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1.
Artigo em Inglês | MEDLINE | ID: mdl-38831225

RESUMO

Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively.

2.
Ophthalmol Retina ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38036083

RESUMO

PURPOSE: To investigate predictors of the development and resolution of cystoid macular edema (CME) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective cross sectional study. SUBJECTS: Patients who underwent primary repair of uncomplicated RRD. METHODS: Demographics, ophthalmic history, visual acuity, RRD features, time to development/resolution of CME, OCT characteristics of CME/epiretinal membrane (ERM), type of surgery, and treatments were collected. Logistic regressions were used to identify predictors of CME development and resolution. MAIN OUTCOME MEASURES: Predictors of CME development and resolution. RESULTS: A total of 708 eyes were included, of which 55 (7.8%) developed CME. Factors associated with an increased risk of CME development included total number of retinal detachment surgeries (odds ratio [OR] 1.66 [1.24-2.23], P < 0.001), prior intraocular surgery (OR 4.43 [1.19-16.51], P = 0.03), and presence of ERM after surgery (OR 4.49 [2.30-8.74], P < 0.001). Patients undergoing pars plana vitrectomy (PPV) were more likely to develop CME compared with patients undergoing scleral buckling (SB; OR 3.09 [1.18-8.10], P = 0.02). A longer average time to CME detection was associated with lower CME resolution (OR 0.94 [0.89-0.998], P = 0.04). In patients who developed an ERM postsurgically, those who developed CME after ERM had a lower rate of resolution compared with those who developed CME before ERM (P = 0.03). CONCLUSIONS: Cystoid macular edema may be more likely to develop in patients undergoing PPV than SB, those who underwent more surgeries for RRD repair, those who had prior intraocular surgery, or those who developed an ERM after RRD repair. Resolution of CME may be affected by the time to detection of CME and ERM development. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

3.
Med Oncol ; 40(11): 334, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37855910

RESUMO

Colorectal cancer (CRC) is a complex disease characterized by genetic and epigenetic alterations, playing a crucial role in its development and progression. This review aims to provide insights into the emerging landscape of these alterations in CRC pathogenesis to develop effective diagnostic tools and targeted therapies. Genetic alterations in signaling pathways such as Wnt/ß-catenin, and PI3K/Akt/mTOR are pivotal in CRC development. Genetic profiling has identified distinct molecular subtypes, enabling personalized treatment strategies. Epigenetic modifications, including DNA methylation and histone modifications, also contribute to CRC pathogenesis by influencing critical cellular processes through gene silencing or activation. Non-coding RNAs have emerged as essential players in epigenetic regulation and CRC progression. Recent research highlights the interplay between genetic and epigenetic alterations in CRC. Genetic mutations can affect epigenetic modifications, leading to dysregulated gene expression and signaling cascades. Conversely, epigenetic changes can modulate genetic expression, amplifying or dampening the effects of genetic alterations. Advancements in understanding pathogenic pathways have potential clinical applications. Identifying genetic and epigenetic markers as diagnostic and prognostic biomarkers promises more accurate risk assessment and early detection. Challenges remain, including validating biomarkers and developing robust therapeutic strategies through extensive research and clinical trials. The dynamic nature of genetic and epigenetic alterations necessitates a comprehensive understanding of their temporal and spatial patterns during CRC progression. In conclusion, the genetic and epigenetic landscape of CRC is increasingly being unraveled, providing valuable insights into its pathogenesis. Integrating genetic and epigenetic knowledge holds great potential for improving diagnostics, prognostics, and personalized therapies in CRC. Continued research efforts are vital to translate these findings into clinical practice, ultimately improving patient outcomes.


