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Pyogenic spondylodiscitis presents significant diagnostic and therapeutic challenges. In Germany, a comprehensive understanding of its epidemiology and inpatient management outcomes is limited, hindering the optimisation of therapeutic strategies. This study aimed to characterise the evolving epidemiological trends of pyogenic spondylodiscitis in Germany, and concurrently evaluate inpatient management strategies and outcomes. We performed a retrospective population-based study of spondylodiscitis cases in Germany from 2005 to 2021, utilising data from the German Federal Statistical Office database. The parameters assessed were incidence trends, demographic characteristics, inpatient management strategies, and inpatient mortality. The study found a significant rise in the population-adjusted incidence of spondylodiscitis in Germany from 2005 to 2021, increasing by 104% from 5.4 to 11.0 cases per 100,000 individuals (p < 0.001). The highest number of diagnoses was recorded in 2019. Age group-adjusted data revealed the largest relative changes in the "90 + " age group, followed by the "80-89" and "70-79" age groups. These increases were not solely attributable to population changes but were also confirmed after calculating the age-group-adjusted incidence rates. Additionally, our statistical analysis demonstrated that both age and year significantly influenced the incidence of spondylodiscitis. Over the same period, inpatient mortality also surged significantly by 347% (p < 0.001), with the highest increase recorded in the 90 + age group, observing a 2450% rise (p < 0.001). The mean length of inpatient stay decreased by 15% (p < 0.05). Concurrently, there was a significant increase in surgical interventions using spinal stabilisation procedures (p < 0.001), which might suggest a shift in the treatment paradigm for spondylodiscitis. The results underscore a concerning rise in spondylodiscitis incidence and mortality in Germany, particularly affecting the ageing population. A notable shift towards surgical intervention was observed. The data highlights the urgent necessity for high-level evidence studies comparing surgical versus conservative treatment, thereby guiding optimised therapeutic strategies.
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Discite , Humanos , Discite/epidemiologia , Discite/terapia , Discite/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento , Coluna Vertebral , Alemanha/epidemiologiaRESUMO
Spondylodiscitis is the commonest spine infection, and pyogenic spondylodiscitis is the most common subtype. Whilst antibiotic therapy is the mainstay of treatment, some advocate that early surgery can improve mortality, relapse rates, and length of stay. Given that the condition carries a high mortality rate of up to 20%, the most effective treatment must be identified. We aimed to compare the mortality, relapse rate, and length of hospital stay of conservative versus early surgical treatment of pyogenic spondylodiscitis. All major databases were searched for original studies, which were evaluated using a qualitative synthesis, meta-analyses, influence, and regression analyses. The meta-analysis, with an overall pooled sample size of 10,954 patients from 21 studies, found that the pooled mortality among the early surgery patient subgroup was 8% versus 13% for patients treated conservatively. The mean proportion of relapse/failure among the early surgery subgroup was 15% versus 21% for the conservative treatment subgroup. Further, it concluded that early surgical treatment, when compared to conservative management, is associated with a 40% and 39% risk reduction in relapse/failure rate and mortality rate, respectively, and a 7.75 days per patient reduction in length of hospital stay (p < 0.01). The meta-analysis demonstrated that early surgical intervention consistently significantly outperforms conservative management in relapse/failure and mortality rates, and length of stay, in patients with pyogenic spondylodiscitis.
