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In this study, for the first time, we analyzed the chemical composition of essential oils (EOs) steam-distilled from the flowers and leaves of Perralderia coronopifolia by GC-FID/MS. The objective was to explore new anticancer and antioxidant bioactive substances and understand their mechanisms of action through the use of plant-derived natural products. The major chemical components characterizing the EOs were cis-chrysanthenyl acetate 1, 6-oxocyclonerolidol 2, cis-8-acetoxychrysanthenyl acetate 3, and 6α-hydroxycyclonerolidol 4, respectively. Furthermore, the EOs inhibited cell proliferation in HeLa (human cervix carcinoma) and PC3 (human prostate cancer) cells and protected plasmid DNA from oxidative damage caused by UV-photolyzed H2 O2 . Employing a molecular docking study, we elucidated the main compounds' inhibition mechanisms. Consequently, the antitumor activity could be related to the inhibitory property of compound 3 against CDC25B phosphatase. The evaluation of ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and the density functional theory (DFT) calculations of the major compounds, especially compound 3, offer potential insights for designing and developing new cancer drug candidates. In conclusion, our study provides a framework for future research and development in the field by establishing a scientific foundation for the use of Perralderia coronopifolia essential oils as a prospective source of antioxidant and anticancer agents.
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Antineoplásicos , Aceites Volátiles , Femenino , Humanos , Aceites Volátiles/química , Antioxidantes/química , Simulación del Acoplamiento Molecular , Estudios Prospectivos , Hojas de la Planta/química , Antineoplásicos/farmacologíaRESUMEN
Mercapto (or sulfanyl)-coumarins are heterocycles of great interest in the development of valuable active structures in material and biological domains. They represent a highly exploitable class of compounds that open many possibilities for further chemical transformations. The present review aims to draw focus toward the synthetic applicability of various forms of mercapto-coumarins and their representations in pharmaceuticals and industries. This work covers the literature issued from 1970 to 2021.
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Antioxidantes , Cumarinas , Cumarinas/químicaRESUMEN
Cdc25 phosphatases have been considered promising targets for anticancer development due to the correlation of their overexpression with a wide variety of cancers. In the last two decades, the interest in this subject has considerably increased and many publications have been launched concerning this issue. An overview is constructed based on data analysis of the results of the previous publications covering the years from 1992 to 2021. Thus, the main objective of the current review is to report the chemical structures of Cdc25s inhibitors and answer the question, how to design an inhibitor with better efficacy and lower toxicity?
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Neoplasias , Fosfatasas cdc25 , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Fosfatasas cdc25/antagonistas & inhibidores , Fosfatasas cdc25/químicaRESUMEN
Aplysinopsins are a class of indole alkaloids that possess various pharmacological activities. Although their action has been studied in regard to many diseases, their effect on prostate cancer has not yet been examined. Therefore, we synthesized a new series of aplysinopsin analogs and investigated their cytotoxic activity against prostate cancer. Five analogs showed high antitumor activity via suppressing the expression of the anti-apoptotic gene Bcl2, simulationously increasing the expression of the pro-apoptotic genes p53, Bax and Caspase 3. The inhibition of BCL2 led to the activation of BAX, which in turn activated Caspase 3, leading to apoptosis. This dual mechanism of action via apoptosis and cell cycle arrest induction is responsible for aplysinopsin analogs antitumor activity. Hence, our newly synthesized analogs are highly promising candidates for further preclinical studies against prostate cancer.
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Alcaloides , Antineoplásicos , Neoplasias de la Próstata , Masculino , Humanos , Caspasa 3/farmacología , Proteínas Reguladoras de la Apoptosis , Proteína X Asociada a bcl-2 , Alcaloides/farmacología , Alcaloides/uso terapéutico , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias de la Próstata/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación CelularRESUMEN
Coumarins are natural heterocycles that widely contribute to the design of various biologically active compounds. Fusing different aromatic heterocycles with coumarin at its 3,4-position is one of the interesting approaches to generating novel molecules with various biological activities. During our continuing interest in assembling information about fused five-membered aromatic heterocycles, and after having presented mono-hetero-atomic five-membered aromatic heterocycles in Part I. The current review Part II is intended to present an overview of the different synthetic routes to coumarin (benzopyrone)-fused five-membered aromatic heterocycles with multi-heteroatoms built on the pyrone ring, covering the literature from 1945 to 2021.
