Population Dynamics is a Cancer Driver.

Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as cell turnover rate (CTOR). Despite being in steady state, tissues have different population dynamics and leading to diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimize the contribution of ANSEL in cancer growth.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Muscle Constitutive Model With a Tangent Modulus Approximation: Ansys Implementation and Verification.

Sophisticated muscle material models are required to perform detailed finite element simulations of soft tissue; however, state-of-the-art muscle models are not among the built-in materials in popular commercial finite element software packages. Implementing user-defined muscle material models is challenging for two reasons: deriving the tangent modulus tensor for a material with a complex strain energy function is tedious and programing the algorithm to compute it is error-prone. These challenges hinder widespread use of such models in software that employs implicit, nonlinear, Newton-type finite element methods. We implement a muscle material model in Ansys using an approximation of the tangent modulus, which simplifies its derivation and implementation. Three test models were constructed by revolving a rectangle (RR), a right trapezoid (RTR), and a generic obtuse trapezoid (RTO) around the muscle's centerline. A displacement was applied to one end of each muscle, holding the other end fixed. The results were validated against analogous simulations in FEBio, which uses the same muscle model but with the exact tangent modulus. Overall, good agreement was found between our Ansys and FEBio simulations, though some noticeable discrepancies were observed. For the elements along the muscle's centerline, the root-mean-square-percentage error in the Von Mises stress was 0.00%, 3.03%, and 6.75% for the RR, RTR, and RTO models, respectively; similar errors in longitudinal strain were observed. We provide our Ansys implementation so that others can reproduce and extend our results.

The Role of VASOGRADE as a Simple Grading Scale to Predict Delayed Cerebral Ischemia and Functional Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The VASOGRADE is a simple aneurysmal subarachnoid hemorrhage (aSAH) grading scale that combines the modified Fisher scale (mFisher) and the World Federation of Neurological Societies (WFNS) grading system, allowing the stratification of delayed cerebral ischemia (DCI) risk. However, the VASOGRADE accuracy in predicting functional outcomes is still to be determined. METHODS: We retrospectively evaluated a multiethnic cohort of consecutive patients with aSAH admitted to a high-volume center in Brazil from January 2016 to January 2019. Patients were classified according to the severity of the clinical presentation (WFNS), the amount of blood in the initial head computerized tomography (mFisher) scan, and the VASOGRADE (green, yellow, red). The primary outcome was to detect DCI-related cerebral infarction, and the secondary outcome was the functional outcome at hospital discharge according to the modified Rankin scale (mRs). Univariate and multivariate logistic regression models were employed. RESULTS: A total of 212 patients (71.7% female, mean age 52.7 ± 12.8) were included. Sixty-nine patients were classified as VASOGRADE-Green (32.5%), 98 patients as VASOGRADE-Yellow (46.9%), and 45 patients as VASOGRADE-Red (20.6%). DCI-related infarction was present in 39 patients (18.9%). The proportions of patients in the VASOGRADE-Green, VASOGRADE-Yellow, and VASOGRADE-Red categories with DCI-related infarction were 7.7, 61.5, and 30.8%, respectively. After a multivariable analysis including age, sex, aneurysm location, and the VASOGRADE classification as variables, both VASOGRADE-Yellow and VASOGRADE-Red were independently associated with DCI-related infarction (odds ratio [OR] 7.69, 95% confidence interval [CI] 2.13-27.8, and OR 8.07, 95% CI 2.03-32.11, respectively) and unfavorable outcome (OR 4.16, 95% CI 1.33-13.03, and OR 25.57, 95% CI 4.45-147.1, respectively). The VASOGRADE discrimination performance for DCI-related infarction (area under the receiver operating characteristic curve) was 0.67 ± 0.04 (95% CI 0.58-0.75; p = 0.001). VASOGRADE-Red had 97.5% specificity for predicting an unfavorable mRs score at discharge (95% CI 92.8-99.5%). Conversely, VASOGRADE-Green had an excellent specificity for predicting favorable outcome at discharge (mRs score 0-2, 95% CI 82.6-95.5%). CONCLUSIONS: In conclusion, in a multiethnic cohort of patients with aSAH, VASOGRADE-Green predicted the absence of DCI and good clinical outcome at discharge with very high specificity, and patients in this category might be selected for early intensive care unit (ICU) discharge, minimizing costs and medical complications associated with prolonged hospital stay. On the other hand, patients categorized as VASOGRADE-Yellow and VASOGRADE-Red were at the highest risk for DCI. They should, therefore, be selected as a priority for care in high-volume aSAH centers, being aggressively monitored for DCI at the ICU. Such stratification methods are crucial, especially in countries with low financial resources and high health care services demand.

