Hospital surgical volume-outcome relationship in caesarean hysterectomy for placenta accreta spectrum.

OBJECTIVE: To examine the association between hospital surgical volume of caesarean hysterectomy and surgical morbidity in women with placenta accreta spectrum (PAS). DESIGN: Population-based retrospective cohort study. SETTING: National Inpatient Sample, January 2016 to December 2018. POPULATION: Six thousand and ten women with PAS who underwent caesarean hysterectomy in 738 centres. METHODS: (1) Comprehensive modelling for relative hospital surgical volume cut-point selection, (2) multinomial regression analysis for characterising hospital surgical volume, and (3) binary logistic regression analysis to examine the volume-outcome relationship. MAIN OUTCOME MEASURES: Surgical morbidity (haemorrhage, coagulopathy, shock, urinary tract injury, and death). RESULTS: The majority of centres had five surgeries over the 3-year period (468 centres, 63.4%) and were grouped as the low-volume group. Surgical morbidity decreased after a relative hospital surgical volume of 25 cases (24 centres, 3.3%) was reached, grouped as the high-volume group. The remaining centres were grouped as the mid-volume group (246 centres, 33.3%). In multivariable analysis, women in the high-volume group were more likely to be Black, have lower median household income, medical comorbidity, previous caesarean delivery, placenta praevia or placenta percreta, and to have undergone surgeries at large urban teaching hospitals compared with those in the low-volume group (all, P < 0.05). After controlling for patient demographics, hospital characteristics and pregnancy factors, performance of caesarean hysterectomy at high-volume centres was associated with a 22% decreased risk of surgical complications compared with surgery at the low-volume centres (adjusted odds ratio 0.78, 95% CI 0.64-0.94). CONCLUSION: Caesarean hysterectomy for PAS is a rare surgical procedure. Higher hospital surgical volume may be associated with improved surgical outcome in PAS. TWEETABLE ABSTRACT: Higher hospital caesarean hysterectomy volume may be associated with improved surgical outcome in PAS.

Fast electron transport dynamics and energy deposition in magnetized, imploded cylindrical plasma.

Inertial confinement fusion approaches involve the creation of high-energy-density states through compression. High gain scenarios may be enabled by the beneficial heating from fast electrons produced with an intense laser and by energy containment with a high-strength magnetic field. Here, we report experimental measurements from a configuration integrating a magnetized, imploded cylindrical plasma and intense laser-driven electrons as well as multi-stage simulations that show fast electrons transport pathways at different times during the implosion and quantify their energy deposition contribution. The experiment consisted of a CH foam cylinder, inside an external coaxial magnetic field of 5 T, that was imploded using 36 OMEGA laser beams. Two-dimensional (2D) hydrodynamic modelling predicts the CH density reaches [Formula: see text], the temperature reaches 920 eV and the external B-field is amplified at maximum compression to 580 T. At pre-determined times during the compression, the intense OMEGA EP laser irradiated one end of the cylinder to accelerate relativistic electrons into the dense imploded plasma providing additional heating. The relativistic electron beam generation was simulated using a 2D particle-in-cell (PIC) code. Finally, three-dimensional hybrid-PIC simulations calculated the electron propagation and energy deposition inside the target and revealed the roles the compressed and self-generated B-fields play in transport. During a time window before the maximum compression time, the self-generated B-field on the compression front confines the injected electrons inside the target, increasing the temperature through Joule heating. For a stronger B-field seed of 20 T, the electrons are predicted to be guided into the compressed target and provide additional collisional heating. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

Conservative surgery for ovarian torsion in young women: perioperative complications and national trends.

