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Epigenetic mechanisms are essential to establish and safeguard cellular identities in mammals. They dynamically regulate the expression of genes, transposable elements and higher-order chromatin structures. Consequently, these chromatin marks are indispensable for mammalian development and alterations often lead to disease, such as cancer. Bivalent promoters are especially important during differentiation and development. Here we used a genetic screen to identify new regulators of a bivalent repressed gene. We identify BEND3 as a regulator of hundreds of bivalent promoters, some of which it represses, and some of which it activates. We show that BEND3 is recruited to a CpG-containg consensus site that is present in multiple copies in many bivalent promoters. Besides having direct effect on the promoters it binds, the loss of BEND3 leads to genome-wide gains of DNA methylation, which are especially marked at regions normally protected by the TET enzymes. DNA hydroxymethylation is reduced in Bend3 mutant cells, possibly as consequence of altered gene expression leading to diminished alpha-ketoglutarate production, thus lowering TET activity. Our results clarify the direct and indirect roles of an important chromatin regulator, BEND3, and, more broadly, they shed light on the regulation of bivalent promoters.
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Metilação de DNA , Proteínas Repressoras , Animais , Humanos , Cromatina/genética , Metilação de DNA/genética , Epigênese Genética , Expressão Gênica , Mamíferos/genética , Neoplasias/genética , Proteínas Repressoras/metabolismoRESUMO
BACKGROUND: Cardiogenic shock (CS) is complicated by high mortality rates. Targeted temperature control (TTC) has been proposed as an adjunct therapy in CS. This study aims to examine the safety of TTC in patients presenting with CS. METHODS AND RESULTS: In this open-label, randomized controlled pilot trial, 20 patients with hemodynamic criteria for CS were assigned to standard of care plus TTC vs standard of care alone. The primary outcome was a composite safety outcome, including well-described complications of TTC. Secondary outcomes included mortality at 90 days, invasive hemodynamic and echocardiographic parameters, electrocardiographic measurements, and inotrope dosing. There were no significant differences in the composite analysis of prespecified safety outcomes (3 events in the TTC group vs 0 events in the control group; Pâ¯=â¯0.24). Patients randomized to TTC demonstrated a statistically significant increase in cardiac index and cardiac power index compared to the control group at 48-96 hours after randomization (3.6 [3.1, 3.9] L/min/m2 vs 2.6 [2.5, 3.15] L/min/m2; Pâ¯=â¯0.029 and 0.61 [0.55, 0.7] W/m2 vs 0.53 [0.435, 0.565] W/m2; Pâ¯=â¯0.029, respectively). CONCLUSION: TTC may be a safe adjunct therapy for patients presenting with CS and may yield improvement in specific hemodynamic parameters.
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Hipotermia Induzida , Choque Cardiogênico , Humanos , Choque Cardiogênico/terapia , Choque Cardiogênico/fisiopatologia , Choque Cardiogênico/mortalidade , Masculino , Feminino , Idoso , Projetos Piloto , Pessoa de Meia-Idade , Hipotermia Induzida/métodos , Resultado do Tratamento , Hemodinâmica/fisiologiaRESUMO
INTRODUCTION: Post-operative analgesia is an important component of patient satisfaction and early discharge from the hospital. A variety of modalities have been tested and are still evolving. The present study is one such evaluation of a novel technique of laparoscopy-guided transverse abdominis plane (LTAP) block for post-operative analgesia in laparoscopic cholecystectomy. PATIENTS AND METHODS: A prospective randomised control trial was conducted to verify the effectiveness of LTAP block over port site local anaesthesia infiltration (PSLAI) for post-operative analgesia in patients undergoing laparoscopic cholecystectomy. This study was done over a period of 18 months in a tertiary hospital. A total of 84 patients were recruited and were divided equally into two groups (LTAP and PSLAI). RESULTS: There was no statistical difference between the two groups with respect to gender distribution, comorbidities, number of gallstones, duration of symptoms and surgery time. The rescue dose of diclofenac requirement was less for the LTAP group in comparison to the PSLAI group. No difference was observed in the pain score at 1st h. However, LTAP proved efficient later in the post-operative course (6 h, 24 h and at discharge). There was significant a difference in the pain scores between the two groups, favouring the LTAP group. Hospital stay in the LTAP group was less in comparison to the PSLAI group. CONCLUSION: LTAP block is an effective method of post-operative analgesia. It impacts analgesia to the whole anterior abdominal wall for a prolonged period when compared to the PSLAI without adding any extra procedural time.