Assuntos
Neoplasias Colorretais , Epigênese Genética , Humanos , Neoplasias Colorretais/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Metilação de DNA , Biomarcadores/metabolismo , Regulação Neoplásica da Expressão Gênica
4.
Cell Mol Neurobiol ; 43(8): 3847-3884, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37725199

RESUMO

Alzheimer's disease (AD) is the primary cause of dementia and is characterized by the death of brain cells due to the accumulation of insoluble amyloid plaques, hyperphosphorylation of tau protein, and the formation of neurofibrillary tangles within the cells. AD is also associated with other pathologies such as neuroinflammation, dysfunction of synaptic connections and circuits, disorders in mitochondrial function and energy production, epigenetic changes, and abnormalities in the vascular system. Despite extensive research conducted over the last hundred years, little is established about what causes AD or how to effectively treat it. Given the severity of the disease and the increasing number of affected individuals, there is a critical need to discover effective medications for AD. The US Food and Drug Administration (FDA) has approved several new drug molecules for AD management since 2003, but these drugs only provide temporary relief of symptoms and do not address the underlying causes of the disease. Currently, available medications focus on correcting the neurotransmitter disruption observed in AD, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate (NMDA) receptor, which temporarily alleviates the signs of dementia but does not prevent or reverse the course of AD. Research towards disease-modifying AD treatments is currently underway, including gene therapy, lipid nanoparticles, and dendrimer-based therapy. These innovative approaches aim to target the underlying pathological processes of AD rather than just managing the symptoms. This review discusses the novel aspects of pathogenesis involved in the causation of AD of AD and in recent developments in the therapeutic armamentarium for the treatment of AD such as gene therapy, lipid nanoparticles, and dendrimer-based therapy, and many more.


Assuntos
Doença de Alzheimer , Dendrímeros , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Dendrímeros/metabolismo , Dendrímeros/uso terapêutico , Inibidores da Colinesterase , Emaranhados Neurofibrilares/metabolismo , Encéfalo/metabolismo , Peptídeos beta-Amiloides/metabolismo
5.
Indian J Otolaryngol Head Neck Surg ; 75(3): 1447-1453, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37636617

RESUMO

Background: FNAC is easy to perform, is minimally invasive and is economical. It has better patient compliance and the cytological diagnosis can be made before any definitive treatment is planned. Materials and methods: This prospective study was carried out in a tertiary care hospital of a medical college having 100 cases in study. The statistical analysis included sensitivity, specificity, positive predictive value, negative predictive value. Result: On cytological examination, 94/100 were benign, 6 malignant or suspicious. On HPE, 92 were benign while 5 malignant from suspicious and malignant cases leaving 3 discordant cases. Sensitivity, specificity, positive predictive value, negative predictive value which was  71.4%, 98.9%,  83.3%,97.8% respectively in our case series. Conclusion: FNAC is a safe, simple procedure. It gives a reliable pre-operative cytological diagnosis based on which surgical procedures or conservative management can be confidently executed. An attempt is made hereby to compare our results with worldwide documented literature. However pitfalls of this method should be kept in mind with careful observation and adequate clinical suspicion.

6.
Med Oncol ; 40(7): 200, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37294501

RESUMO

Immuno-oncology has revolutionized cancer treatment and has opened up new opportunities for developing vaccination methods. DNA-based cancer vaccines have emerged as a promising approach to activating the bodily immune system against cancer. Plasmid DNA immunizations have shown a favorable safety profile and there occurs induction of generalized as well as tailored immune responses in preclinical and early-phase clinical experiments. However, these vaccines have notable limitations in immunogenicity and heterogeneity and these require refinements. DNA vaccine technology has been focusing on improving vaccine efficacy and delivery, with parallel developments in nanoparticle-based delivery systems and gene-editing technologies such as CRISPR/Cas9. This approach has showcased great promise in enhancing and tailoring the immune response to vaccination. Strategies to enhance the efficacy of DNA vaccines include the selection of appropriate antigens, optimizing insertion in a plasmid, and studying combinations of vaccines with conventional strategies and targeted therapies. Combination therapies have attenuated immunosuppressive activities in the tumor microenvironment and enhanced the capability of immune cells. This review provides an overview of the current framework of DNA vaccines in oncology and focuses on novel strategies, including established combination therapies and those still under development.The challenges that oncologists, scientists, and researchers need to overcome to establish DNA vaccines as an avant-garde approach to defeating cancer, are also emphasized. The clinical implications of the immunotherapeutic approaches and the need for predictive biomarkers have also been reviewed upon. We have also tried to extend the role of Neutrophil extracellular traps (NETs) to the DNA vaccines. The clinical implications of the immunotherapeutic approaches have also been reviewed upon. Ultimately, refining and optimizing DNA vaccines will enable harnessing the immune system's natural ability to recognize and eliminate cancer cells, leading the world towards a revolution in cancer cure.


