Quantifying the cost savings and health impacts of improving colonoscopy quality: an economic evaluation.

OBJECTIVE: To estimate and quantify the cost implications and health impacts of improving the performance of English endoscopy services to the optimum quality as defined by postcolonoscopy colorectal cancer (PCCRC) rates. DESIGN: A semi-Markov state-transition model was constructed, following the logical treatment pathway of individuals who could potentially undergo a diagnostic colonoscopy. The model consisted of three identical arms, each representing a high, middle or low-performing trust's endoscopy service, defined by PCCRC rates. A cohort of 40-year-old individuals was simulated in each arm of the model. The model's time horizon was when the cohort reached 90 years of age and the total costs and quality-adjusted life-years (QALYs) were calculated for all trusts. Scenario and sensitivity analyses were also conducted. RESULTS: A 40-year-old individual gains 0.0006 QALYs and savings of £6.75 over the model lifetime by attending a high-performing trust compared with attending a middle-performing trust and gains 0.0012 QALYs and savings of £14.64 compared with attending a low-performing trust. For the population of England aged between 40 and 86, if all low and middle-performing trusts were improved to the level of a high-performing trust, QALY gains of 14 044 and cost savings of £249 311 295 are possible. Higher quality trusts dominated lower quality trusts; any improvement in the PCCRC rate was cost-effective. CONCLUSION: Improving the quality of endoscopy services would lead to QALY gains among the population, in addition to cost savings to the healthcare provider. If all middle and low-performing trusts were improved to the level of a high-performing trust, our results estimate that the English National Health Service would save approximately £5 million per year.

Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Variation in harms and benefits of prostate-specific antigen screening for prostate cancer by socio-clinical risk factors: A rapid review.

Objective: To analyse the latest evidence on the relative harms and benefits of screening and diagnostic pathways with close examination of (i) men aged 50 years or older, (ii) men whose ethnicity places them at higher risk and (iii) men with a family history. Methods: We conducted a literature search using PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases and other sources, from January 1990 to 25 January 2023. Two independent reviewers selected for randomised controlled trials (RCTs) and cohort studies which met our inclusion criteria. Results: Twenty-eight articles were selected, from six trials, including the Göteborg trial-reported separately from European Randomised Study of Screening for Prostate Cancer (ERSPC). Prostate-specific antigen (PSA)-based screening led to the increased detection of low-grade cancer and reduction of advanced/metastatic disease but had contradictory effects on prostate cancer (PCa)-specific mortality (no difference or reduced), possibly due to issues of contamination or compliance. Screening men from a relatively young age (50-55) reduced risk of PCa-specific mortality in a subanalysis of an 18-year follow-up study and in a 17-year cohort study from the main Göteborg trial. Moreover, one Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial analysis reported a trend of reduced risk of PCa-specific mortality for men with a family history who were screened. [Correction added on 05 March 2024, after first online publication: "Cancer Screening Trial" has been added to the preceding sentence.] However, we did not find relevant studies for ethnicity. Conclusion: Under current UK practice, the choice to conduct a PSA test relies on a shared decision-making approach guided by known risk factors. However, we found there was a lack of strong evidence on the harms and benefits of PSA screening by socio-clinical risk factors and suggest further research is required to understand the long-term impact of screening on high-risk populations in the current diagnostic setting.

The impact of pre-biopsy MRI and additional testing on prostate cancer screening outcomes: A rapid review.

