Early derangement of INR predicts liver failure after liver resection for hepatocellular carcinoma.

BACKGROUND: Surgical resection, where appropriate, remains one of the best treatment options for hepatocellular carcinoma (HCC), however outcomes can be compromised by the development of liver failure. We reviewed our experience of liver resection for HCC patients to identify factors that may predict the development of post-hepatectomy liver failure (PHLF) and survival. METHODS: A single centre retrospective cohort study. Data was collected between 1999 and 2017 from all patients undergoing HCC resection in a tertiary university hospital from electronic medical records. PHLF was defined as per the International Study Group for Liver Surgery criteria. Variables with p < 0.15 on univariate analysis were included in a multivariate binary logistic regression model. Kaplan-Meier analyses were used to determine correlations with overall survival (OS) and disease-free survival (DFS), and variables with p < 0.15 on univariate analysis selected for a step-down Cox proportional hazard regression model. RESULTS: Overall, 120 patients underwent liver resection within the study period, of which 22 (18%) developed PHLF. Patients with normal INR ≤1.20 at day 2 did not develop PHLF whereas patients with INR >1.60 were at significant risk. Resection of multiple tumours (odds ratio 21.63, p = 0.002) and deranged postoperative day 2 INR>1.6 (odds ratio 21.05, p < 0.0001) were identified as independent prognostic markers of PHLF. CONCLUSION: The use of INR measurement at day 2 predicts PHLF and may enable us to objectively identify and stratify patients who may be eligible for enhanced recovery programs from those who will merit close monitoring in high dependency areas.

A rational approach to postoperative surveillance for resected non-functional pancreatic neuro-endocrine tumours.

BACKGROUND: Non-functional pancreatic neuroendocrine tumours (NF-PNETs) are rare and have highly variable outcomes. Current guidelines recommend surveillance for NF-PNETs <2 cm. Patients who ultimately have surgical resection are at risk of disease recurrence, and data to support postoperative surveillance protocols are lacking. The aims of this study were to i) identify post-operative predictors of recurrence and ii) risk stratify patients at risk of recurrence. METHODS: Consecutive patients who underwent surgery for NF-PNETs between 2002 and 2015 were identified retrospectively. Data were collected on demographics, pre-operative laboratory results and histopathological tumour characteristics. Statistical analyses were based on penalised Cox-regression modelling and a decision-tree model. Comparison of the variables identified was performed using ROC curves to identify the most sensitive and specific variable associated with disease recurrence. RESULTS: We identified 73 patients (38 males) with a median age of 61.5 years (range: 31-79). The median period of follow-up was 49 months (5-131). During follow up, 10 deaths (13.9%) were recorded and disease recurrence occurred in 12 patients (16.4%). The Kaplan-Meier predicted 1-,3- and 5-year recurrence-free survival rates were 98.6% (95% CI = 95.9, 100%), 85.4% (76.9-94.8%) and 72% (58.7-88.2%) respectively. Cox multivariate analysis identified poor tumour differentiation (WHO G3 grade) and lymph node ratio (LNR) as independent predictors for recurrence (p < 0.05). A simple criterion of 'tumour grade G3 or LNR ≥0.1' was found to be sensitive and specific in detecting disease recurrence. CONCLUSION: Our results have identified a simple and sensitive criterion for risk stratifying post-resection surveillance. Prospective validation in larger patient cohort is now warranted.

Relationship between oviposition, virulence gene expression and parasitism success in Cotesia typhae nov. sp. parasitoid strains.

Studying mechanisms that drive host adaptation in parasitoids is crucial for the efficient use of parasitoids in biocontrol programs. Cotesia typhae nov. sp. (Fernández-Triana) (Hymenoptera: Braconidae) is a newly described parasitoid of the Mediterranean corn borer Sesamia nonagrioides (Lefebvre) (Lepidoptera: Noctuidae). Braconidae are known for their domesticated bracovirus, which is injected with eggs in the host larva to overcome its resistance. In this context, we compared reproductive success traits of four Kenyan strains of C. typhae on a French and a Kenyan populations of its host. Differences were found between the four strains and the two most contrasted ones were studied more thoroughly on the French host population. Parasitoid offspring size was correlated with parasitism success and the expression of bracovirus virulence genes (CrV1 and Cystatin) in the host larva after parasitism. Hybrids between these two parasitoid strains showed phenotype and gene expression profiles similar to the most successful parental strain, suggesting the involvement of dominant alleles in the reproductive traits. Ovary dissections revealed that the most successful strain injected more eggs in a single host larva than the less successful one, despite an equal initial ovocyte number in ovaries. It can be expected that the amount of viral particles increase with the number of eggs injected. The ability to bypass the resistance of the allopatric host may in consequence be related to the oviposition behaviour (eggs allocation). The influence of the number of injected eggs on parasitism success and on virulence gene expression was evaluated by oviposition interruption experiments.

Foreign DNA acquisition by invertebrate genomes.

