Discrimination in the surgical discipline: an international European evaluation (DISDAIN).

BACKGROUND: Negative workplace experiences (NWPEs), such as gender discrimination, bullying, sexual harassment and ethnic discrimination, are concerns in today's surgical society. These negative experiences potentially impair surgeons' performance and might impact patient care or outcomes negatively. This study aimed to assess the experience of NWPEs across the European surgical workforce. METHODS: A prospective online 34-point questionnaire was designed using a combination of Likert scale, multiple-choice and short-answer questions. Invitations were distributed through surgical associations via email/social media between 1 September and 15 November 2019. Data were analysed using non-parametric methods. RESULTS: Some 840 complete responses were included in the analysis. The distribution across genders and stage of surgical training was even. Of the respondents, 20 per cent (168 respondents) considered quitting their job, 4.5 per cent (38) took time off and 0.5% (4) left surgery due to NWPEs; 12.9 per cent of females and 4.4 per cent of males experienced some form of physical harassment. Females and those in training were significantly more likely to experience or witness gender discrimination and sexual harassment. Just over half of the respondents (448) did not report negative experiences, with most of these (375 respondents) being unaware of whom to report to. Nearly a fifth of respondents felt that NWPEs influenced patient care or outcomes negatively. CONCLUSION: NWPEs were frequent, especially among females and those in training. While a substantial proportion of respondents experienced physical harassment, many individuals were unaware of how to raise concerns. Adverse effects on patient outcomes, surgical training and workforce retention indicate a need for urgent action.

Gender representation in editorial boards of international general surgery journals.

BACKGROUND: Despite women constituting over half of new doctors, gender disparity remains an issue. Surgery has shown particularly slow progress towards gender parity. This study aimed to quantify gender representation within editorial boards of the highest ranking international general surgery journals. METHODS: Surgical journals were collated using two indices: SCImago Journal Rank (SJR) and Journal Impact Factor (JIF). Non-general surgery journals were excluded. Journals were contacted, requesting gender editorial team demographics. Editorial board data were collected via journal websites on 28 November 2019. RESULTS: The top 25 general surgery journals according to SJR and JIF ranking methods were determined, identifying 28 unique journals. Editorial board data were publicly available for 27 of these 28 surgical journals, and were examined. Women accounted for 20.2 per cent (568 of 2816) of total editorial board positions. Women constituted 11 per cent (4 of 36) of editor-in-chief positions, 32 per cent (29 of 92) of deputy editors, and 19.1 per cent (369 of 1935) of general editorial board positions. CONCLUSION: The findings demonstrate gender disparity within editorial boards of the most prominent general surgery journals.

Caracterización de programas de formación de especialistas en cirugía maxilofacial en Estados Unidos, Canadá y Chile / Postgraduate programs of maxillofacial surgery in United States, Canada and Chile

La cirugía maxilofacial es una especialidad quirúrgica que nace del trabajo mancomunado de dentistas y médicos cirujanos en el tratamiento de patologías de complejidad creciente. En el mundo actualmente existe diversidad en los requisitos de grado académico al ingreso, en la organización curricular y en el tipo de graduación al egreso de los programas de formación de esta especialidad. Debido a la necesidad de respaldo legal, ético y curricular en el quehacer médico complejo de esta especialidad y la tendencia mundial a desarrollar vías de doble graduación para responder a tal necesidad, se busca conocer la realidad actual de los programas de graduación de la especialidad en Estados Unidos, Canadá y Chile

Maxillofacial Surgery is a surgical specialty developed from mancommunated work of Dentists and Physicians in the treatment of pathologies of increasing complexity. In the world there is currently a diversity in the requirements of academic degree in income, in the curricular organization and in the type of graduation in the training program of this specialty. Need for legal, ethical and curricular support in the complex medical work of this specialty and the worldwide trend in the development of double graduation to respond to this need cause this study to know about potsgraduate programs of the specialty in the United States, Canada and Chile

Correlative vibrational spectroscopy and 2D X-ray diffraction to probe the mineralization of bone in phosphate-deficient mice.