Objective: This work aims to examine the latest evidence on the impact of pre-biopsy MRI, in addition to prostate-specific antigen (PSA) testing, on health outcomes and quality of life. Methods: We conducted a literature search including PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases, with a limited scan of (i) guidelines and (ii) references from trial reports, from January 2005 to 25th January 2023. Two independent reviewers selected randomised controlled trials (RCT) and cohort studies which met our inclusion criteria. Results: One hundred thirty-seven articles were identified, and seven trial articles were selected. Trial interventions were as follows: (i) PSA blood test, (ii) additional tests such as pre-biopsy multiparametric magnetic resonance imaging (mpMRI) and Biparametric MRI (bpMRI), and (iii) MRI targeted biopsy and standard biopsy. Compared with standard biopsy, MRI-based interventions led to increased detection of clinically significant cancers in three studies and decreased detection of clinically insignificant cancer (Gleason grade 3 + 3) in four studies. However, PROstate Magnetic resonance Imaging Study (PROMIS) and Stockholm3 with MRI (STHLM3-MRI) studies reported different trends depending on the scenario studied in PROMIS (MRI triage and MRI directed biopsy vs. MRI triage and standard biopsy) and thresholds used in STHLM3-MRI (≥0·11 and ≥0·15). MRI also helped 8%-49% of men avoid biopsy, in six out of seven studies, but not in STHLM3-MRI at ≥0.11. Interestingly, the proportion of men who experienced sepsis and UTI was low across studies. Conclusion: This review found that a combination of approaches, centred on the use of pre-biopsy MRI, may improve the detection of clinically significant cancers and reduce (i) the diagnosis of clinically insignificant cancers and (ii) unnecessary biopsies, compared with PSA testing and standard biopsy alone. However, the impact of such interventions on longer term outcomes such as prostate cancer-specific mortality has not yet been assessed.

Randomized Controlled Trial Comparing Liposomal to Plain Bupivacaine in the Transversus Abdominis Plane for DIEP Flap Breast Reconstruction.

BACKGROUND: Pain control after autologous breast reconstruction is important for patient satisfaction and early recovery. Transversus abdominis plane (TAP) blocks are commonly used as part of an enhanced recovery after surgery (ERAS) pathway for breast reconstruction. It is uncertain whether liposomal bupivacaine used in TAP blocks offers additional advantages. This study aimed to compare the efficacy of liposomal bupivacaine versus plain bupivacaine for patients undergoing deep inferior epigastric perforator flap reconstruction. METHODS: This double-blinded randomized controlled trial studied patients undergoing abdominally based autologous breast reconstruction between June of 2019 and August of 2020. Subjects were randomly assigned liposomal or plain bupivacaine, performed using ultrasound-guided TAP block technique. All patients were managed according to an ERAS protocol. Primary outcomes were postoperative narcotic analgesia required, measured in oral morphine equivalents from postoperative days 1 to 7. Secondary outcomes included numeric pain scale score on postoperative days 1 to 7, nonnarcotic pain medication use, time to first narcotic use, return of bowel function, and length of stay. RESULTS: Sixty patients were enrolled: 30 received liposomal bupivacaine and 30 received plain bupivacaine. There were no significant differences in demographics, daily oral morphine equivalent narcotic use, nonnarcotic pain medication use, time to narcotic use, numeric pain scale score, time to bowel function, or length of stay. CONCLUSION: Liposomal bupivacaine does not confer advantages over plain bupivacaine when used in TAP blocks for abdominally based microvascular breast reconstruction in patients under ERAS protocols and multimodal approaches for pain control. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Patient safety incidents in endoscopy: a human factors analysis of nonprocedural significant harm incidents from the National Reporting and Learning System (NRLS).

