Review of research output of Australian and New Zealand colorectal surgeons over the past 20 years.

OBJECTIVES: High-quality research has a tangible impact on patient care and should inform all medical decision-makings. Appraising and benchmarking of research is necessary in evidence-based medicine and allocation of funding. The aim of this review is to demonstrate how evidence may be gathered by quantifying the amount and type of research by a group of surgeons over a 20-year period. METHODS: Members of the Colorectal Surgical Society of Australia and New Zealand were identified in April 2020. A search of the Scopus database was conducted to quantify each surgeon's research output from 1999 to 2020. Authorship details such as the Hirsch index and number of papers published were recorded, as were publication-related details. RESULTS: 226 colorectal surgeons were included for analysis, producing a total of 5053 publications. The most frequent colorectal topics were colorectal cancer (32%, n = 1617 of all publications), followed by pelvic floor disorders (4.3%, n = 217) and inflammatory bowel disease (3.5%, n = 177). 56% (n = 2830) of all publications were case series audits (21%, n = 1061), expert opinion pieces (20%, n = 1011) and cohort studies (15%, n = 758). 7% (n = 354) were randomised control or non-randomised control trials, 3% (n = 152) were systematic reviews and 1% (n = 50) were meta-analyses. The top 10% (n = 23) of authors accounted for more than half (54%, n = 2729) of manuscripts published. CONCLUSION: Australasian colorectal surgeons made a significant contribution to the medical literature over the past 20 years and the number of publications is increasing over time. A greater output of higher-level evidence research is needed. This information may be used to better allocate researcher funding and grants for future projects.

Blood Pressure and Early Mobilization After Total Hip and Knee Replacements: A Pilot Study on the Impact of Midodrine Hydrochloride.

BACKGROUND: Early mobilization is an important therapeutic goal after total knee replacement and total hip replacement. Orthostatic hypotension and orthostatic intolerance can impede mobilization. Midodrine hydrochloride, an orally administered vasoconstrictor, may improve blood pressure and diminish the prevalence of adverse mobilization events. METHODS: We conducted a pilot change-of-practice study. Two cohorts, each comprising 10 patients managed with total knee replacement and 10 patients managed with total hip replacement, were managed with blood pressure-adjusted midodrine, which was administered 3 times daily for the first 72 hours postoperatively at either a low dose (2.5 or 5 mg) or a higher dose (5 or 10 mg). These patients were then matched with an equivalent preintervention cohort of patients. RESULTS: The midodrine protocol was instituted effectively and with high compliance. Hypotension was uncommon across all groups, with the mean lowest systolic blood pressure ranging from 110 to 121 mm Hg. Moreover, adverse mobilization events were uncommon across all groups (prevalence, 9.6% in the control group, 5.6% in the low-dose group, and 2.9% in the high-dose group) (p = 0.046 for the high-dose group versus the control group). A midodrine dose of 10 mg generated a significant mean dose-related systolic blood pressure increase of 14 mm Hg at 2 hours after administration (p < 0.001). There were no significant differences between the groups in terms of mean systolic blood pressure, biochemical markers, or intravenous therapy administration. CONCLUSIONS: A dose of 10 mg was found to achieve a significant systolic blood pressure response at 2 hours after administration and, in patients who received higher-dose midodrine, adverse mobilization events appeared less common. Additional investigation with a blinded randomized controlled trial, utilizing 10 mg of midodrine 2 hours before mobilization, would be needed to confirm the efficacy of midodrine therapy. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Correction: Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents.

[This corrects the article DOI: 10.1371/journal.pone.0119549.].

Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents.

Malignant mesothelioma (MM) is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs) that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM.