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Background: Complicated parapneumonic effusions and empyemas are common presentations that carry significant morbidity and mortality. Standard therapy includes antibiotics and chest tube placement. Due to the nature of the fluid, it is often difficult to drain completely using a chest tube. As outlined in multiple studies, intrapleural tissue plasminogen activator (tPA) and dornase alfa (DNase) are effective at helping clear these effusions and the avoidance of surgery. Despite research to better understand the effectiveness of the treatment and possible side effects, there continues to be a lack of data on potential systemic effects. Methods: This prospective observational pilot study was conducted from May 2021 until June 2022. Basic demographics, complications, prothrombin time, activated partial thromboplastin time, D-Dimer, fibrinogen, and thromboelastography scans were measured both before and after infusion of chest tube tPA and DNase to assess for differences in coagulation using Signed Rank tests. Results: A total of 17 patients were enrolled in the study. Two patients were excluded due to protocol deviations. The median change score for lysis of clot at 30 minutes (Ly30), our primary outcome of interest, was 0 (P=0.88). There were no significant changes in other coagulation measures when comparing pre and post treatment. One patient (5.9%) had intrapleural bleeding associated with therapy. Three patients (17.6%) underwent surgical intervention to further treat their complicated pleural effusion. Conclusions: This is the first study to evaluate measurable changes in systemic coagulation after intrapleural tPA and DNase. Our data demonstrates no significant difference in coagulation after intrapleural tPA and DNase infusion, suggesting that there may not be clinically significant absorption.
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OBJECTIVE: To explore and analyse the perspective of patients undergoing and recovering from nasopharyngeal carcinoma (NPC) therapy. METHODS: Thirty-three NPC patients at different stages of treatment were enroled. Seven were actively undergoing treatment, 13 were immediately post-treatment, and 13 were long-term. Patients were interviewed using a structured questionnaire based on a review of the literature that covered different phases of their treatment journey. The interview was recorded and transcribed for qualitative data analysis using a thematic inductive-deductive approach. RESULTS: Three main domains embracing aspects of NPC patients' experiences were identified; side effects, psychosocial well-being, and the role and support of healthcare workers. Side effects were experienced orally, locally, and systemically. Oral side effects (oral mucositis, xerostomia, altered taste, dysphagia) were the most significant challenge experienced by NPC patients. Locally, skin injury (desquamation, fibrosis, darkening of the skin, erythema, pruritus, and swelling around the neck region) and hair loss, resolved after cessation of therapy. Systemic side effects from the treatment were related to general weakness, weight loss and nausea. The psychosocial well-being of NPC patients was influenced by a range of issues including support (healthcare workers and family), pain management, functional limitations, nutritional needs, perceived level of information, emotion, and finances. CONCLUSION: NPC patients were significantly impacted based on the diagnosis, treatment and recovery phase affecting them locally, systemically, and psychologically. The role of family and healthcare staff was also influential in the overall treatment experience, and they have key roles to play in facilitating patients along their treatment journey. CLINICAL SIGNIFICANCE: Oral and general side effects from NPC treatment have significant impact on patients physical and emotional well-being. It is important for healthcare providers to have insights of these so as to understand and support patients during their treatment journey and recovery and be able to empathetically facilitate their clinical management.
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Neoplasias Nasofaríngeas , Estomatitis , Xerostomía , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Xerostomía/etiologíaRESUMEN
Systemic administration of agents that inhibit vascular endothelial growth factor (VEGF) and therefore vascular proliferation is often used to treat various cancers. However, these agents are associated with a number of side effects, including proteinuria and renal injury. Intravitreal injection of anti-VEGF agents has become the cornerstone of macular disease treatment. Since these agents cross the blood-retina barrier and enter the circulation, systemic side effects have been reported. We report the novel case of a 57-year-old patient who presented with macular oedema secondary to central retinal vein occlusion, underwent three monthly loading-dose injections with the anti-VEGF agent ranibizumab, and 2 weeks after the second injection presented with biopsy-verified membranoproliferative glomerulonephritis. Twelve weeks after presenting with renal failure and 10 weeks after his last anti-VEGF injection, the patient demonstrated spontaneous recovery of his kidney function. The patient had a history that promoted renal fragility, including hypertension, liver transplantation 6 years earlier for alcohol-related cirrhosis and new-onset diabetes mellitus after transplant. Our literature review and case suggest that although adverse renal events after intravitreal anti-VEGF injections are very rare, ophthalmologists and nephrologists should be aware of this risk.
