Perineural Low-Dose Dexamethasone Prolongs Interscalene Block Analgesia With Bupivacaine Compared With Systemic Dexamethasone: A Randomized Trial

Background and Objectives Perineural dexamethasone and intravenous (IV) dexamethasone have been shown to prolong peripheral nerve block duration. The effects of perineural and IV dexamethasone have only been compared at doses of 4 mg or greater. This triple-blind, randomized trial examined the effect of 1 mg IV versus perineural dexamethasone on interscalene block (ISB) analgesia duration. Methods Patients undergoing ambulatory shoulder arthroscopy received an ultrasound-guided ISB with 15 mL bupivacaine 0.5% and 1 mg preservative-free dexamethasone that was administered perineurally (PeriD) or IV (IVDex). All patients received IV ketorolac and were discharged on naproxen 500 mg 2 times a day plus oxycodone/acetaminophen as needed. Peripheral nerve block duration, pain, opioid consumption, and block satisfaction were assessed via telephone follow-ups. Results There were 63 PeriD patients and 62 IVDex patients who completed the primary outcome follow-up. The median time until analgesia from the ISB completely wore off was 3.5 hours (95% confidence interval, 1.0–6.0 hours) longer in the PeriD versus IVDex groups; P = 0.007). Time until the pain relief from the ISB began to wear off was also longer in the PeriD versus IVDex group (5.5 hours [95% confidence interval, 2.1–9.0 hours]; P = 0.002). Other secondary outcomes, including opioid consumption, satisfaction, and pain scores, were not different between groups. Conclusions In patients undergoing shoulder arthroscopy, low-dose perineural dexamethasone (1 mg) in combination with 15 mL of 0.5% bupivacaine prolonged the median time until pain relief from the ISB completely wore off compared with 1 mg IV dexamethasone. However, the degree of prolongation was smaller than the a priori–defined minimal clinically meaningful difference of 5 hours. Clinical Trial Registration This study was registered at Clinicaltrials.gov, identifier NCT02506660. Accepted for publication February 12, 2018. Address correspondence to: Richard L. Kahn, MD, Hospital for Special Surgery, 535 E 70th St, New York, NY 10021 (e-mail: KahnR@HSS.edu). This study was funded by East River Medical Associates and the Research and Education Fund, Anesthesiology Department, Hospital for Special Surgery, New York, NY. REDCap use was supported by the National Center for Advancing Translational Science of the National Institutes of Health (UL1TR000457). This was presented in part at the Society for Ambulatory Anesthesia 32nd Annual Meeting (May 4–6, 2017) in Scottsdale, AZ. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia

Abstract

The present observational study aimed to compare the efficacy of azacitidine (AZA) and intensive chemotherapy (IC) in elderly patients with untreated acute myeloid leukemia (AML), diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS), and disease-free survival (DFS). The AZA group included 89 patients; median age was 73 years (range 61–80) and median white blood cell count (WBCc) 2.5 × 10⁹/L (range 0.27–83), 45% of the patients had BM blasts ≥ 30%, and 44 (49%) had a secondary AML (sAML). Karyotype was evaluable in 69 patients: 51 (74%) had intermediate-risk abnormalities and 18 (26%) an unfavorable risk karyotype. IC group consisted of 110 patients who received an induction course with mitoxantrone, cytarabine, and etoposide, followed by two consolidation cycles including idarubicin, cytarabine, and etoposide. Median age was 67 years (range 61–78) and median WBCc 8.0 × 10⁹/L (range 0.69–258); 44 (40%) had a sAML. Karyotype was evaluable in 88 patients, 71 (81%) had intermediate risk, and 17 (19%) unfavorable risk karyotype. To minimize the effects of treatment selection bias, adjustments were made using the propensity-score matching method, which yielded 74 patient pairs. CR rate was significantly higher in IC vs AZA group (73 vs 25%, respectively) (p < 0.0001), but the 3-year OS rates and median OS were not significantly different (21.6 vs 11% and 15.8 vs 13 months, respectively). Our analysis suggests similar outcomes with AZA compared to IC. Controlled, randomized clinical trials are warranted to confirm this conclusion.

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Ocular abnormalities in congenital Zika syndrome: a case report, and review of the literature

As the number of children with Zika virus-related complications grows, the long-term developmental trajectory and its effects on families are unknown. We present the first known case of congenital Zika syndrom...

