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1.
JAMA Netw Open ; 7(5): e2410670, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38758559

RESUMO

Importance: Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials. Objective: To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups. Design, Setting, and Participants: This population-based cross-sectional study analyzed travel times to proton facilities in the US. Census tract variables in the contiguous US were measured between January 1, 2017, and December 31, 2021. Statistical analysis was performed from September to November 2023. Exposures: Drive time in minutes to nearest proton facility. Population totals and prevalence of specific factors measured from the American Community Survey: age; race and ethnicity; insurance, disability, and income status; vehicle availability; broadband access; and urbanicity. Main Outcomes and Measures: Poor access to proton facilities was defined as having a drive-time commute of at least 4 hours to the nearest location. Median drive time and percentage of population with poor access were calculated for the entire population and by population subgroups. Univariable and multivariable odds of poor access were also calculated for certain population subgroups. Results: Geographic access was considered for 327 536 032 residents of the contiguous US (60 594 624 [18.5%] Hispanic, 17 974 186 [5.5%] non-Hispanic Asian, 40 146 994 [12.3%] non-Hispanic Black, and 195 265 639 [59.6%] non-Hispanic White; 282 031 819 [86.1%] resided in urban counties). The median (IQR) drive time to the nearest proton facility was 96.1 (39.6-195.3) minutes; 119.8 million US residents (36.6%) lived within a 1-hour drive of the nearest proton facility, and 53.6 million (16.4%) required a commute of at least 4 hours. Persons identifying as non-Hispanic White had the longest median (IQR) commute time at 109.8 (48.0-197.6) minutes. Multivariable analysis identified rurality (odds ratio [OR], 2.45 [95% CI, 2.27-2.64]), age 65 years or older (OR, 1.09 [95% CI, 1.06-1.11]), and living below the federal poverty line (OR, 1.22 [1.20-1.25]) as factors associated with commute times of at least 4 hours. Conclusions and Relevance: This cross-sectional study of drive-time access to proton beam therapy found that disparities in access existed among certain populations in the US. These results suggest that such disparities present a barrier to an emerging technology in cancer treatment and inhibit equitable access to ongoing clinical trials.


Assuntos
Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Neoplasias , Terapia com Prótons , Viagem , Humanos , Terapia com Prótons/estatística & dados numéricos , Estudos Transversais , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Neoplasias/radioterapia , Estados Unidos , Feminino , Masculino , Viagem/estatística & dados numéricos , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Idoso , Adulto , Fatores de Tempo
3.
Mol Neurobiol ; 61(1): 175-187, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37594653

RESUMO

The factors mitigating the microglia/macrophage activation and inflammatory damage in Japanese encephalitis (JE) virus infected CNS are still being ascertained. We aim to characterize the changes in iron transporter and iron storage proteins along with inflammatory and oxidative stress-mediated signaling during the JE viral infection. Cortical tissue samples from mice with JE viral infection were processed for biochemical, histological, and molecular analysis. Iron storage protein, i.e., ferritin, was found significantly increased post-JE viral infection, and iron accumulation was noted in cortical tissue. Key proinflammatory associated markers, such as TNF-α, IL-6, and its regulator TLR4, were found to be increased, while SOCS1 (anti-inflammatory regulator) transcription decreased with increased levels of oxidative stress markers NOX2-mediated NF-ΚB/p65 and protein carbonyl. Furthermore, it is noted that hepcidin level increased and ferroportin level decreased, and iron transporter gene expression got imbalanced after JE viral infection. This observation was further confirmed by deferoxamine (DFO) treatment to JE viral infection mice model, where the decline in hepcidin transcription level and iron load in cortical tissue of JE viral infected animals was noted. However, no change was found in the ferroportin level compared to JE viral infected animals. Together, these findings suggest that iron overload and hepcidin-ferroportin regulation are involved in JE viral infection disease pathologies and associated with the inflammatory and oxidative status of the host during infection.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Camundongos , Animais , Hepcidinas/metabolismo , Ferro/metabolismo , Estresse Oxidativo
4.
Indian J Ophthalmol ; 72(5): 653-658, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38099390

RESUMO

PURPOSE: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center. METHODS: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality. RESULTS: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma ( n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period. CONCLUSION: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study.