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Objective. Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases characterized by the presence of ectopic fat in the liver and steatosis, which cannot be explained by alcohol consumption. The association between NAFLD and type 2 diabetes mellitus (T2DM) is well established. As liver fibrosis progresses in a patient with NAFLD, insulin resistance (IR) increases and may worsen diabetes control. The aspartate aminotransferase platelet ratio index (APRI) score is a simple and inexpensive bedside marker that can detect liver fibrosis and cirrhosis. Several studies have shown an association between APRI and NAFLD. However, there is a gap in correlation with IR in patients with diabetes. In this study, we sought to correlate IR and NAFLD in diabetes using the APRI score. Methods. This observational hospital-based cross-sectional study was conducted in the Department of General Medicine, one of the tertiary care hospitals in North India, from February 2019 to July 2020. A total of 70 patients were taken for the study. Patients with T2DM, aged >30 years, who had no history of alcohol use and who had or were newly diagnosed with NAFLD were enrolled in the study. Results. Significant differences in mean HbAc1, AST, serum insulin, APRI score and homeo-static model assessment-2 (HOMA2) IR between NAFLD grade 1, grade 2, and grade 3 groups were found. Pearson correlation between APRI score and HOMA2 IR total values revealed a significant positive correlation between them. Conclusions. The data of the present study indicate that the APRI score can be used to assess the IR degree and provide important information for improving glycemic control in T2DM patients with NAFLD.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Aspartato Aminotransferases , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnósticoRESUMO
BACKGROUND: Chronic kidney disease (CKD), due to increasing frequency and prevalence, has become one of the leading public health issues. The Kidney Disease Outcome Quality Initiative (KDOQI) defines CKD as kidney injury or a reduction in the glomerular filtration rate (GFR) to <60 mL/minute/1.73 m2 for at least 3 months. This study aims to compare the effects of decreased renal function on thyroid profile and lipid profile in CKD patients. MATERIALS AND METHODS: This is a prospective cross-sectional observational study conducted among the patients attending Outpatient Department/Inpatient Department (OPD/IPD) at the School of Medical Sciences & Research, Sharda Hospital, Greater Noida, Uttar Pradesh, India, in known cases of CKD, irrespective of the treatment/stage of CKD. All patients of >18 years of age with CKD were included in the study. RESULT: A total of 200 patients who met the inclusion criteria were included after obtaining detailed informed consent, of which 100 were cases and 100 were controls. The mean age of patients in the study was 47.74 years, with the mean age in patients with CKD 52 years, and the control was 43 years. The mean level of triglycerides (TGs) was significantly higher among the cases, and the high-density lipoprotein (HDL) was significantly lower among cases compared to controls (p < 0.05). Pearson's correlation between thyroid-stimulating hormone (TSH) with creatinine showed a weak albeit significant positive association (r = 0.200; p < 0.05). CONCLUSION: Our study shows a higher incidence of alteration in thyroid profile and dyslipidemia among the patients with CKD compared to controls. There is a necessary need to screen routinely for hypothyroidism and dyslipidemia among patients with CKD. Importantly, thyroid hormone levels and their effects on the progression of CKD have not been studied exhaustively.
