSRC. CONCLUSIONS: Delays in initiation of PHB appear to be associated with an increased risk for developing AWSRC. Further research is needed to identify an optimal dosing strategy for TSCU patients at high risk for severe AWS.
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Alcoolismo , Síndrome de Abstinência a Substâncias , Ferida Cirúrgica , Humanos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/etiologia , Alcoolismo/complicações , Estudos Retrospectivos , Estado Terminal/terapia , Benzodiazepinas/efeitos adversos , Fenobarbital/efeitos adversosRESUMO
OBJECTIVE: To explore the prognostic value of the Coma Recovery Scale-Revised (CRS-R) in predicting disability outcomes in patients with severe traumatic brain injury using the Disability Rating Scale (DRS). DESIGN: Secondary analysis including linear and logistic regressions were performed. SETTING: Data were collected in a previous clinical trial. PARTICIPANTS: One hundred eighty-four participants across 3 countries (N=184). MAIN OUTCOME MEASURES: Disability Rating Scales. RESULTS: Analyses showed an inverse relation between CRS-R scores obtained at baseline and change in DRS scores at 6 weeks. Similarly, changes in CRS-R scores between baseline and 4 weeks were also found to have an inverse relation to change in DRS scores at 6 weeks. CONCLUSIONS: This study generates a tool that can be used to predict the probability that a patient with severe traumatic brain injury lands in 1 of 3 disability categories. The CRS-R may be useful in prognostication of disability in patients with severe traumatic brain injury.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Coma/reabilitação , Recuperação de Função Fisiológica , Lesões Encefálicas/reabilitação , Prognóstico , Lesões Encefálicas Traumáticas/complicações , Escala de Coma de GlasgowRESUMO
For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury.
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Injúria Renal Aguda , Fluorocarbonos , Nanopartículas , Humanos , Cisplatino/farmacologia , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Fluorocarbonos/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Rim/metabolismo , ApoptoseRESUMO
The synovium is a multilayer connective tissue separating the intra-articular spaces of the diarthrodial joint from the extra-synovial vascular and lymphatic supply. Synovium regulates drug transport into and out of the joint, yet its material properties remain poorly characterized. Here, we measured the compressive properties (aggregate modulus, Young's modulus, and Poisson's ratio) and hydraulic permeability of synovium with a combined experimental-computational approach. A compressive aggregate modulus and Young's modulus for the solid phase of synovium were quantified from linear regression of the equilibrium confined and unconfined compressive stress upon strain, respectively (HA = 4.3 ± 2.0 kPa, Es = 2.1 ± 0.75, porcine; HA = 3.1 ± 2.0 kPa, Es = 2.8 ± 1.7, human). Poisson's ratio was estimated to be 0.39 and 0.40 for porcine and human tissue, respectively, from moduli values in a Monte Carlo simulation. To calculate hydraulic permeability, a biphasic finite element model's predictions were numerically matched to experimental data for the time-varying ramp and hold phase of a single increment of applied strain (k = 7.4 ± 4.1 × 10-15 m4/N.s, porcine; k = 7.4 ± 4.3 × 10-15 m4/N.s, human). We can use these newly measured properties to predict fluid flow gradients across the tissue in response to previously reported intra-articular pressures. These values for material constants are to our knowledge the first available measurements in synovium that are necessary to better understand drug transport in both healthy and pathological joints.
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Cartilagem Articular , Animais , Cartilagem Articular/fisiologia , Força Compressiva/fisiologia , Elasticidade , Humanos , Modelos Biológicos , Permeabilidade , Estresse Mecânico , Suínos , Membrana SinovialRESUMO
BACKGROUND: This study aimed to examine variations in the incidence rates of sexually transmitted infections (STIs; i.e., chlamydia, gonorrhea, and syphilis) across the urban-rural and area-deprivation continua from January of 2013 to December of 2018 in Yakima County, Washington. The rates of STIs has been increasing in the United States in the past decade. Historically, Yakima County has higher rates of STIs than state and national rates. In addition, Yakima County contains rural areas and areas with greater deprivation that face gaps in access to care. METHODS: The Washington State Department of Health Database Surveillance System was used to conduct the study. The data set included diagnosed cases of chlamydia, gonorrhea, and syphilis with positive laboratory test results for the duration of the study period. Incidence rates of STIs were calculated and statistically analyzed across the urban-rural and area-deprivation continua using rural-urban commuting area codes and the area deprivation index. RESULTS: The incidence rates of STIs increased from January of 2013 to December of 2018. Rates of STI did not differ in micropolitan, small town, and rural block groups compared with the metropolitan block groups. Most-deprived block groups had significantly higher STI rates compared with less deprived block groups. CONCLUSIONS: There is a need for increased STI intervention in higher deprivation areas including STI education. Public health officials and health care providers should be aware of these risk factors and tailor interventions to the neighborhood they serve.
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Infecções por Chlamydia , Gonorreia , Infecções por HIV , Infecções Sexualmente Transmissíveis , Sífilis , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Incidência , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Sífilis/diagnóstico , Sífilis/epidemiologia , Estados Unidos , Washington/epidemiologiaRESUMO
BACKGROUND: Appropriate correction of hyponatremia can reduce complications such as osmotic demyelination syndrome (ODS). OBJECTIVE: To evaluate rates of serum sodium correction in hyponatremic hospitalized patients and identify factors associated with higher rates of overcorrection. METHODS: This is an institutional review board-approved single-center, retrospective chart review of patients ≥18 years of age with at least 1 serum sodium <130 mEq/L during hospitalization. The primary end point was percentage of patients appropriately corrected for hyponatremia. Appropriate correction was defined as a sodium change ≤12 mEq/L over 24 hours and 18 mEq/L over 48 hours, and overcorrection was defined as an increase in serum sodium exceeding these cutoffs. Secondary end points included incidence of ODS, poor neurological outcome, intensive care unit (ICU) and hospital lengths of stay (LOSs), and in-hospital mortality. RESULTS: Of 234 patients evaluated, 100 were included. Mean age was 72 ± 16 years, and 47% were male. Overcorrection occurred in 14 patients. There was no incidence of ODS. Rates of poor neurological outcome (P = 0.77), ICU (P = 0.09) and hospital LOS (P = 0.13), and in-hospital mortality (P = 0.20) were similar between appropriately corrected and overcorrected patients. Using a logistic regression analysis, severe hyponatremia (serum sodium < 120 mEq/L; P = 0.0122) and history of alcohol use disorder (P < 0.001) were risk factors found to be associated with overcorrection. CONCLUSION AND RELEVANCE: Overcorrection of hyponatremia occurred in 14% of patients in this study. To minimize this risk, further caution should be taken when managing patients presenting with identified risk factors.
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Hiponatremia , Idoso , Idoso de 80 Anos ou mais , Mortalidade Hospitalar , Humanos , Hiponatremia/epidemiologia , Hiponatremia/terapia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SódioRESUMO
BACKGROUND: Rice bran extracts (RB) derived from Oryza sativa are part of cultural skin and hair care practices in Asia. Given the knowledge gap regarding clinical efficacy, marketplace availability, and safety, the growing popularity of nutraceuticals calls for better clinician awareness and scientific understanding of their applications and limitations. OBJECTIVE: To review available scientific evidence regarding therapeutic efficacy, safety, and consumer availability of RB on hair health. MATERIALS AND METHODS: A primary literature search was conducted using PubMed to identify articles on RB and hair growth in May 2021. A limited market analysis of rice-derivative-containing hair products was also conducted on Amazon.com. RESULTS: 10 studies were analyzed: six regarding the efficacy of RB for hair growth, and four analyzing the safety profile of RB. Topically applied RB increases expression of growth factors and molecular signals which promote cell proliferation in the anagen phase including β-catenin, while inhibiting enzymes responsible for propagating anagen to catagen/telogen transition including TGFβ and Type I 5α-reductase. RB is non-genotoxic, non-cytotoxic, and appropriate for human use in cosmetics. The Amazon.com search yielded 119 rice-containing hair products, reflecting their over-the-counter popularity. CONCLUSIONS: Current literature is promising for RB promoting hair growth given its ability to increase expression of growth factors and molecular signals associated with maintaining anagen phase, decreasing inflammation, inhibiting 5α-reductase, and promoting melanogenesis. J Drugs Dermatol. 2022;21(2):177-185. doi:10.36849/JDD.6345.