Multiple GIST and pheochromocytoma - A rare association in neurofibromatosis type 1.

We describe a case of coexistence of multiple gastrointestinal stromal tumors (GIST) and pheochromocytoma in a 32-year-old patient with neurofibromatosis type 1. The coexistence of these two conditions in patients with this syndrome is extremely rare.

Bronchobiliary fistula after stenting of biliary duct as the management of iatrogenic bile duct injury during elective cholecystectomy.

BACKGROUND: Bronchobiliary fistula is a rare and complex entity defined by an abnormal communication between the biliary and bronchial systems. The etiopathogenesis is not completely understood, but the most common factors implicated are hepatobiliary tumors, biliary obstruction, iatrogenic damage or trauma. METHODS: Here we present a case of a 69-year-old man that developed a bronchobiliary fistula and a pulmonary abscess after migration of a bile duct stent placed as part of the treatment of an iatrogenic bile duct injury that occurred during elective cholecystectomy. RESULTS: A conservative approach, that included broad-spectrum antibiotic, removal of the stent, and sphincterotomy, was enough for the closure of the fistula and resolution of the symptoms. CONCLUSION: We emphasize the importance of prompt recognition of this entity and a concerted therapeutic strategy to optimize the probability of success, avoiding the destructive consequences of the bile in the pulmonary parenchyma and septic complications.

End-of-life management strategies of pharmaceuticals in Portuguese households.

The end of life of pharmaceutical products through environmentally unsafe routes is a growing concern in our society. However, the studies reported so far, apart from being limited in number, do not reflect the current management practices for the end-of-life management of pharmaceuticals. Published work lacks an in-depth analysis in focusing on the pharmaceutical waste in households. The present work focused on (1) performing a state-of-the art overview to compare worldwide studies and the results and (2) implementing a comprehensive survey in Portugal (n = 454 respondents). The results showed that the delivery to pharmacies was used by the majority of the respondents (72%), indicating a good awareness of pharmaceutical waste management issues, when compared to the reviewed studies. Statistically significant variables for the destination of end-of-use pharmaceuticals include gender, age and distance from the residence to the pharmacy (p < 0.05). Most participants believe that educating the population on existing structures of medication and packaging management is of the utmost importance to improve the national managing system. This is the first study conducted in Portugal; it includes statistical analysis of the data and reflects on the practices that should be adopted to reduce incorrect pharmaceutical waste disposal. These findings call upon the strategies to strengthen the pharmaceutical waste management programme.

Combined superior mesenteric artery syndrome and nutcraker syndrome presenting as acute pancreatitis: a case report.

Superior mesenteric artery syndrome designates compression of the third part of the duodenum between the superior mesenteric artery and the aorta. This condition has a low incidence, being more common in thin young women. Nutcracker syndrome is compression of the left renal vein between the superior mesenteric artery and the aorta. Both entities are rare, and their coexistence has been reported in a few cases. Conservative treatment targeting weight gain is sufficient in most cases. An association between the superior mesenteric artery syndrome and acute pancreatitis has rarely been reported. We intend to describe the case of an 18-year-old girl who was admitted to the emergency room with epigastric pain and emesis. Our investigation revealed acute acalculous pancreatitis. During work-up, we discovered superior mesenteric artery syndrome and a compressed left renal vein. The patient is on conservative treatment, and her symptoms have improved.

A síndrome da artéria mesentérica superior designa compressão da terceira parte do duodeno pela artéria mesentérica superior e a aorta. Essa condição tem uma baixa incidência, sendo mais comum em mulheres jovens magras. A síndrome de quebra-nozes resulta da compressão da veia renal esquerda pela artéria mesentérica superior e a aorta. Ambas as entidades são raras, e a sua coexistência foi descrita em poucos casos. Tratamento conservador com o objetivo de ganho ponderal é suficiente na maioria dos casos. A associação entre a síndrome da artéria mesentérica superior e a pancreatite aguda foi raramente relatada. Pretendemos descrever o caso de uma jovem de 18 anos que recorreu ao serviço de urgência com epigastralgia e vômitos. A investigação realizada revelou pancreatite aguda alitiásica. Durante o estudo complementar, foi identificada a síndrome da artéria mesentérica superior, bem como uma veia renal esquerda comprimida. A paciente encontra-se em tratamento conservador, apresentando melhora clínica.