BACKGROUND: Despite advances in understanding and reducing the risk of endoscopic procedures, there is little consideration of the safety of the wider endoscopy service. Patient safety incidents (PSIs) still occur. We sought to identify nonprocedural PSIs (nPSIs) and their causative factors from a human factors perspective and generate ideas for safety improvement. METHODS: Endoscopy-specific PSI reports were extracted from the National Reporting and Learning System (NRLS). A retrospective, cross-sectional human factors analysis of data was performed. Two independent researchers coded data using a hybrid thematic analysis approach. The Human Factors Analysis and Classification System (HFACS) was used to code contributory factors. Analysis informed creation of driver diagrams and key recommendations for safety improvement in endoscopy. RESULTS: From 2017 to 2019, 1181 endoscopy-specific PSIs of significant harm were reported across England and Wales, with 539 (45.6%) being nPSIs. Five categories accounted for over 80% of all incidents, with "follow-up and surveillance" being the largest (23.4% of all nPSIs). From the free-text incident reports, 487 human factors codes were identified. Decision-based errors were the most common act prior to PSI occurrence. Other frequent preconditions to incidents were focused on environmental factors, particularly overwhelmed resources, patient factors, and ineffective team communication. Lack of staffing, standard operating procedures, effective systems, and clinical pathways were also contributory. Seven key recommendations for improving safety have been made in response to our findings. CONCLUSIONS: This was the first national-level human factors analysis of endoscopy-specific PSIs. This work will inform safety improvement strategies and should empower individual services to review their approach to safety.

Scale-up of the Australian Fans in Training (Aussie-FIT) men's health behaviour change program: a protocol for a randomised controlled hybrid effectiveness-implementation trial.

INTRODUCTION: Improving physical activity (PA) and healthy eating is critical for primary and secondary prevention of cardiovascular disease (CVD). Behaviour change programmes delivered in sporting clubs can engage men in health behaviour change, but are rarely sustained or scaled-up post trial. Following the success of pilot studies of the Australian Fans in Training (Aussie-FIT) programme, a hybrid effectiveness-implementation trial protocol was developed. This protocol outlines methods to: (1) establish if Aussie-FIT is effective at supporting men with or at risk of CVD to sustain improvements in moderate-to-vigorous PA (primary outcome), diet and physical and psychological health and (2) examine the feasibility and utility of implementation strategies to support programme adoption, implementation and sustainment. METHODS AND ANALYSIS: A pragmatic multistate/territory hybrid type 2 effectiveness-implementation parallel group randomised controlled trial with a 6-month wait list control arm in Australia. 320 men aged 35-75 years with or at risk of CVD will be recruited. Aussie-FIT involves 12 weekly face-to-face sessions including coach-led interactive education workshops and PA delivered in Australian Football League (Western Australia, Northern Territory) and rugby (Queensland) sports club settings. Follow-up measures will be at 3 and 6 months (both groups) and at 12 months to assess maintenance (intervention group only). Implementation outcomes will be reported using the Reach, Effectiveness, Adoption, Implementation, Maintenance framework. ETHICS AND DISSEMINATION: This multisite study has been approved by the lead ethics committees in the lead site's jurisdiction, the South Metropolitan Health Service Human Research Ethics Committee (Reference RGS4254) and the West Australian Aboriginal Health Ethics Committee (HREC1221). Findings will be disseminated at academic conferences, peer-reviewed journals and via presentations and reports to stakeholders, including consumers. Findings will inform a blueprint to support the sustainment and scale-up of Aussie-FIT across diverse Australian settings and populations to benefit men's health. TRIAL REGISTRATION NUMBER: This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000437662).

Oral antibiotics and mechanical bowel preparation for colorectal surgery: A prospective observational study of surgical site infection and microbial analysis.

PURPOSE: Surgical site infections (SSIs) are common in colorectal surgery. Mechanical bowel preparation (MBP) in conjunction with oral antibiotics (OABs) have been shown to reduce SSI rates. It however is still unclear which OABs to use, and how this can be implemented in practice. METHODS: This is a prospective observational study carried out in Swansea Bay University Health Board during 2019-2021, evaluating the introduction of OABs in a stepwise manner on the incidence of SSI in major colorectal surgery. A control group having MBP only was compared to two OAB groups: one group had MBP plus metronidazole only and the second MBP plus metronidazole and neomycin. A 30-day follow-up after surgery was ascertained via chart review and telephone contact. Logistic regression was performed to estimate the relation between OAB use and SSI, with adjustment for confounding. In a subset of patients, faecal samples were analysed through 16S rRNA amplicon sequencing before and after OAB treatment, depicting the impact of the gut microbiome. RESULTS: In total 160 patients were analysed: 46 patients had MBP only, whilst 76 patients had MBP plus metronidazole only and 38 patients had MBP with metronidazole/neomycin. The SSI rate in the entire cohort was 33.8%, whilst the adjusted ORs for the single- and dual-OAB groups were 0.76 (95% CI: 0.17-1.81) and 0.50 (95% CI: 0.17-1.52). The microbial analysis demonstrated that the relative abundance for many bacterial genera was changed before and after OAB treatment, but no link with SSI development could be shown. CONCLUSIONS: Introduction of OABs in conjunction with MBP in colorectal surgery is feasible, and may potentially lead to lower rates of SSI, as well as altering the community structure of the faecal microbiome. More research is needed, especially considering different OABs and mechanistic studies of the gut microbiome in the context of colorectal surgery.

