Retraction Note to: Phytofabricated silver nanoparticles of Phyllanthus emblica attenuated diethylnitrosamine‑induced hepatic cancer via knock‑down oxidative stress and inflammation

Inflammopharmacology -     

Final results of a phase II study of CHOEP plus lenalidomide as initial therapy for patients with stage II–IV peripheral T-cell lymphoma

There remains no one standard induction for nodal-based peripheral T-cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination with 10 mg of lenalidomide on days 1–10 of a 21-day cycle for six cycles of therapy followed by observation, high-dose therapy with autologous stem cell rescue, or maintenance lenalidomide per provider preference. Among 39 patients evaluable for efficacy, the objective response rate after six cycles was 69%, with complete response in 49%, partial response in 21%, stable disease in 0% and progressive disease in 13%. Thirty-two patients (82%) completed full induction, and seven patients (18%) discontinued for toxicity, primarily hematologic. Any grade hematologic toxicity occurred in over 50% of patients, with grade 3 or 4 febrile neutropenia occurring in 35% of patients despite mandated growth factors. With a median followup of surviving patients of 21.3 months, the estimated 2-year progression-free and overall survival were 55% (95% CI 37%–70%) and 78% (95% CI 59%–89%), respectively. In sum, six cycles of lenalidomide plus CHOEP resulted in a modest response rate primarily due to hematologic toxicity, which prevented all patients from completing planned induction.     

Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

Nutrition assessment in patients undergoing liver transplant

Liver transplantation (LT) is a major surgery performed on patients with end stage liver disease. Nutrition is an integral part of patient care, and protein-energy malnutrition is almost universally present in patients suffering from liver disease undergoing LT. Nutrition assessment of preliver transplant phase helps to make a good nutrition care plan for the patients. Nutrition status has been associated with various factors which are related to the success of liver transplant such as morbidity, mortality, and length of hospital stay. To assess the nutritional status of preliver transplant patients, combinations of nutrition assessment methods should be used like subjective global assessment, Anthropometry mid arm-muscle circumference, Bioelectrical impedance analysis (BIA) and handgrip strength.     

Surgical and Hardware Complications of Deep Brain Stimulation—A Single Surgeon Experience of 519 Cases Over 20 Years

ObjectiveDeep brain stimulation (DBS) surgery has its own set of risks and complications. This study from a single center and a single surgeon analyzes various risk factors for complications and tries to establish if there is a learning curve effect in minimizing the complications.Materials and MethodsA retrospective analysis of 519 patients (1024 leads) who underwent DBS surgery and 232 patients who underwent implantable pulse generator replacement (IPG), by a single surgeon, between the years 1999 and 2019 was performed. Perioperative and hardware related complications were evaluated.ResultsThe follow-up period ranged from six months to 20 years. Surgery-related complications occurred in 46 (8.9%) cases which included confusion in 31 (5.98%), intracerebral hemorrhage in 7 (1.3%), vasovagal attack in 3 (0.58%), respiratory distress in 2 (0.38%), postoperative aggressiveness in 1 (0.19%), and blepharospasm in 2 (0.38%) patients. Complications related to the DBS hardware were found in 35 cases, including erosion and infection in 22 (2.95%), inaccurate lead placement or migration in 6 (0.6%) lead fracture/extension wire failure in 2 (0.26%), IPG malfunction in 2 (0.26%), and hardware discomfort in 3 (0.4%) cases. In three patients, one lead was repositioned. In cases of infection, 87% of patients had either partial or complete removal of hardware. There was no mortality. The complications were analyzed for every 100 DBS procedures. There was a significant drop in the percentage of complications in from 23% in the first 100 cases to 7% in the last 100 cases (p < 0.0001).ConclusionConfusion remains the most frequent operative and perioperative complication. Erosion and infection of the surgical site represents the most frequent hardware complication. DBS surgery is safe and the complication rates are acceptably low. The complication rate also decreases with cumulative years of experience, demonstrating a learning curve effect.     

Consensus guidelines on evaluation and management of the febrile child presenting to the emergency department in India

Justification

India, home to almost 1.5 billion people, is in need of a country-specific, evidence-based, consensus approach for the emergency department (ED) evaluation and management of the febrile child.

Process

We held two consensus meetings, performed an exhaustive literature review, and held ongoing web-based discussions to arrive at a formal consensus on the proposed evaluation and management algorithm. The first meeting was held in Delhi in October 2015, under the auspices of Pediatric Emergency Medicine (PEM) Section of Academic College of Emergency Experts in India (ACEE-INDIA); and the second meeting was conducted at Pune during Emergency Medical Pediatrics and Recent Trends (EMPART 2016) in March 2016. The second meeting was followed with futher e-mail-based discussions to arrive at a formal consensus on the proposed algorithm.

Objective

To develop an algorithmic approach for the evaluation and management of the febrile child that can be easily applied in the context of emergency care and modified based on local epidemiology and practice standards.

Recommendations

We created an algorithm that can assist the clinician in the evaluation and management of the febrile child presenting to the ED, contextualized to health care in India. This guideline includes the following key components: triage and the timely assessment; evaluation; and patient disposition from the ED. We urge the development and creation of a robust data repository of minimal standard data elements. This would provide a systematic measurement of the care processes and patient outcomes, and a better understanding of various etiologies of febrile illnesses in India; both of which can be used to further modify the proposed approach and algorithm.

     

Kangaroo Mother Care in Reducing Pain in Preterm Neonates on Heel Prick

Objectives

To determine the effect of Kangaroo Mother Care (KMC) of small duration of 15 min in decreasing pain in preterm neonates between 32–36 wk 6 d on heel prick by a 26 gauge needle.

Methods

Randomized controlled double masked crossover trial involving 50 neonates, between 32 wk and 36 wk 6 d gestation and weighing less than 2500 g, within 10 d of birth, vitally stable, breathing without assistance or on Continuous positive airway pressure (CPAP), without any clinically evident neurological signs, not having received analgesics/sedatives within last 24 h and not fed within last 30 min and requiring heel pricking were eligible. Outcome measured was the Premature Infant Pain Profile (PIPP). Analysis was done using independent sample t test, with Bonferroni correction applied for comparing individual components of PIPP score.

Results

The heart rate, behaviour and facial scores were statistically significant and lower in KMC group. But there was no statistically significant difference in oxygen saturation (SpO₂₎. The difference(4.85) in PIPP score was clinically and statistically significant (p?<?0.0001).

Conclusions

The findings suggest that short duration KMC (15 min) has stress reducing benefits. Preterm neonates above 32 wk gestational age can benefit from KMC to decrease pain from heel prick procedure.     

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers

Objective: Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants.

Research design: Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800?mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4?h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24?h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7.

Results: Fifty participants (19?53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27–0.60?h post-dose for fentanyl sublingual spray. Peak (C_max) and total (AUC_0–t, AUC_0–∞) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800?mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses.

Conclusions: Overall, single-dose fentanyl sublingual spray (100–800?mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200?mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses between 400–800?mcg may be administered in settings with nasal cannula oxygenation.