Antifibrotic effect of silymarin on arecoline-induced fibrosis in primary human buccal fibroblasts: an in silico and in vitro analysis.

BACKGROUND: This study aimed to assess silymarin's anticancer and antifibrotic potential through in silico analysis and investigate its impact on in vitro arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). METHODS & RESULTS: The study utilized iGEMDOCK for molecular docking, evaluating nine bioflavonoids, and identified silymarin and baicalein as the top two compounds with the highest target affinity, followed by subsequent validation through a 100ns Molecular Dynamic Simulation demonstrating silymarin's stable behavior with Transforming Growth Factor Beta. HBF cell lines were developed from tissue samples obtained from patients undergoing third molar extraction. Arecoline, a known etiological factor in oral submucous fibrosis (OSMF), was employed to induce fibrogenesis in these HBFs. The inhibitory concentration (IC50) of arecoline was determined using the MTT assay, revealing dose-dependent cytotoxicity of HBFs to arecoline, with notable cytotoxicity observed at concentrations exceeding 50µM. Subsequently, the cytotoxicity of silymarin was assessed at 24 and 72 h, spanning concentrations from 5µM to 200µM, and an IC50 value of 143µM was determined. Real-time polymerase chain reaction (qPCR) was used to analyze the significant downregulation of key markers including collagen, epithelial-mesenchymal transition (EMT), stem cell, hypoxia, angiogenesis and stress markers in silymarin-treated arecoline-induced primary buccal fibroblast cells. CONCLUSION: Silymarin effectively inhibited fibroblast proliferation and downregulated genes associated with cancer progression and EMT pathway, both of which are implicated in malignant transformation. To our knowledge, this study represents the first exploration of silymarin's potential as a novel therapeutic agent in an in vitro model of OSMF.

The Workforce Needed to Address Population Health.

Policy Points Although a single definition of the population health workforce does not yet exist, this workforce needs to have the skills and competencies to address the social determinants of health, to understand intersectionality, and to coordinate and work in concert with an array of skilled providers in social and health care to address multiple health drivers. On-the-job training programs and employer support are needed for the current health workforce to gain skills and competencies to address population health. Funding and leadership combined are critical for developing the population health workforce with the goal of supporting a broad set of workers beyond health and social care to include, for example, those in urban planning, law enforcement, or transportation professions to address population health.

Competencies, Training Needs, and Turnover Among Rural Compared With Urban Local Public Health Practitioners: 2021 Public Health Workforce Interests and Needs Survey.

Objectives. To compare rural versus urban local public health workforce competencies and training needs, COVID-19 impact, and turnover risk. Methods. Using the 2021 Public Health Workforce Interest and Needs Survey, we examined the association between local public health agency rural versus urban location in the United States (n = 29 751) and individual local public health staff reports of skill proficiencies, training needs, turnover risk, experiences of bullying due to work as a public health professional, and posttraumatic stress disorder symptoms attributable to COVID-19. Results. Rural staff had higher odds than urban staff of reporting proficiencies in community engagement, cross-sectoral partnerships, and systems and strategic thinking as well as training needs in data-based decision-making and in diversity, equity, and inclusion. Rural staff were also more likely than urban staff to report leaving because of stress, experiences of bullying, and avoiding situations that made them think about COVID-19. Conclusions. Our findings demonstrate that rural staff have unique competencies and training needs but also experience significant stress. Public Health Implications. Our findings provide the opportunity to accurately target rural workforce development trainings and illustrate the need to address reported stress and experiences of bullying. (Am J Public Health. 2023;113(6):689-699. https://doi.org/10.2105/AJPH.2023.307273).

Building Rural Primary Care Research by Connecting Rural Programs.

Both research and medical education make substantial contributions to rural primary care and health. An inaugural Scholarly Intensive for Rural Programs was conducted in January 2022 to connect rural programs within a community of practice focused on promoting scholarly activity and research in rural primary health care, education, and training. Participant evaluations confirmed that key learning objectives were met, including stimulating scholarly activity in rural health professions education programs, providing a forum for faculty and student professional development, and growing a community of practice that supports education and training in rural communities. This novel strategy brings enduring scholarly resources to rural programs and the communities they serve, teaches skills to health profession trainees and rurally located faculty, empowers clinical practices and educational programs, and supports the discovery of evidence that can improve the health of rural people.