Conventional white light imaging-assisted transurethral resection of bladder tumour (TURBT) versus IMAGE1S-assisted TURBT in non-muscle-invasive bladder cancer patients: trial protocol and 18 months results.

PURPOSE: White light (WL) is the traditional imaging modality for transurethral resection of bladder tumour (TURBT). IMAGE1S is a likely addition. We compare 18-mo recurrence rates following TURBT using IMAGE1S versus WL guidance. METHODS: Twelve international centers conducted a single-blinded randomized controlled trial. Patients with primary and recurrent non-muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by IMAGE1S or WL. Eighteen-month recurrence rates and subanalysis for primary/recurrent and risk groups were planned and compared by chi-square tests and survival analyses. RESULTS: 689 patients were randomized for WL-assisted (n = 354) or IMAGE1S-assisted (n = 335) TURBT. Of these, 64.7% had a primary tumor, 35.3% a recurrent tumor, and 4.8%, 69.2% and 26.0% a low-, intermediate-, and high-risk tumor, respectively. Overall, 60 and 65 patients, respectively, completed 18-mo follow-up, with recurrence rates of 31.0% and 25.4%, respectively (p = 0.199). In patients with primary, low-/intermediate-risk tumors, recurrence rates at 18-mo were significantly higher in the WL group compared with the IMAGE1S group (31.9% and 22.3%, respectively: p 0.035). Frequency and severity of adverse events were comparable in both treatment groups. Immediate and adjuvant intravesical instillation therapy did not differ between the groups. Potential limitations included lack of uniformity of surgical resection, central pathology review, and missing data. CONCLUSION: There was not difference in the overall recurrence rates between IMAGE1S and WL assistance 18-mo after TURBT in patients with NMIBC. However, IMAGE1S-assisted TURBT considerably reduced the likelihood of disease recurrence in primary, low/intermediate risk patients. REGISTRATION: ClinicalTrials.gov Identifier NCT02252549 (30-09-2014).

The effect of facial occlusion on facial impressions of trustworthiness and dominance.

Recognizing the role that facial appearance plays in guiding social interactions, here we investigated how occlusions of the bottom-face region affect facial impressions of trustworthiness and dominance. Previous studies suggesting that different facial features impact inferences on these traits sustain the hypothesis that wearing a face mask will differently affect each trait inference. And specifically, that trustworthiness impressions will be more disrupted by this type of face occlusion than dominance impressions. In two studies, we addressed this possibility by occluding the bottom face region of faces that were previously shown to convey different levels of dominance and trustworthiness, and tested differences in the ability to discriminate between these trait levels across occlusion conditions. In Study 1 faces were occluded by a mask, and in Study 2 by a square image. In both studies, results showed that although facial occlusions generally reduced participants' confidence on their trait judgments, the ability to discriminate facial trustworthiness was more strongly affected than the ability to discriminate facial dominance. Practical and theoretical implications of these findings are discussed.

Prediction models of low-power holmium laser effectiveness in renal stone lithotripsy during retrograde intrarenal surgery.