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Discite , Doenças da Coluna Vertebral , Humanos , Discite/cirurgia , Tratamento Conservador , Bases de Dados Factuais , Intervenção Educacional PrecoceRESUMO
BACKGROUND: Focused ultrasound (FUS) shows promise for enhancing drug delivery to the brain by temporarily opening the blood-brain barrier (BBB), and it is increasingly used in the clinical setting to treat brain tumours. It remains however unclear whether FUS is being introduced in an ethically and methodologically sound manner. The IDEAL-D framework for the introduction of surgical innovations and the SYRCLE and ROBINS-I tools for assessing the risk of bias in animal studies and non-randomized trials, respectively, provide a comprehensive evaluation for this. OBJECTIVES AND METHODS: A comprehensive literature review on FUS in neuro-oncology was conducted. Subsequently, the included studies were evaluated using the IDEAL-D framework, SYRCLE, and ROBINS-I tools. RESULTS: In total, 19 published studies and 12 registered trials were identified. FUS demonstrated successful BBB disruption, increased drug delivery, and improved survival rates. However, the SYRCLE analysis revealed a high risk of bias in animal studies, while the ROBINS-I analysis found that most human studies had a high risk of bias due to a lack of blinding and heterogeneous samples. Of the 15 pre-clinical stage 0 studies, only six had formal ethical approval, and only five followed animal care policies. Both stage 1 studies and stage 1/2a studies failed to provide information on patient data confidentiality. Overall, no animal or human study reached the IDEAL-D stage endpoint. CONCLUSION: FUS holds promise for enhancing drug delivery to the brain, but its development and implementation must adhere to rigorous safety standards using the established ethical and methodological frameworks. The complementary use of IDEAL-D, SYRCLE, and ROBINS-I tools indicates a high risk of bias and ethical limitations in both animal and human studies, highlighting the need for further improvements in study design for a safe implementation of FUS in neuro-oncology.
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Barreira Hematoencefálica , Neoplasias Encefálicas , Animais , Humanos , Encéfalo , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de MedicamentosRESUMO
Background: Spondylodiscitis is a potentially life-threatening infection of the intervertebral disk and adjacent vertebral bodies, with a mortality rate of 2-20%. Given the aging population, the increase in immunosuppression, and intravenous drug use in England, the incidence of spondylodiscitis is postulated to be increasing; however, the exact epidemiological trend in England remains unknown. Objective: The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise the annual activity and longitudinal change of spondylodiscitis in England. Methods: The HES database was interrogated for all cases of spondylodiscitis between 2012 and 2019. Data for the length of stay, waiting time, age-stratified admissions, and 'Finished Consultant Episodes' (FCEs), which correspond to a patient's hospital care under a lead clinician, were analysed. Results: In total, 43135 FCEs for spondylodiscitis were identified between 2012 and 2022, of which 97.1% were adults. Overall admissions for spondylodiscitis have risen from 3 per 100,000 population in 2012/13 to 4.4 per 100,000 population in 2020/21. Similarly, FCEs have increased from 5.8 to 10.3 per 100,000 population, in 2012-2013 and 2020/21 respectively. The highest increase in admissions from 2012 to 2021 was recorded for those aged 70-74 (117% increase) and aged 75-59 (133% increase), among those of working age for those aged 60-64 years (91% increase). Conclusion: Population-adjusted admissions for spondylodiscitis in England have risen by 44% between 2012 and 2021. Healthcare policymakers and providers must acknowledge the increasing burden of spondylodiscitis and make spondylodiscitis a research priority.
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BACKGROUND: Patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) may improve clinically following cerebrospinal fluid (CSF) diversion (shunt) surgery, though the predictors of shunt response remain debated. Currently, radiological features play an important role in the diagnosis of iNPH, but it is not well established which radiological markers most precisely predict shunt responsive iNPH. OBJECTIVE: To conduct a systematic review and meta-analysis to identify radiological predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most predictive radiological features. METHODS: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating radiological predictors of shunt response in iNPH patients. Included studies were assessed using the ROBINS-1 tool, and eligible studies were evaluated using a univariate meta-analysis. RESULTS: Overall, 301 full-text papers were screened, of which 28 studies were included, and 26 different radiological features were identified, 5 of these met the inclusion criteria for the meta-analysis: disproportionately enlarged subarachnoid space (DESH), callosal angle, periventricular white matter changes, cerebral blood flow (CBF), and computerized tomography cisternography. The meta-analysis showed that only callosal angle and periventricular white matter changes significantly differentiated iNPH shunt responders from non-responders, though both markers had a low diagnostic odds ratio (DOR) of 1.88 and 1.01 respectively. None of the other radiological markers differentiated shunt responsive from shunt non-responsive iNPH. CONCLUSION: Callosal angle and periventricular changes are the only diagnostically effective radiological predictors of shunt responsive iNPH patients. However, due to the DORs approximating 1, they are insufficient as sole predictors and are advised to be used only in combination with other diagnostic tests of shunt response. Future research must evaluate the combined use of multiple radiological predictors, as it may yield beneficial additive effects that may allow for more robust radiological shunt response prediction.
