BACKGROUND: Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates. METHODS: One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer. RESULTS: One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years' experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventy-four percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p = 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p = 0.0001), MRI for all RC patients (20% vs. 42%, p = 0.03), and ERUS for all RC patients (43% vs. 21%, p = 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR = 5.67, stage II + III RR = 2.98), quality of pathology report (RR = 4.85), and sphincter-saving surgery (RR = 3.81). CONCLUSIONS: There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods.

While implant-related infections continue to play a relevant role in failure of implantable biomaterials in orthopaedic and trauma there is a lack of standardised microbiological procedures to identify the pathogen(s). The microbiological diagnosis of implant-related infections is challenging due to the following factors: the presence of bacterial biofilm(s), often associated with slow-growing microorganisms, low bacterial loads, previous antibiotic treatments and, possible intra-operative contamination. Therefore, diagnosis requires a specific set of procedures. Based on the Guidelines of the Italian Association of the Clinical Microbiologists (AMCLI), the World Association against Infection in Orthopaedics and Trauma has drafted the present document. This document includes guidance on the basic principles for sampling and processing for implant-related infections based on the most relevant literature. These procedures outline the main microbiological approaches, including sampling and processing methodologies for diagnostic assessment and confirmation of implant-related infections. Biofilm dislodgement techniques, incubation time and the role of molecular approaches are addressed in specific sections. The aim of this paper is to ensure a standardised approach to the main microbiological methods for implant-related infections, as well as to promote multidisciplinary collaboration between clinicians and microbiologists.

Clinical audit of invasive mold disease (IMD) in hematology patients is inefficient due to the difficulties of case finding. This results in antifungal stewardship (AFS) programs preferentially reporting drug cost and consumption rather than measures that actually reflect quality of care. We used machine learning-based natural language processing (NLP) to non-selectively screen chest tomography (CT) reports for pulmonary IMD, verified by clinical review against international definitions and benchmarked against key AFS measures. NLP screened 3014 reports from 1 September 2008 to 31 December 2017, generating 784 positives that after review, identified 205 IMD episodes (44% probable-proven) in 185 patients from 50,303 admissions. Breakthrough-probable/proven-IMD on antifungal prophylaxis accounted for 60% of episodes with serum monitoring of voriconazole or posaconazole in the 2 weeks prior performed in only 53% and 69% of episodes, respectively. Fiberoptic bronchoscopy within 2 days of CT scan occurred in only 54% of episodes. The average turnaround of send-away bronchoalveolar galactomannan of 12 days (range 7-22) was associated with high empiric liposomal amphotericin consumption. A random audit of 10% negative reports revealed two clinically significant misses (0.9%, 2/223). This is the first successful use of applied machine learning for institutional IMD surveillance across an entire hematology population describing process and outcome measures relevant to AFS. Compared to current methods of clinical audit, semi-automated surveillance using NLP is more efficient and inclusive by avoiding restrictions based on any underlying hematologic condition, and has the added advantage of being potentially scalable.

Background: The social, contextual, and behavioral determinants that influence care in patients at risk for invasive fungal diseases (IFD) are poorly understood. This knowledge gap is a barrier to the implementation of emerging antifungal stewardship (AFS) programs. We aimed to understand the barriers and enablers to AFS, opportunities for improvement, and perspectives of AFS for hematology patients at a major medical center in Australia. Methods: Semistructured, face-to-face interviews were conducted with 35 clinicians from 6 specialties (hematology, infectious diseases, pharmacy, nursing, radiology, respiratory), followed by thematic analysis mapped to a behavioral change framework. Results: Access to fungal diagnostics including bronchoscopy was identified as the key barrier to rational prescribing. Collective decision making was the norm, aided by an embedded stewardship model with on-demand access to infectious diseases expertise. Poor self-efficacy/knowledge among prescribers was actually an enabler of AFS, because clinicians willingly deferred to infectious diseases for advice. A growing outpatient population characterized by frequent care transitions was seen as an opportunity for AFS but neglected by an inpatient focused model, as was keeping pace with emerging fungal risks. Ad hoc surveillance, audit, and feedback practices frustrated population-level quality improvement for all actors. Antifungal stewardship was perceived as a specialized area that should be integrated within antimicrobial stewardship but aligned with the cultural expectations of hematologists. Conclusions: Antifungal stewardship is multifaceted, with fungal diagnostics a critical gap and outpatients a neglected area. Formal surveillance, audit, and feedback mechanisms are essential for population-level quality improvement. Resourcing is the next challenge because complex immunocompromised patients require personalized attention and audit of clinical outcomes including IFD is difficult.