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This review gives an up-to-date overview of the different ways (routes) to the synthesis of coumarin (benzopyrone)-fused, five-membered aromatic heterocycles with one heteroatom, built on the pyrone moiety. Covering 1966 to 2020.
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Cumarinas/química , Compuestos Heterocíclicos/síntesis química , Hidrocarburos Aromáticos/síntesis química , Pironas/químicaRESUMEN
Two novel compounds were isolated for the first time from Calycotome spinosa (L.) Link, an alkaloid 5-Hydroxy-1H-indole (4) and a cyclitol D-pinitol (5), together with the three well-known flavonoids; Chrysin-7-O-(ß-D-glucopyranoside) (1), Chrysin-7-O-ß-D-(6â³-acetyl)glycopyranoside (2) and Apigenin-7-O-ß-D-glycopyranoside (3). The chemical structures of the isolated compounds were elucidated by spectroscopic data and mass spectrometric analyses; including a fresh approach 1D-NMR, 2D-NMR with LC-ESI-MS/MS. In this study, the new compound (4) that has been obtained from the leaves MeOH extract presented the best radical scavenging activity (DPPH) (IC50 < 10 µg/mL) compared to the standard butylated hydroxytoluene (BHT, IC50 = 34.73 ± 0.23 µg/mL) and showed the highest total antioxidant capacity (TAC = 985.54 ± 0.13 mg AAE/g extract) in contrast to ascorbic acid (TAC = 905.95 ± 0.07 mg AAE/g extract). Furthermore, the strongest reducing power (EC50 = 344.82 ± 0.02 µg/mL), as well as the remarkable scavenging potential by ABTS assay (IC50 = 7.8 ± 0.43 µg/mL), were exhibited by the same composite (4). Followed by the methanol crude extract and the compound (3) that also showed a potent antioxidant (DPPH; IC50 = 41.04 ± 0.15 and 47.36 ± 0.21 µg/mL, TAC; 671.02 ± 0.21 and 608.67 ± 0.34 mg AAE/g extract, FRAP; EC50 = 763.73 ± 0.32 and 814.61 ± 0.31 µg/mL, ABTS; IC50 = 19.18 ± 0.06 and 63.72 ± 0.64 µg/mL, respectively), but less than the previous samples. On the opposite side, compound (5) had the lowest activity, in which its values were less interesting to determine. Moreover, compound (4) has equally exerted an attractive antibacterial activity against Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa (ATTC- 27853) and Salmonella abony (NCTC 6017), as measured by the disc diffusion assay, with inhibition zones of 16 ± 0.5, 9.83 ± 0.29 and 8 ± 0.28 mm, in that order. To the best of our knowledge, 5-Hydroxy-1H-indole was isolated from plants for the second time in our current work. Thus, the obtained results from this investigation propose that the leaves of C. spinosa are a rich natural source for value molecules as potential antioxidants and antimicrobial agents for best human health.
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Cromatografía Liquida/métodos , Genista/química , Hojas de la Planta/química , Análisis Espectral/métodos , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antioxidantes/farmacología , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología , Polifenoles/análisis , Staphylococcus aureus/efectos de los fármacosRESUMEN
In this work, we describe the preparation of some new Tacrine analogues modified with a pyranopyrazole moiety. A one-pot multicomponent reaction of 3-methyl-1H-pyrazol-5(4H)-one, aryl(or hetero)aldehydes, malononitrile and cyclohexanone involving a Friedländer condensation led to the title compounds. The synthesized heterocyclic analogues of this molecule were evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 0.044 to 5.80⯵M, wherein compounds 5e and 5j were found to be most active inhibitors against AChE with IC50 values of 0.058 and 0.044⯵M respectively. Molecular modeling simulation on AChE and BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes.