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Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Hidrocefalia de Pressão Normal/cirurgia , Imageamento por Ressonância Magnética/métodos , Radiografia , Derivação Ventriculoperitoneal , Derivações do Líquido Cefalorraquidiano/métodosRESUMO
BACKGROUND: Augmented reality (AR) has become a promising tool in neurosurgery. It can minimise the anatomical challenges faced by conventional endoscopic or microscopic transsphenoidal reoperations and can assist in intraoperative guidance, preoperative planning, and surgical training. OBJECTIVES: The aims of this systematic review are to describe, compare, and evaluate the use of AR in endoscopic and microscopic transsphenoidal surgery, incorporating the latest primary research. METHODS: A systematic review was performed to explore and evaluate existing primary evidence for using AR in transsphenoidal surgery. A comprehensive search of MEDLINE and EMBASE was conducted from database inception to 11th August 2021 for primary data on the use of AR in microscopic and endoscopic endonasal skull base surgery. Additional articles were identified through searches on PubMed, Google Scholar, JSTOR, SCOPUS, Web of Science, Engineering Village, IEEE transactions, and HDAS. A synthesis without meta-analysis (SWiM) analysis was employed quantitatively and qualitatively on the impact of AR on landmark identification, intraoperative navigation, accuracy, time, surgeon experience, and patient outcomes. RESULTS: In this systematic review, 17 studies were included in the final analysis. The main findings were that AR provides a convincing improvement to landmark identification, intraoperative navigation, and surgeon experience in transsphenoidal surgery, with a further positive effect on accuracy and time. It did not demonstrate a convincing positive effect on patient outcomes. No studies reported comparative mortalities, morbidities, or cost-benefit indications. CONCLUSION: AR-guided transsphenoidal surgery, both endoscopic and microscopic, is associated with an overall improvement in the areas of intraoperative guidance and surgeon experience as compared with their conventional counterparts. However, literature on this area, particularly comparative data and evidence, is very limited. More studies with similar methodologies and quantitative outcomes are required to perform appropriate meta-analyses and to draw significant conclusions.
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Realidade Aumentada , Neurocirurgia , Cirurgia Assistida por Computador , Endoscopia , Humanos , Procedimentos Neurocirúrgicos/métodos , Cirurgia Assistida por Computador/métodosRESUMO
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH. OBJECTIVE: To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt-responsive iNPH most accurately. METHODS: Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses. RESULTS: The study included 13 studies; seven addressed lumbar CSF levels of amyloid-ß 1-42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-ß 1-42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (- 0.55 SMD, p = 0.04) and Total-Tau (- 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-ß 1-42 (- 0.26 SMD, p = 0.55) or the other included biomarkers. CONCLUSION: This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-ß 1-42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.
