Need For Additional Therapeutic Interventions Research Articles

Disrupted de novo pyrimidine biosynthesis impairs adult hippocampal neurogenesis and cognition in pyridoxine-dependent epilepsy.

Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. It points to a need for additional therapeutic interventions for PDE beyond pyridoxine treatment, which provokes us to investigate the mechanisms underlying the impairment of brain hemostasis by ALDH7A1 deficiency. In this study, we show that ALDH7A1-deficient mice with seizure control exhibit altered adult hippocampal neurogenesis and impaired cognitive functions. Mechanistically, ALDH7A1 deficiency leads to the accumulation of toxic lysine catabolism intermediates, α-aminoadipic-δ-semialdehyde and its cyclic form, δ-1-piperideine-6-carboxylate, which in turn impair de novo pyrimidine biosynthesis and inhibit NSC proliferation and differentiation. Notably, supplementation of pyrimidines rescues abnormal neurogenesis and cognitive impairment in ALDH7A1-deficient adult mice. Therefore, our findings not only define the important role of ALDH7A1 in the regulation of adult hippocampal neurogenesis but also provide a potential therapeutic intervention to ameliorate the defective mental capacities in PDE patients with seizure control.

A Protocolized Management of Walled-Off Necrosis (WON) Reduces Time to WON Resolution and Improves Outcomes

Patients with infected or symptomatic walled-off necrosis (WON) have high morbidity and health care utilization. Despite the recent adoption of nonsurgical treatment approaches, WON management remains nonalgorithmic. We investigated the impact of a protocolized early necrosectomy approach compared with a nonprotocolized, clinician-driven approach on important clinical outcomes. Records were reviewed for consecutive patients with WON who underwent a protocolized endoscopic drainage with a lumen-apposing metal stent (cases), and for patients with WON treated with a lumen-apposing metal stent at the same tertiary referral center who were not managed according to the protocol (control subjects). The protocol required repeat cross-sectional imaging within 14 days after lumen-apposing metal stent placement, with regularly scheduled endoscopic necrosectomy if WON diameter reduction was <50%. Control patients were treated according to their clinician's preference without an a priori strategy. Inverse probability of treatment weighting-adjusted analysis was used to evaluate the influence of being in the protocolized group on time to resolution. A total of 24 cases and 47 control subjects were included. There were no significant differences in baseline characteristics. Although numbers of endoscopies and necrosectomies were similar, cases had lower adverse event rates, shorter intensive care unit stay, and required nutritional support for fewer days. On matched multivariate Cox regression, cases had earlier WON resolution (hazard ratio, 5.73; 95% confidence interval, 2.62-12.5). This was confirmed in the inverse probability of treatment weighting-adjusted analysis (hazard ratio, 3.4; 95% confidence interval, 1.92-6.01). A protocolized strategy resulted in faster WON resolution compared with a discretionary approach without the need for additional therapeutic interventions, and with a better safety profile and decreased health care utilization.

Risk Factors Associated with Clinical Failure of Uterine Artery Embolization for Postpartum Hemorrhage

PurposeTo identify risk factors for clinical failure of uterine artery embolization (UAE) for postpartum hemorrhage (PPH), with particular attention to the uterine artery diameter. Materials and MethodsThis retrospective study included 47 patients who underwent UAE for PPH between January 1, 2010, and January 31, 2021. Technical success was defined as the completion of embolization of the arteries thought to be the cause of the bleeding. Clinical success was defined as no recurrent bleeding or need for additional therapeutic interventions. Univariate and multivariate analyses were performed to examine the risk factors associated with clinical failure of UAE. ResultsOf the 47 patients, 6 had recurrent bleeding. Of the 6 patients, 4 underwent hysterectomy, and 2 underwent repeat embolization. The clinical success rate was 87.2% (41/47), with no major adverse events such as uterine infarction or death. In univariate analysis, there were slight differences in multiparity (P = .115) and placental abruption (P = .128) and a significant difference in the findings of a narrow uterine artery on digital subtraction angiography (DSA) (P = .005). In multivariate analysis, only a narrow uterine artery on DSA was a significant factor (odds ratio, 18.5; 95% confidence interval, 2.5–134.8; P = .004). ConclusionsA narrow uterine artery on DSA was a risk factor for clinically unsuccessful UAE for PPH. It may be prudent to conclude the procedure only after it is ensured that vasospasm has been relieved.