OBJECTIVE: To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women <50 years of age with ovarian torsion. DESIGN: Population-based retrospective observational study. SETTING: Nationwide Inpatient Sample in the USA (2001-2015). POPULATION: In all, 89 177 ovarian torsions including 20 597 (23.1%) conservative surgeries and 68 580 (76.9%) oophorectomies. METHODS: (1) Trend analysis to assess utilisation of conservative surgery over time, (2) multivariable binary logistic regression to identify independent factors associated with conservative surgery and (3) inverse probability of treatment weighting with a generalised estimating equation to analyze perioperative complications. MAIN OUTCOME MEASURES: Trends, characteristics and complications related to conservative surgery. RESULTS: Performance of conservative surgery increased from 18.9 to 25.1% between 2001 and 2015 (32.8% relative increase, P = 0.001) but decreased steadily after age 15, and sharply declined after age 35 (P < 0.001). On multivariable analysis, younger age exhibited the largest effect size for conservative surgery among the independent factors (adjusted odds ratios 3.39-7.96, P < 0.001). In the weighted model, conservative surgery was associated with an approximately 30% decreased risk of perioperative complications overall (10.0% versus 13.6%, odds ratio 0.73, 95% confidence interval 0.62-0.85, P < 0.001) and was not associated with venous thromboembolism (0.2 versus 0.3%, P = 0.457) or sepsis (0.4 versus 0.3%, P = 0.638). CONCLUSION: There has been an increasing utilisation of conservative surgery for ovarian torsion in the USA in recent years. Our study suggests that conservative surgery for ovarian torsion may not be associated with increased perioperative complications. TWEETABLE ABSTRACT: Conservative surgery for ovarian torsion may not be associated with increased perioperative complications.

Proposal for a new classification for perihilar cholangiocarcinoma based on tumour depth.

BACKGROUND: The T system for distal cholangiocarcinoma has been revised from a layer-based to a depth-based approach in the current American Joint Committee on Cancer (AJCC) classification. In perihilar cholangiocarcinoma, tumour depth in the staging scheme has not yet been addressed. The aim of this study was to propose a new T system using measured tumour depth in perihilar cholangiocarcinoma. METHODS: Patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2001 and 2014 were reviewed retrospectively. The vertical distance between the top of the tumour and deepest invasive cells was measured as invasive tumour thickness (ITT) by two independent pathologists. Log rank statistics were used to determine cut-off points, and the concordance (C) index was used to assess survival discrimination of each T system. RESULTS: ITT was measurable in all 440 patients, with a median value of 6·0 (range 0-45) mm. The median difference in ITT between observers was 0·6 (range 0-20) mm. Cut-off points for prognosis were 1, 5 and 8 mm. Five-year survival decreased with increasing ITT (P < 0·001): 67 per cent for ITT less than 1 mm (25 patients), 54·9 per cent for ITT 1 mm and over to less than 5 mm (138 patients), 43·4 per cent for ITT 5 mm and over to less than 8 mm (118 patients), and 32·2 per cent for ITT 8 mm and over (159 patients). The C-index of this classification was comparable to that of the current AJCC T classification (0·598 versus 0·589). CONCLUSION: ITT is a reliable approach for making a depth assessment in perihilar cholangiocarcinoma. A four-tier ITT classification with cut-off points of 1, 5 and 8 mm is an adequate alternative to the current layer-based T classification.

A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Cigarette smoking and cervical cancer risk: an evaluation based on a systematic review and meta-analysis among Japanese women.

BACKGROUND: There is a body of evidence to suggest that cigarette smoking increases the risk of cervical cancer in women, but no study has examined the magnitude of the association in Japanese women. Here, we evaluated the association between cigarette smoking and the risk of cervical cancer in Japanese women based on a systematic review of epidemiological evidence. METHODS: Original data were obtained from a MEDLINE search using PubMed or from a search of the 'Ichushi' database, as well as by a manual search. Evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as evaluated previously by the International Agency for Research on Cancer. Meta-analysis of associations was also conducted to obtain a summarized overview of the data. RESULTS: We identified two cohort studies and three case-control studies. All five studies had indicated strong positive associations between cigarette smoking and the risk of cervical cancer. Our summary estimate indicated that the relative risk (RR) for individuals who had ever-smoked relative to never-smokers was 2.03 (95% confidence interval: 1.49-2.57). Four studies had also demonstrated dose-response relationships between cigarette smoking and the risk of cervical cancer. CONCLUSION: We conclude that there is convincing evidence that cigarette smoking increases the risk of cervical cancer among Japanese women.