5.
Discov Nano ; 18(1): 148, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38047966

RESUMO

Tuning the electronic properties of transition metals using pyrophosphate (P2O7) ligand moieties can be a promising approach to improving the electrochemical performance of water electrolyzers and supercapacitors, although such a material's configuration is rarely exposed. Herein, we grow NiP2O7, CoP2O7, and FeP2O7 nanoparticles on conductive Ni-foam using a hydrothermal procedure. The results indicated that, among all the prepared samples, FeP2O7 exhibited outstanding oxygen evolution reaction and hydrogen evolution reaction with the least overpotential of 220 and 241 mV to draw a current density of 10 mA/cm2. Theoretical studies indicate that the optimal electronic coupling of the Fe site with pyrophosphate enhances the overall electronic properties of FeP2O7, thereby enhancing its electrochemical performance in water splitting. Further investigation of these materials found that NiP2O7 had the highest specific capacitance and remarkable cycle stability due to its high crystallinity as compared to FeP2O7, having a higher percentage composition of Ni on the Ni-foam, which allows more Ni to convert into its oxidation states and come back to its original oxidation state during supercapacitor testing. This work shows how to use pyrophosphate moieties to fabricate non-noble metal-based electrode materials to achieve good performance in electrocatalytic splitting water and supercapacitors.

6.
Med J Armed Forces India ; 79(Suppl 1): S333-S336, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144656

RESUMO

Spontaneous subluxation of the eyeball is a rare phenomenon as there are only few cases reported in the literature. It is a sight-threatening condition and very traumatising for the patient. The globe has to be reposited back within the socket immediately to save vision and to prevent exposure keratitis and optic neuropathy. In all published reports about subluxation of the eyeball, the underlying aetiology which was responsible for this condition was found. Herein, we report a case of recurrent spontaneous subluxation of the eyeball in which the cause could not be ascertained in a middle-aged male patient even after thorough clinical examination and investigation. The case was managed successfully with three-wall orbital decompression and tarsorrhaphy. The patient did not experience any episode of subluxation of the globe following surgery as orbital decompression increased the available space for the orbital contents, thereby averting its occurrence.

7.
JAMA Oncol ; 9(10): 1390-1400, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37589970

RESUMO

Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Exposure: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main Outcomes and Measures: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Results: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). Conclusions and Relevance: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.


Assuntos
COVID-19 , Neoplasias , Tromboembolia Venosa , Humanos , Masculino , Idoso , Feminino , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologia , Anticoagulantes/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos , Teste para COVID-19 , Fator A de Crescimento do Endotélio Vascular , SARS-CoV-2 , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Agentes de Imunomodulação
8.
BMC Cancer ; 23(1): 265, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36949413

RESUMO

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.


Assuntos
COVID-19 , Melanoma , Humanos , COVID-19/terapia , Insuficiência de Múltiplos Órgãos , Melanoma/complicações , Melanoma/terapia , Imunoterapia
9.
Lancet Reg Health Am ; 19: 100445, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36818595

RESUMO

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

10.
Cureus ; 15(1): e33858, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36819451

RESUMO

Eosinophilia with a modest number of blasts (<20%) in the peripheral blood and bone marrow smears raises suspicion for myeloproliferative neoplasms (MPNs) and acute myeloid leukaemia (AML). Here, we present a case of AML in a 16-year-old boy who presented with high-grade fever, respiratory distress, and generalised weakness. Marked eosinophilia with dysplastic features and occasional blasts were found in the peripheral blood. In view of dysplastic eosinophils and occasional blasts in peripheral blood, a bone marrow examination was requested which revealed increased eosinophils and their progenitors with dysplasia and a modest number of blast cells (<20%). The bone marrow findings suggest MPNs, which were eventually identified as AML having translocation (8;21) with the aid of immunophenotyping and cytogenetic studies. Eosinophilia and its phenotypic anomalies are rarely found in peripheral blood smears of AML patients with translocation (8;21) which may have been related to the leukaemic process.

11.
Cancer Epidemiol Biomarkers Prev ; 32(1): 3-5, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36620898

RESUMO

Multiple prior studies have shown an increased risk of severe disease and death from SARS-CoV-2 infection in patients with cancer. Nolan and colleagues conducted a multi-institution, electronic health record (EHR)-based study of adults hospitalized with COVID-19 delineating the difference in outcomes when stratified by current versus former cancer diagnosis and found that only a current diagnosis appears to confer an increased risk of severe COVID-19 and death.We review these findings in the context of other studies examining outcomes for individuals with cancer diagnoses and COVID-19. We also address questions raised by this type of study about the significant challenges of EHR-based studies and discuss potential avenues for future research in this arena. See related article by Nolan et al., p. 12.