Assuntos
Vacinas Anticâncer , Neoplasias , Vacinas de DNA , Humanos , Vacinas de DNA/uso terapêutico , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Vacinas Anticâncer/uso terapêutico , Terapia Combinada , Microambiente Tumoral
7.
ACS Pharmacol Transl Sci ; 6(5): 748-770, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37200803

RESUMO

Multitargeted agents with tumor selectivity result in reduced drug resistance and dose-limiting toxicities. We report 6-substituted thieno[2,3-d]pyrimidine compounds (3-9) with pyridine (3, 4), fluorine-substituted pyridine (5), phenyl (6, 7), and thiophene side chains (8, 9), for comparison with unsubstituted phenyl (1, 2) and thiophene side chain (10, 11) containing thieno[2,3-d]pyrimidine compounds. Compounds 3-9 inhibited proliferation of Chinese hamster ovary cells (CHO) expressing folate receptors (FRs) α or ß but not the reduced folate carrier (RFC); modest inhibition of CHO cells expressing the proton-coupled folate transporter (PCFT) by 4, 5, 6, and 9 was observed. Replacement of the side-chain 1',4'-phenyl ring with 2',5'-pyridyl, or 2',5'-pyridyl with a fluorine insertion ortho to l-glutamate resulted in increased potency toward FR-expressing CHO cells. Toward KB tumor cells, 4-9 were highly active (IC50's from 2.11 to 7.19 nM). By metabolite rescue in KB cells and in vitro enzyme assays, de novo purine biosynthesis was identified as a targeted pathway (at 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFTase) and glycinamide ribonucleotide formyltransferase (GARFTase)). Compound 9 was 17- to 882-fold more potent than previously reported compounds 2, 10, and 11 against GARFTase. By targeted metabolomics and metabolite rescue, 1, 2, and 6 also inhibited mitochondrial serine hydroxymethyl transferase 2 (SHMT2); enzyme assays confirmed inhibition of SHMT2. X-ray crystallographic structures were obtained for 4, 5, 9, and 10 with human GARFTase. This series affords an exciting new structural platform for potent multitargeted antitumor agents with FR transport selectivity.

8.
Oncol Lett ; 25(5): 194, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37113402

RESUMO

Medulloblastoma (MB) is one of the most common pediatric malignant tumors arising from the central nervous system with an unknown etiology and variable prognosis. Relapsed or refractory MB in pediatric patients after intensive anticancer therapy (chemo-, radiotherapy) is associated with treatment resistance and poor survival prognosis. Metronomic chemotherapy in combination with mTOR inhibitors may have advantages due to an alternate mechanism of cytotoxicity and a favourable adverse effects profile. Furthermore, it is considered to be a prospective anticancer regimen regardless of the presence/absence of molecular targets. The present study reported a successful result of this treatment option with optimal tolerability in relapsed MB in a pediatric male patient and highlighted the advantages for a selected group of patients.

9.
Med Oncol ; 40(5): 135, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37014489

RESUMO

Cancer immunotherapy is one of the recently developed cancer treatment modalities. When compared with conventional anticancer drug regimens, immunotherapy has shown significantly better outcomes in terms of quality of life and overall survival. It incorporates a wide range of immunomodulatory modalities that channel the effects of the immune system either by broadly modulating the host immune system or by accurately targeting distinct tumor antigens. One such treatment modality that has gained interest is cancer vaccine therapy which acts by developing antibodies against tumor cells. Cancer vaccines target individual peptides or groups of antigens that are released by tumor cells and presented by the APCs. This also initiates an effective process to activate the host immune responses. Studies on various types of cancer vaccines are conducted, out of which only few are approved by FDA for clinical uses. Despite of documented safety and efficacy of conventional chemotherapy and cancer vaccines, individually they did not produce substantial results in eradication of the cancer as a monotherapy. Hence, the combination approach holds the extensive potential to provide significant improvement in disease outcomes. Certain chemotherapy has immunomodulatory effects and is proven to synergize with cancer vaccines thereby enhancing their anti-tumor activities. Chemotherapeutic agents are known to have immunostimulatory mechanisms apart from its cytotoxic effect and intensify the anti-tumor activities of vaccines by various mechanisms. This review highlights various cancer vaccines, their mechanism, and how their activity gets affected by chemotherapeutic agents. It also aims at summarizing the evidence-based outcome of the combination approach of a cancer vaccine with chemotherapy and a brief on future aspects.


Assuntos
Vacinas Anticâncer , Imunoterapia , Neoplasias , Humanos , Neoplasias/prevenção & controle , Antígenos de Neoplasias , Imunoterapia/métodos , Antineoplásicos/farmacologia
10.
Technol Cancer Res Treat ; 22: 15330338221150559, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36683526

RESUMO

The immune system plays a significant role in the development, invasion, progression, and metastasis of head and neck cancer. Over the last decade, the emergence of immunotherapy has irreversibly altered the paradigm of cancer treatment. The current treatment modalities for head and neck squamous cell carcinoma (HNSCC) include surgery, radiotherapy, and adjuvant or neoadjuvant chemotherapy which has failed to provide satisfactory clinical outcomes. To encounter this, there is a need for a novel or targeted therapy such as immunological targets along with conventional treatment strategy for optimal therapeutic outcomes. The immune system can contribute to promoting metastasis, angiogenesis, and growth by exploiting the tumor's influence on the microenvironment. Immunological targets have been found effective in recent clinical studies and have shown promising results. This review outlines the important immunological targets and the medications acting on them that have already been explored, are currently under clinical trials and are further being targeted.


Assuntos
Neoplasias de Cabeça e Pescoço , Imunomodulação , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia/métodos , Microambiente Tumoral
11.
Cancers (Basel) ; 15(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36672492

RESUMO

Immune checkpoints are unique components of the body's defense mechanism that safeguard the body from immune responses that are potent enough to harm healthy body cells. When proteins present on the surface of T cells recognize and bind to the proteins present on other tumor cells, immune checkpoints are triggered. These proteins are called immunological checkpoints. The T cells receive an on/off signal when the checkpoints interact with companion proteins. This might avert the host's immune system from eliminating cancer cells. The standard care plan for the treatment of non-small cell lung cancer (NSCLC) has been revolutionized with the use of drugs targeting immune checkpoints, in particular programmed cell death protein 1. These drugs are now extended for their potential to manage SCLC. However, it is acknowledged that these drugs have specific immune related adverse effects. Herein, we discuss the use of immune checkpoint inhibitors in patients with NSCLC and SCLC, their outcomes, and future perspectives.

12.
Eye (Lond) ; 37(4): 684-691, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35338355

RESUMO

OBJECTIVE: To investigate practice patterns and clinical outcomes in the repair of uncomplicated rhegmatogenous retinal detachments (RRD) in a real-world setting over a 10-year period. METHODS: We compared preferences for scleral buckling (SB), pars plana vitrectomy (PPV), PPV/SB, or pneumatic retinopexy (PR) over time, and examined the 1-year single surgery anatomic success (SSAS) and best-corrected visual acuity (BCVA) at a tertiary academic institution from 2008-2018. RESULTS: Eight hundred eight eyes had RRD repair between 2008-2011 (n = 240), 2012-2014 (n = 271), and 2015-2017 (n = 297). Compared to 2008-2011, PPV was preferred over SB in 2012-2014 (OR: 2.93; 95% CI: 1.86-4.63) and 2015-2017 (OR: 5.94; 95% CI: 3.76-9.38), and over PPV/SB in 2012-2014 (OR: 2.74; 95% CI: 1.65-4.56) and 2015-2017 (OR: 3.16; 95% CI: 31.96-5.12). PR was uncommonly utilized (<10%). Younger surgeons (graduating 2010-2017) favored PPV over SB when compared to older surgeons [graduating 1984-2000 (OR: 1.77; 95% CI: 1.18-2.65) and 2001-2009 (OR 1.73; 95% CI: 1.14-2.65)], but similarly selected PPV vs. PPV/SB as their older counterparts (p > 0.05). Compared to PPV, SSAS was higher with SB (OR: 1.53; 95% CI: 1.03-2.26) and PPV/SB (OR: 2.55; 95% CI: 1.56-4.17). One-year BCVA was markedly improved compared to baseline only for eyes that achieved SSAS (p < 0.001). CONCLUSIONS: Over the past 10 years, PPV has become the favored approach to repair uncomplicated RRD and this appears to be driven by younger surgeons' preferences. Given the superior long-term SSAS in SB and PPV/SB as compared to PPV, SB and PPV/SB should be more frequently considered when determining the appropriate repair strategy for uncomplicated RRD.