Degradable bone implants are designed to foster the complete regeneration of natural tissue after large-scale loss trauma. Polycaprolactone (PCL) and hydroxyapatite (HA) composites are promising scaffold materials with superior mechanical and osteoinductive properties compared to the single materials. However, producing three-dimensional (3D) structures with high HA content as well as tuneable degradability remains a challenge. To address this issue and create homogeneously distributed PCL-nanoHA (nHA) scaffolds with tuneable degradation rates through both PCL molecular weight and nHA concentration, we conducted a detailed characterisation and comparison of a range of PCL-nHA composites across three molecular weight PCLs (14, 45, and 80 kDa) and with nHA content up to 30% w/w. In general, the addition of nHA results in an increase of viscosity for the PCL-nHA composites but has little effect on their compressive modulus. Importantly, we observe that the addition of nHA increases the rate of degradation compared to PCL alone. We show that the 45 and 80 kDa PCL-nHA groups can be fabricated via indirect 3D printing and have homogenously distributed nHA even after fabrication. Finally, the cytocompatibility of the composite materials is evaluated for the 45 and 80 kDa groups, with the results showing no significant change in cell number compared to the control. In conclusion, our analyses unveil several features that are crucial for processing the composite material into a tissue engineered implant.

Background: The management of oligometastatic clear cell renal cell carcinoma (ccRCC) varies widely, ranging from observation to resection or systemic therapies. Prolonged survival has been observed following resection or stereotactic ablative body radiotherapy (SABR). Immunotherapy combinations have shown survival benefits, however, toxicity is higher than that for monotherapy and complete response rates remain less than 10%. The combination of effective local therapies in conjunction with immunotherapy may provide more durable control and pre-clinical models have suggested a synergistic immune-priming effect of SABR. Objectives: and Methods: RAPPORT is a prospective, single arm, phase I/II study assessing the safety, efficacy and biological effects of single fraction SABR followed by pembrolizumab for oligometastatic ccRCC. The study will include 30 patients with histological confirmed ccRCC and 1-5 oligometastases, one or more of which must be suitable for SABR. Patients can have received prior systemic therapy but not prior immunotherapy. A single 20Gy of SABR is followed 5 days later by 8 cycles of 200 mg pembrolizumab, every 3 weeks. Adverse events are recorded using CTCAE V4.03 and tumour response evaluated by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Tumour tissue and peripheral blood samples will be collected pre-, during and post-treatment to assess longitudinal changes in immune subsets. Outcomes and significance: The RAPPORT study will provide important safety and early efficacy data on the combination of SABR and pembrolizumab in oligometastatic ccRCC and will provide an insight into the underlying biological effects of combination therapy. Trial registration: clinicaltrials.gov ID NCT02855203.

BACKGROUND: Guided rehabilitation beyond 6-months is rare following anterior cruciate ligament reconstruction (ACLR), despite high prevalence of unacceptable symptoms and quality of life (QoL). Our primary aim was to determine the feasibility of a randomised controlled trial (RCT) evaluating a physiotherapist-guided intervention for individuals 1-year post-ACLR with persistent symptoms. Our secondary aim was to determine if a worthwhile treatment effect could be observed for the lower-limb focussed intervention (compared to the trunk-focussed intervention), for improvement in knee-related QoL, symptoms, and function. DESIGN: Participant- and assessor-blinded, pilot feasibility RCT. METHODS: Participant eligibility criteria: i) 12-15 months post-ACLR; ii) < 87.5/100 on the Knee injury and Osteoarthritis Outcome Score (KOOS) QoL subscale; and either a one-leg rise test < 22 repetitions, single-hop < 90% limb symmetry; or Anterior Knee Pain Scale < 87/100. Participants were randomised to lower-limb or trunk-focussed focussed exercise and education. Both interventions involved 8 face-to-face physiotherapy sessions over 16-weeks. Feasibility was assessed by eligibility rate (> 1 in 3 screened), recruitment rate (> 4 participants/month), retention (< 20% drop-out), physiotherapy attendance and unsupervised exercise adherence (> 80%). Between-group differences for knee-related QoL (KOOS-QoL, ACL-QoL), symptoms (KOOS-Pain, KOOS-Symptoms), and function (KOOS-Sport, functional performance tests) were used to verify that the worthwhile effect (greater than the minimal detectable change for each measure) was contained within the 95% confidence interval. RESULTS: 47% of those screened were eligible, and 27 participants (3 participants/month; 48% men, 34±12 years) were randomised. Two did not commence treatment, and two were lost to follow-up (16% drop-out). Physiotherapy attendance was > 80% for both groups but reported adherence to unsupervised exercise was low (< 55%). Both interventions had potentially worthwhile effects for KOOS-QoL and ACL-QoL, while the lower-limb focussed intervention had potentially greater effects for KOOS-Sport, KOOS-Pain, and functional performance. CONCLUSIONS: A larger-scale RCT is warranted. All feasibility criteria were met, or reasonable recommendations could be made to achieve the criteria in future trials. Strategies to increase recruitment rate and exercise adherence are required. The potential worthwhile effects for knee-related QoL, symptoms, and function indicates a fully-powered RCT may detect a clinically meaningful effect. TRIAL REGISTRATION: Prospectively registered ( ACTRN12616000564459 ).