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Cosméticos , Oryza , Proliferação de Células , Cabelo , Folículo Piloso , HumanosRESUMO
BACKGROUND: Approximately 30% to 40% of alopecia areata (AA) patients have atopic dermatitis. Studies suggest that antihistamines and dupilumab may be effective treatments; however, the potential benefit of these therapies as either adjunct or monotherapy has yet to be elucidated. OBJECTIVE: To evaluate the use of antihistamines and dupilumab in the treatment of AA. METHODS: A literature search was conducted in August 2021 according to PRISMA guidelines. Inclusion criteria were articles describing the use of antihistamines or dupilumab for AA or those discussing AA development as an adverse event of these therapies. RESULTS: Forty-two articles with 395 patients describe the use of antihistamines or dupilumab in AA. The most common antihistamine regimens were oxatomide 30 mg twice a day, fexofenadine 60 or 120 mg/day, and ebastine 10 mg/day; and the majority of cases reported significant hair regrowth, decreased pruritus, and erythema. Studies on the use of dupilumab for AA demonstrated remarkable hair growth in some patients (n=23), no change in others (n=3), and no new hair loss in a patient with resolved alopecia universalis (AU) (n=1). In contrast, dupilumab therapy for AD has been implicated as a cause of AA (n=21), drug-induced alopecia (n=2), and AA-like psoriasis (n=1). CONCLUSION: Current literature is promising for the use of antihistamines as adjunct treatments for AA, while monotherapy needs to be further explored. The role of dupilumab in AA treatment and/or development also requires further research.J Drugs Dermatol. 2022;21(10):1070-1083. doi:10.36849/JDD.6553.
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Alopecia em Áreas , Alopecia/tratamento farmacológico , Alopecia em Áreas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , HumanosRESUMO
Near-infrared (NIR) dye-peptide conjugates are widely used for tissue-targeted molecular fluorescence imaging of pathophysiologic conditions. However, the significant contribution of both dye and peptide to the net mass of these bioconjugates implies that small changes in either component could alter their photophysical and biological properties. Here, we synthesized and conjugated a type I collagen targeted peptide, RRANAALKAGELYKCILY, to either a hydrophobic (LS1000) or hydrophilic (LS1006) NIR fluorescent dye. Spectroscopic analysis revealed rapid self-assembly of both LS1000 and LS1006 in aqueous media to form stable dimeric/H aggregates, regardless of the free dye's solubility in water. We discovered that replacing the cysteine residue in LS1000 and LS1006 with acetamidomethyl cysteine to afford LS1001 and LS1107, respectively, disrupted the peptide's self-assembly and activated the previously quenched dye's fluorescence in aqueous conditions. These results highlight the dominant role of the octadecapeptide, but not the dye molecules, in controlling the photophysical properties of these conjugates by likely sequestering or extruding the hydrophobic or hydrophilic dyes, respectively. Application of the compounds for imaging collagen-rich tissue in an animal model of inflammatory arthritis showed enhanced uptake of all four conjugates, which retained high collagen-binding affinity, in inflamed joints. Moreover, LS1001 and LS1107 improved the arthritic joint-to-background contrast, suggesting that reduced aggregation enhanced the clearance of these compounds from non-target tissues. Our results highlight a peptide-driven strategy to alter the aggregation states of molecular probes in aqueous solutions, irrespective of the water-solubilizing properties of the dye molecules. The interplay between the monomeric and aggregated forms of the conjugates using simple thiol-modifiers lends the peptide-driven approach to diverse applications, including the effective imaging of inflammatory arthritis joints.