The Current State of Antiracism Curricula in Undergraduate and Graduate Medical Education: A Qualitative Study of US Academic Health Centers.

PURPOSE: We undertook a study to evaluate the current state of pedagogy on antiracism, including barriers to implementation and strengths of existing curricula, in undergraduate medical education (UME) and graduate medical education (GME) programs in US academic health centers. METHODS: We conducted a cross-sectional study with an exploratory qualitative approach using semistructured interviews. Participants were leaders of UME and GME programs at 5 institutions participating in the Academic Units for Primary Care Training and Enhancement program and 6 affiliated sites from November 2021 to April 2022. RESULTS: A total of 29 program leaders from the 11 academic health centers participated in this study. Three participants from 2 institutions reported the implementation of robust, intentional, and longitudinal antiracism curricula. Nine participants from 7 institutions described race and antiracism-related topics integrated into health equity curricula. Only 9 participants reported having "adequately trained" faculty. Participants mentioned individual, systemic, and structural barriers to implementing antiracism-related training in medical education such as institutional inertia and insufficient resources. Fear related to introducing an antiracism curriculum and undervaluing of this curriculum relative to other content were identified. Through learners and faculty feedback, antiracism content was evaluated and included in UME and GME curricula. Most participants identified learners as a stronger voice for transformation than faculty; antiracism content was mainly included in health equity curricula. CONCLUSIONS: Inclusion of antiracism in medical education requires intentional training, focused institutional policies, enhanced foundational awareness of the impact of racism on patients and communities, and changes at the level of institutions and accreditation bodies.

Simulating the low-temperature, metastable electrochromism of Photosystem I: Applications to Thermosynechococcus vulcanus and Chroococcidiopsis thermalis.

Low-temperature, metastable electrochromism has been used as a tool to assign pigments in Photosystem I (PS I) from Thermosynechococcus vulcanus and both the white light and far-red light (FRL) forms of Chroococcidiopsis thermalis. We find that a minimum of seven pigments is required to satisfactorily model the electrochromism of PS I. Using our model, we provide a short list of candidates for the chlorophyll f pigment in FRL C. thermalis that absorbs at 756 nm, whose identity, to date, has proven to be controversial. Specifically, we propose the linker pigments A40 and B39 and two antenna pigments A26 and B24 as defined by crystal structure 1JB0. The pros and cons of these assignments are discussed, and we propose further experiments to better understand the functioning of FRL C. thermalis.

Clinico-radiological findings of neuroendocrine tumour metastases to the orbit.

PURPOSE: We present the clinico-radiological findings of neuroendocrine tumour metastases to the orbit. METHODS: This was a multicentre, retrospective study of patients with neuroendocrine tumour metastases to the orbit. Data was collected from medical records across five different sites within Australia and the United Kingdom. RESULTS: Nine patients (eleven lesions) were identified. The most common presenting complaint was diplopia (5/9, 56%). Disease occurred bilaterally in two patients. Seven patients (78%) had extraocular muscle involvement. The lateral recti (4/9, 44%) and superior recti (2/9, 22%) were the most commonly affected. Ocular presentation preceded primary tumour diagnosis in three patients (33%). On orbital imaging, metastases were most commonly reported as well circumscribed, ovoid or round, heterogeneous, contrast-enhancing masses. Features of intralesional haemorrhage and bony invasion are uncommonly reported. CONCLUSIONS: Neuroendocrine tumour metastasis to the orbit is uncommon. Metastases have a propensity for the extraocular muscles, commonly presenting as heterogeneous, well circumscribed, contrast-enhancing lesions on neuroimaging. New ocular symptoms, a history of neuroendocrine tumours, and these radiological findings, should lead to high clinical suspicion of metastatic disease. Atypical findings warrant biopsy to exclude other causes of orbital lesions.

Reduction of breast lymphoedema secondary to breast cancer: a randomised controlled exercise trial.

BACKGROUND: Breast lymphoedema can occur following surgical treatment for breast cancer. We investigated whether an exercise program reduced breast lymphoedema symptoms compared to a non-exercise control group. METHODS: A single-blinded randomised controlled trial was conducted in which women with stable breast lymphoedema (n = 89) were randomised into an exercise (n = 41) or control (n = 47) group. The intervention comprised a 12-week combined aerobic and resistance training program, supervised weekly by an accredited exercise physiologist. All participants completed a weekly symptoms diary and were assessed monthly to ensure that there was no exacerbation of their lymphoedema. Changes in the breast were captured physically with ultrasound and bioimpedance spectroscopy and changes in symptoms were captured using European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer (BR23) and Lymphoedema Symptom Intensity and Distress questionnaires. RESULTS: The exercise group reported a greater reduction in breast-related symptoms than the control group, assessed by the EORTC BR23 breast symptom questions. Measures of extracellular fluid, assessed with bioimpedance spectroscopy ratio, decreased in the exercise group compared to the control group. No significant difference was detected in dermal thickness in the breast, assessed by ultrasound. Session attendance in the exercise sessions was high, with two musculoskeletal adverse events reported, but no exacerbations of lymphoedema observed. CONCLUSION: Combined resistance and aerobic exercise training is safe for women living with breast lymphoedema. Preliminary data suggest exercise training can reduce breast lymphoedema symptoms to a greater extent than usual care.

Telepsychiatric Consultation as a Training and Workforce Development Strategy for Rural Primary Care.

PURPOSE: There is a shortage of rural primary care personnel with expertise in team care for patients with common mental disorders. Building the workforce for this population is a national priority. We investigated the feasibility of regular systematic case reviews through telepsychiatric consultation, within collaborative care for depression, as a continuous training and workforce development strategy in rural clinics. METHODS: We developed and pilot-tested a qualitative interview guide based on a conceptual model of training and learning. We conducted individual semistructured interviews in 2018 with diverse clinical and nonclinical staff at 3 rural primary care sites in Washington state that used ongoing collaborative care and telepsychiatric consultation. Two qualitative researchers independently analyzed transcripts with iterative input from other research team members. RESULTS: A total of 17 clinical, support, and administrative staff completed interviews. Participants' feedback supported the view that telepsychiatric case review-based consultation enhanced skills of diverse clinical team members over time, even those who had not directly participated in case reviews. All interviewees identified specific ways in which the consultations improved their capacity to identify and treat psychiatric disorders. Perceived benefits in implementation and sustainability included fidelity of the care process, team resilience despite member turnover, and enhanced capacity to use quality improvement methods. CONCLUSIONS: Weekly systematic case reviews using telepsychiatric consultation served both as a model for patient care and as a training and workforce development strategy in rural primary care sites delivering collaborative care. These are important benefits to consider in implementing the collaborative care model of behavioral health integration.

Ventilator Mode Does Not Influence Blood Loss or Transfusion Requirements During Major Spine Surgery: A Retrospective Study.

BACKGROUND: Blood loss during adult spinal deformity surgery is multifactorial. Anesthetic-related factors, such as mode of mechanical ventilation, may contribute to intraoperative blood loss. The aim of this study was to determine the influence of ventilator mode and ventilator parameters on intraoperative blood loss and transfusion requirements in patients undergoing prone position spine surgery. METHODS: This single-center retrospective study examined electronic medical records of patients ≥18 years of age who underwent elective prone position spine surgery between May 2015 and June 2016. Associations between ventilator mode and ventilator parameters with intraoperative estimated blood loss (EBL), packed red blood cells (PRBCs), fresh-frozen plasma (FFP), cryoprecipitate and platelet transfusions, and subfascial drain output were examined using multiple linear regression models controlling for age, sex, American Society of Anesthesiologist (ASA) physical status score, body mass index (BMI), preoperative blood coagulation parameters and laboratory values, operative levels, cage constructs, osteotomies, transforaminal lumbar interbody fusions, laminectomies, reoperation, spine surgery invasiveness index, and operative time. In a secondary analysis, EBL, blood product transfusions, and postoperative drain output were compared between pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) propensity score-matched cohorts. RESULTS: Nine hundred forty-six records were reviewed, and 822 were included in the analysis. After adjusting for confounding, no statistically significant associations were observed between mode of ventilation and intraoperative EBL (estimate, -2; 95% confidence interval [CI], -248 to 245; P = .99) or blood product transfusions (PRBC: estimate, -9; 95% CI, -154 to 135; P = .90; FFP: estimate, -3; 95% CI, -59 to 54; P = .93; cryoprecipitate: estimate, -14; 95% CI, -70 to 43; P = .63; platelets: -7; 95% CI, -39 to 24; P = .64). After propensity score matching (n = 27 per group), no significant differences were observed in EBL (mean difference, 525 mL; 95% CI, -15 to 1065; P = .056) or blood transfusions (PRBC: mean difference, 208 mL; 95% CI, -23 to 439; P = .077; FFP (mean difference, 34 mL; 95% CI, -17 to 84; P = .19); cryoprecipitate (mean difference, 55 mL; 95% CI, -24 to 133; P = .17); or platelets (mean difference, 26 mL; 95% CI, -12 to 64; P = .18) between PCV and VCV groups. CONCLUSIONS: In prone position spine surgery, neither mode of mechanical ventilation nor airway pressure is associated with intraoperative blood loss or need for allogeneic transfusion. Use of modern ventilation strategies using lung protective techniques may mitigate differences in blood loss previously observed between PCV and VCV modes.