Assuntos
Descolamento Retiniano , Humanos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/etiologia , Resultado do Tratamento , Acuidade Visual , Estudos Retrospectivos , Recurvamento da Esclera/efeitos adversos , Vitrectomia/efeitos adversos
13.
Med Oncol ; 40(1): 66, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36583766

RESUMO

A combination of monoclonal antibodies prescribed along with the conventional standard of care has a potential to provide significant improvement in patients suffering from head and neck cancer. This combination has also shown a significant decrease in toxicities and improved overall quality of life. Cetuximab acts by inhibiting the human epidermal growth factors as its overexpression in head and neck tumours that are responsible for treatment failure, resistance, and metastasis. Whereas, bevacizumab acts by inhibiting the vascular endothelial growth factor since its overexpression leads to induction of tumour angiogenesis. Current research has not shown any remarkable beneficial effect in disease outcomes. Thus, the addition of these monoclonal antibodies to the standard regimen for head and neck cancer can be considered a prospect that might be beneficial. Cetuximab has already been included as an option under special recommendations in recurrent/metastatic head and neck cancer by NCCN in a platinum-based regimen as well as in combination with radiation therapy. This review outlines the applicability of cetuximab and bevacizumab in the treatment of head and neck cancer as well as the clinical trials performed that give an idea about the efficacy and safety of these monoclonal antibodies. Based upon the literature reviewed, it can be deduced that immunotherapy is to be adopted and different targets are to be explored in it in order to combat head and neck cancer. Currently, immunotherapeutic drugs of two major targets have been discussed. These agents are even effective in combination with other therapeutic modalities that are not being able to achieve desirable outcomes due to issues such as resistance and toxicities. Thus, newer targets as well as newer agents acting on established targets are to be explored in order to improve disease outcomes.


Assuntos
Antineoplásicos , Neoplasias de Cabeça e Pescoço , Humanos , Cetuximab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Bevacizumab/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Qualidade de Vida , Anticorpos Monoclonais Humanizados/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/uso terapêutico
14.
Vaccines (Basel) ; 10(10)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36298605

RESUMO

Tuberculosis is a stern, difficult to treat chronic infection caused by acid-fast bacilli that tend to take a long time to be eradicated from the host's environment. It requires the action of both innate and adaptive immune systems by the host. There are various pattern recognition receptors present on immune cells, which recognize foreign pathogens or its product and trigger the immune response. The epigenetic modification plays a crucial role in triggering the susceptibility of the host towards the pathogen and activating the host's immune system against the invading pathogen. It alters the gene expression modifying the genetic material of the host's cell. Epigenetic modification such as histone acetylation, alteration in non-coding RNA, DNA methylation and alteration in miRNA has been studied for their influence on the pathophysiology of tuberculosis to control the spread of infection. Despite several studies being conducted, many gaps still exist. Herein, we discuss the immunopathophysiological mechanism of tuberculosis, the essentials of epigenetics and the recent encroachment of epigenetics in the field of tuberculosis and its influence on the outcome and pathophysiology of the infection.

15.
Clin Ophthalmol ; 16: 389-399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35177897

RESUMO

PURPOSE: To evaluate baseline characteristics, microbiological spectrum, management, and outcomes of patients with culture-proven fungal keratitis. METHODS: Retrospective review of all patients with culture-proven fungal keratitis seen over 6 years at a tertiary referral center. RESULTS: The present study included 62 eyes from 62 patients. Infection with filamentous organisms was more common than with yeast (66.1% vs 27.4%). The most common filamentous organisms were Fusarium (17.7%) and Aspergillus (16.1%), while the most common yeast was Candida (24.2%). The main predisposing factor for filamentous keratitis was contact lens use. Yeast keratitis is most associated with an immunocompromised host and ocular surface disease. Corneal perforation (20.0%) and surgical interventions (46.8%) were common, with 27.4% of eyes requiring at least one penetrating keratoplasty. Filamentous keratitis is more likely than yeast keratitis to require urgent penetrating keratoplasty or enucleation and to receive more than one topical and systemic antifungal agent. Visual outcomes were poor with nearly half of the eyes remaining at 20/200 or worse upon resolution of infection. Worse visual outcomes were associated with poor vision at presentation and a history of ocular surface disease. Antifungal susceptibility testing was not routinely performed, but it demonstrated a relatively high minimum inhibitory concentration for at least one antifungal drug in 90% of cases when performed (16.1%) and guided the direction of treatment for 80% of the cases. CONCLUSION: Fungal keratitis is visually devastating. Infections with filamentous fungi predominated over yeast and were generally treated more aggressively both medically and surgically. Filamentous and yeast keratitis had similar durations of infections and visual outcomes. Antifungal susceptibility testing influenced treatment in 80% of cases in which it was performed.