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BACKGROUND AND OBJECTIVES: To demonstrate that high color fidelity light-emitting diode (LED) sources are preferred by dermatologists for the evaluation of patients during standard-of-care, outpatient visits when compared to low color fidelity LED sources similar to fluorescent lighting. STUDY DESIGN/MATERIALS AND METHODS: Three different LED sources were installed in exam rooms at a single, academic, medical institution (low color fidelity [82 color rendering index (CRI)] similar to fluorescent lighting, and high color fidelity [97 CRI and 96+red CRI]). A cross-sectional survey study was conducted in three parts. Naturalness (i.e. ability to reproduce natural, daylight conditions), effectiveness, color contrast, comfort, and overall performance of each LED source were rated on a 5-point scale from 0 to 4 with 0 being the worse, and 4 being the best. The first part included a survey of board-certified dermatologists (n = 3) assessing their visual experience while clinically evaluating a subset of patients during standard-of-care outpatient visits. The second survey was completed by dermatologic medical providers (n = 55) at three separate monthly departmental Grand Rounds sessions in which standardized patients were evaluated with the LED sources. Lastly, patients (n = 75) finished a survey assessing the comfort level of the LED sources. RESULTS: In the first part of the study, all dermatologists significantly preferred the high color fidelity sources over low color fidelity sources based on all five evaluation criteria, with two preferring the 97 CRI LED source overall, while the third dermatologist favored 96+red CRI. Assessments provided by the 55 participants at Grand Rounds demonstrated that the 97 CRI was most "liked." Patients also preferred the high color fidelity LED source, reporting the 96+red CRI source was the "most comfortable." CONCLUSION: Dermatologists, dermatologists-in-training and mid-level providers significantly prefer high color fidelity LED sources for outpatient evaluation of dermatologist patients in enclosed spaces, rating them the more natural, effective, comfortable, and providing superior color contrast than low color sources. Patients also favor high color fidelity LED sources as being the most comfortable in the clinic room. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
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Iluminação , Pacientes Ambulatoriais , Estudos Transversais , HumanosRESUMO
BACKGROUND: "Thread lifting" has quickly gained popularity as a minimally invasive treatment for facial rejuvenation. However, the effectiveness is questionable, and the safety and adverse effects are often not discussed. OBJECTIVE: To identify and discuss the adverse effects associated with various types of threads. MATERIALS AND METHODS: Studies describing the use of thread lifts were identified using a PubMed search. Inclusion criteria included studies in which barbed and nonbarbed threads were used for the face and neck. RESULTS: Fifty-nine articles consisting of 14,222 patients (14,134 barbed, 81 nonbarbed, and 7 combined cases) were included. The most common side effects overall were facial asymmetry (n = 6,143), edema/tumefaction (n = 453), and ecchymosis (n = 407). Serious adverse effects were rare and consisted of paresthesias, alopecia, and injuries to vessels/glands. Most adverse effects were transient and self-resolving, with the exception of contour irregularities, injuries to vessels/glands, infections, and inflammatory reactions. CONCLUSION: Most side effects associated with threads were self-resolving, whereas more serious cases subsided with treatment. Future studies are critical to further determine whether thread lifting provides long-lasting, safe, and satisfying results.
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Face , Pescoço , Ritidoplastia/métodos , Medicina Baseada em Evidências , Humanos , Complicações Pós-Operatórias/etiologia , Ritidoplastia/efeitos adversos , SuturasRESUMO
Alopecia areata (AA) is an autoimmune hair loss condition that is difficult to treat and frequently disruptive to the psychosocial well-being of patients. Platelet-rich plasma (PRP) is an innovative therapy that provides concentrated GFs that impart anti-inflammatory effects. Optical coherence tomography (OCT) is a noninvasive imaging modality with the potential for providing quantitative monitoring of AA response to PRP. Our objective is to share our experience using OCT to monitor the therapeutic progress of patients with AA treated with PRP. Two patients with patchy AA and one with alopecia universalis were treated with PRP three times at 6-week intervals as part of a larger clinical trial. Patients were followed from baseline to week 24 with OCT imaging. OCT demonstrates an increase in hair density associated with improvement in inflammation at week 24. Conversely, the patient with alopecia universalis did not experience any significant change in follicular activity. This case series exemplifies the potential of PRP in inflammatory regulation as well as hair regrowth in patchy AA, whereas there is no notable advantage in alopecia universalis. Our findings add evidence on the possible value of OCT in quantitatively assessing hair growth progress throughout a treatment course.