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Survival benefit of adjuvant brachytherapy after hysterectomy with positive surgical margins in cervical cancer

Publication date: Available online 8 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Richard Li, Ashwin Shinde, Yi-Jen Chen, Arya Amini, Stephen Lee, Thanh Dellinger, Ernest Han, Mark Wakabayashi, Rebecca Nelson, Sushil Beriwal, Scott Glaser
PurposeWe evaluated the utilization of brachytherapy (BT) in addition to external beam radiation therapy (EBRT) and the resulting impact on survival in patients with cervical cancer after hysterectomy with positive surgical margins.Methods and MaterialsPatients with cervical cancer diagnosed from 2004 to 2015 who underwent hysterectomy followed by adjuvant EBRT were identified using the National Cancer Data Base. Only patients with positive surgical margins were included for analysis. Logistic regression was used to evaluate predictors of BT utilization and for propensity score matching. Survival was compared between patients receiving EBRT alone and EBRT combined with BT for adjuvant treatment. Survival analysis using log-rank test and Cox proportional hazards modeling was performed in the overall and propensity score-matched cohorts.ResultsWe identified 1,719 patients who received hysterectomy with positive surgical margins followed by adjuvant radiation therapy, of which 778 patients (45.3%) received additional BT. Predictors of increased receipt of BT included age > 55 years, private rather than government insurance, radiation treatment duration ≥7 weeks, external beam radiation dose ≥4500 cGy, and time between radiation and surgery ≤9 weeks. With a median follow-up of 3.8 years, 3-year overall survival was 79.4% in patients receiving BT compared to 71.9% in patients receiving EBRT alone (log-rank p<0.001). On multivariate analysis, EBRT and BT was associated with significantly improved survival (hazard ratio 0.77; 95% confidence interval 0.64-0.92; p=0.003) compared to EBRT alone. The survival benefit of combining EBRT and BT persisted on propensity score-matched analysis (log-rank p=0.005).ConclusionsIn women with positive margins after hysterectomy for cervical cancer, the combination of EBRT and BT showed significantly improved overall survival compared to EBRT alone. However, only 45.3% of patients in our cohort received BT.

Teaser

We analyzed a cohort of patients from the National Cancer Database who underwent hysterectomy for cervical cancer with positive surgical margins followed by adjuvant radiation therapy. We found that the addition of brachytherapy to external beam radiation therapy was associated with improved overall survival compared to external beam radiation therapy alone. However, only 45% of patients in this cohort received brachytherapy.


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Dexmedetomidine facilitates extubation in children who require intubation and respiratory support after airway foreign body retrieval: a case–cohort analysis of 57 cases

Abstract

Purpose

This study aimed to investigate whether dexmedetomidine had sedative weaning advantage for extubation after airway foreign body (FB) removal in children.

Methods

A retrospective case–cohort comparison study with total of 57 critical children who required mechanical ventilation after rigid bronchoscopy was performed. After tracheal intubation, group D (received dexmedetomidine 1 µg/kg over 10 min, followed by an infusion of 0.8 µg/kg/h), and group RP (received remifentanil–propofol 6–10 µg/kg/h and 1–3 mg/kg/h, respectively). The primary outcome was successful extubation rate on first weaning trial. The minor outcomes included weaning time, emergency agitation, coughing score and the incidence of respiratory adverse complications on emergency.

Main results

All 57 patients were included in the analysis, with 30 patients in group D and 27 controlled cases in group RP. The success rate of first weaning trial in the D group was 96.7 vs 77.8% in the RP group, risk ratio (RR) 1.56, 95% CI [0.78–1.98]. Time for resuming spontaneous breathing after termination infusion was shorter in the D group (median 8 min, IQR 15 min) vs RP group (median 12 min, IQR 19 min, P = 0.02, RR 0.56, 95% CI 0.14–6.57).

Conclusions

In mechanical ventilation of pediatric patients following rigid bronchoscopy, in comparison to remifentanil–propofol, dexmedetomidine is proved to have high success rate for weaning strategy.

What is already known?

Remifentanil is proved to be effective for weaning in ICU patients. Dexmedetomedine can provide similar rates of smooth extubation for pediatric patients who underwent airway surgery.

What this article adds?

Invasive ventilation is used for patients with severe comorbidity after airway surgery, but the correct strategy for pediatric extubation after removal of airway foreign body remains unclear. For these patients with short-term mechanical ventilation, dexmedetomedine may improve the extubation rate, when compared with remifentanil–propofol.

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Principles and Practice of HDR Penile Brachytherapy: Planning and Delivery Techniques

Publication date: Available online 8 June 2018
Source:Practical Radiation Oncology
Author(s): Shireen Parsai, Sheen Cherian, Ryan K. Berglund, Byron Lee, Matthew Kolar, Nancy Nagle-Hernan, Allan Wilkinson, Jay Ciezki
ObjectivesTo allow for organ preservation, high dose rate brachytherapy may be used in the treatment of localized penile cancer. Penile cancer is a rare malignancy, accounting for less than one percent of cancers in men in the United States. The standard treatment for localized disease is partial amputation of the penis. However, patients with T1b or T2 disease, less than 4 cm in maximum dimension and confined to the glans penis may be treated with brachytherapy as an organ-sparing approach. Previous works have described the technique involved for low dose rate brachytherapy, whereas we detail the techniques involved with high dose rate brachytherapy.MethodsCircumcision should precede brachytherapy. Interstitial brachytherapy needles are placed in the operating room under general anesthesia with the goal of allowing appropriate target coverage. Target definition is done via CT-based simulation and planning. Radiation is delivered using a prescription dose of 3840 cGy in 12 fractions twice daily over a course of 6 days.ResultsAcute toxicities peak upon completion of radiation therapy and may include dermatitis, sterile urethritis and adhesions in the urethra. These are reversible, and generally take 2-3 months to heal. The two most common and significant late complications of radiation therapy for penile cancer are soft tissue necrosis and meatal stenosis. An increased risk of necrosis has been reported with T3 tumors and with higher-volume implants (>30 cc). Erectile function is generally maintained, as the erectile tissues including the penile shaft and corpora have not been irradiated.ConclusionsOrgan preservation is feasible using high dose rate brachytherapy with favorable acute and late toxicities.



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The utility of routine surveillance screening with magnetic resonance imaging (MRI) to detect tumour recurrence in children with low-grade central nervous system (CNS) tumours: a systematic review

Abstract

Background

Magnetic resonance imaging (MRI) is routinely used as a surveillance tool to detect early asymptomatic tumour recurrence with a view to improving patient outcomes. This systematic review aimed to assess its utility in children with low-grade CNS tumours.

Methods

Using standard systematic review methods, twelve databases were searched up to January 2017.

Results

Seven retrospective case series studies (n = 370 patients) were included, with average follow-up ranging from 5.6 to 7 years. No randomised controlled trials (RCTs) were identified. Due to study heterogeneity only a descriptive synthesis could be undertaken. Imaging was most frequent in the first year post-surgery (with 2–4 scans) reducing to around half this frequency in year two and annually thereafter for the duration of follow-up. Diagnostic yield ranged from 0.25 to 2%. Recurrence rates ranged from 5 to 41%, with most recurrences asymptomatic (range 65–100%). Collectively, 56% of recurrences had occurred within the first year post-treatment (46% in the first 6-months), 68% by year two and 90% by year five. Following recurrence, 90% of patients underwent treatment changes, mainly repeat surgery (72%). Five-year OS ranged from 96 to 100%, while five-year recurrence-free survival ranged from 67 to 100%. None of the studies reported quality of life measures.

Conclusion

This systematic review highlights the paucity of evidence currently available to assess the utility of MRI surveillance despite it being routine clinical practice and costly to patients, their families and healthcare systems. This needs to be evaluated within the context of an RCT.

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Meta-analysis of segmentectomy versus wedge resection in stage IA non-small-cell lung cancer

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Blood cell count indexes as predictors of outcomes in advanced non-small-cell lung cancer patients treated with Nivolumab

Abstract

Lung cancer is the most common malignancy worldwide. Despite significant advances in diagnosis and treatment, mortality rates remain extremely high, close to incidence rates. Several targeted therapies have been recently introduced for the treatment of non-small cell lung cancer (NSCLC), the most common type of lung cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1), was the first immune checkpoint inhibitor approved for the treatment of patients with advanced/metastatic NSCLC not responding to platinum-based chemotherapy. Biomarkers predicting response to these therapies would allow early identification of non-responders and timely implementation of appropriate combination strategies, avoiding inadequate and expensive therapies. The role of the neutrophil to lymphocyte ratio and other blood cell count indexes as possible biomarkers of response has been recently investigated. We discuss the encouraging results reported on the topic, provide new data from our personal experience, and discuss opportunities for further research.