Endoscopic endonasal surgery outcomes for pediatric craniopharyngioma: a systematic review.

OBJECTIVE: The goal of this study was to systematically review the outcomes of endoscopic endonasal surgery (EES) for pediatric craniopharyngiomas so as to assess its safety and efficacy. METHODS: A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2019. All studies assessing outcomes following EES for pediatric craniopharyngiomas were included. RESULTS: Of the total 48 articles identified in the original literature search, 13 studies were ultimately selected. This includes comparative studies with other surgical approaches, retrospective cohort studies, and case series. CONCLUSIONS: EES for pediatric craniopharyngiomas is a safe and efficacious alternative to other surgical approaches. Achieving gross-total resection with minimal complications is feasible with EES and is comparable, if not superior in some cases, to traditional means of resection. Ideally, a randomized controlled trial might be implemented in the future to further elucidate the effectiveness of EES for resection of craniopharyngiomas.

Rotational thromboelastometry-guided transfusion during lumbar pedicle subtraction osteotomy for adult spinal deformity: preliminary findings from a matched cohort study.

OBJECTIVESignificant blood loss and coagulopathy are often encountered during adult spinal deformity (ASD) surgery, and the optimal intraoperative transfusion algorithm is debatable. Rotational thromboelastometry (ROTEM), a functional viscoelastometric method for real-time hemostasis testing, may allow early identification of coagulopathy and improve transfusion practices. The objective of this study was to investigate the effect of ROTEM-guided blood product management on perioperative blood loss and transfusion requirements in ASD patients undergoing correction with pedicle subtraction osteotomy (PSO).METHODSThe authors retrospectively reviewed patients with ASD who underwent single-level lumbar PSO at the University of Virginia Health System. All patients who received ROTEM-guided blood product transfusion between 2015 and 2017 were matched in a 1:1 ratio to a historical cohort treated using conventional laboratory testing (control group). Co-primary outcomes were intraoperative estimated blood loss (EBL) and total blood product transfusion volume. Secondary outcomes were perioperative transfusion requirements and postoperative subfascial drain output.RESULTSThe matched groups (ROTEM and control) comprised 17 patients each. Comparison of matched group baseline characteristics demonstrated differences in female sex and total intraoperative dose of intravenous tranexamic acid (TXA). Although EBL was comparable between ROTEM versus control (3200.00 ± 2106.24 ml vs 3874.12 ± 2224.22 ml, p = 0.36), there was a small to medium effect size (Cohen's d = 0.31) on EBL reduction with ROTEM. The ROTEM group had less total blood product transfusion volume (1624.18 ± 1774.79 ml vs 2810.88 ± 1847.46 ml, p = 0.02), and the effect size was medium to large (Cohen's d = 0.66). This difference was no longer significant after adjusting for TXA (ß = -0.18, 95% confidence interval [CI] -1995.78 to 671.64, p = 0.32). More cryoprecipitate and less fresh frozen plasma (FFP) were transfused in the ROTEM group patients (cryoprecipitate units: 1.24 ± 1.20 vs 0.53 ± 1.01, p = 0.03; FFP volume: 119.76 ± 230.82 ml vs 673.06 ± 627.08 ml, p < 0.01), and this remained significant after adjusting for TXA (cryoprecipitate units: ß = 0.39, 95% CI 0.05 to 1.73, p = 0.04; FFP volume: ß = -0.41, 95% CI -772.55 to -76.30, p = 0.02). Drain output was lower in the ROTEM group and remained significant after adjusting for TXA.CONCLUSIONSFor ASD patients treated using lumbar PSO, more cryoprecipitate and less FFP were transfused in the ROTEM group compared to the control group. These preliminary findings suggest ROTEM-guided therapy may allow early identification of hypofibrinogenemia, and aggressive management of this may reduce blood loss and total blood product transfusion volume. Additional prospective studies of larger cohorts are warranted to identify the appropriate subset of ASD patients who may benefit from intraoperative ROTEM analysis.