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Inhibidores de la Colinesterasa/farmacología , Colinesterasas/metabolismo , Simulación del Acoplamiento Molecular , Pirazoles/farmacología , Tacrina/farmacología , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Pirazoles/química , Relación Estructura-Actividad , Tacrina/químicaRESUMEN
Chronic increased workload of the human heart causes ventricular hypertrophy, re-expression of the atrial essential myosin light chain (hALC-1), and improved contractile function. Although hALC-1 is an important positive inotropic regulator of the human heart, little is known about its regulation. Therefore, we investigated the role of the sex hormone 17ß-estradiol (E2) on hALC-1 gene expression, the underlying molecular mechanisms, and the impact of this regulatory process on cardiac contractile function. We showed that E2 attenuated hALC-1 expression in human atrial tissues of both sexes and in human ventricular AC16 cells. E2 induced the nuclear translocation of estrogen receptor alpha (ERα) and hALC-1 in AC16 cells, where they cooperatively regulate the transcriptional activity of hALC-1 gene promoter. E2-activated ERα required the estrogen response element (ERE) motif within the hALC-1 gene promoter to reduce its transcriptional activity (vehicle: 15.55 ± 4.80 vs. E2: 6.51 ± 3.69; ~2 fold). This inhibitory effect was potentiated in the presence of hALC-1 (vehicle: 11.13 ± 3.66 vs. E2: 2.18 ± 1.10; ~5 fold), and thus, hALC-1 acts as a co-repressor of ERα-mediated transcription. Yeast two-hybrid screening of a human heart cDNA library revealed that ERα interacts physically with hALC-1 in the presence of E2. This interaction was confirmed by Co-Immunoprecipitation and immunofluorescence in human atrium. As a further novel effect, we showed that chronic E2-treatment of adult mouse cardiomyocytes overexpressing hALC-1 resulted in reduced cell-shortening amplitude and twitching kinetics of these cells independent of Ca2+ activation levels. Together, our data showed that the expression of hALC-1 gene is, at least partly, regulated by E2/ERα, while hALC-1 acts as a co-repressor. The inotropic effect of hALC-1 overexpression in cardiomyocytes can be significantly repressed by E2.
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Estradiol/metabolismo , Receptor alfa de Estrógeno/metabolismo , Regulación de la Expresión Génica/genética , Contracción Miocárdica/fisiología , Cadenas Ligeras de Miosina/biosíntesis , Animales , Western Blotting , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoprecipitación , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Miocitos Cardíacos/metabolismo , Cadenas Ligeras de Miosina/genética , Reacción en Cadena de la Polimerasa , Técnicas del Sistema de Dos HíbridosRESUMEN
In this review, we will present the different aspects of coumarins and derivatives, from natural origins or synthetically prepared, and their action on inflammation. Coumarins and also furo- and pyranocoumarins are found in many different plants. These compounds are very often investigated for antioxidant properties. Other biological properties are also possible and anti-inflammation activity is one of these. As coumarins are also available quite easily via synthesis, natural ones can be prepared this way but derivatives with special substituents are also feasible. A review on the same topic appeared in 2004 and our contribution will take into account everything published since then.
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Antiinflamatorios/farmacología , Cumarinas/química , Cumarinas/farmacología , Inflamación/tratamiento farmacológico , Animales , Antiinflamatorios/química , Cumarinas/síntesis química , Furocumarinas/farmacología , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Piranocumarinas/farmacología , Relación Estructura-ActividadRESUMEN
OBJECTIVE: This article introduces the Adaptive Current Tomograph 5 (ACT5) Electrical Impedance Tomography (EIT) system. ACT5 is a 32 electrode applied-current multiple-source EIT system that can display real-time images of conductivity and susceptivity at 27 frames per second. The adaptive current sources in ACT5 can apply fully programmable current patterns with frequencies varying from 5 kHz to 500 kHz. The system also displays real-time ECG readings during the EIT imaging process. METHODS: The hardware and software design and specifications are presented, including the current source design, FPGA hardware, safety features, calibration, and shunt impedance measurement. RESULTS: Images of conductivity and susceptivity are presented from ACT5 data collected on tank phantoms and a human subject illustrating the system's ability to provide real-time images of pulsatile perfusion and ECG traces. SIGNIFICANCE: The portability, high signal-to-noise ratio, and flexibility of applied currents over a wide range of frequencies enable this instrument to be used to obtain useful human subject data with relative clinical ease.
