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1.
Histopathology ; 84(5): 810-821, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38192219

RESUMO

AIMS: The neutrophil-lymphocyte ratio (NLR) is a systemic reflection of cancer-associated inflammation and a prognostic marker for breast cancer. For the local tumour microenvironment, tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) are also highly correlated with breast cancer survival. This study aimed to explore the relationship between the circulating and local immune microenvironment, and to further delineate the prognostic role of NLR in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: A cohort of breast cancer patients receiving NAC with subsequent surgery was retrieved. Clinical data were reviewed. Histological slides and CD8 immunohistochemistry from biopsy (pre-chemotherapy) and excision (postchemotherapy) specimens were assessed for TILs and TAMs. RESULTS: A total of 146 patients were included. There was a significant positive correlation between pre- and postsurgery NLR at a cut-off of 2.6 (median pre-chemotherapy NLR) (P < 0.001). NLR pre-chemotherapy was associated positively with necrosis on biopsy (P = 0.027) and excision (P = 0.021) and TAMs on excision (P = 0.049). NLR 1 year postsurgery was associated with high tumour stage (P = 0.050) and low histological grade (P = 0.008). TIL count was lower in NLR-high cases at almost all time-points by histological assessment and CD8 immunostaining (P < 0.050). In multivariate analysis, postsurgery NLR is an independent predictor for overall survival [OS; hazard ratio (HR) = 9.524, P < 0.001], breast cancer-specific survival (BCSS) (HR = 10.059, P = 0.001) and disease-free survival (DFS; HR = 2.824, P = 0.016). CONCLUSIONS: The association between NLR with tumour necrosis, TAMs and TILs illustrates an interaction between the circulating and local immune microenvironment. Late NLR is a strong indicator of outcome and may be useful for prognostication and disease monitoring.


Assuntos
Neoplasias da Mama , Linfócitos do Interstício Tumoral , Humanos , Feminino , Linfócitos do Interstício Tumoral/patologia , Neoplasias da Mama/patologia , Neutrófilos/patologia , Terapia Neoadjuvante , Macrófagos Associados a Tumor/patologia , Linfócitos/patologia , Prognóstico , Necrose/patologia , Estudos Retrospectivos , Microambiente Tumoral
2.
Mov Disord Clin Pract ; 10(12): 1738-1749, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38094640

RESUMO

Background: Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. Objectives: Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism." Results: The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%-75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%-87%] vs. 45% [95% CI = 33%-57%], P = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment. Conclusions: We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA.

5.
Cochrane Database Syst Rev ; 7: CD013611, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37458279

RESUMO

BACKGROUND: Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease. OBJECTIVES: To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence. MAIN RESULTS: We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Adulto , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Indução de Remissão
7.
J Crohns Colitis ; 17(12): 1920-1930, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37346013

RESUMO

BACKGROUND AND AIMS: Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients. METHODS: Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [>8 weeks] leukopenia, and relative risk of developing leukopenia. RESULTS: Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C > T C/T diplotype was 13% (95% confidence interval [CI]: 10-18%), *3/*3 c.415C > T T/T diplotype was 2% [95% CI: 1-2%], *1/*5 c.52G > A G/A diplotype was 2% [95% CI: 1-3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4-12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16-24%] and Chinese patients [18%, 95% CI: 12-27%]. The incidence of early leukopenia was 20% [95% CI: 16-26%] in *1/*3 patients, 99% [95% CI: 7-100%] in *3/*3 patients, and 49% [95% CI: 29-69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26-49%] in *1/*3 patients. CONCLUSIONS: NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.


Assuntos
Doenças Inflamatórias Intestinais , Leucopenia , Purinas , Compostos de Sulfidrila , Adulto , Humanos , Mercaptopurina/efeitos adversos , Incidência , Prevalência , Predisposição Genética para Doença , Fatores de Risco , Pirofosfatases/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/induzido quimicamente , Leucopenia/induzido quimicamente , Leucopenia/epidemiologia , Leucopenia/genética
8.
Diagnostics (Basel) ; 13(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37189571

RESUMO

We developed a MALDI-TOF mass spectrometry method for the detection of the SARS-CoV-2 virus in saliva-gargle samples using Shimadzu MALDI-TOF mass spectrometers in the UK. This was validated in the USA to CLIA-LDT standards for asymptomatic infection detection remotely via sharing protocols, shipping key reagents, video conferencing, and data exchange. In Brazil, more so than in the UK and USA, there is a need to develop non-PCR-dependent, rapid, and affordable SARS-CoV-2 infection screening tests that also identify variant SARS-CoV-2 and other virus infections. In addition, travel restrictions necessitated remote collaboration with validation on the available clinical MALDI-TOF-the Bruker Biotyper (microflex® LT/SH)-and on nasopharyngeal swab samples, as salivary gargle samples were not available. The Bruker Biotyper was shown to be almost log103 more sensitive at the detection of high molecular weight spike proteins. A protocol for saline swab soaks out was developed, and duplicate swab samples collected in Brazil were analyzed by MALDI-TOF MS. The swab collected sample spectra that varied from that of saliva-gargle in three additional mass peaks in the mass region expected for IgG heavy chains and human serum albumin. A subset of clinical samples with additional high mass, probably spike-related proteins, were also found. Further, spectral data comparisons and analysis, subjected to machine learning algorithms in order to resolve RT-qPCR positive from RT-qPCR negative swab samples, showed 56-62% sensitivity, 87-91% specificity, and a 78% agreement with RT-qPCR scoring for SARS-CoV-2 infection.

9.
Heliyon ; 9(2): e13611, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36879752

RESUMO

A microstrip circuit is designed, constructed, and tested based on the nest microstrip add-drop filters (NMADF). The multi-level system oscillation is generated by the wave-particle behaviors of AC driven along the microstrip ring circular path. The continuous successive filtering is applied via the device input port. The higher-order harmonic oscillations can be filtered, from which the two-level system known as a Rabi oscillation is achieved. The outside microstrip ring energy is coupled to the inside rings, from which the multiband Rabi oscillations can be formed within the inner rings. The resonant Rabi frequencies can be applied for multi-sensing probes. The relationship between electron density and Rabi oscillation frequency of each microstrip ring output can be obtained and used for multi-sensing probe applications. The relativistic sensing probe can be obtained by the warp speed electron distribution at the resonant Rabi frequency respecting the resonant ring radii. These are available for relativistic sensing probe usage. The obtained experimental results have shown that there are 3-center Rabi frequencies obtained, which can be used for 3-sensing probes simultaneously. The sensing probe speeds of 1.1c, 1.4c, and 1.5c are obtained using the microstrip ring radii of 14.20, 20.12, and 34.49 mm, respectively. The best sensor sensitivity of 1.30 ms is achieved. The relativistic sensing platform can be used for many applications.

10.
Diagnostics (Basel) ; 12(10)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36292212

RESUMO

The prefusion spike protein of SARS-CoV-2 binds advanced glycation end product (AGE)-glycated human serum albumin (HSA) and a higher mass (hyperglycosylated/glycated) immunoglobulin (Ig) G3, as determined by matrix assisted laser desorption mass spectrometry (MALDI-ToF). We set out to investigate if the total blood plasma of patients who had recovered from acute respiratory distress syndrome (ARDS) as a result of COVID-19, contained more glycated HSA and higher mass (glycosylated/glycated) IgG3 than those with only clinically mild or asymptomatic infections. A direct serum dilution, and disulphide bond reduction, method was developed and applied to plasma samples from SARS-CoV-2 seronegative (n = 30) and seropositive (n = 31) healthcare workers (HCWs) and 38 convalescent plasma samples from patients who had been admitted with acute respiratory distress (ARDS) associated with COVID-19. Patients recovering from COVID-19 ARDS had significantly higher mass AGE-glycated HSA and higher mass IgG3 levels. This would indicate that increased levels and/or ratios of hyper-glycosylation (probably terminal sialic acid) IgG3 and AGE glycated HSA may be predisposition markers for the development of COVID-19 ARDS as a result of SARS-CoV2 infection. Furthermore, rapid direct analysis of serum/plasma samples by MALDI-ToF for such humoral immune correlates of COVID-19 presents a feasible screening technology for the most at risk; regardless of age or known health conditions.