Bone crystallite chemistry and structure change during bone maturation. However, these properties of bone can also be affected by limited uptake of the chemical constituents of the mineral by the animal. This makes probing the effect of bone-mineralization-related diseases a complicated task. Here it is shown that the combination of vibrational spectroscopy with two-dimensional X-ray diffraction can provide unparalleled information on the changes in bone chemistry and structure associated with different bone pathologies (phosphate deficiency) and/or health conditions (pregnancy, lactation). Using a synergistic analytical approach, it was possible to trace the effect that changes in the remodelling regime have on the bone mineral chemistry and structure in normal and mineral-deficient (hypophosphatemic) mice. The results indicate that hypophosphatemic mice have increased bone remodelling, increased carbonate content and decreased crystallinity of the bone mineral, as well as increased misalignment of crystallites within the bone tissue. Pregnant and lactating mice that are normal and hypophosphatemic showed changes in the chemistry and misalignment of the apatite crystals that can be related to changes in remodelling rates associated with different calcium demand during pregnancy and lactation.

TRIP12 as a mediator of human papillomavirus/p16-related radiation enhancement effects.

Patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) have better responses to radiotherapy and higher overall survival rates than do patients with HPV-negative HNSCC, but the mechanisms underlying this phenomenon are unknown. p16 is used as a surrogate marker for HPV infection. Our goal was to examine the role of p16 in HPV-related favorable treatment outcomes and to investigate the mechanisms by which p16 may regulate radiosensitivity. HNSCC cells and xenografts (HPV/p16-positive and -negative) were used. p16-overexpressing and small hairpin RNA-knockdown cells were generated, and the effect of p16 on radiosensitivity was determined by clonogenic cell survival and tumor growth delay assays. DNA double-strand breaks (DSBs) were assessed by immunofluorescence analysis of 53BP1 foci; DSB levels were determined by neutral comet assay; western blotting was used to evaluate protein changes; changes in protein half-life were tested with a cycloheximide assay; gene expression was examined by real-time polymerase chain reaction; and data from The Cancer Genome Atlas HNSCC project were analyzed. p16 overexpression led to downregulation of TRIP12, which in turn led to increased RNF168 levels, repressed DNA damage repair (DDR), increased 53BP1 foci and enhanced radioresponsiveness. Inhibition of TRIP12 expression further led to radiosensitization, and overexpression of TRIP12 was associated with poor survival in patients with HPV-positive HNSCC. These findings reveal that p16 participates in radiosensitization through influencing DDR and support the rationale of blocking TRIP12 to improve radiotherapy outcomes.

Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.

Reactive oxygen species and p21Waf1/Cip1 are both essential for p53-mediated senescence of head and neck cancer cells.

Treatment of head and neck squamous cell carcinoma, HNSCC, often requires multimodal therapy, including radiation therapy. The efficacy of radiotherapy in controlling locoregional recurrence, the most frequent cause of death from HNSCC, is critically important for patient survival. One potential biomarker to determine radioresistance is TP53 whose alterations are predictive of poor radiation response. DNA-damaging reactive oxygen species (ROS) are a by-product of ionizing radiation that lead to the activation of p53, transcription of p21(cip1/waf1) and, in the case of wild-type TP53 HNSCC cells, cause senescence. The expression of p21 and production of ROS have been associated with the induction of cellular senescence, but the intricate relationship between p21 and ROS and how they work together to induce senescence remains elusive. For the first time, we show that persistent exposure to low levels of the ROS, hydrogen peroxide, leads to the long-term expression of p21 in HNSCC cells with a partially functional TP53, resulting in senescence. We conclude that the level of ROS is crucial in initiating p53's transcription of p21 leading to senescence. It is p21's ability to sustain elevated levels of ROS, in turn, that allows for a long-term oxidative stress, and ensures an active p53-p21-ROS signaling loop. Our data offer a rationale to consider the use of either ROS inducing agents or therapies that increase p21 expression in combination with radiation as approaches in cancer therapy and emphasizes the importance of considering TP53 status when selecting a patient's treatment options.

Inflammation-related genetic variants predict toxicity following definitive radiotherapy for lung cancer.