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Hidrocefalia de Pressão Normal , Doenças Neurodegenerativas , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Proteínas tau/líquido cefalorraquidianoRESUMO
OBJECTIVES: Extended reality (XR), encompassing both virtual reality (VR) and augmented reality, allows the user to interact with a computer-generated environment based on reality. In essence, the immersive nature of VR and augmented reality technology has been warmly welcomed in all aspects of medicine, gradually becoming increasingly feasible to incorporate into everyday practice. In recent years, XR has become increasingly adopted in thoracic surgery, although the extent of its applications is unclear. Here, we aim to review the current applications of XR in thoracic surgery. METHODS: A systematic database search was conducted of original articles that explored the use of VR and/or augmented reality in thoracic surgery in EMBASE, MEDLINE, Cochrane database and Google Scholar, from inception to December 2020. RESULTS: Our search yielded 1494 citations, of which 21 studies published from 2007 to 2019 were included in this review. Three main areas were identified: (i) the application of XR in thoracic surgery training; (ii) preoperative planning of thoracic procedures; and (iii) intraoperative assistance. Overall, XR could produce progression along the learning curve, enabling trainees to reach acceptable standards before performing in the operating theatre. Preoperatively, through the generation of 3D-renderings of the thoracic cavity and lung anatomy, VR increases procedural accuracy and surgical confidence through familiarization of the patient's anatomy. XR-assisted surgery may have therapeutic use particularly for complex cases, where conventional methods would yield inadequate outcomes due to inferior accuracy. CONCLUSION: XR represents a salient step towards improving thoracic surgical training, as well as enhancing preoperative planning and intraoperative guidance.
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Realidade Aumentada , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Realidade Virtual , Humanos , Salas CirúrgicasRESUMO
BACKGROUND: Positive shunt response (SR) remains the gold standard for diagnosing idiopathic normal pressure hydrocephalus (iNPH). However, multiple pathologies mimic iNPH symptoms, making it difficult to select patients who will respond to shunt surgery. Although presenting features, extended lumbar drainage (ELD), infusion test (IT), intracranial pressure monitoring (ICPM), and tap test (TT) have been used to predict SR, uncertainty remains over which diagnostic test to choose. OBJECTIVE: To conduct a systematic review and meta-analysis to identify clinical predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most effective diagnostic tests. METHODS: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating clinical predictors of SR in iNPH patients. Included studies were assessed using the QUADAS-2 tool, and eligible studies were evaluated using univariate and bivariate meta-analyses. RESULTS: Thirty-five studies were included. Nine studies discussed the diagnostic use of presenting clinical features, 8 studies ELD, 8 studies IT, 11 studies ICPM, and 6 studies TT. A meta-analysis of 21 eligible studies was conducted for TT, ELD, IT, and ICPM. ICPM yielded the highest diagnostic effectiveness, with diagnostic odds ratio (DOR) = 50.9 and area under curve (AUC) = 0.836. ELD yielded DOR = 27.70 and AUC = 0.753, IT had DOR = 5.70 and AUC = 0.729, and TT scored DOR = 3.86 and AUC = 0.711. CONCLUSION: Intraparenchymal ICPM is statistically the most effective diagnostic test, followed by ELD, IT, and lastly TT. Due to the higher accessibility of TT and IT, they are recommended to be used first line, using a timed-up-and-go improvement ≥ 5.6 s or a Rout cut-off range between 13 and 16 mmHg, respectively. Patients who test negative should ideally be followed up with ICPM, using mean ICP wave amplitude [Formula: see text] 4 mmHg, or 1- to 4-day ELD with an MMSE cut-off improvement [Formula: see text] 3. Future research must use standardized methodologies for each diagnostic test and uniform criteria for SR to allow better comparison.