Randomized clinical trial of duct-to-mucosa versus invagination pancreaticojejunostomy after pancreatoduodenectomy.

BACKGROUND: The postoperative pancreatic fistula (POPF) rate for duct-to-mucosa and invagination anastomosis after pancreatoduodenectomy is still debated. The aim of this RCT was to investigate the POPF rate for duct-to-mucosa versus invagination pancreaticojejunostomy. METHODS: Patients were stratified by pancreatic texture and diameter of the main pancreatic duct and randomized to the duct-to-mucosa or invagination group. The primary endpoint was the rate of clinically relevant POPF (defined as grade B or C). Secondary endpoints were suture material cost for pancreaticojejunostomy, drain insertion duration and duration of postoperative hospital stay. RESULTS: Some 120 patients undergoing pancreatoduodenectomy were included following consent. Clinically relevant POPF developed in six of 59 patients (10 per cent) in the invagination group and in 14 of 61 patients (23 per cent) in the duct-to-mucosa group (P = 0·077). Duration of drain insertion (6 versus 7 days respectively; P = 0·027) and postoperative hospital stay (19 versus 24 days; P = 0·015) were shorter in the invagination group. Subgroup analysis for 61 patients with a soft pancreas revealed a lower rate of clinically relevant POPF in the invagination group (10 per cent versus 42 per cent in the duct-to-mucosa group; P = 0·010). Among 20 patients with a clinically relevant POPF, the six patients in the invagination group had a shorter duration of drain insertion (38·5 days versus 49 days for 14 patients in the duct-to-mucosa group; P = 0·028) and postoperative hospital stay (42 versus 54·5 days respectively; P = 0·028). CONCLUSION: This study did not demonstrate a superiority of invagination over duct-to-mucosa pancreaticojejunostomy in the risk of POPF. However, in high-risk patients with a soft pancreas, invagination may reduce the risk of clinically relevant POPF compared with duct-to-mucosa. Registration number: UMIN000005890 (http://www.umin.ac.jp).

Evidence-based cancer prevention recommendations for Japanese.

A comprehensive evidence-based cancer prevention recommendation for Japanese was developed. We evaluated the magnitude of the associations of lifestyle factors and infection with cancer through a systematic review of the literature, meta-analysis of published data, and pooled analysis of cohort studies in Japan. Then, we judged the strength of evidence based on the consistency of the associations between exposure and cancer and biological plausibility. Important factors were extracted and summarized as an evidence-based, current cancer prevention recommendation: 'Cancer Prevention Recommendation for Japanese'. The recommendation addresses six important domains related to exposure and cancer, including smoking, alcohol drinking, diet, physical activity, body weight and infection. The next step should focus on the development of effective behavior modification programs and their implementation and dissemination.

Development of an oesophageal stimulation method to elicit swallowing reflex in humans.

Swallowing reflex is known to be evoked by gastroesophageal regurgitation or oesophageal stimulation in animal studies. However, details regarding the stimulating material, bolus size and stimulation area remain unclear for the stimulation-induced type of swallowing reflex in humans. Here, we evaluated the effects of different kinds of stimulation via water and air injection of the oesophagus on the initiation of the swallowing reflex. Nine healthy individuals participated in this study. A fibre-optic endoscope was passed transnasally, and a thin catheter for injection was passed through the other side. The tip of the catheter was placed at the upper, upper middle, lower middle or lower region of the oesophagus, and the rate of injection was controlled at 0.2 mL/s. Swallowing reflex latency was calculated as the time from injection via air or thin/thick fluid until the onset of white-out in endoscopic images. Reflex latency was significantly shorter when injection occurred at the upper region of the oesophagus than at the lower region, for both thin and thick fluids (P < .01). At the upper region of the oesophagus, the latency was significantly shorter after injection of thin fluid than with thick fluid (P < .05). Injection of air did not induce the swallowing reflex at all sites. These findings suggest that while the swallowing reflex is evoked by stimulation via fluid injection of the oesophagus in humans, sensitivity is greatest in the upper region of the oesophagus compared with the lower region and can vary depending on the injecting material.

Evaluation of the safety of ramucirumab in Japanese patients with advanced gastric cancer.