Definitive radiotherapy improves locoregional control and survival in inoperable non-small cell lung cancer patients. However, radiation-induced toxicities (pneumonitis/esophagitis) are common dose-limiting inflammatory conditions. We therefore conducted a pathway-based analysis to identify inflammation-related single-nucleotide polymorphisms associated with radiation-induced pneumonitis or esophagitis. A total of 11,930 single-nucleotide polymorphisms were genotyped in 201 stage I-III non-small cell lung cancer patients treated with definitive radiotherapy. Validation was performed in an additional 220 non-small cell lung cancer cases. After validation, 19 single-nucleotide polymorphisms remained significant. A polygenic risk score was generated to summarize the effect from validated single-nucleotide polymorphisms. Significant improvements in discriminative ability were observed when the polygenic risk score was added into the clinical/epidemiological variable-based model. We then used 277 lymphoblastoid cell lines to assess radiation sensitivity and expression quantitative trait loci (eQTL) relationships of the identified single-nucleotide polymorphisms. Three genes (PRKCE, DDX58, and TNFSF7) were associated with radiation sensitivity. We concluded that inflammation-related genetic variants could contribute to the development of radiation-induced toxicities.

ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients.

PURPOSE: Operable thoracic esophageal/gastroesophageal junction carcinoma (EC) is often treated with chemoradiation and surgery but tumor responses are unpredictable and heterogeneous. We hypothesized that aldehyde dehydrogenase-1 (ALDH-1) could be associated with response. METHODS: The labeling indices (LIs) of ALDH-1 by immunohistochemistry in untreated tumor specimens were established in EC patients who had chemoradiation and surgery. Univariate logistic regression and 3-fold cross validation were carried out for the training (67% of patients) and validation (33%) sets. Non-clinical experiments in EC cells were performed to generate complimentary data. RESULTS: Of 167 EC patients analyzed, 40 (24%) had a pathologic complete response (pathCR) and 27 (16%) had an extremely resistant (exCRTR) cancer. The median ALDH-1 LI was 0.2 (range, 0.01-0.85). There was a significant association between pathCR and low ALDH-1 LI (p ≤ 0.001; odds-ratio [OR] = 0.432). The 3-fold cross validation led to a concordance index (C-index) of 0.798 for the fitted model. There was a significant association between exCRTR and high ALDH-1 LI (p ≤ 0.001; OR = 3.782). The 3-fold cross validation led to the C-index of 0.960 for the fitted model. In several cell lines, higher ALDH-1 LIs correlated with resistant/aggressive phenotype. Cells with induced chemotherapy resistance upregulated ALDH-1 and resistance conferring genes (SOX9 and YAP1). Sorted ALDH-1+ cells were more resistant and had an aggressive phenotype in tumor spheres than ALDH-1- cells. CONCLUSIONS: Our clinical and non-clinical data demonstrate that ALDH-1 LIs are predictive of response to therapy and further research could lead to individualized therapeutic strategies and novel therapeutic targets for EC patients.

Results of the baseline positron emission tomography can customize therapy of localized esophageal adenocarcinoma patients who achieve a clinical complete response after chemoradiation.

BACKGROUND: Patients with localized esophageal adenocarcinoma (EAC) who achieve a clinical complete response (clinCR) after preoperative chemoradiation (trimodality therapy; TMT) or definitive chemoradiation (bimodality therapy; BMT) live longer than those who achieve a

Improving imaging diagnosis of persistent nodal metastases after definitive therapy for oropharyngeal carcinoma: specific signs for CT and best performance of combined criteria.

BACKGROUND AND PURPOSE: Criteria for detection of persistent nodal metastases in treated oropharyngeal tumors are sensitive but nonspecific, leading to unnecessary nodal dissections. Developing specific imaging criteria for persistent nodal metastases could improve diagnosis while decreasing patient morbidity. MATERIALS AND METHODS: Patients with oropharyngeal squamous cell carcinoma with nodal metastases treated by definitive radiation therapy and subsequent nodal dissection were retrospectively evaluated. One hundred thirty-eight patients had pre- and posttherapy contrast-enhanced CTs evaluated by radiologists blinded to the status of pathologically proved hemineck persistent nodal metastases. Composite scoring criteria for CT, combined from individual parameters, were compared with radiologists' opinions, previous multiparameter criteria, and outcome data. RESULTS: New low-attenuation areas and a lack of size change (<20% cross sectional area) were both highly specific for persistent nodal metastases (99%; P = .0004). Extranodal disease on pretherapy imaging was moderately specific (86%; P = .001). The CSC correctly placed 29 patients in a low-risk category compared with 14 by previously reported criteria and radiologist reports. With good second-rater reliability, the CSC cutoff values stratified patients at highest risk of persistent nodal metastases, thereby improving specificity while maintaining sensitivity. CONCLUSIONS: Comparing pre- and posttherapy examinations improves specificity by discriminating focal findings and size change compared with a single time point. The CSC can categorize the risk of persistent nodal metastases more accurately than previous CT methods. This finding has the potential to improve resource use and reduce surgical morbidity.

Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios.

Vertebral metastases are a common manifestation of many cancers, potentially leading to vertebral collapse and neurological complications. Conventional treatment often involves percutaneous vertebroplasty/kyphoplasty followed by external beam radiation therapy. As a more convenient alternative, we have introduced radioactive bone cement, i.e. bone cement incorporating a radionuclide. In this study, we used a previously developed Monte Carlo radiation transport modeling method to evaluate dose distributions from phosphorus-32 radioactive cement in simulated clinical scenarios. Isodose curves were generally concentric about the surface of bone cement injected into cadaveric vertebrae, indicating that dose distributions are relatively predictable, thus facilitating treatment planning (cement formulation and dosimetry method are patent pending). Model results indicated that a therapeutic dose could be delivered to tumor/bone within ∼4 mm of the cement surface while maintaining a safe dose to radiosensitive tissue beyond this distance. This therapeutic range should be sufficient to treat target volumes within the vertebral body when tumor ablation or other techniques are used to create a cavity into which the radioactive cement can be injected. With further development, treating spinal metastases with radioactive bone cement may become a clinically useful and convenient alternative to the conventional two-step approach of percutaneous strength restoration followed by radiotherapy.

¿Y antes de Fauchard qué?: la odontología en las cavernas, los templos, los hospitales y las universidades / And what was there before Fauchard?: dentistry in caverns, temples, hospitals and universities

Este trabajo muestra los orígenes de la odontología entre los primitivos habitantes del planeta, entre los médicos de la Antigüedad, el Renacimiento y la Edad Media hasta los tiempos modernos y la instauración del concepto de hospital clínico universitario. Sostiene que la práctica de la odontología es por definición un acto médico que tiene por objeto al ser humano en la sociedad y la salud a restablecer como bien único e indivisible, siendo ambos conceptos los que delimitan y enmarcan toda la práctica médica. La odontología nace junto con el ser humano, junto con el enfermar, el envejecer y el morir.

This paper shows the origin of dentistry among the primitive inhabitants of the planet, the physicians of the Antiquity, Renaissance and Middle Ages up to the modern times and the establishment of the concept of university clinical hospital. It endorses the practice of dentistry by definition as a medical act that has the human being in the society as the object of the act itself, and the health to restore as the one and indivisible good to enhance. Both concepts are the limits and natural frame of all the medical practice. Dentistry was born with the human being, together with getting sick, ageing and dying.

An investigation into the causes of unexpected intra-operative transoesophageal echocardiography findings.

There is uncertainty regarding echocardiography before cardiac surgery, especially with regard to timing and disease progression as well as potential errors. We investigated the causes of unexpected intra-operative transoesophageal echocardiography findings by performing a 33-month audit. We found that there were 50/797 (6%) unexpected findings that led to an alteration in surgical strategy in 34 (4%) patients. Of the unexpected findings, 25 (50%) were unrelated to pre-operative pathology. After reviewing pre-operative studies and reports, unexpected findings were found to be due to: reporting errors in 20 patients (44%); limitations in transthoracic compared to transoesophageal echocardiography in 14 patients (30%); disease progression in 10 patients (22%); and inter-observer variability in two patients (4%). We identified six reports out of 797 (0.8%) that contained potentially serious errors. Surgical management changed in 18/20 (90%) patients in whom the unexpected change was due to reporting error, compared to 16/30 (53%) patients whose pre-operative echocardiogram was correctly reported (p = 0.006). Our study suggests that pre-operative echocardiography reporting errors are common and important.

