Combined Ganglioneuroma-Schwannoma of the Retroperitoneum: An Exceedingly Rare Hybrid Nerve Sheath-Ganglioneural Tumor.

Combined ganglioneuroma-schwannoma is an exceedingly rare tumor that has only been described in isolated case reports. We document a 64-year-old man with an incidentally discovered combined ganglioneuroma-schwannoma of the retroperitoneum that was intimately associated with sympathetic ganglia. We highlight the morphological and immunohistochemical findings of this rare tumor, and show evidence of its origin from sympathetic ganglia.

A Phase II Study Assessing Long-term Response to Ibrutinib Monotherapy in Recurrent or Refractory CNS Lymphoma.

Purpose: Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase. We previously reported the safety and short-term antitumor activity of ibrutinib in 20 patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL).

Patients And Methods: We enrolled 26 additional patients with r/r PCNSL/SCNSL into the dose-expansion cohort of the trial into a combined cohort of 46 patients (31 with PCNSL and 15 with SCNSL).

Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer.

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs).

Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics.

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity.

Locally invasive recurrence or metastasis of pheochromocytoma into the liver?-clinicopathological challenges.

Pheochromocytomas (PCC) are rare and functional neuroendocrine tumors developing from adrenal chromaffin cells. Predicting malignant behavior especially in the absence of metastasis can be quite challenging even in the era of improved understanding of the molecular mechanisms involved in PCCs. Currently, two histopathological grading systems Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) score are used in clinical practice, but these are subject to significant interobserver variability.

The clinical impact of anti-hypertensive treatment drug-gene pairs in the asian population: a systematic review of publications in the past decade.

Pharmacogenetics play an important role in determining the anti-hypertensive effects of blood pressure-lowering medications and have the potential to improve future patient care. Current literature on the topic, however, has a heavy focus on Caucasians and may not be generalisable to the Asian populations. Therefore, we have conducted this systematic review to summarise and evaluate the literature of the past decade.

Preclinical Evaluation of Ga- and Lu-Labeled Integrin αβ-Targeting Radiotheranostic Peptides.

The integrin αβ, an epithelium-specific cell surface receptor, is overexpressed on numerous malignancies, including the highly lethal pancreatic ductal adenocarcinomas. Here, we developed and tested a novel αβ-targeting peptide, DOTA-5G () radiolabeled with Ga, for PET/CT imaging and Lu for treatment. With the goal to develop a radiotheranostic, further modifications were made for increased circulation time, renal recycling, and tumor uptake, yielding DOTA-albumin-binding moiety-5G ().

Therapeutic drug monitoring of meropenem and piperacillin-tazobactam in the Singapore critically ill population - A prospective, multi-center, observational study (BLAST 1).

Purpose: To determine percentage of patients with sub-therapeutic beta-lactam exposure in our intensive care units (ICU) and to correlate target attainment with clinical outcomes.

Materials And Methods: Multi-centre, prospective, observational study was conducted in ICUs from three hospitals in Singapore from July 2016 to May 2018. Adult patients (≥21 years) receiving meropenem or piperacillin-tazobactam were included.

Analysis of Short-Term versus Long-Term Readmission-Free Survival After Metastatic Spine Tumor Surgery.

Background: Readmission-free survival (ReAFS) is a novel clinical and quality metric after metastatic spine tumor surgery (MSTS). We believe that factors influencing ReAFS after index MSTS vary based on time. We considered 2 time frames and defined short-term ReAFS as survival without an unplanned hospital readmission up to 90 days and long-term ReAFS as survival without unplanned hospital readmission up to 1 year after MSTS.

Evaluation of Copper-64-Labeled αβ-Targeting Peptides: Addition of an Albumin Binding Moiety to Improve Pharmacokinetics.

The incorporation of non-covalent albumin binding moieties (ABMs) into radiotracers results in increased circulation time, leading to a higher uptake in the target tissues such as the tumor, and, in some cases, reduced kidney retention. We previously developed [F]AlF NOTA-K(ABM)-αβ-BP, where αβ-BP is a peptide with high affinity for the cell surface receptor integrin αβ that is overexpressed in several cancers, and the ABM is an iodophenyl-based moiety. [F]AlF NOTA-K(ABM)-αβ-BP demonstrated prolonged blood circulation compared to the non-ABM parent peptide, resulting in high, αβ-targeted uptake with continuously improving detection of αβ(+) tumors using PET/CT.

Incidence of a subsequent carbapenem-resistant Enterobacteriaceae infection after previous colonisation or infection: a prospective cohort study.

Objectives: In patients with a history of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE), the need for CP-CRE targeted treatment in subsequent sepsis episodes is unclear. This study aimed to characterise the incidence of subsequent CP-CRE infective episodes in individuals with prior CP-CRE colonisation and/or infection, and identify predictors for these subsequent CP-CRE infections.

Methods: All adult inpatients with CP-CRE detected from any site between June 2012 and May 2014 at a tertiary-care hospital were prospectively followed for two years to assess for any subsequent CP-CRE infections.

Are vancomycin dosing guidelines followed? A mixed methods study of vancomycin prescribing practices.