Impact of epinephrine volume on further bleeding due to high-risk peptic ulcer disease in the combination therapy era.

BACKGROUNDIn monotherapy studies for bleeding peptic ulcers, large volumes of epinephrine were associated with a reduction in rebleeding. However, the impact of epinephrine volume in patients treated with combination endoscopic therapy remains unclear. AIMTo assess whether epinephrine volume was associated with bleeding outcomes in individuals who also received endoscopic thermal therapy and/or clipping.METHODSData from 132 patients with Forrest class Ia, Ib, and IIa peptic ulcers were reviewed. The primary outcome was further bleeding at 7 d; secondary outcomes included further bleeding at 30 d, need for additional therapeutic interventions, post-endoscopy blood transfusions, and 30-day mortality. Logistic and linear regression and Cox proportional hazards analyses were performed.RESULTSThere was no association between epinephrine volume and all primary and secondary outcomes in multivariable analyses. Increased odds for further bleeding at 7 d occurred in patients with elevated creatinine values (aOR 1.96, 95%CI 1.30-3.20; P < 0.01) or hypotension requiring vasopressors (aOR 6.34, 95%CI 1.87-25.52; P < 0.01). Both factors were also associated with all secondary outcomes.CONCLUSIONEpinephrine maintains an important role in the management of bleeding ulcers, but large volumes up to a range of 10-20 mL are not associated with improved bleeding outcomes among individuals receiving combination endoscopic therapy. Further bleeding is primarily associated with patient factors that likely cannot be overcome by increased volumes of epinephrine. However, in carefully-selected cases where ulcer location or size pose therapeutic challenges or when additional modalities are unavailable, it is conceivable that increased volumes of epinephrine may still be beneficial.

Analysis of the psychopathological profile, quality of life, and cost-effectiveness of oral lichen planus patients treated with photobiomodulation.

To evaluate the effect of PBM on the psychological profile and quality of life of patients with oral lichen planus (OLP) in comparison to corticoid and to investigate the cost-effectiveness of both treatments. Patients were randomized into two groups: Control (clobetasol propionate 0.05%) and Photobiomodulation (660nm, 100mW, 177J/cm2, 5s, 0.5J) twice a week for 30days. The Hospital Anxiety and Depression Scale (HADS) and OHIP-14 were used in different treatment time points and at follow-up. The cost-effectiveness was calculated using the improvement in OHIP-14 after treatment. OLP patients showed detected levels of anxiety, depression, and poor quality of life at baseline. No improvement in anxiety and depression was noticed after treatments. However, PBM and corticoid significantly improved the quality of life of OLP patients, considering the OHIP-14-T and the physical pain domain. The treatment with corticoid was more cost-effective than PBM. Psychological distress was not improved after both treatments and PBM is as effective as corticoids in promoting a better quality of life in OLP patients, despite its higher cost. This study highlights the need for additional therapeutic interventions in OLP patients, to early recognize and to manage the alterations in their psychological profile. Moreover, PBM is an effective therapy in OLP patient's quality of live and although it was a more expensive, the advantage of being a minimally invasive therapy associated with no side effects must be considered in clinical practice, especially in those patients with refractory disease. This study is registered at ClinicalTrials.gov; the registration number is NCT03320460, registered in 17/10/2017.

PD56-01 PROSTATE SPECIFIC ANTIGEN KINETICS PREDICT INCIDENTAL PROSTATE CANCER PROGRESSION FOLLOWING HOLMIUM LASER ENUCLEATION OF THE PROSTATE

