Aldoxorubicin for the treatment of soft tissue sarcoma

Intoduction: Soft tissue sarcomas (STS) encompass a group of rare tumors arising from mesenchymal tissue. Traditionally, anthracycline-based chemotherapy, with doxorubicin, is the main treatment for advanced STS.

Areas covered: Aldoxorubicin is a doxorubicin derivative containing a carboxylic hydrazone and serves as a prodrug of doxorubicin. It covalently binds to albumin in the blood until reaching the acidic tumor environment, which dissolves the hydrazone linker, thus releasing doxorubicin into the tissue. In this review paper, we analyze the pharmacokinetics, current phase I, phase II, and phase III trials, as well as adverse effect profile of aldoxorubicin in patients with advanced STS.

Expert opinion: Aldoxorubicin represents a promising drug for treatment of sarcomas. The drug has minimal cardiac toxicity, which represents a significant advantage to doxorubicin. Preliminary phase 3 study results demonstrate PFS advantage in patients with leiomyosarcoma and liposarcoma. However, more studies are needed to establish the role of aldoxorubicin in sarcoma treatment.     

ERP Correlates of Recognition Memory in Autism Spectrum Disorder

Recognition memory in autism spectrum disorder (ASD) tends to be undiminished compared to that of typically developing (TD) individuals (Bowler et al. 2007), but it is still unknown whether memory in ASD relies on qualitatively similar or different neurophysiology. We sought to explore the neural activity underlying recognition by employing the old/new word repetition event-related potential effect. Behavioural recognition performance was comparable across both groups, and demonstrated superior recognition for low frequency over high frequency words. However, the ASD group showed a parietal rather than anterior onset (300–500 ms), and diminished right frontal old/new effects (800–1500 ms) relative to TD individuals. This study shows that undiminished recognition performance results from a pattern of differing functional neurophysiology in ASD.     

Bortezomib Subcutaneous Injection in Combination Regimens for Myeloma or Systemic Light-Chain Amyloidosis: A Retrospective Chart Review of Response Rates and Toxicity in Newly Diagnosed Patients

Background

Bortezomib is a first-in-class proteasome inhibitor approved by the US Food and Drug Administration for the treatment of all phases of multiple myeloma (MM) and light-chain amyloidosis (AL). The subcutaneous formulation of bortezomib was approved in 2012 based on data from Phase III studies in patients with relapsed MM.

Objective

This article reports experience with subcutaneous bortezomib in patients with newly diagnosed MM or AL in a tertiary care center.

Methods

This retrospective study analyzed data from all patients newly diagnosed with MM or AL and treated at our center between April 1, 2011, when the hospital pharmacy approved and implemented the option of subcutaneous bortezomib, and April 1, 2013. Patients who received subcutaneous bortezomib as a part of the first line of therapy were identified through the pharmacy’s database. Data were abstracted from electronic medical records, and data on demographic characteristics, disease profiles, toxicities, responses, and survival were collected.

Results

Data from 29 patients (MM, 16; AL, 13; 62% male; median age, 66 years [range, 46–84]) were analyzed. Ninety percent of patients received cyclophosphamide, bortezomib, and dexamethasone (CyBorD) as the first line of treatment. None of the patients developed grade 3/4 peripheral neuropathy, whereas 1 patient experienced grade 3 diarrhea, and 2 patients developed grade 3 thrombocytopenia requiring dose reductions. The overall response rate was 93%, with 59% of patients achieving very good partial response or complete response.

Conclusions

With the use of subcutaneous bortezomib in combination regimens in patients with newly diagnosed MM or AL, there was a high overall response rate and minimal toxicity. These results are consistent with the findings from prior studies and provide a basis for further studies comparing new proteasome inhibitors to subcutaneous bortezomib in combination regimens for patients with newly diagnosed MM or AL.     

Efficacy of local drug delivery of 0.5% clarithromycin gel as an adjunct to non-surgical periodontal therapy in the treatment of current smokers with chronic periodontitis: a randomized controlled clinical trial

Background: The relationship between cigarette smoking and periodontal disease has been examined extensively. Local delivery of antimicrobials into periodontal pockets improves periodontal health. The present study is designed to investigate the adjunctive effects of subgingivally delivered 0.5% clarithromycin (CLM) as an adjunct to scaling and root planing for treating chronic periodontitis in smokers. Methods: Sixty‐one patients were randomized and categorized into two treatment groups: group 1, in which 31 individuals received scaling and root planing plus 0.5% CLM, and group 2, in which 30 individuals received scaling and root planing plus placebo gel. Clinical parameters were recorded at baseline and at 1, 3, and 6 months; they included plaque index (PI), modified sulcus bleeding index (mSBI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL). The mean concentration of 0.5% CLM in gingival crevicular fluid (GCF) was estimated by reverse‐phase high‐performance liquid chromatography. Results: Both therapies resulted in significant improvements. At the end of 6 months, the mean GI, PI, mSBI, PD, and CAL for the CLM group were 1.06 ± 0.28, 2.82 ± 0.64, 1.36 ± 0.24, 4.64 ± 0.63, and 4.90 ± 0.46, respectively, versus 1.38 ± 0.41, 3.22 ± 0.57, 1.44 ± 0.27, 6.07 ± 0.88, and 5.69 ± 0.46, respectively, for the placebo group. Using an individual‐based analysis, individuals in group 1 showed enhanced clinical outcome (P <0.05) over a period of 6 months compared with those in group 2. CLM was detected in GCF until a period of 7 weeks after the local drug delivery. Conclusion: Although both treatment strategies seemed to benefit the individuals, the adjunctive use of 0.5% CLM as a controlled drug delivery system enhanced the clinical outcome.     