Aims: Despite the availability of international consensus guidelines, vancomycin dosing and therapeutic drug monitoring (TDM) remain suboptimal. This study aimed to assess concordance of vancomycin dosing and TDM with institutional guidelines and to identify factors taken into consideration by clinicians when prescribing vancomycin.

Methods: A retrospective audit of 163 patients receiving vancomycin therapy (≥48 hours) was undertaken.

Systematic Review and Meta-Analysis of Prophylactic Transarterial Embolization for High-Risk Bleeding Peptic Ulcer Disease.

The present systematic review determined the role of transarterial embolization (TAE) as a prophylactic treatment in bleeding peptic ulcers after initial successful endoscopic hemostasis. PubMed and Ovid Medline databases were searched from inception until July 2019 for studies that included patients deemed high-risk based on Forrest Classification, Rockall score ≥ 5, or endoscopic evaluation in addition to those who underwent prophylactic TAE after initial successful endoscopic hemostasis. Meta-analysis was performed to compare patients who underwent endoscopic therapy (ET) and TAE with those who underwent ET alone.

The INTEND 1 randomized controlled trial of duct endoscopy as an indicator of margin excision in breast conservation surgery.

Purpose: With early detection, breast conservation surgery with adequate surgical margins is the standard of care. The aim of this study was to evaluate the use of pre-operative duct endoscopy (DE) to target surgical resection, improve adequate margins and reduce re-excision operations.

Methods: Women with DCIS, stage I and II breast cancer suitable for breast conservation were randomized to DE-assisted wide local excision versus standard wide local excision (without DE).

The Effects of an Albumin Binding Moiety on the Targeting and Pharmacokinetics of an Integrin αβ-Selective Peptide Labeled with Aluminum [F]Fluoride.

Purpose: The αβ-BP peptide selectively targets the integrin αβ, a cell surface receptor recognized as a prognostic indicator for several challenging malignancies. Given that the 4-[F]fluorobenzoyl (FBA)-labeled peptide is a promising PET imaging agent, radiolabeling via aluminum [F]fluoride chelation and introduction of an albumin binding moiety (ABM) have the potential to considerably simplify radiochemistry and improve the pharmacokinetics by increasing biological half-life.

Procedures: The peptides NOTA-αβ-BP (1) and NOTA-K(ABM)-αβ-BP (2) were synthesized on solid phase, radiolabeled with aluminum [F]fluoride, and evaluated in vitro (integrin ELISA, albumin binding, cell studies) and in vivo in mouse models bearing paired DX3puroβ6 [αβ(+)]/DX3puro [αβ(-)], and for [F]AlF 2, BxPC-3 [αβ(+)] cell xenografts (PET imaging, biodistribution).

Construction of the secondary care administrative records frailty (SCARF) index and validation on older women with operable invasive breast cancer in England and Wales: a cohort study.

Objectives: Studies that use national datasets to evaluate the management of older women with breast cancer are often constrained by a lack of information on patient fitness. This study constructed a frailty index for use with secondary care administrative records and evaluated its ability to improve models of treatment patterns and overall survival in women with breast cancer.

Design: Retrospective cohort study.

Correction to: Evaluation of Two Optical Probes for Imaging the Integrin αvβ6- In Vitro and In Vivo in Tumor-Bearing Mice.

This article was updated to correct the axes in Figures 4e and 5d.

Evaluation of Two Optical Probes for Imaging the Integrin αβ- In Vitro and In Vivo in Tumor-Bearing Mice.

Purpose: The purpose of this study was to develop and evaluate two αβ-targeted fluorescent imaging agents. The integrin subtype αβ is significantly upregulated in a wide range of epithelial derived cancers, plays a key role in invasion and metastasis, and expression is often located at the invasive edge of tumors. αβ-targeted fluorescent imaging agents have the potential to guide surgical resection leading to improved patient outcomes.

Addressing frailty in patients with breast cancer: A review of the literature.

Various studies have documented variation in the management of older patients with breast cancer, and some of this variation stems from different approaches to balancing the expected benefit of different treatments, with the ability of patients to tolerate them. Frailty is an emerging concept that can help to make clinical decisions for older patients more consistent, not least by providing a measure of 'biological' ageing. This would reduce reliance on 'chronological' age, which is not a reliable guide for decisions on the appropriate breast cancer care for older patients.

Surgery and adjuvant radiotherapy for unilateral ductal carcinoma in situ (DCIS) in women aged over 70 years: A population based cohort study.

Background: There is little clinical evidence to guide treatment decisions for ductal carcinoma in situ (DCIS) in older women. This study evaluated how the management of DCIS in women aged 70 or more compared with women aged 50-69 in England and Wales.

Method: The study identified women aged ≥50 years with new unilateral DCIS diagnosed between 2014 and 2016 from linked cancer registration and routine hospital datasets for England and Wales.

Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma.

Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase (BTK) and has shown single-agent activity in recurrent/refractory central nervous system (CNS) lymphoma. Clinical responses are often transient or incomplete, suggesting a need for a combination therapy approach. We conducted a phase 1b clinical trial to explore the sequential combination of ibrutinib (560 or 840 mg daily dosing) with high-dose methotrexate (HD-MTX) and rituximab in patients with CNS lymphoma (CNSL).