Approaches to 3D printing teeth from X-ray microtomography.

Artificial teeth have several advantages in preclinical training. The aim of this study is to three-dimensionally (3D) print accurate artificial teeth using scans from X-ray microtomography (XMT). Extracted and artificial teeth were imaged at 90 kV and 40 kV, respectively, to create detailed high contrast scans. The dataset was visualised to produce internal and external meshes subsequently exported to 3D modelling software for modification before finally sending to a slicing program for printing. After appropriate parameter setting, the printer deposited material in specific locations layer by layer, to create a 3D physical model. Scans were manipulated to ensure a clean model was imported into the slicing software, where layer height replicated the high spatial resolution that was observed in the XMT scans. The model was then printed in two different materials (polylactic acid and thermoplastic elastomer). A multimaterial print was created to show the different physical characteristics between enamel and dentine. LAY DESCRIPTION: Objectives Trainee dentists practice procedures using artificial teeth that are far from real teeth. Using x-rays and 3D printing technology the project will recreate a real tooth, artificially. Methods X-rays produce a 3D image that can be printed out as a physical replica, after several conversions of files. Different settings can be used to allow the printed model, to be as accurate as possible. Data were collected on the forces from a dental drill on a tooth's surface, to measure hardness and resistance. Results Multiple teeth replicas were printed with a high accuracy. The materials printed did not mimic actual tooth properties, but using the data from real teeth, materials can be tested in future.

Unconscious priming dissociates 'free choice' from 'spontaneous urge' responses.

Advances in neuroscience offer the exciting prospect of understanding 'free' choices - the subject of the free will debate in philosophy. However, while physiological techniques and analysis have progressed rapidly to meet this challenge, task design has not. The challenge is now to develop laboratory tasks that adequately capture 'free' picking or choosing. To isolate 'internally' generated intentions from those impelled by external stimulus, observers are asked to 'choose freely' or to wait for a felt 'urge'. However, no previous work has explicitly distinguished between instructions that refer to 'urges' versus to 'choosing'. The philosopher Alfred Mele (e.g., 2009; 2014) has argued that the distinction is of crucial conceptual importance, but the two have not yet been empirically distinguished. Here, we show that conscious and unconscious, task-irrelevant primes, bias observers' binary choices when they are instructed to 'choose freely', not when they 'wait for an urge', underscoring the practical importance of Mele's conceptual distinction. Neuroscience must incorporate this distinction if we are to understand processes underpinning free choice.

Service provision and quality outcomes in home health for rural Medicare beneficiaries at high risk for unplanned care.

Multiple barriers exist to providing home health care in rural areas. This study examined relationships between service provision and quality outcomes among rural, fee-for-service Medicare beneficiaries who received home health care between 2011 and 2013 for conditions associated with high-risk for unplanned care. More skilled nursing visits, visits by more types of providers, more timely care, and shorter lengths of stay were associated with significantly higher odds of hospital readmission and emergency department use and significantly lower odds of community discharge. Results may indicate unmeasured clinical severity and care needs among this population. Additional research regarding the accuracy of current severity measures and adequacy of case-mix adjustment for quality metrics is warranted, especially given the continued focus on value-based payment policies.

High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients.

Background: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival. Results: KRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls. Conclusions: Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction.

NEW FINDINGS: What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes. Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal-averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT-PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara-Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal-averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2, KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after-depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+ -Ca2+ exchange current. These data suggest that diabetes leads to pro-arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population.

Microsurgical versus endoscopic transsphenoidal resection for acromegaly: a systematic review of outcomes and complications.