Impact of cell salvage during cardiac surgery on the thrombelastomeric coagulation profile: a pilot study.

Intraoperative cell salvage of the cardiopulmonary bypass residual volume can dilute platelets and coagulation factors. This is a report of a randomised control trial of 20 patients undergoing coronary bypass surgery. Residual cardiopulmonary bypass volume was processed and transfused after surgery in the cell salvage group and the residual volume was transfused unprocessed in the control group. The coagulation profile was measured using the Rotem(®) thrombelastometry system. Mean (SD) maximum clot firmness after surgery was 52.8 (5.4) mm in the cell salvage group compared to 57.2 (5.0) mm in the control group (p=0.04). Clot formation time was prolonged after surgery by 39 (27) s in the cell saver group compared to 19 (17) s in the control group (p=0.045). Platelet count was reduced after surgery by 96 (32) x 10(9).L(-1) in the cell saver group and 70 (19) x 10(9).L(-1) in the control group (p=0.03). Blood volume in the chest drains 4 hours after surgery was similar in both groups. There was a strong association between clot formation time after surgery and blood loss (R = 0.68, p=0.001). The increase in blood loss was 4.1 ml for every one-second increase in clot formation time (95% CI 1.9 - 6.4, p=0.001). Cell salvage of the residual cardiopulmonary bypass volume reduced platelet numbers and prolonged clot formation time and maximum clot firmness was less in this group.

Evaluation of a radiation transport modeling method for radioactive bone cement.

Spinal metastases are a common and serious manifestation of cancer, and are often treated with vertebroplasty/kyphoplasty followed by external beam radiation therapy (EBRT). As an alternative, we have introduced radioactive bone cement, i.e. bone cement incorporated with a radionuclide. In this study, we present a Monte Carlo radiation transport modeling method to calculate dose distributions within vertebrae containing radioactive cement. Model accuracy was evaluated by comparing model-predicted depth-dose curves to those measured experimentally in eight cadaveric vertebrae using radiochromic film. The high-gradient regions of the depth-dose curves differed by radial distances of 0.3-0.9 mm, an improvement over EBRT dosimetry accuracy. The low-gradient regions differed by 0.033-0.055 Gy/h/mCi, which may be important in situations involving prior spinal cord irradiation. Using a more rigorous evaluation of model accuracy, four models predicted the measured dose distribution within the experimental uncertainty, as represented by the 95% confidence interval of the measured log-linear depth-dose curve. The remaining four models required modification to account for marrow lost from the vertebrae during specimen preparation. However, the accuracy of the modified model results indicated that, when this source of uncertainty is accounted for, this modeling method can be used to predict dose distributions in vertebrae containing radioactive cement.

Early replication in pulmonary B cells after infection with Marek's disease herpesvirus by the respiratory route.

Abstract Natural infection with Marek's disease virus occurs through the respiratory mucosa after chickens inhale dander shed from infected chickens. The early events in the lung following exposure to the feather and squamous epithelial cell debris containing the viral particles remain unclear. In order to elucidate the virological and immunological consequences of MDV infection for the respiratory tract, chickens were infected by intratracheal administration of infective dander. Differences between susceptible and resistant chickens were immediately apparent, with delayed viral replication and earlier onset of interferon (IFN)-gamma production in the latter. CD4(+) and CD8(+) T cells surrounded infected cells in the lung. Although viral replication was evident in macrophages, pulmonary B cells were the main target cell type in susceptible chickens following intratracheal infection with MDV. In accordance, depletion of B cells curtailed viremia and substantially affected pathogenesis in susceptible chickens. Together the data described here demonstrate the role of pulmonary B cells as the primary and predominant target cells and their importance for MDV pathogenesis.