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Dislipidemias , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Glândula Tireoide , Estudos Transversais , Estudos Prospectivos , Centros de Atenção Terciária , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Diálise Renal , Triglicerídeos , Dislipidemias/complicaçõesRESUMO
Intussusception in adults represents 1% of bowel obstructions and up to 0.02% of all hospital admissions. Amongst these, colo-colic intussusception of the descending colon forms the rarest of causes due to the fixed nature of the descending colon. Most of adult intussusceptions follow a lead point and are commonly due to colonic malignancy which may get missed on pre-operative evaluation. Surgery is usually warranted as these patients are usually symptomatic and at risk of vascular compromise, leading to perforations and obscure malignancies. We present a case of laparoscopic limited hemicolectomy and primary anastomosis in a middle-aged male who presented with colo-colic intussusception, which appeared to be following a malignant mass on imaging and lipoma on colonoscopic biopsy done twice. Keeping in mind the possibility of a malignant lead point, no attempt was made to reduce the intussusception and a vessel first approach with 5 cm margin on either side was performed.
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BACKGROUND: The long-term effects of COVID on the lungs remain unclear, but, given the extent of the pandemic, it has the potential to become a significant chronic global health problem .Aim of our study was to ascertain the proportion of patients with moderate to severe pneumonia but without mechanical ventilation who have compromised exercise capacity, pulmonary function test and presence of radiological abnormalities and to study any correlation between clinical features with radiological abnormalities. METHODS: In a hospital-based study, COVID-19 patients with moderate and severe pneumonia were followed 3 months after discharge and assessed with chest computed tomography (CT) imaging, 6 minute walk test and pulmonary function tests. RESULTS: A total of 102 participants were enrolled, including64 patients who had recovered from moderate disease and 38 patients from severe COVID-19. The patients with critical disease and who required mechanical ventilation or who had previously known chronic lung disease were excluded. High proportion of patients of both groups showed radiological abnormalities and deranged pulmonary function tests 3 months after recovery from acute illness which had significant correlation with severity of disease. CONCLUSIONS: Pulmonary function and radiological abnormalities remained in significant propotion of patients 3 months after recovery from COVID-19 that needs more attention on pulmonary rehabilitation and long term follow up of these patients.
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COVID-19 , Pneumonia , Tolerância ao Exercício , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Pneumonia/epidemiologia , Respiração Artificial , SARS-CoV-2RESUMO
BACKGROUND: Hyperuricemia has been associated with chronic kidney disease, evidence suggests that hyperuricemiamight plays a role in progression of renal damage. Whether hyperuricemia can lead to renal tubular injury remains unclear. In this study we aimed to determine serum NGAL and urinary NGAL/creatinine ratio as markers of reanal tubular injury in metabolic syndrome patientshave hyper or normouricemia. MATERIAL AND METHODS: In this hospital based cross- sectional study,180 par ticipants with metabolic syndrome were included,90 patients had hyperuricemia and 90 were with normouricemia. Clinical biochemical parameters of serum NGAL and urinary NGAL were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Receiver operating characteristic(ROC) curve was analysis was employed to assess the sensitivity and specificity of serum NGAL and urine NGAL/creatinine ratio. RESULTS: Out of all, 96 were males and 84 were females. The mean age of participants was 45 ± 7 years. Serum NGAL levels and Urinary NGAL/creatinine ratio were higher in metabolic syndrome patients with hyperuricemia. High Serum NGAL was positively correlated with presence of hypertension; HbA1c and waist-hip ratio and negatively correlated with HDL. CONCLUSION: Serum NGAL levels and urinary NGAL/creatinine ratio were higher in metabolic syndrome patients with hyperuricemia that indicates presence of renal tubular injury in these patients. High Serum NGAL was positively correlated with presence of hypertension; HbA1c and waist-hip ratio.
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Hiperuricemia , Síndrome Metabólica , Proteínas de Fase Aguda , Adulto , Feminino , Humanos , Hiperuricemia/diagnóstico , Lipocalina-2 , Lipocalinas , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Proteínas Proto-OncogênicasRESUMO
INTRODUCTION: Coronavirus disease associated mucormycosis (CAM), perturbed a lot by reaching to epidemic proportions particularly during the second wave of the pandemic. MATERIAL AND METHODS: This was a retrospective, observational study of patients with COVID-19-associated mucomycosis admitted in April-May 2021 at a tertiary care teaching hospital. Demographic profile, clinical and laboratory parameters were recorded Multidisciplinary treatment including antifungals and surgical interventions were noted. RESULTS: This study included 98patients of mucormycosis, diagnosed on the basis of clinical and radiological findings and later were confirmed by microbiological investigations. Out of 98 patients, 72 had rhino orbital, 24 had rhino-orbitalcerebral and 2 had pulmonary mucormycosis. Twelve had coinfection of covid 19 while 86 had developed mucormycosis within 3 weeks. CONCLUSION: CAM has posed as a continuum of challenges faced during the pandemic of covid 19. This rare and life threatening complication requires high index of suspicion for early diagnosis. Multidisciplinary involvement and timely interventions including antifungal pharmacotherapy, stringent glycemic control and surgical debridement can reduce the mortality. Mucormycosis is uniformly associated with low iron levels but role of zinc needs to be further studied.