11.
Viruses ; 14(9)2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-36146765

RESUMO

Applying MALDI-ToF mass spectrometry as a clinical diagnostic test for viruses is different from that of bacteria, fungi and other micro-organisms. This is because the systems biology of viral infections, the size and chemical nature of specific viral proteins and the mass spectrometry biophysics of how they are quantitated are fundamentally different. The analytical challenges to overcome when developing a clinical MALDI-ToF mass spectrometry tests for a virus, particularly human pathogenic enveloped viruses, are sample enrichment, virus envelope disruption, optimal matrix formulation, optimal MALDI ToF MS performance and optimal spectral data processing/bioinformatics. Primarily, the instrument operating settings have to be optimized to match the nature of the viral specific proteins, which are not compatible with setting established when testing for bacterial and many other micro-organisms. The capacity to be a viral infection clinical diagnostic instrument often stretches current mass spectrometers to their operational design limits. Finally, all the associated procedures, from sample collection to data analytics, for the technique have to meet the legal and operational requirement for often high-throughput clinical testing. Given the newness of the technology, clinical MALDI ToF mass spectrometry does not fit in with standard criteria applied by regulatory authorities whereby numeric outputs are compared directly to similar technology tests that have already been authorized for use. Thus, CLIA laboratory developed test (LDT) criteria have to be applied. This article details our experience of developing a SAR-CoV-2 MALDI-ToF MS test suitable for asymptomatic carrier infection population screening.


Assuntos
COVID-19 , Viroses , Vírus , Bactérias/química , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Proteínas Virais , Viroses/diagnóstico
12.
Compr Psychoneuroendocrinol ; 10: 100128, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35755206

RESUMO

Background: Neurocognitive impairment is common in people with Sickle Cell Disease (SCD) and evidence is accumulating that sleep disturbances play a role. The interaction between cortisol and sleep in the general population is associated with cognition as well as general wellbeing but there are few data in SCD. We aimed to understand the relationship between cortisol and sleep in individuals with SCD and explored associations with cognition. Methods: Forty-five participants of black heritage (SCD: N = 27, 9-29 years, 16 females; Controls: N = 18, 11-25 years, 13 females) were recruited from the community between 2018 - 2020. Participants completed standardized questionnaires about their sleep behaviour and wore actigraphy MotionWatch8 for 7 nights to assess nocturnal sleep patterns. Salivary cortisol samples were taken on wakening and 3 times after 14:00. Cognition was assessed using the Wechsler Intelligence Scales for children and adults. Results: People with SCD took longer to fall asleep and experienced greater wake bouts, mobile minutes and fragmented sleep compared to controls. Although non-significant, people with SCD experienced lower morning cortisol, with a flattened diurnal cortisol ratio compared to controls. Interestingly, SCD participants, but not controls, with low diurnal variation scored lowest on processing speed (PSI) and perceptual reasoning index (PRI). A moderator analysis revealed that the effect of morning cortisol and diurnal cortisol ratio on PRI by group health (i.e., SCD and healthy controls) depended on sleep quality. Discussion: Sleep and cortisol may play a crucial role in the expression of cognitive difficulties seen in SCD. This should be considered for the development of interventions to optimise cognitive functioning and sleep. This, in turn, could positively impact on secretion of cortisol and general health in SCD.