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Hidrocefalia de Pressão Normal , Derivações do Líquido Cefalorraquidiano , Testes Diagnósticos de Rotina , Drenagem , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Monitorização FisiológicaRESUMO
BACKGROUND: Psychological safety is the concept by which individuals feel comfortable expressing themselves in a work environment, without fear of embarrassment or criticism from others. Psychological safety in healthcare is associated with improved patient safety outcomes, enhanced physician engagement and fostering a creative learning environment. Therefore, it is important to establish the key levers which can act as facilitators or barriers to establishing psychological safety. Existing literature on psychological safety in healthcare teams has focused on secondary care, primarily from an individual profession perspective. In light of the increased focus on multidisciplinary work in primary care and the need for team-based studies, given that psychological safety is a team-based construct, this study sought to investigate the facilitators and barriers to psychological safety in primary care multidisciplinary teams. METHODS: A mono-method qualitative research design was chosen for this study. Healthcare professionals from four primary care teams (n = 20) were recruited using snowball sampling. Data collection was through semi-structured interviews. Thematic analysis was used to generate findings. RESULTS: Three meta themes surfaced: shared beliefs, facilitators and barriers to psychological safety. The shared beliefs offered insights into the teams' background functioning, providing important context to the facilitators and barriers of psychological safety specific to each team. Four barriers to psychological safety were identified: hierarchy, perceived lack of knowledge, personality and authoritarian leadership. Eight facilitators surfaced: leader and leader inclusiveness, open culture, vocal personality, support in silos, boundary spanner, chairing meetings, strong interpersonal relationships and small groups. CONCLUSION: This study emphasises that factors influencing psychological safety can be individualistic, team-based or organisational. Although previous literature has largely focused on the role of leaders in promoting psychological safety, safe environments can be created by all team members. Members can facilitate psychological safety in instances where positive leadership behaviours are lacking - for example, strengthening interpersonal relationships, finding support in silos or rotating the chairperson in team meetings. It is anticipated that these findings will encourage practices to reflect on their team dynamics and adopt strategies to ensure every member's voice is heard.
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Pessoal de Saúde , Equipe de Assistência ao Paciente , Humanos , Liderança , Atenção Primária à Saúde , Pesquisa QualitativaRESUMO
Intra-arterial chemotherapy (IAC), also known as superselective ophthalmic artery chemotherapy or chemosurgery, is currently widely accepted as one of the primary treatment modalities for intraocular retinoblastoma worldwide. Following the introduction of the technique in 1998, IAC has evolved over the past decades to be safer and more effective. Accumulated evidence shows that IAC is more effective in providing eye salvage in group D and E retinoblastoma as compared to conventional systemic intravenous chemotherapy (IVC). In contrast to IVC, IAC has the added benefits of reduced overall treatment duration and minimal systemic toxicity. This review provides a comprehensive update on the history, technique, indications, contraindications, and outcome of IAC. We have also identified the strengths, weaknesses, opportunities and threats (SWOT analysis) of the technique in this review.
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Antineoplásicos/administração & dosagem , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Humanos , Injeções Intra-Arteriais , Artéria OftálmicaRESUMO
An effective and environmentally friendly recycling process designed for LiCoO2 cathode powders of spent Li-ion batteries using mixture of mild organic acids, citric acid (CA), tartaric acid (TA) and ascorbic acid (AA), to recover the metals. Almost complete dissolution of Li and nearly 90% dissolution of Co occurred in at 80⯰C for 6â¯h. The reducing agent, ascorbic acid (AA), converts the dissolved Co(III) to Co(II) thereby selective recovery of Co as Co(II)-oxalate is possible. The formation of Co(III)-and Co(II) complex is evident from the UV-Vis spectra of the dissolved solution as a function of dissolution time. Thus, the reductive-complexing dissolution mechanism is proposed here. These mild organic acids are environmentally benign unlike the mineral acids.
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The increasing numbers of people with dementia in the UK, as well as the associated costs have led to an effort to improve dementia services for the benefit of patients, caregivers and the taxpayer. These efforts have frequently emphasised the importance of early diagnosis in dementia care. We sought to test the hypotheses that the mean cognitive score of new referrals to a secondary care memory assessment service increased while mean age decreased over a period of 20 years. We retrospectively analysed the data of 1476 patients. The passage of time was associated with a significant increase in mean cognitive scores, while there was no association between time and age after controlling for other factors. We suggest that memory services need to be designed to meet the needs of less cognitively impaired patients. In practice this means that using simple screening tests is not sufficient in this group of patients.