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COVID-19 , Mucormicose , Antifúngicos/uso terapêutico , Humanos , Ferro , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Pandemias , SARS-CoV-2 , Zinco/uso terapêuticoRESUMO
BACKGROUND: Clinical studies have correlated severe deterioration of COVID-19 patients due to excessive and uncontrolled production of cytokines. There is a pressing need to explore therapies, which could prevent the cytokine storm rather than terminating it. AIMS AND OBJECTIVES: The aim of the study is to evaluate the effect of itolizumab on clinical outcomes of patients with moderate-severe COVID-19 disease admitted to ICU. The primary aim of the current study is to find out any mortality benefit in 14 days. The secondary aim is to assess the morbidity outcomes in terms of reduction in inflammatory markers and also the duration of hospital stays to assess the prognostication. MATERIALS AND METHODS: It is a retrospective case-control study in which laboratory-confirmed COVID-19 patients admitted to ICU were taken. A total of 62 patients were recruited, 31 patients received itolizumab (cases/treatment group) and 31 patients didn't receive itolizumab (designated as controls). RESULTS: Among the total patients recruited, 68% of the study population was male and 32% were female. A total of 12 patients expired among cases and 13 expired among controls. Overall mortality in both groups was noted to be almost similar. The control group showed mortality at lower computed tomography (CT) scores compared to the cases. There is a significant reduction in inflammatory markers, like interleukins-6 (IL-6) and D-dimer in cases compared to the control group. CONCLUSION: In conclusion, treating patients with cytokine storms before they require intubation/mechanical ventilation is crucial to preventing deaths. Itolizumab has shown no clinical benefit in critically ill COVID-19 patients, however, timely initiation of itolizumab therapy may serve as a key therapeutic option in preventing the mortality and morbidity outcomes in moderate-severe COVID-19 patients.
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COVID-19 , Humanos , Masculino , Feminino , SARS-CoV-2 , Estudos de Casos e Controles , Estudos Retrospectivos , Centros de Atenção Terciária , Unidades de Terapia IntensivaRESUMO
PURPOSE: To determine the effect of partial nephrectomy (PN) in the solitary kidney on systolic and diastolic blood pressures (SBP and DBP, respectively), and use of antihypertensive medications. METHODS: We performed a retrospective cohort study of solitary kidney patients who underwent PN for kidney cancer from 1999-2015. Primary outcomes evaluated were blood pressure (BP) and antihypertensive medication changes from baseline up to 5 years postoperatively. Using a multivariable mixed-effects model to account for repeated measurements, we evaluated the effect of PN on the outcome measurements while controlling for baseline patient, pathologic, and perioperative characteristics. RESULTS: 292 patients who underwent PN on solitary kidneys met inclusion criteria (median [range] age, 63 [24-84] years; 179 men [61%]). SBP decreased immediately postoperatively (- 1.7 mmHg [- 2.6, - 0.7], p < 0.001), and further decreased by 0.04 mmHg per year (p = 0.01) postoperatively, for a total change of - 1.9 [- 3.9, 0.2] mmHg at 5 years (p = 0.01). DBP decreased immediately postoperatively (- 2.2 mmHg [- 2.7, - 1.7], p < 0.001), and then rebounded by 0.37 mmHg per year (p = 0.003) postoperatively, for a total change of - 0.4 [- 1.5, 0.7] mmHg at 5 years (p = 0.003). Antihypertensive medication use increased at 5 years (0.35 more medications per patient, p < 0.001). CONCLUSIONS: Our results suggest a minimal change in BP after PN, although patients increased antihypertensive medication use. This data suggests damage to renal parenchyma or hilar nerves during PN did not significantly impact BP regulation in our cohort.