Assuntos
COVID-19 , Neoplasias , Adulto , Humanos , Registros Eletrônicos de Saúde , Universidades , Wisconsin , SARS-CoV-2 , Neoplasias/diagnóstico , Teste para COVID-19
12.
Int Ophthalmol ; 43(2): 371-380, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35857192

RESUMO

PURPOSE: This study was taken up to look into the various causes of recurrence, clinicopathological profile and final outcomes in recurrent cases of ocular surface squamous neoplasia (OSSN). METHODOLOGY: A prospective cohort study was conducted and total 18 patients were recruited. All patients were subjected to detailed history, comprehensive eye examination and imaging studies. A treatment plan was formulated based on the size and extent of the lesion. The primary outcome measure was complete response to treatment with no evidence of recurrence after12 months and secondary outcome measure was complication associated with each treatment modality. RESULTS: The common cause of recurrence in our study was misdiagnosis of the lesion as in 15 cases it was diagnosed as pterygium and in 03 cases it was actinic keratosis. Excision Biopsy with adjunctive cryotherapy was the preferred treatment modality followed by topical interferon-alpha 2b drop-in our study. We could achieve good outcomes in terms of complete response to the treatment in 16 cases. The complication associated with this treatment was minimal in our study as few patients complained redness and irritation which subsided after application of topical lubricants. There was no sign of recurrence even at 12 months of follow-up in all 18 cases. CONCLUSION: The current study provided clinicopathological characteristics and treatment outcomes in recurrent cases of OSSN. In our study, adopting appropriate treatment strategy, regular follow-up to assess the response to treatment and change over to new treatment plan in cases with inadequate response helped in achieving good outcomes in recurrent cases of OSSN.


Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Humanos , Interferon alfa-2 , Neoplasias Oculares/diagnóstico , Centros de Atenção Terciária , Estudos Prospectivos , Estudos Retrospectivos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/terapia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico
13.
Mol Oncol ; 17(5): 839-856, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35838343

RESUMO

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 (SLIT2) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue. In addition, the expression of the SLIT2 receptor, roundabout guidance receptor 1 (ROBO1), is upregulated. We find a positive association between SLIT2 expression and the Yes1 associated transcriptional regulator (YAP1)-expressing SCLC subtype (SCLC-Y), which shows a better prognosis. Using genetically engineered SCLC cells, adenovirus gene therapy, and preclinical xenograft models, we show that SLIT2 overexpression or the deletion of ROBO1 restricts tumor growth in vitro and in vivo. Mechanistic studies revealed significant inhibition of myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs) in the SCLC tumors. In addition, SLIT2 enhances M1-like and phagocytic macrophages. Molecular analysis showed that ROBO1 knockout or SLIT2 overexpression suppresses the transforming growth factor beta 1 (TGF-ß1)/ß-catenin signaling pathway in both tumor cells and macrophages. Overall, we find that SLIT2 and ROBO1 have contrasting effects on SCLC tumors. SLIT2 suppresses, whereas ROBO1 promotes, SCLC growth by regulating the Tgf-ß1/glycogen synthase kinase-3 beta (GSK3)/ß-catenin signaling pathway in tumor cells and TAMs. These studies indicate that SLIT2 could be used as a novel therapeutic agent against aggressive SCLC.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Fator de Crescimento Transformador beta1/farmacologia , beta Catenina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/farmacologia , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Transdução de Sinais , Carcinoma de Pequenas Células do Pulmão/genética , Neoplasias Pulmonares/genética , Macrófagos/metabolismo
14.
JAMA Oncol ; 9(1): 128-134, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326731

RESUMO

Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.