The objectives of this study are to develop prediction models for total laser energy (TLE) in order to infer surgical time and assist operative planning of intrarenal low-power Ho:YAG laser lithotripsy, and to predict the fragmented volume as well as the stone-free status (SFS). A retrospective review was performed, comprising all single surgeon standardized retrograde intrarenal surgery and low-power Ho:YAG laser lithotripsy at a tertiary care centre between October 2014 and September 2019. Automated measurement of stone volume and stone density (MSD), measured in Hounsfield units (HU), was employed in both pre- and post-operative non-contrast-enhanced computed tomography (NCCT), using a standardized technique on Osirix Lite® software. SFS was defined as complete absence of stone fragments, or fragments < 0.1 cm on meticulous inspection at the end of the procedure, and residual stone burden < 0.0005 cm3 on postoperative NCCT at 3 months. Statistical analysis was performed using the STATA® version 13.1 software for regression models. A p value < .05 was considered statistically significant. A total of 100 patients met the inclusion criteria, requiring a median of 22.3 kJ/cm3 (13.4-36.0) and resulting in a SFS of 41% at 3 months. In a multivariate analysis, according to stone composition, predicted TLE is equal: for uric acid (UA), 11.17 × volume(cm3) + 0.17 × MSD(HU) + 7.48 kJ; for mixed stones, 11.17 × volume(cm3) + 0.17 × MSD(HU) + 6.26 kJ; for calcium oxalate monohydrate (CaOM) stones, 11.17 × volume(cm3) + 0.17 × MSD(HU) + 1.14 kJ; and for calcium phosphate (CaPh) stones 11.17 × volume(cm3) + 0.17 × MSD(HU) - 1.94 kJ. Predicted fragmented volume is equal to 0.93 × volume(cm3) cm3. The significant predictors for SFS were UA stones, the presence of multiple stones, and lower TLE. In clinical practice, our models for intrarenal low-power Ho:YAG laser lithotripsy indicate that larger, denser, and UA stones are associated to higher TLE, and that single and UA stones are more commonly associated to SFS. Since higher TLE means longer operative time, when adjusting for laser parameters, our prediction models may help urologists plan surgeries more precisely based on stone characteristics, ultimately optimizing patients' treatment.

Disruption of the GHRH receptor and its impact on children and adults: The Itabaianinha syndrome.

Since 1994, we have been studying an extended kindred with 105 subjects (over 8 generations) residing in Itabaianinha County, in the Brazilian state of Sergipe, who have severe isolated GH deficiency (IGHD) due to a homozygous inactivating mutation (c.57 + 1G > A) in the GH releasing hormone (GHRH) receptor (GHRHR) gene. Most of these individuals have never received GH replacement therapy. They have low GH, and very low and often undetectable levels of serum IGF-I. Their principal physical findings are proportionate short stature, doll facies, high-pitched-voice, central obesity, wrinkled skin, and youthful hair with delayed pigmentation, and virtual absence of graying. The newborns from this cohort are of normal size, indicating that GH is not needed for intra-uterine growth. However, these IGHD individuals exhibit a myriad of phenotypic changes throughout the body, with a greater number of beneficial than harmful consequences. This GHRH signal disruption syndrome has been a valuable model to study the GH roles in body size and function. This reviews summarized the findings we have reported on this cohort.

The Potential of Big Data Research in HealthCare for Medical Doctors' Learning.

The main goal of this article is to identify the main dimensions of a model proposal for increasing the potential of big data research in Healthcare for medical doctors' (MDs') learning, which appears as a major issue in continuous medical education and learning. The paper employs a systematic literature review of main scientific databases (PubMed and Google Scholar), using the VOSviewer software tool, which enables the visualization of scientific landscapes. The analysis includes a co-authorship data analysis as well as the co-occurrence of terms and keywords. The results lead to the construction of the learning model proposed, which includes four health big data key areas for MDs' learning: 1) data transformation is related to the learning that occurs through medical systems; 2) health intelligence includes the learning regarding health innovation based on predictions and forecasting processes; 3) data leveraging regards the learning about patient information; and 4) the learning process is related to clinical decision-making, focused on disease diagnosis and methods to improve treatments. Practical models gathered from the scientific databases can boost the learning process and revolutionise the medical industry, as they store the most recent knowledge and innovative research.

Fate and behaviour of acetaminophen, 17α-ethynylestradiol and carbamazepine in aqueous solution.

Pharmaceuticals are invaluable tools for the prevention and treatment of human and animal diseases. Human evolution led to the increase of life expectancy, which promoted the increase of consumption of pharmaceuticals. These compounds are consistently detected in superficial waters, and whilst degradation processes are expected to mitigate their levels, they also induce the formation of potentially harmful by-products. The compounds studied in this work were acetaminophen, 17α-ethynylestradiol and carbamazepine. High-performance liquid chromatography coupled with ultraviolet diode-array detection was used to follow the degradation reactions, whilst liquid chromatography associated with ultraviolet diode-array detection and mass spectrometry was applied in the determination of by-products. Ethynylestradiol proved to be the most reactive (t1/2 = 38.6 ± 1.9 seconds) and carbamazepine the least reactive (t1/2 = 481.4 ± 16.7 minutes) when exposed to active chlorine. In relation to disinfection by-products, two monochlorinated analogues were detected for acetaminophen, one monochlorinated for carbamazepine, and one mono- and one trichlorinated for ethynylestradiol. Chlorine levels and water pH proved to be the most influential variables on the degradation of the compounds, with and without dissolved organic matter in solution. All pharmaceuticals displayed significant photostability towards artificial solar radiation, with acetaminophen being slightly more stable.