13.
Int J Mol Sci ; 23(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35456942

RESUMO

The immune response to SARS-CoV-2 infection requires antibody recognition of the spike protein. In a study designed to examine the molecular features of anti-spike and anti-nucleocapsid antibodies, patient plasma proteins binding to pre-fusion stabilised complete spike and nucleocapsid proteins were isolated and analysed by matrix-assisted laser desorption ionisation-time of flight (MALDI-ToF) mass spectrometry. Amongst the immunoglobulins, a high affinity for human serum albumin was evident in the anti-spike preparations. Careful mass comparison revealed the preferential capture of advanced glycation end product (AGE) forms of glycated human serum albumin by the pre-fusion spike protein. The ability of bacteria and viruses to surround themselves with serum proteins is a recognised immune evasion and pathogenic process. The preference of SARS-CoV-2 for AGE forms of glycated serum albumin may in part explain the severity and pathology of acute respiratory distress and the bias towards the elderly and those with (pre)diabetic and atherosclerotic/metabolic disease.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Idoso , Anticorpos Antivirais , Humanos , SARS-CoV-2 , Albumina Sérica , Albumina Sérica Humana , Glicoproteína da Espícula de Coronavírus/metabolismo
14.
Ann Thorac Surg ; 114(5): 1824-1832, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35351425

RESUMO

BACKGROUND: The Lung Cancer Study Group has shown that lobectomy provides the best survival in patients with non-small cell lung cancer. However, as patients become older, lobectomy may not provide a survival advantage compared with sublobar resection. METHODS: We analyzed the National Cancer Database for octogenarians with pathologic stage I lung cancer from 2004 to 2016. We then evaluated the patients who underwent lobectomy or sublobar (segmentectomy or wedge) resection for the treatment of cancer. We analyzed the 5-year survival rates of the groups as well as a cubic spline plot to determine age cutoffs where lobectomy does not provide improved survival. RESULTS: Among the octogenarians (227 134), there were 25 362 (26%) who had pathologic stage I lung cancer. There were 6370 (30%) patients who had sublobar resections (segmentectomy [n = 1192] and wedge resection [n = 5178]), whereas 14 594 (70%) patients had a lobectomy. There was significantly improved survival at 5 years with lobectomy compared with sublobar resection (48.5% vs 41.1%; P < .001). The cubic spline plot provided evidence that there was no age at which sublobar resection provided survival better than or equal to lobectomy (P < .001). CONCLUSIONS: In octogenarians with pathologic stage I lung cancer, lobectomy provided better 5-year survival compared with sublobar resection regardless of the age at surgical procedure. Hence, all patients with stage I cancer should be considered for a lobectomy if they are medically able to tolerate such a procedure.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso de 80 Anos ou mais , Humanos , Neoplasias Pulmonares/patologia , Pneumonectomia/métodos , Estadiamento de Neoplasias , Taxa de Sobrevida , Estudos Retrospectivos
15.
Surg Endosc ; 36(4): 2365-2372, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33948715

RESUMO

BACKGROUND: Manometry is the gold standard diagnostic test for achalasia. However, there are incidences where manometry cannot be obtained preoperatively, or the results of manometry is inconsistent with the patient's symptomatology. We aim to determine if intraoperative use of EndoFLIP can provide a diagnosis of achalasia and provide objective information during Heller myotomy and Dor fundoplication. METHODS: To determine the intraoperative diagnostic EndoFLIP values for patients with achalasia, we determined the optimal cut-off points of the distensibility index (DI) between patients with a diagnosis of achalasia and patients with a diagnosis of hiatal hernia. To evaluate the usefulness of EndoFLIP values during Heller myotomy and Dor fundoplication, we obtained a cohort of patients with EndoFLIP values obtained after Heller myotomy and after Dor fundoplication as well as Eckardt score before and after surgery. RESULTS: Our analysis of 169 patients (133 hiatal hernia and 36 achalasia) showed that patients with DI < 0.8 have a >99% probability of having achalasia, while DI > 2.3 have a >99% probability of having hiatal hernia. Patients with a DI 0.8-1.3 have a 95% probability of having achalasia, and patients with a DI of 1.4-2.2 have a 94% probability of having a hiatal hernia. There were 40 patients in the cohort to determine objective data during Heller myotomy and Dor fundoplication. The DI increased from a median of 0.7 to 3.2 after myotomy and decreased to 2.2 after Dor fundoplication (p < 0.001). The median Eckardt score went down from a median of 4.5 to 0 (p < 0.001). CONCLUSIONS: Our study shows that intraoperative use of EndoFLIP can facilitate the diagnosis of achalasia and is used as an adjunct to diagnose achalasia when symptoms are inconsistent. The routine use of EndoFLIP during Heller myotomy and Dor fundoplication provides objective data during the operation in a group of patients with excellent short-term outcomes.


Assuntos
Acalasia Esofágica , Miotomia de Heller , Hérnia Hiatal , Laparoscopia , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/cirurgia , Fundoplicatura/métodos , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/cirurgia , Humanos , Laparoscopia/métodos , Resultado do Tratamento
16.
Rep Pract Oncol Radiother ; 26(3): 400-407, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277093

RESUMO

BACKGROUND: Cervical cancer is a major health problem, especially in developing countries like India. Extended field radiotherapy (EFRT) for cancer cervix treatment remains a challenging task for radiation oncologists. In the last decade studies have shown that EFRT using intensity modulated radiotherapy (IMRT) is feasible in treating gynaecological malignancies but there is a dearth of literature on this specific topic from this part of the world where patient profile differs greatly in several aspects from that of the western world. The aim of the study was evaluation of treatment response and toxicity profile in cases of carcinoma cervix with metastatic para-aortic nodes treated with intensity modulated radiotherapy technique. MATERIALS AND METHODS: In this retrospective study the treatment records of 45 para-aortic node positive cervical cancer patients treated with EFRT (IMRT) and concurrent cisplatin were analysed for evaluation of loco-regional control and toxicities. RESULTS: Forty-four patients received full course of treatment. Among those 44 patients, 93.2% achieved complete response. Overall, the treatment was tolerated well and toxicities were within acceptable limits. Acute grade 3-4 toxicities were observed mostly in the form of anaemia and leucopenia. Most common late toxicities were those of small and large intestine. CONCLUSION: EFRT with concurrent chemotherapy was successfully delivered for para-aortic nodes positive cervical cancer patients in Indian scenario where under-nutrition, infection, anaemia and several other factors adversely influence treatment outcome. Pelvic and para-aortic control rates were satisfactory. The technique was associated with an acceptable acute and late toxicity profile.

17.
Methodist Debakey Cardiovasc J ; 17(1): 24-35, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-34104317

RESUMO

Ventricular arrhythmias are potentially life-threatening disorders that are commonly treated with medications, catheter ablation and implantable cardioverter defibrillator (ICD). Adult patients who continue to be symptomatic, with frequent ventricular arrhythmia cardiac events or defibrillation from ICD despite medical treatment, are a challenging subgroup to manage. Surgical cardiac sympathetic denervation has emerged as a possible treatment option for people refractory to less invasive medical options. Recent treatment guidelines have recommendedcardiac sympathectomy for ventricular tachycardia (VT) or VT/fibrillation storm refractory to antiarrhythmic medications, long QT syndrome, and catecholaminergic polymorphic VT, with much of the data pertaining to pediatric literature. However, for the adult population, the disease indications, complications, and risks of cardiac sympathectomy are less understood, as are the most effective surgical cardiac denervation techniques for this patient demographic. This systematic review navigates available literature evaluating surgical denervation disease state indications, techniques, and sympathectomy risks for medically refractory ventricular arrhythmia in the adult patient population.


Assuntos
Frequência Cardíaca , Coração/inervação , Simpatectomia , Sistema Nervoso Simpático/cirurgia , Taquicardia Ventricular/cirurgia , Fibrilação Ventricular/cirurgia , Potenciais de Ação , Humanos , Complicações Pós-Operatórias/etiologia , Recidiva , Medição de Risco , Fatores de Risco , Simpatectomia/efeitos adversos , Sistema Nervoso Simpático/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/fisiopatologia
18.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802374

RESUMO

There have been over 8 million babies born through in vitro fertilization (IVF) and this number continues to grow. There is a global trend to perform elective single embryo transfers, avoiding risks associated with multiple pregnancies. It is therefore important to understand where current research of noninvasive testing for embryos stands, and what are the most promising techniques currently used. Furthermore, it is important to identify the potential to translate research and development into clinically applicable methods that ultimately improve live birth and reduce time to pregnancy. The current focus in the field of human reproductive medicine is to develop a more rapid, quantitative, and noninvasive test. Some of the most promising fields of research for noninvasive assays comprise cell-free DNA analysis, microscopy techniques coupled with artificial intelligence (AI) and omics analysis of the spent blastocyst media. High-throughput proteomics and metabolomics technologies are valuable tools for noninvasive embryo analysis. The biggest advantages of such technology are that it can differentiate between the embryos that appear morphologically identical and has the potential to identify the ploidy status noninvasively prior to transfer in a fresh cycle or before vitrification for a later frozen embryo transfer.