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Demência/diagnóstico , Intervenção Médica Precoce/tendências , Encaminhamento e Consulta/tendências , Idoso , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Instituições de Assistência Ambulatorial/tendências , Diagnóstico Precoce , Intervenção Médica Precoce/estatística & dados numéricos , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Psicológicos , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Reino UnidoRESUMO
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy used in the management of cardiopulmonary failure. Continuous renal replacement therapy (CRRT) is often added to the treatment for the correction of fluid and electrolyte imbalance in patients with acute kidney injury. Most of the literature on the use of combined ECMO and CRRT has been on pediatric patients. There are limited outcome data on the use of these combined modalities in adult patients. METHODS: This is a retrospective analysis of all the patients above the age of 18 years who underwent combined ECMO and CRRT at a tertiary care medical center during the period January 2007 to January 2012. The primary outcomes measured were mortality at one year and renal recovery or dialysis dependence at one month. RESULTS: A total of 40 patients who were treated concurrently with ECMO and CRRT were identified. The mean age was 47.01 ± 18.29 years. The most common indications for initiation of CRRT were combined fluid overload and electrolyte imbalance. Mortality at one month was (32/40) 80%. Among the 8 survivors (20%), 3 patients required continuation of hemodialysis and 5 patients were independent of dialysis at 30 days. CONCLUSIONS: Mortality of patients treated with combined ECMO and CRRT is high. Initiation of CRRT in these patients is simply an indicator of severity of illness and fatality. Younger age, higher arterial pH, left ventricular dysfunction and use of VA ECMO are associated with improved survival in these patients.
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Oxigenação por Membrana Extracorpórea , Diálise Renal , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Desequilíbrio Hidroeletrolítico/terapiaRESUMO
Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are gaining attention as potentially gastric-sparing NSAIDs. Herein, we report a novel class of '1-(nitrooxy)ethyl ester' group-containing NSAIDS as efficient NO releasing 'true' prodrugs of aspirin and naproxen. While an aspirin prodrug exhibited comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin, a naproxen prodrug exhibited better bioavailability than naproxen. These promising NO-NSAIDs protected experimental rats from gastric damage. We therefore believe that these promising NO-NSAIDs could represent a new class of potentially 'Safe NSAIDs' for the treatment of arthritic pain, inflammation and cardiovascular disorders in the case of NO-aspirin.
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Aspirina/análogos & derivados , Naproxeno/análogos & derivados , Nitratos/química , Pró-Fármacos/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Área Sob a Curva , Aspirina/química , Aspirina/farmacocinética , Aspirina/farmacologia , Aspirina/toxicidade , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Desenho de Fármacos , Estabilidade de Medicamentos , Mucosa Gástrica/efeitos dos fármacos , Meia-Vida , Humanos , Naproxeno/química , Naproxeno/farmacocinética , Naproxeno/farmacologia , Naproxeno/toxicidade , Nitratos/farmacocinética , Nitratos/farmacologia , Nitratos/toxicidade , Óxido Nítrico/metabolismo , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacocinética , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/toxicidade , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Pró-Fármacos/toxicidade , Curva ROC , Ratos , Ratos Sprague-Dawley , Tromboxano B2/metabolismoRESUMO
Membranous nephropathy is a common cause of nephrotic syndrome in adults. It usually occurs secondary to underlying disease processes such as autoimmune disorders, malignancy, infection, and drugs. The presentation of nephrotic syndrome with concomitant precipitous decline in renal function warrants investigation of a coexistent disorder.We report the case of a 30-year-old male who presented with symptoms and signs of hypothyroidism.A diagnosis of Hashimoto's thyroiditis was contemplated based on the presence of high serum levels of antithyroglobulin and antithyroid peroxidase antibodies. Upon initiation of treatment with levothyroxine, patient symptomatology improved; however, the laboratory studies demonstrated continued elevated creatinine, hematuria, and proteinuria, which had not been addressed. Two months following treatment initiation, he had progressive deterioration in renal function and proteinuria. A renal biopsy revealed coexistent necrotizing and crescentic glomerulonephritis and membranous nephropathy.The final diagnosis was necrotizing, crescentic glomerulonephritis with superimposed membranous nephropathy likely secondary to Hashimoto's thyrodiitis.Induction treatment with oral cyclophosphamide and prednisone was started.At the end of 6 months of treatment, there was improvement in renal function and proteinuria and maintenance treatment with azathioprine and low-dose prednisone was initiated. This case highlights the importance of precise and detailed evaluation of patients with autoimmune diseases such as Hashimoto's thyroiditis particularly in the presence of active urine sediment. Proper evaluation and diagnosis of such patients has implications on the prognosis and response to treatment.