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Pressão Sanguínea , Hipertensão/complicações , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Rim Único/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE OF REVIEW: Rezum® is a novel convection-based thermal therapy for benign prostatic hyperplasia (BPH) induced lower urinary tract symptoms (LUTS). This review provides an overview of its safety, efficacy, cost, and potential role in the paradigm of BPH/LUTS therapies. RECENT FINDINGS: Data regarding Rezum® stems primarily from one large randomized controlled trial of 197 patients with 4 years of follow-up. The efficacy and safety of Rezum® is further supported by 4 additional studies including 1 prospective pilot study, 1 crossover study, and 2 retrospective studies. Durable improvements in IPSS (47-60%), QoL (38-52%), Qmax (45-72%), and PVR (11-38%) were seen without causing deterioration of sexual function. Rezum® offers a cost-effective and safe approach to treating BPH/LUTS and should be considered as a possible first-line therapy for patients with moderate to severe symptoms.
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Técnicas de Ablação/métodos , Sintomas do Trato Urinário Inferior/cirurgia , Hiperplasia Prostática/cirurgia , Vapor , Ressecção Transuretral da Próstata/métodos , Técnicas de Ablação/economia , Técnicas de Ablação/tendências , Convecção , Cistoscopia , Humanos , Hipertermia Induzida/economia , Hipertermia Induzida/métodos , Hipertermia Induzida/tendências , Sintomas do Trato Urinário Inferior/economia , Sintomas do Trato Urinário Inferior/etiologia , Imageamento por Ressonância Magnética , Masculino , Próstata/diagnóstico por imagem , Próstata/cirurgia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/economia , Ressecção Transuretral da Próstata/economia , Ressecção Transuretral da Próstata/tendências , Resultado do TratamentoRESUMO
The proper tissue-specific regulation of gene expression is essential for development and homeostasis in metazoans. However, the illegitimate expression of normally tissue-restricted genes-like testis- or placenta-specific genes-is frequently observed in tumors; this promotes transformation, but also allows immunotherapy. Two important questions are: how is the expression of these genes controlled in healthy cells? And how is this altered in cancer? To address these questions, we used an unbiased approach to test the ability of 350 distinct genetic or epigenetic perturbations to induce the illegitimate expression of over 40 tissue-restricted genes in primary human cells. We find that almost all of these genes are remarkably resistant to reactivation by a single alteration in signaling pathways or chromatin regulation. However, a few genes differ and are more readily activated; one is the placenta-expressed gene ADAM12, which promotes invasion. Using cellular systems, an animal model, and bioinformatics, we find that a non-canonical but druggable TGF-ß/KAT2A/TAK1 axis controls ADAM12 induction in normal and cancer cells. More broadly, our data show that illegitimate gene expression in cancer is an heterogeneous phenomenon, with a few genes activatable by simple events, and most genes likely requiring a combination of events to become reactivated.