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Inhibidores de la Angiogénesis , Glomerulonefritis Membranoproliferativa , Humanos , Persona de Mediana Edad , Inhibidores de la Angiogénesis/efectos adversos , Bevacizumab , Factor A de Crecimiento Endotelial Vascular , Inhibidores de Crecimiento , Glomerulonefritis Membranoproliferativa/inducido químicamente , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Inyecciones Intravítreas , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de FusiónRESUMEN
Glaucoma is a progressive loss of retinal ganglion cells leading to visual field loss. Lowering intraocular pressure is currently the only modifiable risk factor to slow glaucoma progression. Intraocular pressure-lowering options include topical and systemic medications, lasers, and surgical procedures. Glaucoma eye drops play a major role in treating this blinding disease. Similar to all medications, the glaucoma medications have their own adverse effects. The majority of glaucoma medications work by stimulating or inhibiting adrenergic, cholinergic, and prostaglandin receptors, which are distributed all over the body. Therefore, the glaucoma medications can affect organs other than the eye. This review will discuss the systemic adverse effects of carbonic anhydrase inhibitors, sympathomimetics, para-sympathomimetics, beta blockers, prostaglandin analogs, hyperosmotic agents, and novel glaucoma medications with a stress on pregnant patients, breastfeeding mothers, and paediatric patients.
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Glaucoma , Antagonistas Adrenérgicos beta/efectos adversos , Inhibidores de Anhidrasa Carbónica/efectos adversos , Niño , Glaucoma/inducido químicamente , Glaucoma/tratamiento farmacológico , Humanos , Presión Intraocular , Soluciones Oftálmicas/uso terapéuticoRESUMEN
Since introduced in 1961, intralesional (IL) agent has become an essential part of the dermatological practice. The term IL referred to the direct delivery of agent percutaneously into skin lesions. This therapeutic approach is relatively safe, easy to perform and applicable for a broad range of dermatological conditions. On the other hand, immediate side effects, including pain during administration, bleeding, high risk of infection and allergic reaction, and subsequent side effects involving skin changes such as atrophy, telangiectasia, pigmentary changes, and striae are usually associated with this modality. This review paper highlights the pros and cons of IL agents in modern dermatology practice.
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BACKGROUND: The optimal management of patients with endophthalmitis is challenging and includes both intravitreal and, in some cases, systemic antimicrobials. Systemic antimicrobials may be administered either intravenously or orally. In this article we review systemic antimicrobial options currently available for the treatment of types of endophthalmitis and the role of systemic antimicrobials (antibiotics and antifungals) in these treatments. REVIEW: While systemic antimicrobials are not universally utilized in the management of endophthalmitis, they may be helpful in some circumstances. The blood-retinal barrier affects the penetration of systemic medications into the posterior segment of the eye differently; for example, moxifloxacin and imipenem cross the blood-retinal barrier relatively easily while vancomycin and amikacin do not. However, inflammation, including endophthalmitis, may disrupt the blood-retinal barrier, enhancing the penetration of systemic agents into the eye. CONCLUSION: Systemic antimicrobials may be particularly beneficial in patients with certain types of endophthalmitis; as such, they are standard treatment in the management of endogenous endophthalmitis (fungal and bacterial) and also widely used for prophylaxis and treatment of open-globe injuries. Although systemic antimicrobials are used in some patients with acute-onset postoperative endophthalmitis following cataract surgery, the literature generally does not support this practice. It is noted that there are currently no randomized clinical trials demonstrating a benefit of systemic antibiotics for any category of endophthalmitis.
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Despite advances in photodynamic therapy (PDT) for treating superficial tumor, the prospect of this monotherapy remains challenges in the context of systemic phototoxicity and poor efficacy. In this work, a physiologically self-degradable microneedle (MN)-assisted platform is developed for combining PDT and immunotherapy via controlled co-delivery of photosensitizer (PS) and checkpoint inhibitor anti-CTLA4 antibody (aCTLA4), which generates synergistic reinforcement outcome while reducing side effects. MN is composed of biocompatible hyaluronic acid integrated with the pH-sensitive dextran nanoparticles, which is fabricated to simultaneously encapsulate hydrophobic (Zinc Phthalocyanine) and hydrophilic agents (aCTLA4) via a double emulsion method. This co-loading carrier can aggregate effectively around topical tumor by microneedle-assisted transdermal delivery. In vivo studies using 4T1 mouse models, PDT firstly exerts its effect to killing tumor and triggers the immune responses, subsequently, facilitating the immunotherapy with immune checkpoint inhibitor (aCTLA4). The possible mechanism and systemic effects of the combined therapy are investigated, which demonstrate that this co-administration platform can be a promising tool for focal cancer treatment.