Is robotic-assisted radical cystectomy (RARC) with intracorporeal diversion becoming the new gold standard of care?

BACKGROUND: Totally intracorporeal robotic-assisted radical cystectomy (RARC) has perceived difficulties compared to open radical cystectomy (ORC). As the technique is increasingly adopted around the world, the benefits of RARC with intra- or extracorporeal urinary diversion or ORC for the patients are still unclear. In this article, we consider the current evidence for this issue. METHODS: We assessed two questions through using expert opinion and the medical literature: (A) Is RARC better than ORC for removing the cancer surgery and outcome? (B) Is RARC better than ORC for the urinary diversion? OUTCOMES: (A) RARC is better than ORC for shorter length of stay, blood loss and complication rates. (B) Intracorporeal orthotopic neobladder may have a significant physiological and surgical benefit to the patient recovery. CONCLUSIONS: RARC with total intracorporeal reconstruction has potential benefits to the patient. We recommend that all surgeons document patient-related outcome measures, urodynamics and enhanced recovery protocols for cystectomy patients to help us understand the real improvements within bladder cancer surgery and reconstruction.

Metabolic phenotyping of an adoptive transfer mouse model of experimental colitis and impact of dietary fish oil intake.

Inflammatory bowel diseases are acute and chronic disabling inflammatory disorders with multiple complex etiologies that are not well-defined. Chronic intestinal inflammation has been linked to an energy-deficient state of gut epithelium with alterations in oxidative metabolism. Plasma-, urine-, stool-, and liver-specific metabonomic analyses are reported in a naïve T cell adoptive transfer (AT) experimental model of colitis, which evaluated the impact of long-chain n-3 polyunsaturated fatty acid (PUFA)-enriched diet. Metabolic profiles of AT animals and their controls under chow diet or fish oil supplementation were compared to describe the (i) consequences of inflammatory processes and (ii) the differential impact of n-3 fatty acids. Inflammation was associated with higher glycoprotein levels (related to acute-phase response) and remodeling of PUFAs. Low triglyceride levels and enhanced PUFA levels in the liver suggest activation of lipolytic pathways that could lead to the observed increase of phospholipids in the liver (including plasmalogens and sphingomyelins). In parallel, the increase in stool excretion of most amino acids may indicate a protein-losing enteropathy. Fecal content of glutamine was lower in AT mice, a feature exacerbated under fish oil intervention that may reflect a functional relationship between intestinal inflammatory status and glutamine metabolism. The decrease in Krebs cycle intermediates in urine (succinate, α-ketoglutarate) also suggests a reduction in the glutaminolytic pathway at a systemic level. Our data indicate that inflammatory status is related to this overall loss of energy homeostasis.

Older individuals heterozygous for a growth hormone-releasing hormone receptor gene mutation are shorter than normal subjects.

Growth hormone (GH)-releasing hormone (GHRH) is the most important stimulus for GH secretion by the pituitary gland. Subjects homozygous for GHRH receptor (GHRHR) gene (GHRHR) inactivating mutations have severe GH deficiency, resulting in severe short stature if not treated. We previously reported that young adults heterozygous for the c.57+1G>A null GHRHR mutation (MUT/N) have reduced weight and body mass index (BMI) but normal stature. Here we have studied whether older MUT/N have an additional phenotype. In a cross-sectional study, we measured height, weight and blood pressure, and calculated BMI in two groups (young, 20-40 years of age) and old (60-80 years) of individuals heterozygous for the same GHRHR mutation, and compared with a large number of individuals of normal genotype residing in the same geographical area. Standard deviation score (SDS) of weight was lower, and BMI had a trend toward reduction in young heterozygous compared with young normals, without significant difference in stature. Conversely, SDS of height was lower in older heterozygous individuals than in controls, corresponding to a reduction of 4.2 cm. These data show a reduced stature in older subjects heterozygous for the c.57+1G>A GHRHR mutation, indicating different effects of heterozygosis through lifespan.

[Post Traumatic Pseudoaneurysm of the Hepatic Artery - Clinical report]. / Aneurisma da Artéria Hepática Comum Pós-Traumatismo - Caso Clínico.