16.
JAMA Ophthalmol ; 140(3): 227-234, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35050347

RESUMO

IMPORTANCE: It is important to recognize presenting features and factors associated with mortality in abusive head trauma (AHT) owing to the severity of the diagnosis and the necessity for prompt action. OBJECTIVE: To describe the prevalence and economic burden of AHT and identify factors associated with mortality. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, cross-sectional study used the Nationwide Emergency Department Sample database to identify all emergency department visits in the US for patients younger than 5 years with a primary diagnosis of abusive head trauma between January 1, 2006, and December 31, 2018. This study was conducted in 2021. MAIN OUTCOMES AND MEASURES: Prevalence, demographic characteristics, clinical characteristics, mortality, and economic burden associated with AHT. Weighted national estimates were calculated using sampling weights provided in the Nationwide Emergency Department Sample database. RESULTS: From 2006 to 2018, there were an estimated 12 287 cases of emergency department visits in the US for patients younger than 5 years with a primary diagnosis of AHT. The estimated number of AHT cases decreased by 672 (95% CI, 403-940; P < .001) from 2006 to 2018. The incidence decreased by 6.7% each year (incidence rate ratio, 0.93; 95% CI, 0.93-0.94; P < .001) between 2006 and 2018. During the course of a hospital visit, 646 patients (5.3%) died. The majority of patients with a diagnosis of AHT were younger than 1 year (n = 7046; 57.3%), were male (n = 7268; 59.2%) and had Medicaid insurance (n = 8585; 70.0%). After controlling for demographic characteristics, factors associated with increased mortality were age greater than 1 year (odds ratio [OR], 2.45; 95% CI, 1.50-3.99; P < .001), first or second income quartile (OR, 1.78; 95% CI, 1.08-2.91; P = .02), midwestern United States (OR, 2.04; 95% CI, 1.04-4.00; P = .04), level 1 trauma center (OR, 2.69; 95% CI, 1.07-6.75; P = .04), orbital fracture (OR, 15.38; 95% CI, 2.41-98.18; P = .004), cerebral edema (OR, 8.49; 95% CI, 5.57-12.93; P < .001), intracranial hemorrhage (OR, 4.27; 95% CI, 1.71-10.67; P = .002), hypoxic ischemic brain injury (OR, 4.16; 95% CI, 2.13-8.10; P < .001), skull fractures (OR, 3.20; 95% CI, 1.76-5.82; P < .001), subarachnoid hemorrhage (OR, 2.43; 95% CI, 1.22-4.83; P = .01), retinal hemorrhage (OR, 2.17; 95% CI, 1.40-3.38; P < .001), and subdural hemorrhage (OR, 2.05; 95% CI, 1.05-3.98; P = .04). CONCLUSIONS AND RELEVANCE: This study's findings suggest that health care disparities may be present in the treatment of AHT. Recognizing factors suggested in this investigation to be associated with higher mortality, public health efforts should be targeted toward low-income areas and in the midwestern United States.