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Nanopartículas , Fotoquimioterapia , Animales , Línea Celular Tumoral , Inmunoterapia , Ratones , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
BACKGROUND: Systemic corticosteroids are often used to treat atopic dermatitis (AD). However, few studies have assessed the safety and efficacy of systemic corticosteroids in AD. OBJECTIVE: To systematically review the literature on efficacy and safety of systemic corticosteroid use (oral, intramuscular, and intravenous) in AD. METHODS: PubMed, Embase, Medline, Scopus, Web of Science, and Cochrane Library were searched. We included systematic reviews, guidelines, and treatment reviews of systemic corticosteroid use among patients of all ages with a diagnosis of AD (52 reviews and 12 studies). RESULTS: There was general consensus in the literature to limit the use of systemic steroids to short courses as a bridge to steroid-sparing therapies. Systemic side effects include growth suppression in children, osteoporosis, osteonecrosis, adrenal insufficiency, Cushing syndrome, hypertension, glucose intolerance, diabetes, gastritis, gastroesophageal reflux, peptic ulcer disease, weight gain, emotional lability, behavioral changes, opportunistic infections, cataracts, glaucoma, myopathy, myalgia, dysaesthesia, pseudotumor cerebri, hyperlipidemia, malignancy, thrombosis, skin atrophy, sleep disturbance, and rebound flaring. LIMITATIONS: Baseline clinical severity, corticosteroid delivery and dose, and treatment response were reported incompletely and heterogeneously across studies. CONCLUSIONS: Evidence is not strong enough to determine optimal delivery or duration of systemic corticosteroids in AD.
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Corticoesteroides/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Corticoesteroides/efectos adversos , Humanos , Resultado del TratamientoRESUMEN
OnabotulinumtoxinA intradetrusor injections are considered a highly effective localized therapy for refractory detrusor overactivity. However, despite evidence for distant systemic effects of onabotulinumtoxinA, little is known on potential systemic side effects following intradetrusor injections. Given that onabotulinumtoxinA is a highly potent toxin this is an important safety issue specifically with regard to repeat injections and parallel treatments with botulinum toxin. Hence, it was the purpose of this prospective study to investigate, using heart rate variability (HRV) analysis, whether onabotulinumtoxinA causes systemic effects on cardiac function following intradetrusor injections. Patients with neurogenic detrusor overactivity (NDO) and age-matched healthy controls were recruited. Concomitant medication and diseases affecting the cardio-vascular system were exclusion criteria. A 3-channel resting electrocardiogram (ECG) was recorded in supine position for 15min during four consecutive visits: 1) 2weeks prior onabotulinumtoxinA intradetrusor injections, 2) 10min prior injections, 3) 30min after injections, and 4) 6weeks after injections. NDO patients received intradetrusor injections (300units Botox®) between visits 2 and 3. The control group had no intervention. Short-term (5min) HRV analysis included assessment of frequency and time domain parameters. Statistical analysis was performed using ANOVA with repeated measures and the t-test. Due to multiple comparisons, α was corrected to 0.0125 (Bonferroni method). Twelve healthy volunteers (5â, 7â; 46±12years old) and 12 NDO patients (5â, 7â; 46±13years old) completed all measurements. Comparing both groups, resting heart rate was significantly higher in the patients group at visit 4 only. No further significant differences in time and frequency domain parameters were discovered. Within the NDO group, standard deviation of the normal to normal intervals (SDNN) in the ECG demonstrated a significant decrease (1.70 to 1.53ms, p=0.003) from visit 3 to 4, whereas the total power (TP) significantly increased (3.05 to 3.29ms2, p=0.009) from visit 2 to 3. This increase subsided until visit 4. STUDY LIMITATIONS: single treatment investigation under resting conditions only. In conclusion, onabotulinumtoxinA intradetrusor injections do not seem to affect resting state cardiac function. Short-term changes such as total power might rather result from natural cardio-vascular responses to the procedure itself (e.g. discomfort, stress). Further detailed investigations also under physical stress and repeated injections are necessary to fully exclude systemic cardiac side effects of onabotulinumtoxinA intradetrusor injections.