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Tomografía Computarizada por Rayos X , Tomografía , Humanos , Impedancia Eléctrica , Tomografía/métodos , Conductividad Eléctrica , ComputadoresRESUMEN
Owing to its high interest as prolific source of diverse bioactive compounds referred in our previous research work, we have scaled-up the fermentation of the marine Aspergillus terreus LGO13 on a liquid culture medium to isolate and identify the very minor/further promising bioactive secondary metabolites and to study their antibacterial, cytotoxic, and antiviral properties. Twenty-three known bioactive metabolites, including the recently discovered microbial natural product N-benzoyl-tryptophan (1), were obtained herein. Their structures were determined using HR-ESI-MS 1D/2D NMR spectroscopy and data from the literature. The biological properties of the microbial extract and the resulting compounds were examined using a set of microorganisms, cervix carcinoma KB-3-1, nonsmall cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulations were used to investigate the potential targets of the separated metabolites as anti-SARS-CoV-2 drugs. According to the current study, a viral protein that may be the target of anticovid drugs is a papain-like protease (PLpro), and chaetominine (2) appears to be a viable choice against this protein. We evaluated the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2 based on MD data. Chaetominine (2) and azaspirofuran A (9) displayed intermediate selectivity indices (SI = 6.6 and 3.2, respectively), while fumitremorgin C (6) displayed a high selectivity index (SI = 19.77). These findings show that fumitremorgin C has promising antiviral action against SARS-CoV-2.
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Strategies to minimize immune-suppressive medications after liver transplantation are limited by allograft rejection. Biopsy of liver is the current standard of care in diagnosing rejection. However, it adds to physical and economic burden to the patient and has diagnostic limitations. In this review, we aim to highlight the different biomarkers to predict and diagnose acute rejection. We also aim to explore recent advances in molecular diagnostics to improve the diagnostic yield of liver biopsies.
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Four bioactive metabolites; ergosterol (1), peroxy ergosterol (2), α-cyclopiazonic acid (3) and kojic acid (4), were isolated from the fungal sp. Trichoderma viride MM21. Their structures were assigned by cumulative analysis of NMR and mass spectra, and comparison with literature. The antimicrobial activity of the fungus supernatant, mycelial cake, cumulative crude extract and compounds 1-4 was broadly studied against 11 diverse pathogens, revealing auspicious activity results. Based on the molecular docking, ergosterol (1) and peroxy ergosterol (2) were picked up to be computationally tested against topoisomerase IV of Staphylococcus aureus. The nominated enzyme is a possible target for the antibacterial activity of triterpenoidal/steroidal compounds. Compounds 1, 2 showed a deep inserting inside the enzyme groove recording a good binding affinity of -8.1 and -8.4 kcal/mol, respectively. Noteworthy that the antibacterial activity of ergosterol was higher (14-17 mm) than peroxy ergosterol (11-14 mm), although ergosterol formed only one hydrogen bond with the target, while peroxy ergosterol formed three hydrogen bonds. Such higher antibacterial activity of ergosterol may be attributed to its interference with other proteins included in this inhibition. The cytotoxic activity was tested against brine shrimp, revealing 100% mortality for the supernatant, crude extract and whole isolated compounds. Such strong cytotoxicity is attributed most likely to the abundant productivity/concentration of α-cyclopiazonic acid and kojic acid.