New Zealand Blackcurrant Increases Postexercise Hypotension Following Sustained Moderate-Intensity Exercise.

Previous observations demonstrate New Zealand blackcurrant (NZBC) extract to alter cardiovascular responses at rest without prior exercise. However, the prolonged effects of NZBC on blood pressure and heart rate variability following exercise are not known. Participants (n15 [five women], age: 31 ± 9 years, maximal oxygen uptake: 44 ± 9 ml·kg-1·min-1) undertook a control condition of 2 hr of lying supine rest. Subsequently, in a double-blind, placebo (PLA)-controlled, randomized crossover design participants completed 1 hr of treadmill exercise at 50% maximal oxygen uptake followed by 2-hr supine rest with blood pressure and heart rate variability measurement following a 7-day intake of NZBC and PLA. With NZBC, there was an increase in average fat oxidation (NZBC: 0.24 ± 0.11 vs. PLA: 0.17 ± 0.11 g/min, p = .005), and larger high-frequency relative power during the exercise (p = .037). In the 2-hr rest period, delta change for systolic pressure was larger with NZBC than PLA (Control vs. NZBC: -5.6 ± 6.4, Control vs. PLA: -3.5 ± 6.0 mmHg, p = .033) but was not different for diastolic or mean arterial pressure. There were no alterations in heart rate variabilities during the 2 hr following the exercise with NZBC. A 7-day intake of NZBC causes a larger postexercise hypotension response in young, physically active men and women following 1 hr of treadmill exercise at 50% maximal oxygen uptake.

A Non-Healing Lesion on the Anterior Chest of a Patient Receiving Hemodialysis: A Case Study.

Basal cell carcinoma is the most common type of skin cancer, and patients receiving hemodialysis are at increased risk of developing them. This article describes a case of a patient with a basal cell carcinoma in which the diagnosis was delayed due to the lesion masquerading as granulation tissue at the site of a previous tunnelled hemodialysis catheter. Early detection of basal cell carcinomas is important because delayed detection increases the risk of local invasion and the requirement for more complex surgical management.

Effectiveness and cost-effectiveness of text messages with or without endowment incentives for weight management in men with obesity (Game of Stones): study protocol for a randomised controlled trial.