Assuntos
Maus-Tratos Infantis , Traumatismos Craniocerebrais , Criança , Maus-Tratos Infantis/diagnóstico , Traumatismos Craniocerebrais/diagnóstico , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/etiologia , Estudos Transversais , Feminino , Hematoma Subdural/complicações , Humanos , Lactente , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia
17.
Telemed J E Health ; 28(6): 858-864, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34619063

RESUMO

Background:Utilizing telemedicine is one approach to reduce the ever-increasing burden of patients on emergency departments (EDs) and consulting physicians. Utilization of telemedicine services in the ED may also benefit resident education.Materials and Methods:Ten first-year ophthalmology residents were trained to use a Topcon 3D Optical Coherence Tomography (OCT)-1 Maestro to capture OCT images and fundus photos in patients presenting to the ED with urgent ophthalmic concerns. Findings were communicated to the supervising ophthalmologist. Retrospective chart review was conducted to obtain patient characteristics and final ophthalmologist diagnosis. Residents rated ease of use, technical reliability, and educational value through a survey.Results:From December 1, 2019, to December 1, 2020, the device was used in 109 patient encounters, capturing 887 images (average 8.1 images per encounter). Patients on whom the device was used were on average 48.5 years old (±17.2, range 17-90) and 59.6% were female. The imaging device was utilized most commonly for evaluating papilledema (n = 21, 18.6%), new-onset visual acuity/visual field defects (n = 12, 10.6%), retinal detachment/tear (n = 8, 7.1%), and ophthalmic trauma workup (n = 8, 7.1%). Eight residents completed the survey and most (n = 7) agreed or strongly agreed that the device helped them diagnose patients more accurately. Technical issues such as machine malfunction, image artifacts, and problems syncing with the electronic health record and computer were noted by survey respondents.Conclusions:The most common use of teleophthalmology in the ED setting was evaluation of papilledema; the majority of residents perceived an educational benefit from this tool. Efforts should be made to address the technical challenges to increase the utility of this device.


Assuntos
Oftalmologia , Papiledema , Telemedicina , Emergências , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oftalmologia/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Telemedicina/métodos
18.
Ophthalmology ; 129(4): 388-396, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34756939

RESUMO

PURPOSE: To determine which patient-reported symptoms best distinguish patients with and without glaucoma and explain the most variance in visual field (VF) damage and to compare the amount of variance that can be explained by symptoms versus retinal nerve fiber layer (RNFL) thickness. DESIGN: Cross-sectional study. PARTICIPANTS: Adults diagnosed with glaucoma or suspicion of glaucoma (controls). METHODS: Worse-eye VF damage was defined on the basis of perimetric testing. Thickness of RNFL was defined by OCT imaging. Patients rated their visual symptoms on questions collated from several published questionnaires, rating the frequency and severity of 28 symptoms on a scale of 1 (never/not at all) to 4 (very often/severe). Multivariable regression models identified patient-reported symptoms that contributed the highest variance in VF damage. MAIN OUTCOME MEASURES: Patient-reported symptoms that explained the most variance in VF damage and amount of variance in VF damage explained by patient-reported symptoms and RNFL. RESULTS: A total of 170 patients (mean age: 64 years; 58% female; 47% employed) completed testing, including 95 glaucoma suspects and 75 glaucoma patients. In glaucoma patients, median mean deviation of VF damage in the worse eye was -19.3 and ranged from -5.3 to -34.7 decibels. Symptoms more common among glaucoma patients compared with glaucoma suspects included better vision in 1 eye, blurry vision, glare, sensitivity to light, cloudy vision, missing patches of vision, and little peripheral vision. Worse severity ratings for the symptom "little peripheral vision" explained the most variance in VF damage (43%). A multivariable model including the frequency of cloudy vision, severity of having little peripheral vision, missing patches, 1 eye having better vision, and vision worsening, plus sociodemographic features, explained 62% of the variance in VF damage. Comparatively, a multivariable model of worse-eye RNFL thickness and sociodemographic features explained 42% of the variance in VF damage, whereas a model including only sociodemographic features explained 8% of the variance in VF damage. CONCLUSIONS: Five patient-reported symptoms explain a significant amount of the variance in VF damage. Asking patients about their symptoms may optimize patient-physician communication and be a useful adjunct to clinical testing in some patients to estimate disease severity.