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Alopecia em Áreas/diagnóstico por imagem , Alopecia em Áreas/terapia , Fatores Biológicos/uso terapêutico , Plasma Rico em Plaquetas , Couro Cabeludo/diagnóstico por imagem , Tomografia de Coerência Óptica , Idoso , Alopecia/diagnóstico por imagem , Alopecia/terapia , Feminino , Cabelo/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE: To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS: A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS: A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS: This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION: The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
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Vacinas Anticâncer/uso terapêutico , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/uso terapêutico , Neoplasias/tratamento farmacológico , Verrugas/tratamento farmacológico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Feminino , Humanos , Infecções por Papillomavirus/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias Vulvares/tratamento farmacológico , Displasia do Colo do Útero/tratamento farmacológicoRESUMO
BACKGROUND: Elderly transplant recipients experience lower rates of acute rejection with higher rates of infectious complications compared to their younger counterparts. While less intensive immunosuppression may be preferable, there are no recommendations for depleting versus non-depleting induction strategies. We sought to compare infectious complications between anti-thymocyte globulin (ATG) and basiliximab (IL2RA) induction in elderly kidney transplant recipients (KTRs). METHODS: We reviewed 146 KTRs ≥65 years receiving ATG or IL2RA induction. Per institution protocol, ATG was administered to patients with the following characteristics, irrespective of age: African American (AA), PRA ≥20%, and/or re-transplantation. Infectious complications (bacterial, viral, and invasive fungal) at 1 year were compared. RESULTS: There were significantly more AA, deceased donors, and sensitized KTRs in the ATG group, reflecting criteria for induction agent. ATG KTRs experienced higher rates of overall infectious complications (77% vs 56%, P = .01), driven by increased bacterial (54% vs 39%, P = .08) and viral infections (51% vs 35%, P = .05). Urinary tract infections (UTIs) and CMV in particular occurred at high rates among ATG patients (46% and 32%, respectively). In multivariate analysis, the only independent risk factor associated with increased risk for infection was induction with ATG (adjusted HR 1.71 [95% CI 1.04-2.83], P = .04). Overall rates of immunologic outcomes were low. CONCLUSION: Elderly KTRs receiving ATG are at an increased risk for infectious complications, largely attributed to high rates of UTIs and CMV. Additional strategies aimed at mitigating these complications in elderly patients requiring ATG may be beneficial.
Assuntos
Soro Antilinfocitário/efeitos adversos , Basiliximab/efeitos adversos , Doenças Transmissíveis/etiologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Transplantados/estatística & dados numéricos , Fatores Etários , Idoso , Doenças Transmissíveis/virologia , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Factor D (FD) is an essential component of the complement alternative pathway (AP). It is an attractive pharmaceutical target because it is an AP-specific protease circulating in blood. Most components of the complement activation pathways are produced by the liver, but FD is highly expressed by adipose tissue. Two critical questions are: 1) to what degree does adipose tissue contribute to circulating FD levels and 2) what quantity of FD is sufficient to maintain a functional AP? To address these issues, we studied a novel mouse strain with complete lipodystrophy (LD), the fld mouse with partial LD, an FD-deficient mouse, and samples from lipodystrophic patients. FD was undetectable in the serum of LD mice, which also showed minimal AP function. Reconstitution with purified FD, serum mixing experiments, and studies of partial LD mice all demonstrated that a low level of serum FD is sufficient for normal AP activity in the mouse system. This conclusion was further supported by experiments in which wild-type adipose precursors were transplanted into LD mice. Our results indicate that almost all FD in mouse serum is derived from adipose tissue. In contrast, FD levels were reduced â¼50% in the sera of patients with congenital generalized LD. Our studies further demonstrate that a relatively small amount of serum FD is sufficient to facilitate significant time-dependent AP activity in humans and in mice. Furthermore, this observation highlights the potential importance of obtaining nearly complete inhibition of FD in treating alternative complement activation in various autoimmune and inflammatory human diseases.