Hepatic artery aneurysms are a rare condition that can be fatal if rupture happens. Often, they are incidentally identified in routine imaging. Intervention is indicated when symptomatic, if they reach 2cm or more of size, in patients presenting with multiple hepatic artery aneurysms and in all pseudoaneurysms. We describe the case of a 57 year-old female, to whom a post-traumatic hepatic artery aneurysm was diagnosed. Open surgical repair was successfully accomplished.

Modern medical schools curricula: Necessary innovations and priorities for change.

Medical schools' curricula have expanded over the decades to incorporate important new medical breakthroughs and discoveries. Their current focus and overall structures remain, however, stubbornly captive of early 20th-century thinking, with changes having been undertaken in a piecemeal fashion. Indeed, since the notable Flexner reform in 1910, medical schools' study plans have suffered successive and typically always partial adjustments which have failed to keep up with scientific, technological and sociological change. This difficulty may be attributable to the well-known conservatism of medical schools, where updating study plans is a process that invariably encounters numerous barriers to change. These observations were afforded detailed attention some 15 years ago when de Oliveira wrote: 'it is now perfectly demonstrated that public medical schools have not been able to adapt their operation in depth and in due time to the new demands of teaching dictated by an explosive scientific and technological development'. Recent advances in communication and information technologies, as well as the introduction of new pedagogical techniques, have the potential to bring significant benefits to medical practice and healthcare systems, but these have not in the main become properly taught and utilized. The proposition that healthcare is evolving from reactive disease care to care that is predictive, preventive, personalized and participatory was initially regarded as highly speculative, yet systems approaches to biology and medicine are now beginning to provide experience of both health and disease at the molecular, cellular and organ levels. Medicine is a broad scientific field. In contrast to the 19th century, current medical 'sectarianism' is a positive by-product of rapid and gratifying medical progress, and the multiplicity of new models means that the lines of evidence legitimately bearing on practice and health policymaking are already highly diverse and likely to become ever more variegated over time. Put simply, most sound decisions, by definition, will be evidence-informed and not evidence-based, where divergence may be as informative as convergence. Here, the most enduring lesson of history is, perhaps, that clinical medicine is constantly rediscovering its humanistic core. Complexities create opportunities for innovation. In innovative environments, high-performing organizations are finding ways to create a culture that supports a diverse workforce preparing to deliver different models of care, with direct implications for excellence of patient experience and strong repercussions for medical education. The COVID-19 crisis saw major increases in the use of telemedicine, virtual office visits and other forms of online contact, and these are likely to increase considerably. This particular transformation will not be easy or comfortable to make. But reconfiguration of medical education seems inevitable, fuelled by online educational technology and the need to transform clinical training to more outpatient settings with promotion based on competency and person-centeredness, not simply time. As we prepare to enter 2024, this is an exciting time to be working in healthcare. We have more evidence than ever about how to provide high quality, person-centered care, and to keep patients safe. Shame on us if there is any hesitation about applying this knowledge to make the healthcare experience better for patients and providers. Embracing change and making continuous improvements are essential and urgent priorities for medicine and healthcare and, as we describe in the current article, will become more and more indispensably important in our rapidly changing world.

Prognostic impact of thrombocytosis in gastric cancer-A retrospective study.

BACKGROUND: Solid tumors are a common cause of secondary thrombocytosis, which has been identified as a prognostic factor in various cancers. However, the impact of thrombocytosis on the prognosis of gastric cancer is not yet well defined. The aim of this study was to assess the prevalence and prognostic value of thrombocytosis in patients with gastric cancer. METHODS: This was a retrospective study of patients with gastric carcinoma treated surgically, with curative intent, in our hospital, Centro Hospitalar Vila Nova de Gaia/Espinho, between January 2009 and December 2019. Clinical files were consulted and clinicopathological characteristics were analyzed. RESULTS: In the present sample (n = 352), the prevalence of pretreatment thrombocytosis was 16.5%. Thrombocytosis was associated with more advanced T stage, greater number of metastatic nodes, and more frequent lymphatic and venous permeation. The presence of thrombocytosis had a negative impact on disease-free survival (hazard ratio [HR] 3.54, 95% confidence interval [CI] 2.35-5.33, P < .001) and overall survival (HR 4.45, 95% CI 2.95-6.71, P < .001). CONCLUSIONS: The presence of pretreatment thrombocytosis had a negative impact on overall survival and disease-free survival and thus could be used as an independent prognostic factor.