As a result of the RAINBOW trial, ramucirumab plus paclitaxel was established as a second-line treatment of advanced gastric cancer. Regarding the safety of ramucirumab plus paclitaxel in the Japanese, a subgroup analysis of the RAINBOW trial was conducted. The incidence of neutropenia was higher in Japanese patients. However, information is lacking concerning the safety of ramucirumab after marketing in Japanese patients. Therefore, the aim of this study was to evaluate the safety of ramucirumab in Japanese patients with advanced gastric cancer. The inclusion criteria were patients diagnosed with advanced gastric cancer who had commenced treatment with ramucirumab plus paclitaxel or paclitaxel only at Ogaki Municipal Hospital (Gifu, Japan) between January 2015 and December 2016. There were 26 patients in the ramucirumab plus paclitaxel group and 22 patients in the paclitaxel only group. Treatment-related adverse events were documented in 100.0% of the patients in the ramucirumab plus paclitaxel group (Grade 3-4, 73.1%) and 90.9 % of the patients in the paclitaxel only group (Grade 3-4, 45.5 %). The most frequently observed adverse event in both treatment groups was anemia. The second common adverse event was neutropenia. The incidence of neutropenia of Grade ≥3 was significantly higher in the ramucirumab plus paclitaxel group than in the paclitaxel only group. In conclusion, the incidence of neutropenia is high. However, we believe that ramucirumab plus paclitaxel can be safely administered.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. PATIENTS AND METHODS: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. RESULTS: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.

Exome sequencing for bipolar disorder points to roles of de novo loss-of-function and protein-altering mutations.

Although numerous genetic studies have been conducted for bipolar disorder (BD), its genetic architecture remains elusive. Here we perform, to the best of our knowledge, the first trio-based exome sequencing study for BD to investigate potential roles of de novo mutations in the disease etiology. We identified 71 de novo point mutations and one de novo copy-number mutation in 79 BD probands. Among the genes hit by de novo loss-of-function (LOF; nonsense, splice site or frameshift) or protein-altering (LOF, missense and inframe indel) mutations, we found significant enrichment of genes highly intolerant (first percentile of intolerant genes assessed by Residual Variation Intolerance Score) to protein-altering variants in general population, an observation that is also reported in autism and schizophrenia. When we performed a joint analysis using the data of schizoaffective disorder in published studies, we found global enrichment of de novo LOF and protein-altering mutations in the combined group of bipolar I and schizoaffective disorders. Considering relationship between de novo mutations and clinical phenotypes, we observed significantly earlier disease onset among the BD probands with de novo protein-altering mutations when compared with non-carriers. Gene ontology enrichment analysis of genes hit by de novo protein-altering mutations in bipolar I and schizoaffective disorders did not identify any significant enrichment. These results of exploratory analyses collectively point to the roles of de novo LOF and protein-altering mutations in the etiology of bipolar disorder and warrant further large-scale studies.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Porphyromonas gingivalis lipopolysaccharide regulates ephrin/Eph signalling in human periodontal ligament fibroblasts.

OBJECTIVE: EphrinA2-EphA2 and ephrinB2-EphB4 critically engage in bidirectional signalling to modulate alveolar bone remodelling. The present study aimed to investigate the effects of lipopolysaccharides (LPS) derived from Porphyromonas gingivalis on ephrin/Eph signalling in periodontal ligament fibroblasts (PDLFs). MATERIAL AND METHODS: The primary cultured PDLFs were incubated in the absence (as a control) or presence of P. gingivalisLPS at 0.001-10 µg/mL for 24 hours. The PDLFs were then stimulated with P. gingivalisLPS at the optimal concentration (0.1 µg/mL) for different periods (6-48 hours). The expression of ephrinA2, ephrinB2, EphA2 and EphB4 was assessed by quantitative reverse-transcription real-time polymerase chain reaction and western blotting. The osteoblastic markers alkaline phosphatase, osteocalcin and Runt-related transcription factor 2 (Runx2), and the osteoclastogenesis-related factors receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin were also evaluated. RESULTS: The ephrinA2 and EphA2 expression was upregulated and EphB4 expression was downregulated by stimulation of P. gingivalisLPS. EphrinA2 mRNA expression in the PDLFs was significantly upregulated from 12 to 48 hours (P<.05), whereas EphA2 exhibited no change for the first 24 hours, after which there was a significant increase at 48 hours (P<.05). EphB4 exhibited lower mRNA expression at 12 and 24 hours than did the control (P<.05), but the change was insignificant at 48 hours. In contrast, the expression of ephrinB2 remained unchanged. The expressions of ephrinA2, EphA2, ephrinB2 and EphB4 at the protein level showed a similar pattern to that at the mRNA level. The expression of Runx2 and osteocalcin significantly decreased, whereas that of RANKL/osteoprotegerin increased. CONCLUSION: The present study suggest that P. gingivalisLPS would contribute to a dysregulation of bone remodelling, whereby ephrinA2/EphA2 expression is stimulated and EphB4 expression is inhibited.