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Risk Analysis of Prostate Cancer Treatments in Promoting Metabolic Syndrome Development and the Influence of Increased Metabolic Syndrome on Prostate Cancer Therapeutic Outcome

Abstract

In clinical practice, few prostate cancer (PCa) patients are associated with metabolic syndrome (MetS), while few others acquire MetS during treatment. Whether the treatment of PCa increases the occurrence of MetS remains to be confirmed. This study reviewed the changes in MetS patients before and after PCa treatment to evaluate the effects of various treatment methods on MetS. We analyzed data of 1162 PCa patients, whether or not diagnosed with MetS, and changes in MetS patients after PCa treatment. Data of lower urinary tract symptoms, C-reactive protein (CRP), platelet distribution width (PDW), prostate-specific antigen (PSA), Gleason score, clinical stage, treatment methods, and progressive incidents were evaluated using logistic regression according to MetS diagnosis. The results showed significant differences in the prevalence of MetS before (17.38%) and after (23.67%) PCa treatment (P < 0.001). Bad diet, living habits, and prostate cancer treatment were considered as risk factors for MetS (OR = 1.731, 95%CI 1.367–2.193, P < 0.001). Radical prostatectomy (RP), androgen deprivation therapy including surgical castration and medical castration, iodine-125 seed brachytherapy (¹²⁵I limited), and chemotherapy were independent risk factors of MetS. The MetS incidence rates after treatment in ADT+¹²⁵I limited+chemotherapy compared to RP+TURP+EBRT were statistically significant at the corresponding risk grade (all P < 0.001). After treatment, the occurrence rates of progressive incidences were higher in MetS-PCa patients compared to non-MetS-PCa patients (all P < 0.001). So, the findings suggested that among PCa patients, multiple factors contribute to the occurrence of MetS, and PCa treatment is one among them. ADT+¹²⁵I limited+chemotherapy may be the most influential treatment for MetS.

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Cancers, Vol. 10, Pages 191: WIP-YAP/TAZ as A New Pro-Oncogenic Pathway in Glioma

Cancers, Vol. 10, Pages 191: WIP-YAP/TAZ as A New Pro-Oncogenic Pathway in Glioma

Cancers doi: 10.3390/cancers10060191

Authors: Sergio Rivas Inés M. Antón Francisco Wandosell

Wild-type p53 (wtp53) is described as a tumour suppressor gene, and mutations in p53 occur in many human cancers. Indeed, in high-grade malignant glioma, numerous molecular genetics studies have established central roles of RTK-PI3K-PTEN and ARF-MDM2-p53 INK4a-RB pathways in promoting oncogenic capacity. Deregulation of these signalling pathways, among others, drives changes in the glial/stem cell state and environment that permit autonomous growth. The initially transformed cell may undergo subsequent modifications, acquiring a more complete tumour-initiating phenotype responsible for disease advancement to stages that are more aggressive. We recently established that the oncogenic activity of mutant p53 (mtp53) is driven by the actin cytoskeleton-associated protein WIP (WASP-interacting protein), correlated with tumour growth, and more importantly that both proteins are responsible for the tumour-initiating cell phenotype. We reported that WIP knockdown in mtp53-expressing glioblastoma greatly reduced proliferation and growth capacity of cancer stem cell (CSC)-like cells and decreased CSC-like markers, such as hyaluronic acid receptor (CD44), prominin-1 (CD133), yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). We thus propose a new CSC signalling pathway downstream of mtp53 in which Akt regulates WIP and controls YAP/TAZ stability. WIP drives a mechanism that stimulates growth signals, promoting YAP/TAZ and &beta;-catenin stability in a Hippo-independent fashion, which allows cells to coordinate processes such as proliferation, stemness and invasiveness, which are key factors in cancer progression. Based on this multistep tumourigenic model, it is tantalizing to propose that WIP inhibitors may be applied as an effective anti-cancer therapy.

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