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Inhibidores de la Liberación de Acetilcolina/administración & dosificación , Toxinas Botulínicas Tipo A/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Neurogénica/fisiopatología , Inhibidores de la Liberación de Acetilcolina/farmacología , Adulto , Análisis de Varianza , Toxinas Botulínicas Tipo A/farmacología , Estudios de Casos y Controles , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Escala Visual AnalógicaRESUMEN
OBJECTIVES: The object of the study is to experimentally investigate the possible systemic side effects of Oxymetazoline including its nasal spray which has been in use for a long time both by the physicians and patients. There is no study in the literature to address the damages of oxymetazoline on the end organ. MATERIALS AND METHODS: The study conducted on 2 groups of rat. Group 1 (n = 8): Control; and Group 2 (n = 8): Oxymetazoline. During 4 week, the control group was applied with 2 drops of saline water on each nasal cavity 3 times a day and the other group was applied with 2 drops of oxymetazoline HCl 3 times a day. At the end of experiment, samples from mandible, parotid and tails of the rats were taken in 10% formalin for histopathological investigations. RESULTS: In histopathological experiments, when compared with the control group, the oxymetazoline group showed significant increase in many of the histopathological parameters (ischemic changes: P = 0.0001; congestion: P = 0.0006; arterial thrombosis: P = Ns; PNL accumulations: P = 0.001; necrosis: P = 0.0001; and ulceration: P = 0.014). The results of histopathologic tests on the samples taken from mandible and parotid gland, in comparison with the control group, showed no significant increase (focal inflammation: P = Ns; and lymphocyte aggregation: P = Ns). CONCLUSION: Due to the damage that the long-term use of nasal spray including oxymetazoline, it may cause injury on the end organ, which we revealed in our histopathological experiments. We believe that it's essential for the physicians to provide information on the side effects of the medicine to their patients who use for a long term.
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INTRODUCTION: The frequent use of inhaled corticosteroids (ICSs), especially at higher doses, has been accompanied by concern about both systemic and local side effects. Patients suffering from chronic obstructive pulmonary disease (COPD) are more at risk from side effects, likely because of the use of higher doses of ICS in COPD to overcome corticosteroid unresponsiveness. AREAS COVERED: There is considerable concern about increased incidence of pneumonia, osteoporosis and hyperglycemia in diabetic patients and cataracts. The local side effects of ICSs, such as hoarseness and pharyngeal discomfort, oral and oropharyngeal candidiasis, cough during inhalation, and a sensation of thirst, are not usually serious but are of clinical importance because they may lead to patients discontinuing therapy. EXPERT OPINION: The possibility that ICSs induce adverse side effects should not lead us to avoid their use in patients in whom clinical evidence suggests that they may be helpful. However, clinicians should balance the potential benefits of ICSs in COPD against their potential side effects and always consider using the lowest possible dose to achieve the best possible management.
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Glucocorticoides/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Relación Dosis-Respuesta a Droga , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Humanos , Resultado del TratamientoRESUMEN
The treatment of neovascular age-related macular degeneration (AMD) and other pathologic ocular conditions that overexpress the vascular endothelial growth factor (VEGF) has been revolutionized in the last decade by the introduction of intravitreal agents that target the VEGF pathway. Since treatment trials are designed primarily to assess the prevention of vision loss caused by ocular conditions, they are inadequate for detecting rare, but potentially serious, systemic side effects. The aim of this article is to present what the ophthalmologist needs to know about systemic complications from anti-VEGF therapy and review the likelihood that these side effects occur in the context of small, but often-repeated, intravitreal doses of these potent biological medications. Preferred practice patterns need to be developed that weigh the ability of these medications to mitigate potentially blinding conditions, while at the same time minimizing the risk of adverse outcomes in specific patient populations that possess multiple and often interrelated medical comorbidities.
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Inhibidores de la Angiogénesis/efectos adversos , Inyecciones Intravítreas/efectos adversos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/administración & dosificación , Humanos , Degeneración Macular/tratamiento farmacológico , Medicina , Oftalmología , Pautas de la Práctica en Medicina/normasRESUMEN
Molecular docking studies were performed on 18 17ß-carboxamide steroids in order to select compounds with potential local anti-inflammatory activity. These derivatives are amides of cortienic acids (obtained from hydrocortisone, prednisolone, and methylprednisolone) with methyl or ethyl esters of six amino acids. Interactions with the glucocorticoid receptor (GR), binding energies and ligand efficiency values of these compounds were compared with dexamethasone and cortienic acid obtained from prednisolone (inactive metabolite). On the basis of molecular docking studies, seven compounds were selected and their binding affinities for the GR were predicted by use of the exponential model created in this study. Subsequently, selected compounds were synthesized in good yields by use of modified N,N'-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) coupling procedure. Finally, the local anti-inflammatory activity of the synthesized compounds was examined by use of the croton oil-induced ear edema test. In vivo evaluation of systemic side effects as well as in silico prediction of metabolism were performed on the derivative with the best local anti-inflammatory activity. The combination of molecular docking studies and the exponential model for the GR binding affinity prediction could be used as an in silico tool for the rational design of novel 17ß-carboxamide steroids with potentially better biological profile than dexamethasone.