Assuntos
Glaucoma , Hipertensão Ocular , Doenças do Nervo Óptico , Adulto , Estudos Transversais , Feminino , Glaucoma/complicações , Glaucoma/diagnóstico , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fibras Nervosas , Doenças do Nervo Óptico/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Células Ganglionares da Retina , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/diagnóstico , Testes de Campo Visual/métodos , Campos Visuais
19.
Clin Ophthalmol ; 15: 783-790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658754

RESUMO

PURPOSE: To evaluate the outcomes of a 4-point scleral-fixated foldable Akreos AO60 intraocular lens (IOL) insertion using Gore-Tex suture performed by trainees under supervision of a single attending surgeon. METHODS: Retrospective chart review for 53 eyes of 50 patients whose surgery was performed by trainees under supervision of a single surgeon between 2015 and 2018 at a tertiary care hospital (Johns Hopkins Wilmer Eye Institute, Baltimore, MD). Indications for surgery, preoperative risk factors, and intraoperative techniques were analyzed. Outcome measures included final best-corrected visual acuity (BCVA), change in BCVA, difference between expected and final spherical equivalent (SE), and postoperative complications. RESULTS: Mean patient age was 62.8 years (range 26.9 to 88.4). The most common indication for surgery was IOL dislocation (59.6%) due to trauma in 21 cases (40.4%) and pseudoexfoliation in 6 (11.5%). Combined pars plana vitrectomy was performed simultaneously in 46 cases (88.5%). Mean BCVA improved from 20/100 to 20/40 (p < 0.001). The difference between expected and final SE was within 1.0 D in 28 cases (53.8%). Postoperative hypotony occurred in 12 eyes (21.2%) on day 1; all were resolved at last follow-up. Postoperative cystoid macular edema (CME) occurred in 20 cases (38.5%); 11 (21.2%) persisted through last follow-up. CONCLUSION: Scleral-fixation of Akreos AO60 IOL in absence of capsular support can be performed by trainees under supervision and results in effective visual rehabilitation. Postoperative CME occurred at a higher rate than previously reported in the literature. Future studies should assess the rates of postoperative complications amongst different techniques of secondary IOL fixation performed by trainees to determine which is the safest.

20.
Acta Ophthalmol ; 99(8): 916-921, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33583148

RESUMO

PURPOSE: To determine the prevalence and reasons for delays in diagnosis in patients with Acanthamoeba keratitis (AK) presenting to Wilmer Eye Institute, Baltimore, Maryland. METHODS: This retrospective study analysed all patients with culture-positive AK seen between 2012 and 2019 at a tertiary referral centre. Patient demographic information, clinical history, risk factors, symptom duration, referral patterns, slit lamp examination findings, visual acuity and need for surgery were collected. RESULTS: The study included 45 eyes of 43 patients. On average, patients were symptomatic for 52.6 days before culture collection. Thirty-one percent of patients were diagnosed within 28 days of symptom onset while 69% were diagnosed after 28 days. Before presentation to a tertiary care centre, 69% of patients were evaluated by an ophthalmologist outside of this institution and 27% were evaluated by a provider other than an ophthalmologist. AK was most commonly misdiagnosed as herpetic keratitis, occurring in 38% of patients. The strongest risk factor for AK was contact lens use. Only 11% of patients presented with the classic ring infiltrate and 82% had pain. Patients with an early versus late diagnosis had a mean Snellen visual acuity (VA) of 20/224 versus 20/296 at presentation (p = 0.33) and a mean Snellen VA of 20/91 versus 20/240 at final visit (p = 0.07). 11% of patients required a therapeutic penetrating keratoplasty. CONCLUSION: Delayed diagnosis of AK in our cohort occurred due to a misdiagnosis as herpetic keratitis, non-specific clinical signs including the lack of pain in a number of patients, and a delay in referral to a tertiary care centre. Any contact lens wearer with an atypical keratitis should be referred promptly for Acanthamoeba cultures.


Assuntos
Ceratite por Acanthamoeba/diagnóstico , Acanthamoeba/isolamento & purificação , Córnea/parasitologia , Diagnóstico Tardio , Infecções Oculares Parasitárias/diagnóstico , Centros de Atenção Terciária/estatística & dados numéricos , Acuidade Visual , Ceratite por Acanthamoeba/epidemiologia , Ceratite por Acanthamoeba/parasitologia , Adulto , Córnea/diagnóstico por imagem , Infecções Oculares Parasitárias/epidemiologia , Infecções Oculares Parasitárias/parasitologia , Feminino , Seguimentos , Humanos , Masculino , Microscopia Confocal , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
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