PURPOSE: The aim of this systematic review is to evaluate the long-term endocrine outcomes and postoperative complications following endoscopic vs. microscopic transsphenoidal resection (TSR) for the treatment of acromegaly. METHODS: A literature review was performed, and studies with at least five patients who underwent TSR for acromegaly, reporting biochemical remission criteria and long-term remission outcomes were included. Data extracted from each study included surgical technique, perioperative complications, biochemical remission criteria, and long-term remission outcomes. RESULTS: Fifty-two case series from 1976 to 2016 met the inclusion criteria, comprising 4375 patients. Thirty-six reports were microsurgical (n = 3144) and 13 were endoscopic (n = 940). Three studies compared microsurgical (n = 111) to endoscopic TSR outcomes (n = 180). The overall initial and long-term remission rates were 58.2 vs. 57.4% and 69.2 vs. 70.2% for the microsurgical and endoscopic groups, respectively. For microadenomas, the initial and long-term remission rates were 77.6 vs. 82.2% and 76.9 vs. 73.5% for microsurgical and endoscopic approaches, respectively. For macroadenomas, the initial and long-term remission rates were 46.9 vs. 60.0% and 40.2 vs. 61.5% for microsurgical and endoscopic approaches, respectively. The rates of postoperative CSF leak were 3.0 vs. 2.3% for the microscopic and endoscopic groups, respectively. The rates of hypopituitarism and transient diabetes insipidus were 6.7 vs. 6.4% and 9.0 vs. 7.8% for the microscopic and endoscopic groups, respectively. CONCLUSIONS: Both endoscopic and microsurgical approaches for TSR of growth hormone-secreting adenomas are viable treatment options for patients with acromegaly, and yield similarly high rates of remission under the most current consensus criteria.

Variability in testing policies and impact on reported Clostridium difficile infection rates: results from the pilot Longitudinal European Clostridium difficile Infection Diagnosis surveillance study (LuCID).

Lack of standardised Clostridium difficile testing is a potential confounder when comparing infection rates. We used an observational, systematic, prospective large-scale sampling approach to investigate variability in C. difficile sampling to understand C. difficile infection (CDI) incidence rates. In-patient and institutional data were gathered from 60 European hospitals (across three countries). Testing methodology, testing/CDI rates and case profiles were compared between countries and institution types. The mean annual CDI rate per hospital was lowest in the UK and highest in Italy (1.5 vs. 4.7 cases/10,000 patient bed days [pbds], p < 0.001). The testing rate was highest in the UK compared with Italy and France (50.7/10,000 pbds vs. 31.5 and 30.3, respectively, p < 0.001). Only 58.4 % of diarrhoeal samples were tested for CDI across all countries. Overall, only 64 % of hospitals used recommended testing algorithms for laboratory testing. Small hospitals were significantly more likely to use standalone toxin tests (SATTs). There was an inverse correlation between hospital size and CDI testing rate. Hospitals using SATT or assays not detecting toxin reported significantly higher CDI rates than those using recommended methods, despite testing similar testing frequencies. These data are consistent with higher false-positive rates in such (non-recommended) testing scenarios. Cases in Italy and those diagnosed by SATT or methods NOT detecting toxin were significantly older. Testing occurred significantly earlier in the UK. Assessment of testing practice is paramount to the accurate interpretation and comparison of CDI rates.

Serum LAMC2 enhances the prognostic value of a multi-parametric panel in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) lacks reliable serological biomarkers for predicting patients' survival and response to treatment. The present study examined the capability of serum LAMC2 and four known tumour markers for disease prognosis and patients' risk stratification. METHODS: LAMC2, CA 125, CEA, CYFRA 21-1 and SCC levels were retrospectively measured in sera obtained from 127 patients diagnosed with NSCLC by commercial immunoassays. Prognostic performance of the markers was compared with established clinical parameters and multivariate models were constructed to assess the prognostic complementarity of variables. RESULTS: LAMC2 showed significant prognostic ability for overall survival (hazards ratio: 1.607, 95% confidence interval: 1.268-2.037, P<0.0001) in the full cohort. LAMC2 and CYFRA 21-1 combination enhanced prognostic models based on common clinical parameters (c-index: 0.81 vs 0.72, P=0.00018), further enabling stratification of patients into clear risk groups. A bootstrap-based cross-validation analysis was supportive of our findings. Combination of LAMC2 and CA 125 showed similar performance. CONCLUSIONS: Our preliminary study proposes LAMC2 as a novel NSCLC prognostic factor. LAMC2 combined with CA 125 and CYFRA 21-1 could aid in clinical prediction of NSCLC patients' overall survival and inform clinical practice. Larger studies are necessary to unravel LAMC2's full potential as a new NSCLC biomarker.