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy & New Technology III (PD56)1 Apr 2020PD56-01 PROSTATE SPECIFIC ANTIGEN KINETICS PREDICT INCIDENTAL PROSTATE CANCER PROGRESSION FOLLOWING HOLMIUM LASER ENUCLEATION OF THE PROSTATE Kyle Rose*, Kassem Faraj, Anojan Navaratnam, Marlene Girardo, Amihay Nevo Pima, Karan Arora, Scott Cheney, and Mitchell Humphreys Kyle Rose*Kyle Rose* More articles by this author , Kassem FarajKassem Faraj More articles by this author , Anojan NavaratnamAnojan Navaratnam More articles by this author , Marlene GirardoMarlene Girardo More articles by this author , Amihay Nevo PimaAmihay Nevo Pima More articles by this author , Karan AroraKaran Arora More articles by this author , Scott CheneyScott Cheney More articles by this author , and Mitchell HumphreysMitchell Humphreys More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000966.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Holmium laser enucleation of the prostate (HoLEP) allows for the definitive management of benign prostatic hyperplasia and histopathologic analysis. The complete adenomectomy of HoLEP allows for the diagnosis of incidental prostate cancer (PCA). Outcomes data regarding the clinical progression of PCA following HoLEP is lacking. The objective of this study is to describe the clinical course of patients diagnosed with PCA after HoLEP, and identify predictors for clinical progression in this population. METHODS: HoLEP cases performed at our institution by a single surgeon from 2008-2018 were reviewed and monitored for incidentally diagnosed PCA. Clinical progression of PCA was defined as the need for additional therapeutic intervention or the development of metastatic disease. Univariate analysis was conducted using Chi-squared and T-tests when appropriate. Kaplan Meier estimates were used to evaluate survival. RESULTS: Of 1,288 HoLEP patients, 133 patients were diagnosed with incidental PCA. Seventeen (12.7%) patients met criteria for clinical progression at a median of 20 months postoperatively. On univariate logistic regression, predictors of clinical progression included preoperative prostate specific antigen density (PSAD) >0.15 (OR 3.4, 95% CI 1.7-6.6, p<0.01), T1b vs. T1a (OR 2.9, 95% CI 1.6-5.2), first postoperative PSA >1 (OR 2.1, 95% CI 1.9-2.3, p<0.01), PSADT <36 months (OR 9.2, 95% CI 1.15-74.8, P=0.01) and PSA velocity >0.75 (OR 14.6, 95% CI 3.5-60.7, p<0.01). When predicting clinical progression, the sensitivity of PSADT <36 months was 94%, the negative predictive values for first postop PSA >1 was 94%, PSA velocity >0.75 ng/mL/year was 95%, and PSA DT <36 months was 97%. Progression-free survival was 101.9 months in T1a vs. 61.5 months in T1b disease (p<0.01). CONCLUSIONS: PSA kinetics are informative in predicting clinical progression following HoLEP. These parameters can be used to risk stratify patients diagnosed with incidental PCa after HoLEP. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1188-e1188 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kyle Rose* More articles by this author Kassem Faraj More articles by this author Anojan Navaratnam More articles by this author Marlene Girardo More articles by this author Amihay Nevo Pima More articles by this author Karan Arora More articles by this author Scott Cheney More articles by this author Mitchell Humphreys More articles by this author Expand All Advertisement PDF downloadLoading ...

Hemangioma Infantil e Recomendações Terapêuticas Atuais

O hemangioma infantil é o tumor vascular benigno mais frequente na idade pediátrica, com uma incidência de 2% a 12% em recém-nascidos caucasianos, com predominância no sexo feminino. A International Society for The Study of Vascular Anomalies dividiu as anomalias vasculares em duas categorias: tumores vasculares e malformações vasculares, integrando-se o hemangioma infantil nos tumores vasculares benignos. A evolução clínica é característica, compreendendo uma fase proliferativa e uma fase de involução. O diagnóstico é habitualmente clínico, mas pode haver necessidade de recorrer a métodos auxiliares de diagnóstico. A maioria dos hemangiomas infantis tem evolução favorável no sentido da resolução espontânea, mas nalguns casos pode haver complicações locais ou sistémicas, com necessidade de intervenção terapêutica por situações de risco vital, funcional ou estético. Atualmente, o propranolol oral é o tratamento de escolha para o hemangioma infantil e o único aprovado para esta indicação, devendo ser administrado o mais precocemente possível para uma maior eficácia e um menor número de complicações. Outras opções terapêuticas podem ser equacionadas em segunda linha: corticoides orais, tópicos ou intralesionais, betabloqueantes tópicos, laser ou cirurgia.