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Regulação da Expressão Gênica/genética , Neoplasias/genética , Especificidade de Órgãos/genética , Transcrição Gênica/genética , Proteína ADAM12/genética , Proteína ADAM12/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Cromatina/genética , Cromatina/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Histona Acetiltransferases/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , Transdução de Sinais/genética , Fator de Crescimento Transformador beta1/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
BACKGROUND: In December 2019, SARS-COV-2 infection emerged in Wuhan, China causing COVID-19 and subsequently spread throughout the globe. A great uncertainty is associated with the disease progression, as the risk of severe COVID-19 is not uniform among all the patients. Systemic inflammation has been reported as a predictor for COVID-19 outcomes. Elevated levels of inflammatory markers are shown to be associated with endothelial dysfunction, cytokine storm and coagulopathy in COVID-19. There is a growing body of evidence, that these findings exert influence in the causation of mortality in patients with severe Covid-19. The present study is carried out with an aim to evaluate the clinical outcomes of patients by interrelating their clinical severity with inflammatory markers and CT (Computed tomography) severity score (CTSS). OBJECTIVES: The aim of the study is to correlate COVID-19 severity with inflammatory markers and CT severity score. We also aim to determine the optimal cut-off values for inflammatory markers and CT severity scores in order to establish their interrelationship to the disease severity. MATERIALS AND METHODS: It is a hospital-based retrospective observational study. The study was conducted over a period of four months (July 2020 to October 2020) based on data obtained from the records of patients, admitted with a laboratory confirmed SARS-COV-2 infection. The current study included a total of 84 patients, admitted to ICU with the severe COVID-19.Study tools included serum CRP, serum ferritin, D-dimer, neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) and 25-point CT severity score obtained from HRCT (high resolution computerized tomography) chest. RESULTS: Out of 84 patients recruited, 54 patients were survivors and 30 patients were non-survivors (deceased). 78% of the study population was male and 22% was female. For survivors, average CTSS was 12.43 ± 5.7 and whereas average CTSS for non-survivors was 18.87 ± 4.68(p<0001). Average D-dimer was 2.5 ± 1.43 in the survivor group and 3.39 ± 0.95 for non-survivors (p<0.004). Correlation coefficient of CTSS with FiO2 is 0.685 (p<0.0001). The optimal cut-off value for predicting mortality for D-dimer is >2.4 (p<0.0012) and for CTSS is >15 (p<0.0001). CONCLUSION: The disease severity was significantly correlated with CTSS and D- dimer. Severe COVID-19 was also associated with a high NLR (neutrophil to lymphocyte ratio) and moderately elevated inflammatory markers (CRP, Ferritin, IL-6). CTSS >15 and D-dimer >2.4 correlate strongly with mortality. CTSS has the greatest diagnostic accuracy for stratifying the disease severity and predicting the mortality among the markers/ characteristics compared.
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COVID-19 , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Centros de Atenção Terciária , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Axillary dissection is one of the important components of modified radical mastectomy (MRM). The present study was conducted to compare surgical outcomes by using monopolar electrocautery and ultrasonic dissector for axillary dissection in MRM. METHODS: A parallel randomised controlled single blinded study was conducted with a sample size of 70 patients who were randomised into two groups. One group underwent MRM using ultrasonic dissector (Group A) and the other one using electrocautery (Group B). Intra- and post-operative outcomes were compared. RESULTS: Group A had an average operating time of 30.86 min, which was statistically less than that of Group B. The mean mop count and the daily drain output in Group A were less as compared to Group B and the differences were statistically significant. Drain was removed early in Group A as compared to Group B. However, post-operative pain scores and seroma formation were not statistically significant among the two groups. CONCLUSION: Ultrasonic dissector group had significantly lesser intra-operative bleeding, operating time and post-operative drain output when compared to electrocautery group. However, the two groups had no significant difference in post-operative pain scores and seroma formation.
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OBJECTIVE: Metabolomics, the study of global alterations in small metabolites, is a useful tool to look for novel biomarkers. Recently, we reported a reprogramming of the serum metabolomic profile by nuclear magnetic resonance (NMR) spectroscopy following treatment in lupus nephritis (LN). This study aimed to compare the urine excretory levels of citrate and acetate in patients with biopsy-proven LN before and six months after cyclophosphamide induction therapy and to evaluate their correlation with the Systemic Lupus Erythematosus Disease Activity Index 2K (SLEDAI 2K) and renal SLEDAI. METHODS: Urine obtained from LN patients (N = 18, 16 female) at diagnosis and six months following induction therapy with cyclophosphamide and healthy controls (HC; N = 18, median age = 35 years, all female) were stored at -80°C. Metabolomic profiling was done using high resolution 800 MHz 1D 1H NMR spectroscopy. The urinary ratio of metabolites was calculated as (metabolite×1000)/creatinine. Disease activity was measured using the SLEDAI. Metabolomic profiles were compared between groups and correlated with clinical parameters. RESULTS: Compared to HC, LN patients had significantly lower median urinary citrate/creatinine levels (LN = 18.26, range 12.80-27.62; HC = 107.7, range 65.39-138.4; p < 0.0001) which significantly increased after six months of cyclophosphamide treatment (51.05, range 11.51-170.2; p = 0.03). LN patients also differed from HC by having a higher mean urinary acetate/creatinine ratio (LN = 17.44, range 11.6-32.7; HC = 9.61, range 7.97-13.71; p = 0.054) with a non-significant fall in values after six months of treatment. The Area under curve for differentiating LN from HC for urinary citrate was 0.9136, and urinary acetate was 0.6883. The urinary acetate levels correlated with SLEDAI (r = 0.337, p = 0.048). Urinary citrate levels correlated positively with C3 (r = 0.362, p = 0.03) and negatively with urine protein/creatinine (r = -0.346, p = 0.039). CONCLUSIONS: Urinary citrate, which reflects dampened aerobic glycolysis and oxidative phosphorylation, improved significantly and is a potential non-invasive biomarker for diagnosis and monitoring treatment response in LN.
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Acetatos/urina , Ácido Cítrico/urina , Quimioterapia de Indução/efeitos adversos , Nefrite Lúpica/tratamento farmacológico , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Testes de Função Renal , Nefrite Lúpica/metabolismo , Nefrite Lúpica/urina , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Índice de Gravidade de Doença , Adulto JovemRESUMO
Disease associated with SARS-CoV-2 also termed as Coronavirus disease 2019 or COVID-19, has become a potential threat to public health by spreading across more than 200 countries worldwide within a short span of time. Tuberculosis (TB) is already existing as unprecedented pandemic worldwide over several years. Both diseases have many overlapping features but there are striking differences too. There is usually chronicity of symptoms in TB as compared to acute or rapid progression in COVID-19. Little evidence exists regarding TB and COVID-19 coinfection. It is anticipated that person with TB either in active, previously treated or latent forms are more at risk of poor outcomes with COVID-19. The relationship between the two diseases is still unclear at present, and more studies are needed to enable analyses of interactions and determinants of outcomes in patients affected by both the diseases. Most of the countries across the world imposed nationwide lockdown to promote social distancing, which is one important preventive measure to mitigate the spread of COVID-19 pandemic. However, it becomes quite challenging to ensure smooth functioning of programmatic services, leading to disruption of routine TB care, leading to transmission of infection. Health authorities should frame polices that can support TB patients by providing diagnostic, management and prevention services without any interruption during this era of ongoing COVID-19 pandemic. Effort should be made to control both the diseases simultaneously and avoid unfavourable outcome in near future.
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Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Tuberculose Pulmonar/epidemiologia , COVID-19 , Coinfecção , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Tuberculose Pulmonar/prevenção & controle , Tuberculose Pulmonar/terapiaRESUMO
INTRODUCTION: Scrotoplasty has become a common practice during insertion of penile prosthesis, improving patient perception of penile length. Previous reports on scrotoplasty outcomes have only focused on the perceived benefits. The risk of wound complications after scrotoplasty is unknown. AIM: Identify wound complications and associated risk factors of scrotoplasty with insertion of penile prosthesis. METHODS: A retrospective review of a single-surgeon series (T.S.K.) of patients who underwent scrotoplasty with initial insertion of inflatable penile prosthesis (IPP) was performed from 2009-2014. Surgical outcomes and wound complications after scrotoplasty were examined, along with patient information, including basic demographics, medical comorbidities, and perioperative data. MAIN OUTCOME MEASURES: Studied outcomes included rate of wound complications after scrotoplasty and IPP insertion and identification of risk factors for wound dehiscence. RESULTS: Of the 103 scrotoplasties performed during the study period, a total of 15 had mild, moderate, or major wound dehiscence. Of these 15 cases, 9 had mild dehiscence and 5 cases had moderate dehiscence and required stitches to be placed in clinic to reinforce the closure. 1 patient had a major dehiscence requiring a return to the operating room for a washout, with exchange of IPP to malleable prosthesis. Multiple risk factors for wound dehiscence were found, including diabetes (odds ratio 6.1, CI 1.5, 25.0, P = .0129) and scrotoplasty technique (odds ratio 4.9, CI 1.2, 8.6, P = .003). Other examined variables, including patient age, Peyronie's disease, hypertension, intraoperative penile modeling, smoking, and device manufacturer, were not associated with wound dehiscence. CLINICAL IMPLICATIONS: Patients with diabetes and scrotoplasties performed via V-Y plasty are more likely to experience wound dehiscence. STRENGTHS & LIMITATIONS: Strengths include a single surgeon, thus lending continuity of skill and technique, a consecutive series, and 100% short-term follow-up. Limitations include retrospective design, single institution series, and lack of long-term follow-up. CONCLUSION: Although scrotoplasty can improve patient satisfaction with IPP, scrotoplasty can lead to increased patient morbidity. Diabetic patients are at increased risk for wound complication after scrotoplasty. Gupta NK, Sulaver R, Welliver C, et al. Scrotoplasty at Time of Penile Implant is at High Risk for Dehiscence in Diabetics. J Sex Med 2019;16:602-608.