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Antibacterianos , Hypocreales , Simulación del Acoplamiento Molecular , Antibacterianos/química , Ergosterol/farmacología , Estructura MolecularRESUMEN
Exercises for the core can be categorized as promoting core-stability, core-strength, or functionality, as these are crucial aspects of most sports activities. This study aimed to examine the effects of using core complex training (CCT), complex training (CT), and core exercise (CE) on some aspects of muscle strength and shooting performance in basketball players. The 36 participants were divided into three groups of 12 each, and then the experimental approach was applied to each group. The groups were labeled as follows: the core complex training group (N = 12; age, 18.58 ± 0.67 years; height, 178.08 ± 0.79 cm; weight, 76.42 ± 1.38 kg; training age, 7.42 ± 0.51 years); the complex training group (N = 12; age, 18.50 ± 0.52 years; height, 177.92 ± 1.31 cm; weight, 76.67 ± 1.78 kg; training age, 7.33 ± 0.49 years); and the core exercise group (n = 12; age, 18.42 ± 0.52 years; height, 177.75 ± 1.29 cm; weight, 76.58 ± 1.38 kg; training age, 7.42 ± 0.67 years). For ten weeks, each of the three groups participated in three training sessions every week. This study investigates the impact of core complex training on basketball shooting ability and muscle strength. The eight-week program, consisting of weight training, plyometric exercises, and core exercises, yielded improvements in muscle strength and shooting accuracy. In tests of muscular strength and basketball shooting ability, the CCT group outperformed the CE and CT groups. The F value varied from 3.75 to 58.77, which are function values with a p < 0.05 significance level. The core complex training group exhibited superior muscle strength to that of both the complex training group and the core exercise group, in some areas. This is shown in the results of the javelin quadrathlon medicine ball test, the core muscle strength and stability test, the sit-up abdomen test, the sit-up back test, the standing long jump test, the Sargent jump test, and the shooting test (p < 0.005). Due to the effect of the core complex training program on improving performance efficiency and muscle strength, which affects the results of matches, we have recommended using the proven basic strength training program at other age stages, with the objective of including the concept, importance, and design of compound basic strength training in training programs used by basketball coaches.
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Background Bronchoscopy is an essential procedure for evaluating, diagnosing, and treating pediatric respiratory diseases. In this study, we demonstrate the indications and contraindications of bronchoscopy done in a tertiary referral hospital, Al Qassimi Woman's and Children's Hospital (AQWCH) in Sharjah, United Arab Emirates (UAE), in order to achieve better service. This study aims to evaluate patients' characteristics, diagnostic and therapeutic indications, and complications of bronchoscopy. Material and method This retrospective chart review included children aged between one day and 13 years, admitted to AQWCH, who underwent bronchoscopy (rigid or flexible) procedures between January 2018 and December 2019. All patients were identified by using a computerized search of hospital discharge diagnosis, which was codiï¬ed as "pediatric bronchoscopy, flexible, rigid, bronchoalveolar lavage". The main study outcome measure was to evaluate patients' characteristics, diagnostic or therapeutic indications, bronchoalveolar lavage (BAL) analysis, as well as complications of bronchoscopy at AQWCH. Results There were 72 pediatric bronchoscopies (rigid and flexible) performed in patients aged less than 13 years old; the reason for bronchoscopy procedure was diagnostic in 51% and both diagnostic and therapeutic in 49%. Cough was the most common symptom (n=53; 74%), and chest recession was the most common clinical finding (n=46; 64%). Foreign body aspiration was the main indication (n=23; 32%), followed by stridor (26%). Consolidation was the most common radiological finding. Foreign body was the common finding, seen in 25% of bronchoscopies, followed by tracheomalacia in 17%. The suspected diagnosis was confirmed in 89%, and management change was needed in 54% of patients. The main complication during the procedure was desaturation (26%), and cough was the main post-bronchoscopy complication (14%). BAL was done for 28 (39%) patients, in which BAL culture was positive in 75%. Rigid bronchoscopy was done when foreign body aspiration was suspected based on positive history in 70%, abnormal physical examination in 60%, and chest X-ray abnormalities in 39% of patients. Sensitivity and specificity for patient history, physical examination, and chest X-ray were 80% and 83%, 66% and 60%, and 40% and 66 %, respectively. Conclusion Bronchoscopy is an important tool for evaluating, diagnosing, and treating pediatric respiratory diseases. While it is a safe procedure, it still needs a careful selection of patients as it is invasive.