BACKGROUND: Obesity increases the risk of type 2 diabetes, heart disease, stroke, mobility problems and some cancers, and its prevalence is rising. Men engage less than women in existing weight loss interventions. Game of Stones builds on a successful feasibility study and aims to find out if automated text messages with or without endowment incentives are effective and cost-effective for weight loss at 12 months compared to a waiting list comparator arm in men with obesity. METHODS: A 3-arm, parallel group, assessor-blind superiority randomised controlled trial with process evaluation will recruit 585 adult men with body mass index of 30 kg/m2 or more living in and around three UK centres (Belfast, Bristol, Glasgow), purposively targeting disadvantaged areas. Intervention groups: (i) automated, theory-informed text messages daily for 12 months plus endowment incentives linked to verified weight loss targets at 3, 6 and 12 months; (ii) the same text messages and weight loss assessment protocol; (iii) comparator group: 12 month waiting list, then text messages for 3 months. The primary outcome is percentage weight change at 12 months from baseline. Secondary outcomes at 12 months are as follows: quality of life, wellbeing, mental health, weight stigma, behaviours, satisfaction and confidence. Follow-up includes weight at 24 months. A health economic evaluation will measure cost-effectiveness over the trial and over modelled lifetime: including health service resource-use and quality-adjusted life years. The cost-utility analysis will report incremental cost per quality-adjusted life years gained. Participant and service provider perspectives will be explored via telephone interviews, and exploratory mixed methods process evaluation analyses will focus on mental health, multiple long-term conditions, health inequalities and implementation strategies. DISCUSSION: The trial will report whether text messages (with and without cash incentives) can help men to lose weight over 1 year and maintain this for another year compared to a comparator group; the costs and benefits to the health service; and men's experiences of the interventions. Process analyses with public involvement and service commissioner input will ensure that this open-source digital self-care intervention could be sustainable and scalable by a range of NHS or public services. TRIAL REGISTRATION: ISRCTN 91974895 . Registered on 14/04/2021.

Acral fibromyxoma: a rare plantar nodule.

Acral fibromyxomas are benign tumours ranging in size between 0.6 and 5 cm, commonly found around the nailbed. The often asymptomatic presentation of acral fibromyxomas means that there is often a delay in their diagnosis and subsequent treatment. The objective of this paper is to present the unique case of a fibromyxoma present in the acral region, as well as a review of the literature.

Painful ulcerations: the sole clinical sign of mixed cryoglobulinaemia secondary to marginal zone lymphoma.

A man in his 70s with background vascular disease presented with 7 months of painful non-resolving lower leg ulcers with eschar and petechiae, left lower ear lobe ulceration and dusky inflammation of the right ear. He demonstrated good bilateral pedal pulses and no peripheral oedema. No lymphadenopathy was palpated.Biopsy suggested leucocytoclastic vasculitis on chronic stasis changes. Blood investigations showed elevated rheumatoid factor and mixed polyclonal IgG and monoclonal IgM cryoglobulins. He was diagnosed with mixed cryoglobulinaemia, and consequent conducted flow cytometry revealed CD5 +marginal zone lymphoma with elevated serum free light chains and kappa/lambda ratio.One-month following rituximab and chlorambucil therapy, the patient's pain had much improved, ear ulcers had healed and several leg ulcers had reduced in width and depth. The petechial eruption had also resolved.

Using a dark logic model to explore adverse effects in audit and feedback: a qualitative study of gaming in colonoscopy.

BACKGROUND: Audit and feedback (A&F) interventions improve patient care but may result in unintended consequences. To evaluate plausible harms and maximise benefits, theorisation using logic models can be useful. We aimed to explore the adverse effects of colonoscopy A&F using a feedback intervention theory (FIT) dark logic model before the National Endoscopy Database Automated Performance Reports to Improve Quality Outcomes Trial study. METHODS: We undertook a qualitative study exploring A&F practices in colonoscopy. Interviews were undertaken with endoscopists from six English National Health Service endoscopy centres, purposively sampled for professional background and experience. A thematic framework analysis was performed, mapping paradoxical effects and harms using FIT and the theory of planned behaviour. RESULTS: Data saturation was achieved on the 19th participant, with participants from nursing, surgical and medical backgrounds and a median of 7 years' experience.When performance was below aspirational targets participants were falsely reassured by social comparisons. Participants described confidence as a requirement for colonoscopy. Negative feedback without a plan to improve risked reducing confidence and impeding performance (cognitive interference). Unmet targets increased anxiety and prompted participants to question messages' motives and consider gaming.Participants described inaccurate documentation of subjective measures, including patient comfort, to achieve targets perceived as important. Participants described causing harm from persevering to complete procedures despite patient discomfort and removing insignificant polyps to improve detection rates without benefiting the patient. CONCLUSION: Our dark logic model highlighted that A&F interventions may create both desired and adverse effects. Without a priori theorisation evaluations may disregard potential harms. In colonoscopy, improved patient experience measures may reduce harm. To address cognitive interference the motivation of feedback to support improvement should always be clear, with plans targeting specific behaviours and offering face-to-face support for confidence. TRIAL REGISTRATION NUMBER: ISRCTN11126923.