Ureteroscopy under conscious sedation: A proof-of-concept study

IntroductionUreteroscopy (URS) is commonly performed under general anesthesia (GA) to maximize patient tolerability and minimize surgical complications; however, given the improvements in endoscopic technology and risks associated with GA, alternate forms of anesthesia have been postulated. We aimed to evaluate the outcomes of URS under conscious sedation.MethodsWe completed a retrospective cohort study from November 2019 to June 2020 at a tertiary-level hospital. All URSs that were performed under urologist-directed conscious sedation were included. Our primary outcome was the ability to complete URS, defined as success rate. Secondary outcomes included: stone-free rate, intraoperative complication rate, hospital admission rate, and sedation requirement. Univariate- and multivariate-adjusted logistic regression analyses were employed.ResultsNinety-nine URSs were included. Most (73/99, 73.7%) were performed for urolithiasis. The overall success rate was 83.8% (83/99), with 81.0% (34/42) intra-renal and 70.0% (16/23) proximal ureter success rates. The stone-free rate was 80.8% (59/73). No intraoperative complications nor hospital admissions were reported. The mean amount of sedation required was 3 mg (interquartile range [IQR] 2–4] of midazolam and 100 μg (100–150) of fentanyl. On multivariate analysis, midazolam was significantly associated with increased success (odds ratio 2.496, 95% confidence interval 1.057–5.892, p=0.037).ConclusionsWe have shown that proximal and intrarenal URS under conscious sedation is safe and effective. We were limited by our lack of followup, small sample size, selection bias to chose healthy patients, and lack of patient tolerability data. Patients and healthcare systems may benefit from implementing this innovation more broadly.

KEY MESSAGES

• We demonstrated the ability to effectively perform diagnostic and therapeutic ureteroscopy under urologist- directed conscious sedation, especially in the proximal ureter and renal pelvis. This approach may expedite patient care without compromising safety.
• This study is of extra importance during the restraints on our healthcare system during the COVID-19 pandemic.

     

Chronic hepatitis B and C infection in the United States: a review of current guidelines,disease burden and cost effectiveness of screening

Chronic hepatitis B and C infection are the leading causes of hepatocellular carcinoma and liver related death in the world and in the United States respectively. Screening guidelines have been developed based on estimated prevalence determined by NHANES data. However, individuals with the most risk of chronic infection (incarcerated, homeless, immigrants, nursing home residents, and hospitalized persons) are underrepresented in this cohort leading to an underestimation of the true prevalence of chronic hepatitis B and C infection. This has led to recent updates in the screening guidelines. This review examines the change in the guidelines, the likely true seroprevalence of hepatitis B and C virus, as well as the burden of chronic infection in this population.     

Locally Delivered 0.5% Azithromycin as an Adjunct to Non‐Surgical Treatment in Patients With Chronic Periodontitis With Type 2 Diabetes: A Randomized Controlled Clinical Trial

Background: Several epidemiologic studies have identified a greater incidence of periodontitis in patients with type 2 diabetes. Recent developments suggest that local delivery of antimicrobials into periodontal pockets improve periodontal health. The present study is designed to investigate the adjunctive effects of subgingivally delivered azithromycin (AZM; 0.5% concentration) as an adjunct to scaling and root planing (SRP) for treating chronic periodontitis in patients with type 2 diabetes. Methods: A total of 63 patients were categorized into two treatment groups: 1) group 1: SRP + placebo gel and 2) group 2: SRP + 0.5% AZM. Clinical parameters were recorded at baseline and 3, 6, and 9 months; they included modified sulcus bleeding index (mSBI), plaque index (PI), probing depth (PD), and clinical attachment level (CAL). Results: Both therapies resulted in significant improvements. Using a patient‐based analysis, patients in group 2 treated with SRP + 0.5% AZM showed enhanced reductions in PI, GI, mSBI, and PD and gains in CAL (P <0.05) over 9 months compared with group 1. Conclusion: Although both treatment strategies seem to benefit the patients, the adjunctive use of 0.5% AZM as a controlled drug delivery system enhances the clinical outcome.