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BACKGROUND AND AIMS: Contrast-enhanced cross-sectional imaging is the cornerstone in the diagnosis, staging, and management of HCC, including eligibility for liver transplantation (LT). Radiological-histopathological discordance may lead to improper staging and may impact patient outcomes. We aimed to assess the radiological-histopathological discordance at the time of LT in HCC patients and its impact on the post-LT outcomes. METHODS: We analyzed further the effect of 6-month waiting policy on the discordance. Using United Network for Organ Sharing-Organ Procurement and Transplantation Network (UNOS-OPTN) database, we examined the discordance between pre-LT imaging and explant histopathology for all adult HCC patients who received liver transplants from deceased donors between April 2012 and December 2017. Kaplan-Meier methods and Cox regression analyses were used to evaluate the impact of discordance on 3-year HCC recurrence and mortality. RESULTS: Of 6842 patients included in the study, 66.7% were within Milan criteria on both imaging and explant histopathology, and 33.3% were within the Milan based on imaging but extended beyond Milan on explant histopathology. Male gender, increasing numbers of tumors, bilobar distribution, larger tumor size, and increasing AFP are associated with increased discordance. Post-LT HCC recurrence and death were significantly higher in patients who were discordant, with histopathology beyond Milan (adj HR 1.86, 95% CI 1.32-2.63 for mortality and 1.32, 95% CI 1.03-1.70 for recurrence). Graft allocation policy with 6-month waiting time led to increased discordance (OR 1.19, CI 1.01-1.41), although it did not impact post-LT outcome. CONCLUSION: Current practice for staging of HCC based on radiological imaging features alone results in underestimation of HCC burden in one out of three patients with HCC. This discordance is associated with a higher risk of post-LT HCC recurrence and mortality. These patients will need enhanced surveillance to optimize patient selection and aggressive LRT to reduce post-LT recurrence and increase survival.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Adulto , Humanos , Masculino , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/etiología , Factores de Riesgo , Radiografía , Recurrencia Local de Neoplasia/epidemiología , Estudios RetrospectivosRESUMEN
Purpose: Immune checkpoint inhibitor (ICI) use can lead to immune-related adverse events (irAEs) that require treatment with immunosuppressive medications in moderate to severe cases. Oncology society guidelines recommend systemic steroids and immunosuppressants such as infliximab and vedolizumab for the treatment of refractory cases. Limited information is available about the safety profile and potential adverse effects of these immunosuppressants. We have investigated the safety profile of multiple immunosuppressants which are used in the treatment of ICI-related irAEs. Methods: We performed a systematic review of studies reporting irAEs, from ICI use, and their medical management with immunosuppressants in adult cancer patients. We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov from inception through September 1, 2022, using the following keywords or their equivalents: ICI, immunosuppressant, and irAE. We extracted observational studies and clinical trials that matched our criteria. A random effects model was used to estimate the overall incidence of infections associated with the treatment of irAEs. Results: Among the 11 studies included in this review (1036 total patients), melanoma (548 patients, 52.9%) was the most common primary cancer, followed by lung cancer (139 patients, 13.4%) and genitourinary cancers (131 patients, 12.6%). PD-1/PD-L1 monotherapy (460 patients, 44.4%) was used most, followed by a combination of PD-1/PD-L1 and CTLA-4 therapy (350 patients, 33.8%) and CTLA-4 monotherapy (226 patients, 22%). A total of 1024 (98.8%) patients had their irAEs treated with systemic steroids with majority having colitis and hepatobiliary irAEs; 335 patients (32.3%) were also treated with infliximab (mainly for colitis). Our review found 22.3% of patients treated for irAEs developed infectious adverse events (95% CI: 15.6%-29.1%, p<0.001). Among the 3 studies reporting the types of infections (41 total patients), bacterial (80.5%), followed by fungal (36.6%), infections were most common. Conclusions: Adverse events from irAE treatment occurred in about one-third of patients that received either steroids or a combination of steroids and other immunosuppressants. Clinicians should be aware of these immunosuppressant-related adverse effects, which can negatively impact cancer treatment and patient outcomes, when treating irAEs and consider shortening treatment duration or using alternative strategies when possible to mitigate these complications, future prospective studies should further investigate the safety of immunosuppressants in treating irAEs.
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The current source is one of the most critical circuits in electrical impedance tomography (EIT) hardware systems. The simplicity and excellent performance of the Howland current source makes it a prime candidate for this role in EIT systems. Although the Howland source and its family may be the best option for the high-frequency EIT operation, its low frequency noise may also limit the implementation of a system to simultaneously collect electrocardiogram (ECG) and EIT signals from the electrodes. This paper proposes modifications to the conventional Howland source to make is suitable for simultaneous EIT and ECG. The preliminary experimental results of this modified Howland show significant improvement in the collected ECG signal quality in the presence of the EIT signal.