The Wire Study-a protocol for a multi-stage feasibility study evaluating K-wire fixation of hand fractures in the UK.

BACKGROUND: Hand fractures are common and sometimes require surgery to restore function. Placement of Kirschner wires (K-wires) is the most common form of surgical fixation. After placement, a key decision is whether to bury the end of a K-wire or leave it protruding from the skin (exposed). A recent systematic review found no evidence to support either approach and a national clinician and surgeon survey demonstrated further uncertainty. We aim to determine the design of a definitive randomised controlled trial assessing the cost and clinical effectiveness of buried versus exposed Kirschner wires for adults with metacarpal or phalangeal fractures. METHODS: We will employ three methodologies: a national service evaluation of current clinical practice, patient and surgeon focus groups and a consensus meeting to finalise the protocol for a randomised controlled trial. For the service evaluation, all outcomes will be summarised using descriptive statistics overall and split by group (buried versus exposed K-wires). Information collected in the patient focus groups will be analysed thematically. The surgeon consensus meeting will address each part of the design in turn and through discussion agree a final protocol. DISCUSSION: The study may be monitored, or audited in accordance with the current approved protocol, Good Clinical Practice (GCP), relevant regulations and standard operating procedures. The Chief Investigator will submit and, where necessary, obtain approval from the above parties for all substantial amendments to the original approved documents. A feasibility study report will be published by the Wire Study Steering committee. Additional members of the steering group and citable collaborators will be listed within the manuscript and their roles identified.

Melanoma Radiological Surveillance: A Review of Current Evidence and Clinical Challenges.

Melanoma is a common cancer in both young and older populations in many western countries. Rates of melanoma diagnosis worldwide are increasing. With the introduction of both targeted and immunotherapies there have been dramatic improvements in the care of patients with metastatic melanoma. With these new therapies being increasingly offered to patients with stage III metastatic melanoma and stage IV disease, radiological surveillance of melanoma has become a widely used method of monitoring melanoma patients for early locoregional and distant metastasis. However, concerns have been raised about risk of false positive results, which patients to consider radiological surveillance for, and at what intervals to do so. To date, there are no published review articles on the topic of radiological surveillance in melanoma patients identified in the MEDLINE database. A comprehensive literature review was performed by searching the MEDLINE database to review all published works on this topic. This article aims to present an extensive review of literature surrounding radiological surveillance in melanoma patients, a discussion of controversies, and recommendations for surveillance modalities.

One week of magnesium supplementation lowers IL-6, muscle soreness and increases post-exercise blood glucose in response to downhill running.

PURPOSE: Magnesium supplementation modulates glucose metabolism and inflammation, which could influence exercise performance and recovery. This study investigated the effect of magnesium intake on physiological responses and performance during eccentric exercise and recovery. METHODS: Nine male recreational runners completed a counterbalanced, double-blind, placebo-controlled, cross-over study, registered at ClinicalTrial.gov. Participants consumed low magnesium diets and were supplemented with 500 mg/day of magnesium (SUP) or placebo (CON) for 7 days prior to a 10 km downhill (- 10%) running time trial (TT), separated by a 2-week washout period. At baseline and 24 h post-TT, maximal muscle force was measured. Interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R) and creatine kinase (CK) were measured at rest, 0 h, 1 h and 24 h post-TT. Muscle soreness was measured at the previous times plus 48 h and 72 h post. Glucose and lactate were measured during the TT. RESULTS: The main effect of condition was detected for IL-6 (SUP: 1.36 ± 0.66 vs CON: 2.06 ± 1.14 pg/ml) (P < 0.05, η2 = 0.54), sIL-6R (SUP: 27,615 ± 8446 vs CON: 24,368 ± 7806 pg/ml) (P < 0.05, η2 = 0.41) and muscle soreness (P < 0.01, η2 = 0.67). Recovery of blood glucose and muscle soreness were enhanced in SUP post-TT. There were no differences in glucose and lactate during the TT, or post measures of CK and maximal muscle force. CONCLUSION: Magnesium supplementation reduced the IL-6 response, enhanced recovery of blood glucose, and muscle soreness after strenuous exercise, but did not improve performance or functional measures of recovery.