E8. Clinical applications of circulating tumour cells

Introduction The clinical potential of detecting minimal residual disease (MRD) in primary and metastatic breast cancer stretches far beyond its mere prognostic relevance, and may contribute to individualising systemic treatment. The role of MRD in the development of tailored treatment may comprise the following aspects: • detection of MRD could serve as an early tool for evaluating treatment efficacy, leading to a more individualised therapeutic approach; • detection of MRD could be implemented in everyday patient care to select patients with an increased risk for recurrence of their disease, and who might benefit from a change in treatment, or where there might be a need for additional therapeutic interventions; • MRD could serve as a source to understand tumour biology in MRD well after the completion of primary treatment; • phenotyping MRD might lead to a more individualised and thus targeted treatment based on the phenotype of persistent MRD. Thus, the significance of MRD may reach far beyond the potential of established prognostic parameters at the time of primary diagnosis of breast cancer.

HDL Therapy: the Next Big Step in the Treatment of atherosclerosis?

Despite significant reductions in mortality with statins and increasingly lower targets of low-density-lipoprotein cholesterol, two thirds of cardiovascular events cannot be prevented with current treatments. Therefore, a clear need for additional therapeutic interventions to complement the results of low-density lipoprotien lowering, exists. One prime target for new interventions is high-density lipoprotein (HDL) and/or its apolipoproteins. While lifestyle interventions and well-established drugs, such as fibrates and nicotinic acid, modestly increase HDL, the most promising current approaches are direct infusion of HDL-like particles (e.g., apolipoprotein AI Milano-phospholipid complexes) and inhibition of one of the key enzymes in HDL metabolism, cholesterol ester transfer protein. These methods have been shown to have dramatic effects on the incidence of atherosclerosis and/or HDL cholesterol. This review will focus on treatments that raise HDL cholesterol or enhance reverse cholesterol transport. Old and new drugs will be discussed as well as combination therapy and novel approaches such as plasma delipidation and recombinant apolipoprotein AI.

Ulex Europeus Agglutinin (UEA-I) Lectin Binding in Breast Carcinoma and its Relationship to Prognostic Factors

In this study, lectin binding was compared with pathological prognostic factors and clinical follow-up details. Formalin-fixed, paraffin-embedded tissues from 43 cases of breast carcinoma were studied for binding with Ulex Europeus Agglutinin (UEA-I) lectin. Staining results were compared with tumor size, histologic and nuclear grade, lymph node status (number, capsular and pericapsular invasion), blood and lymphatic vessel invasion, ER and PR status, clinical stage and the patients' short-term follow-up details. Analysis of staining with UEA-I showed a significant relationship with blood vessel invasion (P < 0.01) and lymphatic vessel invasion (P < 0.05). Furthermore, PR showed a significant inverse correlation with lectin binding (P < 0.05). Staining with UEA-I related significantly with axilliary lymph node metastases (P < 0.05). UEA-I was positive in four (66.6%) out of six cases with distant organ mestastasis. This study confirms that, in breast cancer, lectin binding to the cancer cells can be a reliable indicator for axilliary metastases, and the need for additional therapeutic interventions.

Stage B ( [formula omitted]) transitional cell carcinoma of bladder highly curable by radical cystectomy

Seventy-one patients with pathologic Stage B ( P 2 3 a N 0 ) transitional cell carcinoma (TCC) of the bladder underwent radical cystectomy alone without preoperative radiotherapy or perioperative chemotherapy between 1983 and 1987 and have been followed a median of fifty months. The five-year actuarial survival and disease free survival rates were 82 percent and 77 percent, respectively, and only 13 patients (18%) have relapsed. Histologic parameters were evaluated as to prognostic impact; none correlated with disease-free survival rates although the presence of vessel involvement portended a worse disease free survival rate (68% versus 80%). During this same period, an additional 15 patients underwent radical cystectomy for pathologic Stage B disease but received adjuvant chemotherapy on the basis of vessel invasion. Their disease free survival rate at five years was 80 percent, comparable to the disease free survival rate for patients with vessel invasion treated by surgery alone (68%). Although the role of systemic chemotherapy in the management of invasive bladder cancer remains under investigation, it would appear that patients with Stage B TCC are best treated with radical cystectomy alone. Continued analysis of modern surgical results grouped by current pathologic staging criteria is needed to identify patients who have a relatively low risk of relapse and thus little need for additional therapeutic intervention. These results demonstrate that Stage P 2 3 a N 0 TCC of the bladder is highly curable by surgery.