Assuntos
COVID-19 , Neoplasias , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , COVID-19/epidemiologia , SARS-CoV-2 , Estudos de Coortes , Estudos Retrospectivos , Teste para COVID-19 , Síndrome da Liberação de Citocina/etiologia , Terapia de Imunossupressão , Imunoterapia/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/terapia
15.
Int Ophthalmol ; 43(3): 957-964, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36070117

RESUMO

PURPOSE: To compare the surgical outcomes of tarsofrontalis sling surgery using silicon rod versus supramaximal levator resection in patients of unilateral congenital ptosis with poor levator function (≤ 4 mm). MATERIALS AND METHODS: This randomized control study was conducted over a period of 18 months. 44 patients were enrolled in the study group. The study population was randomly divided into two groups (22 in each group). In Group A, congenital ptosis was treated with tarsofrontalis sling surgery using silicon rod and supramaximal levator resection was done in the group B. Follow-up examination was done at postoperative day 1, one week, 1 month, 6 months and 12 months. Surgical outcome measures were change in marginal reflex distance-1 (MRD 1), vertical palpebral fissure height (VPFH) and inter-eyelid difference of margin reflex distance 1 and complications in two groups. RESULTS: The mean age of patients in group A was 7.25 ± 6.10 years ranging from 1-18 years and mean age of patients in group B was 5.64 ± 2.44 years ranging from 3 to 11 years. Good surgical outcome was obtained in 73-77% of both groups. MRD1and VPFH increased significantly after surgery from baseline in both the groups (p value < 0.001). Inter-eyelid MRD 1 difference also improved significantly in both groups following ptosis surgery. CONCLUSION: Both supramaximal levator resection and tarsofrontalis sling surgery are equally effective in cases of unilateral ptosis patients with poor levator function and should be part of the surgical armamentarium for treating congenital ptosis.


Assuntos
Blefaroplastia , Blefaroptose , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Blefaroplastia/efeitos adversos , Silício , Músculos Oculomotores/cirurgia , Estudos Retrospectivos , Blefaroptose/congênito , Resultado do Tratamento
16.
J Cancer Res Ther ; 19(Suppl 2): S912-S916, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38384078

RESUMO

ABSTRACT: Various treatment modalities are available for treatment of ocular tumors, which include chemotherapy, laser, and radiotherapy (external beam radiation therapy or brachytherapy). Brachytherapy using plaque applicator is preferred over external beam radiation therapy when the tumor is well localized, as this therapy delivers radiation dose to the tumor with lower doses to normal tissues in the vicinity. However, plaque therapy is expensive and beyond the reach of many poor patients in India. The Bhabha Atomic Research Center (BARC) recently introduced an indigenous Ruthenium-106 plaque to make brachytherapy treatment available and affordable to all needy patients in India. In the present case series, we report our experience using the indigenous Ru-106 plaque for the treatment of a spectrum of ocular tumors.


Assuntos
Braquiterapia , Neoplasias Oculares , Melanoma , Humanos , Braquiterapia/efeitos adversos , Neoplasias Oculares/radioterapia , Neoplasias Oculares/tratamento farmacológico , Radioisótopos de Rutênio/efeitos adversos , Melanoma/patologia , Dosagem Radioterapêutica
17.
Photodiagnosis Photodyn Ther ; 39: 103000, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35793781

RESUMO

Photodynamic therapy (PDT) using verteporfin Visudyne®(Novartis International AG, Basel, Switzerland) is widely used to treat various chorio-retinal diseases. PDT targets choroidal vascular abnormalities and induces selective occlusion of vessels. PDT was originally used in combination with full-dose verteporfin to treat neovascular age-related macular degeneration. Currently, the clinical targets of PDT have shifted to other chorioretinal conditions such as central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal hemangioma. Clinical studies have also facilitated the optimization of treatment outcomes in choroidal hemangiomas through changes in protocols including the introduction of reduced treatment settings; such as PDT with half-dose verteporfin and half-fluence PDT. Here, we review various evolving trends in clinical application of PDT and its use for choroidal hemangiomas from a practical perspective.


Assuntos
Coriorretinopatia Serosa Central , Neoplasias da Coroide , Hemangioma , Fotoquimioterapia , Porfirinas , Coriorretinopatia Serosa Central/tratamento farmacológico , Neoplasias da Coroide/tratamento farmacológico , Angiofluoresceinografia , Hemangioma/tratamento farmacológico , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Verteporfina/uso terapêutico
19.
Cancers (Basel) ; 14(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35267489

RESUMO

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC.

20.
JAMA Netw Open ; 5(3): e224304, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35344045

RESUMO

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19. Design, Setting, and Participants: This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021. Exposures: Black and White race recorded in patient's electronic health record. Main Outcomes and Measures: An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death. Results: Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]). Conclusions and Relevance: These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.


Assuntos
COVID-19 , Neoplasias , Idoso , População Negra , COVID-19/epidemiologia , Teste para COVID-19 , Feminino , Humanos , Neoplasias/epidemiologia , Estudos Retrospectivos
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