Background: Delayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF. Methods: Data sources included the Biogen DMF integrated clinical trial data set, a retrospective US chart abstraction study, and data from MSBase. We assessed rate and time course of lymphocyte reconstitution after DMF discontinuation. Results: The majority of patients who developed lymphopenia while treated with DMF and subsequently discontinued treatment experienced ALC reconstitution. The median time to reach ALC ≥0.8 × 109/L was 2-4 months after discontinuation for patients treated in real-world data sets; the median time to reach ALC ≥0.91 × 109/L was 2 months after discontinuation in DMF clinical trials. Severity of lymphopenia on treatment and decline in ALC within the first 6 months did not affect the ALC reconstitution rate after DMF discontinuation; rather, on-treatment lymphopenia duration influenced the reconstitution rate. In patients with severe, prolonged lymphopenia for ≥3 years, lymphocyte reconstitution to ≥0.91 × 109/L was 12-18 months vs 2-3 months in patients with lymphopenia persisting <6 months. Conclusions: The majority of patients who discontinued DMF due to lymphopenia experienced ALC reconstitution within 2-4 months following DMF discontinuation. This may help guide clinicians in managing patients who develop lymphopenia during DMF treatment. Prolonged lymphopenia on DMF treatment is associated with slow lymphocyte recovery after DMF discontinuation.

Background: The effectiveness of telerehabilitation for a patient with knee osteoarthritis may depend upon the person's adherence to intervention. Thus, the aim of this study was to investigate whether people with knee osteoarthritis would adhere to exercise-therapy facilitated via multiple media in Brazil, a newly industrialized country. Method: This is a feasibility study, pre-post intervention. Middle aged (40-50 years) and elderly (≥70 years) people with knee osteoarthritis received in-person exercise-therapy instructions on the first day, along with a booklet and DVD (videos) to take home. Participants also received six motivational phone calls throughout the 12-week treatment. Satisfaction and adherence were assessed one week after intervention with the Exercise Adherence Rating Scale (EARS), sections B and C. Preference on the method used to adhere to exercises was recorded. Conclusion: Telerehabilitation was well accepted by middle-aged and elderly Brazilians with knee osteoarthritis. The preferred media to enhance adherence, was a booklet with descriptions of the exercises, especially for the elderly cohort.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of graft-versus-host disease (GvHD), a strong prognostic predictor of early mortality within the first 2 years following allo-HSCT. The objective of this study was to describe the harm outcomes reported among patients receiving second- and third-line treatment as part of the management for GvHD via a systematic literature review. Methods: A total of 34 studies met the systematic review inclusion criteria, reporting adverse events (AEs) across 12 different second- and third-line therapies. Results: A total of 14 studies reported AEs across nine different therapies used in the treatment of acute GvHD (aGvHD), 17 studies reported AEs of eight different treatments for chronic GvHD (cGvHD) and 3 reported a mixed population. Infections were the AE reported most widely, followed by haematologic events and laboratory abnormalities. Reported infections per patient were lower under extracorporeal photopheresis (ECP) for aGvHD (0.267 infections per patient over 6 months) relative to any of the therapies studied (ranging from 0.853 infections per patient per 6 months under etanercept up to 1.998 infections per patient on inolimomab). Conclusion: The reported incidence of infectious AEs in aGvHD and grade 3-5 AEs in cGvHD was lower on ECP compared with pharmaceutical management.

While the advent of biologic therapy has led to improved outcomes in perianal fistulizing Crohn's disease (pfCD), loss of response is common. Previous studies suggest that patients who achieve radiological healing (with healing of underlying tracts on magnetic resonance imaging [MRI]) have a longer duration of response. The aim of this study was to characterize MRI outcomes of pfCD at a specialist inflammatory bowel disease (IBD) unit and compare the long‐term clinical outcomes between patients achieving MRI and clinical healing.

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.