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Diabetes Mellitus/epidemiologia , Implante Peniano/métodos , Prótese de Pênis/efeitos adversos , Pênis/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Doenças do Pênis/cirurgia , Complicações Pós-Operatórias/etiologia , Implantação de Prótese/métodos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND & STUDY AIMS: Gastric intestinal metaplasia (GIM) is the most common precursor of gastric cancer. Our aim is to determine if presenting symptoms predict gastric cancer precursor lesions in a high-risk population. PATIENT AND METHODS: Consecutive unique patients evaluated by endoscopy for upper gastrointestinal symptoms at the Los Angeles County Hospital between 2010 and 2014 were evaluated. Presenting symptoms were classified as low- or high-risk depending on the procedure indication as coded using the Clinical Outcomes Research Initiative (CORI) system. Endoscopy and histology results were used to classify findings as benign, GIM, high-risk GIM, or malignant. The primary outcome was the proportion of patients with premalignant or malignant gastric findings who had high-risk clinical indications for endoscopy relative to those with benign results. RESULTS: A total of 3699 patients underwent endoscopy to evaluate upper gastrointestinal symptoms. There were 373 (10.1%) patients with GIM of which 278 had high-risk GIM. One hundred and sixty (4.3%) patients were diagnosed with gastric cancer. High-risk indications for upper endoscopy predicted gastric cancer (OR 1.8 [95% CI 1.3-2.6]) but not GIM (OR 1.0 [0.8-1.3]) or high-risk GIM (OR 0.9 [0.7-1.2]). Hispanic or Asian patients and patients >50 years old were more likely to have GIM, high-risk GIM, and cancer. CONCLUSIONS: Performance of upper endoscopy for high-risk indications is inadequate to detect GIM and marginal for malignancy. At risk patients should undergo upper endoscopy for both low- and high-risk symptoms. Screening certain populations deserve additional study and may, in fact, be cost-effective.
Assuntos
Trato Gastrointestinal/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Feminino , Gastroscopia , Humanos , Los Angeles , Masculino , Metaplasia , Pessoa de Meia-Idade , Vigilância da População , Lesões Pré-Cancerosas/diagnóstico , Fatores de Risco , Neoplasias Gástricas/diagnósticoRESUMO
PURPOSE OF REVIEW: Compare outcomes of medical therapy as compared to minimally invasive surgical therapy (MIST) for treatment of bladder outlet obstruction RECENT FINDINGS: Treatment for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) remains largely driven by patient symptomatology with medical therapy or watchful waiting as the first-line management strategies. However, most patients are not adherent to prescribed medical therapies and are hesitant to accept the risks associated with more invasive therapies. Minimally invasive surgical therapies are treatments providing short-term symptom relief superior to medical therapies without the sequela of more invasive procedures. Though there are few direct comparisons, MIST seems to relieve LUTS/BPH symptoms at least as well as medical therapy without the need for daily adherence.