Assuntos
Meios de Cultura/metabolismo , Técnicas de Cultura Embrionária/métodos , Transferência Embrionária/métodos , Embrião de Mamíferos/citologia , Inteligência Artificial , Blastocisto/citologia , Feminino , Fertilização in vitro/métodos , Humanos , Gravidez
19.
Cognit Comput ; : 1-14, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33456619

RESUMO

Light fidelity (LiFi) and wireless fidelity (WiFi) can be applied with the same network under the different constraints, which is suitable for COVID-19 surveillance in hospitals. The LiFi network is a high-capacity and security platform. A COVID-19 surveillance system using LiFi is proposed, which consists of two switching modes: communication and surveillance. Firstly, the communication targets are to accommodate the electromagnetic interference (EMI) immunity and high-capacity and security data transmission, where secondly the COVID-19 surveillance can be applied. In operation, the up and downlink system uses a metamaterial antenna embedded by Mach Zehnder interferometer (MZI). An antenna consists of silver bars embedded at the microring center with two-phase modulators at its sides. The entangled source namely a dark soliton is applied to form the transmission, where the information security based on quantum cryptography can be managed. By using the suitable parameters, the whispering gallery modes (WGMs) are generated and the up and downlink nodes are formed. The input information is multiplexed with time to form the multiplexed signals, where the big data transmission (40 Pbit  s - 1 ) can be employed. By using the surveillance mode, the plasmonic antenna can be applied for temperature and electric force sensors, which can offer the disinfectant spray and temperature sensor for COVID-19 applications. The optimum plasma force sensitivity is 0.16 N kg-1 mW-1. The center frequencies of 191.48 THz and 199.41 THz are obtained for uplink and downlink antennas, respectively. The optimum temperature sensitivity is 0.05 rads-1 °C-1. In conclusion, the novelty of proposed work is that the integrated sensor circuits are employed for COVID-19 surveillance in the hospital. The fuzzy-based system is designed for critical patient monitoring alert using this surveillance and management inside the hospital for COVID-19 patients.

20.
Curr Med Chem ; 28(32): 6532-6547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33109029

RESUMO

Current methods for diagnosing human disease are still incapable of rapidly and accurately screening for multiple diseases simultaneously on a large scale, and at an affordable price. MALDI-ToF mass spectrometry is an ultra-sensitive, ultra-fast, lowcost, high-throughput technology that has the potential to achieve this goal, allowing human phenotype characterization and thus phenomic screening for multiple disease states. In this review, we will discuss the main advances achieved so far, putting forward targeted applications of MALDI-ToF mass spectrometry in the service of human disease detection. This review focuses on the methodological workflow as MALDI-ToF data processing for phenomic analysis, using state-of-the-art bioinformatic pipelines and software tools. The role of mathematical modelling, machine learning, and artificial intelligence algorithms for disease screening are considered. Moreover, we present some previously developed tools for disease diagnostics and screening based on MALDI-ToF analysis. We discuss the remaining challenges that are ahead when implementing MALDI-ToF into clinical laboratories. Differentiating a standard profile from a single disease phenotype is challenging, but the potential to simultaneously run multiple algorithm screens for different disease phenotypes may only be limited by computing power once this initial hurdle is overcome. The ability to explore the full potential of human clinical phenomics may be closer than imagined; this review gives an insight into the benefits this technology may reap for the future of clinical diagnostics.


Assuntos
Biologia Computacional , Fenômica , Inteligência Artificial , Humanos , Aprendizado de Máquina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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