Non-Diagnostic CT-Guided Percutaneous Needle Biopsy of the Lung: Predictive Factors and Final Diagnoses.

OBJECTIVE: To investigate the predictive factors for a non-diagnostic result and the final diagnosis of pulmonary lesions with an initial non-diagnostic result on CT-guided percutaneous transthoracic needle biopsy. MATERIALS AND METHODS: All percutaneous transthoracic needle biopsies performed over a 4-year period were retrospectively reviewed. The initial pathological results were classified into three categories-malignant, benign, and non-diagnostic. A non-diagnostic result was defined when no malignant cells were seen and a specific benign diagnosis could not be made. The demographic data of patients, lesions' characteristics, technique, complications, initial pathological results, and final diagnosis were reviewed. Statistical analysis was performed using binary logistic regression. RESULTS: Of 894 biopsies in 861 patients (male:female, 398:463; mean age 67, range 18-92 years), 690 (77.2%) were positive for malignancy, 55 (6.2%) were specific benign, and 149 (16.7%) were non-diagnostic. Of the 149 non-diagnostic biopsies, excluding 27 cases in which the final diagnosis could not be confirmed, 36% revealed malignant lesions and 64% revealed benign lesions. Predictive factors for a non-diagnostic biopsy included the size ≤ 15 mm, needle tract traversing emphysematous lung parenchyma, introducer needle outside the lesion, procedure time > 60 minutes, and presence of alveolar hemorrhage. Non-diagnostic biopsies with a history of malignancy or atypical cells on pathology were more likely to be malignant (p = 0.043 and p = 0.001). CONCLUSION: The predictive factors for a non-diagnostic biopsy were lesion size ≤ 15 mm, needle tract traversing emphysema, introducer needle outside the lesion, procedure time > 60 minutes, and presence of alveolar hemorrhage. Thirty-six percent of the non-diagnostic biopsies yielded a malignant diagnosis. In cases with a history of malignancy or the presence of atypical cells in the biopsy sample, a repeat biopsy or surgical intervention should be considered.

Dexamethasone Increases Cisplatin-Loaded Nanocarrier Delivery and Efficacy in Metastatic Breast Cancer by Normalizing the Tumor Microenvironment.

Dexamethasone is a glucocorticoid steroid with anti-inflammatory properties used to treat many diseases, including cancer, in which it helps manage various side effects of chemo-, radio-, and immunotherapies. Here, we investigate the tumor microenvironment (TME)-normalizing effects of dexamethasone in metastatic murine breast cancer (BC). Dexamethasone normalizes vessels and the extracellular matrix, thereby reducing interstitial fluid pressure, tissue stiffness, and solid stress. In turn, the penetration of 13 and 32 nm dextrans, which represent nanocarriers (NCs), is increased. A mechanistic model of fluid and macromolecule transport in tumors predicts that dexamethasone increases NC penetration by increasing interstitial hydraulic conductivity without significantly reducing the effective pore diameter of the vessel wall. Also, dexamethasone increases the tumor accumulation and efficacy of ∼30 nm polymeric micelles containing cisplatin (CDDP/m) against murine models of primary BC and spontaneous BC lung metastasis, which also feature a TME with abnormal mechanical properties. These results suggest that pretreatment with dexamethasone before NC administration could increase efficacy against primary tumors and metastases.