Rinderpest eradication: challenges for remaining disease free and implications for future eradication efforts.

In 2011, the World Organisation for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) declared global freedom from rinderpest, formally announcing that rinderpest virus infections had been eliminated from susceptible livestock populations. At the same time, it was recognised that rinderpest virus, and material containing rinderpest virus, remained stored in an unspecified number of facilities across the world. Although natural infections had been eliminated, there remained a risk that rinderpest could reoccur if such infectious material accidentally leaked or was intentionally released from one of these facilities into a susceptible animal population. To minimise this risk, the OIE and FAO, with the support of international partners, set in place a framework to: reduce the quantity of remaining rinderpest-virus-containing material; ensure that such material was only stored in high-security facilities; regulate any handling or manipulation of the virus; maintain vigilance amongst livestock keepers and Veterinary Services in the post-eradication era; and develop contingency plans to deal with any suspected or actual reoccurrence of rinderpest disease. In 2016, five years after the declaration of global freedom from rinderpest, official reports to the OIE show that virus and virus-containing material remain stored in 21 countries worldwide in 22 separate facilities, of which only five have been inspected and approved for holding rinderpest virus or vaccine. There is still much work to be done to further reduce the risk of a reoccurrence.

En 2011, l'Organisation mondiale de la santé animale (OIE) et l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) ont annoncé officiellement l'élimination de l'infection due au virus de la peste bovine dans les populations d'animaux d'élevage sensibles, déclarant ainsi la planète indemne de cette maladie. Parallèlement, les deux organisations faisaient état de l'existence d'un nombre indéterminé d'établissements dans le monde détenant des stocks du virus bovipestique ainsi que des produits contenant ce virus. Malgré l'élimination de l'infection chez ses hôtes naturels, un risque de réapparition de la peste bovine subsiste en cas de fuite accidentelle ou d'émission délibérée de ces produits infectieux dans les populations animales sensibles à partir de l'un de ces établissements. Afin de minimiser ce risque, l'OIE et la FAO soutenus par leurs partenaires internationaux ont mis en place un cadre visant plusieurs objectifs : réduire les quantités restantes de produits contenant le virus de la peste bovine dans le monde ; veiller à ce que ces produits ne soient stockés que dans des établissements de haute sécurité ; réglementer les conditions de détention et de manipulation du virus ; poursuivre la surveillance exercée par les éleveurs et les Services vétérinaires au cours de la phase post-éradication ; concevoir des plans d'urgence visant à faire face à toute réapparition suspectée ou confirmée de la peste bovine. En 2016, soit cinq ans après la déclaration de l'éradication mondiale de la peste bovine, il ressort des rapports officiels adressés à l'OIE que 21 pays détiennent encore des stocks du virus de la peste bovine ou des produits contenant ce virus, répartis en 22 établissements distincts dont seulement cinq ont fait l'objet d'une inspection et ont été dûment habilités à détenir des stocks de virus de la peste bovine ou de vaccins contre cette maladie. Il reste donc encore beaucoup à faire pour continuer à réduire le risque de réapparition de la peste bovine.