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Glomerulonefrite Membranosa/patologia , Doença de Hashimoto/complicações , Adulto , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Glomerulonefrite/etiologia , Glomerulonefrite Membranosa/tratamento farmacológico , Doença de Hashimoto/tratamento farmacológico , Humanos , Masculino , Prednisolona/uso terapêutico , Tiroxina/uso terapêuticoRESUMO
Association of statins with autoimmune disorders is rarely reported. We report a case of an apparently healthy 76-year-old woman who was on long-term statin therapy presenting with severe rhabdomyolysis, autoimmune hepatitis, and positive lupus antibodies. Patient presented with complaints of worsening fatigue, leg cramps, and progressive weakening of lower extremities over 3 weeks. The patient was on simvastatin daily for several years. Clinical examination on admission included muscle tenderness, lower extremity edema, and ascites. Her laboratory values on admission showed elevated creatine kinase and transaminases. Immunologic workup revealed positive ANA, anti-dsDNA and anti-SSA antibodies. F-actin antibody was also positive at high titer. Magnetic resonance imaging of the lower extremities showed findings consistent with myositis. Patient underwent biopsy of the thigh muscles, which showed inflammatory myositis. Liver biopsy was characteristic of autoimmune hepatitis. Patient responded well to immunosuppressive therapy with azathioprine and prednisone. Although statins are generally considered safe, recent data from long-term follow-up on patients who are on statins for long duration suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reaction is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. The role of statins in inducing an endoplasmic reticular stress response with associated upregulation of major histocompatibility complex-1 expression and antigen presentation by muscle fibers has also been reported. Systemic immunosuppressive therapy has proven to be effective in many reported cases.
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Hepatite Autoimune/etiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Sinvastatina/efeitos adversos , Idoso , Autoanticorpos/imunologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Biópsia , Feminino , Hepatite Autoimune/imunologia , Hepatite Autoimune/fisiopatologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/uso terapêutico , Rabdomiólise/etiologia , Rabdomiólise/imunologia , Rabdomiólise/fisiopatologia , Fatores de Risco , Sinvastatina/administração & dosagem , Sinvastatina/uso terapêutico , Fatores de TempoRESUMO
Infective endocarditis is a potentially life threatening condition. It is associated with high mortality and morbidity resulting mostly due to cardiorespiratory failure. Extracorporeal membrane oxygenation is a modality of treatment used to support hypoxic respiratory failure especially in patients who are already on mechanical ventilation. Continuous renal replacement therapy is added mainly for maintaining fluid and electrolyte balance. Here we report a case series of patients diagnosed with infective endocarditis who were treated with combined extracorporeal membrane oxygenation and continuous renal replacement therapy. Three patients in the age group 20-60 years were admitted with clinical features suggestive of infective endocarditis. During the course of hospital stay they developed cardiorespiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation support for refractory hypoxia. It was complicated by heart failure, renal failure and fluid overload which required initiation of continuous renal replacement therapy. All the three patients succumbed in spite of the aggressive treatment. In addition to the role played by each complication, delayed start of continuous renal replacement therapy might have also contributed to the high mortality. Early initiation of continuous renal replacement therapy for management of fluid overload needs to be considered in the management of these critically ill patients.