En 2011, la Organización Mundial de Sanidad Animal (OIE) y la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) anunciaron oficialmente que las infecciones causadas por el virus de la peste bovina habían sido eliminadas de las poblaciones sensibles de ganado, declarando así que el mundo quedaba libre de la enfermedad. Al mismo tiempo, significaron que un número no especificado de instalaciones dispersas por el mundo albergaban muestras del virus y otros productos que lo contenían. Aunque las infecciones naturales habían quedado eliminadas, subsistía el riesgo de reaparición de la peste bovina si en una de esas instalaciones se producía una fuga accidental o una liberación intencionada de material infeccioso y este entraba en contacto con una población animal sensible. Para reducir al mínimo tal riesgo, la OIE y la FAO, con apoyo de colaboradores internacionales, definieron un dispositivo encaminado a: reducir el volumen de material restante con contenido viral de la peste bovina; garantizar que ese material fuera conservado únicamente en instalaciones de alta seguridad; reglamentar toda manipulación del virus; mantener la vigilancia entre cuidadores de ganado y Servicios Veterinarios en el periodo posterior a la erradicación; y elaborar planes de emergencia para responder a toda reaparición, presunta o confirmada, de la peste bovina. En 2016, cinco años después de la declaración de ausencia mundial de peste bovina, los informes oficiales remitidos a la OIE daban fe de que había virus y productos que lo contenían en 22 instalaciones situadas en 21 países del mundo, de las que solo cinco habían sido inspeccionadas y homologadas para albergar virus de la peste bovina o vacunas contra la enfermedad. Queda pues mucho trabajo por delante para reducir en mayor medida el riesgo de reaparición.

The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium.

BACKGROUND: Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. METHODS: In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. RESULTS: Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. CONCLUSION: Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Associations between oral complications and days to death in palliative care patients.

PURPOSE: Adverse oral symptoms gradually appear in advanced cancer patients as the disease progresses. We retrospectively investigated the associations between the incidence of oral problems and the days to death (DTD) in patients receiving palliative care. METHODS: The dental assessment sheets and medical charts of 105 patients who had been admitted into the palliative care unit at our hospital were examined. Case data included evaluations of organic and functional oral conditions at the time of admission for all patients. The cohort was divided into two groups according to the DTD as the short group (<28 days from the time of dental assessment until death) and the long group (≥28 days). We compared the incidences of organic and functional oral problems between these groups. RESULTS: Dry mouth, tongue inflammation, and bleeding spots were significantly more frequent in the short group than in the long group (78 vs. 54% for dry mouth, 67 vs. 46% for tongue inflammation, 35 vs. 14% for bleeding spots, respectively; p < 0.05). Tongue coating and candidiasis were comparable between the two groups. Dysphagia was significantly more common in the short group (43%) than in the long group (20%) (p = 0.01), as was assistance with oral health care (76 vs. 50%) (p = 0.01). CONCLUSIONS: Our findings suggest that, during palliative care, oral complications appear more frequently when the DTD period is shorter. These symptoms may be useful indicators when deciding on the proper timing of intensive oral care intervention to decrease oral problems and pain in terminally ill patients.

P450 oxidoreductase deficiency with maternal virilization during pregnancy.

PURPOSE: The authors report on a rare case of maternal virilization during pregnancy caused by autosomal recessive P450 oxidore- ductase (POR) deficiency. MATERIALS AND METHODS: A 24-year-old primigravida developed a deepening voice and hirsutism in the second trimester. Prenatal ultrasonography failed to detect any fetal abnormality and fetal growth was normal. POR deficiency was suspected, but the mother declined fetal genetic testing. A female neonate was delivered by cesarean section at 41 weeks' gestation. RESULTS: The neonate had skeletal abnormalities. Mutational analysis of the POR gene demonstrated homozygosity for c.1370 G>A and p.R457H in the patient and heterozygosity in her parents. POR deficiency was confirmed in the neonate. CONCLUSION: POR deficiency should be suspected in cases of maternal virilization. Maternal urinary estriol, fetal magnetic resonance imaging, and parental genetic testing should be performed. Parental consent for fetal genetic testing should be sought to ensure prompt diagnosis and early treatment.