Recent studies have highlighted that the accidental acquisition of DNA from other species by invertebrate genomes is much more common than originally thought. The transferred DNAs are of bacterial or eukaryote origin and in both cases the receiver species may end up utilising the transferred genes for its own benefit. Frequent contact with prokaryotic DNA from symbiotic endocellular bacteria may predispose invertebrates to incorporate this genetic material into their genomes. Increasing evidence also points to viruses as major players in transferring genes and mobile elements between the species they infect. Unexpectedly a gene flux between Hymenoptera and Lepidoptera mediated by endogenous viruses of parasitic wasps has been recently unravelled, suggesting we are probably just seeing the tip of the iceberg concerning horizontal gene transfers in invertebrates. In the context of insect for feed and food, if the new technology of insect genome editing (such as Crisper/Cas9) were used to modify the genome of reared insects it is important to take into account the risk that an introduced gene can be transferred. More generally, although insects are traditionally consumed in Asia and Africa, knowledge on insect viruses is still limited rendering it difficult to predict the impact they might have in the context of insect rearing at an industrial scale.

When one becomes more: minimum renal artery length in laparoscopic live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy may convert short main arteries into multiple arteries, increasing the technical challenge of implantation. We evaluated our experience to identify factors predictive of multiple arteries after laparoscopic nephrectomy. METHODS: All laparoscopic nephrectomies from the start of our program in November 2002 until June 2013 were studied, and preoperative imaging reviewed for donor artery length and multiplicity together with operative findings. RESULTS: A total of 287 consecutive laparoscopic live donor nephrectomies (64 right and 223 left nephrectomies) were studied. Renal artery length was measured from preoperative donor magnetic resonance or computed tomography angiogram and nephrectomy performed using a laparoscopic stapling device. Nine left kidneys with a single artery (6, 7, 9, 10, 11, 12, 13, 14, and 16 mm in length) and five right kidneys with a single artery (5, 13, 15, 20, and 26 mm) on imaging resulted in multiple renal arteries at implantation. Complex renal vein anatomy was associated with multiple arteries following retrieval. CONCLUSION: A main renal artery length of more than 16 mm on the left and 26 mm on the right is unlikely to result in multiple arteries to implant. The possibility of multiple arteries should be borne in mind when the donor renal artery is short.

Latent tuberculosis infection treatment completion in Biscay: differences between regimens and monitoring approaches.

Introduction: Contact tracing and treatment of latent tuberculosis infection (LTBI) is a key element of tuberculosis (TB) control in low TB incidence countries. A TB control and prevention program has been active in the Basque Country since 2003, including the development of the nurse case manager role and a unified electronic record. Three World Health Organization-approved LTBI regimens have been used: isoniazid for 6 months (6H), rifampicin for 4 months (4R), and isoniazid and rifampicin for 3 months (3HR). Centralized follow-up by a TB nurse case manager started in January 2016, with regular telephone follow-up, telemonitoring of blood test results, and monitoring of adherence by electronic review of drugs dispensed in pharmacies. Objective: To estimate LTBI treatment completion and toxicity of different preventive treatment regimens in a real-world setting. Secondary objective: to investigate the adherence to different approaches to preventive treatment monitoring. Methods: A multicentre retrospective cohort study was conducted using data collected prospectively on contacts of patients with TB in five hospitals in Biscay from 2003 to 2022. Results: A total of 3,066 contacts with LTBI were included. The overall completion rate was 66.8%; 86.5% of patients on 3HR (n = 699) completed treatment vs. 68.3% (n = 1,260) of those on 6H (p < 0.0001). The rate of toxicity was 3.8%, without significant differences between the regimens. A total of 394 contacts were monitored by a TB nurse case manager. In these patients, the completion rate was 85% vs. 67% in those under standard care (p < 0.001). A multivariate logistic regression model identified three independent factors associated with treatment completion: being female, the 3HR regimen, and nurse telemonitoring. Conclusion: 3HR was well tolerated and associated with a higher rate of treatment completion. Patients with nurse telemonitoring follow-up had better completion rates.

Abdominal aortic aneurysm surgery in renal, cardiac and hepatic transplant recipients.

With advancements in transplantation and improved long-term allograft survival, the once rare clinical scenario of an abdominal aortic aneurysm (AAA) in a patient with a functioning allograft has become much more frequent. In transplant recipients, AAA repair has the potential to cause irreversible ischaemic injury to the transplanted organ. Different case series and case reports have mentioned a variety of techniques to offer protection to the transplanted organs during aneurysm repair such as cold perfusion, shunting, temporary surgical bypass and extracorporeal circuits etc. Critical review of these adjuncts seems to suggest that that they do not give any better results than just using a "clamp and go" approach. Endovascular aneurysm repair (EVAR) may offer some advantages for transplant patients who have suitable anatomy for endovascular stent deployment. In addition to these surgical techniques, various aspects of medical management for renal, cardiac and hepatic transplant recipients undergoing AAA repair are discussed.

Resistance of human hair cuticle after a shaking process in wet conditions: comparison between Chinese and Caucasian hair.

Hair cuticle is the first protection shield of hair against external aggressions such as daily combing or brushing that induce friction, mechanical stress leading to ageing process. The identification of alterations of the hair surface induced by shaking process of various hair fibres, such as virgin and chemically treated Chinese and Caucasian hair, sheds some light on some specific features, e.g. Chinese cuticle is torn out in smaller particles than Caucasian, which seems to be related to geometrical rather than ethnic reasons. The present work also shows that two geometrical parameters of human hair, the inter-scale distance and the scale angle are directly linked to fibre dimensions, regardless of ethnic origin. Representative of hair with an average larger cross-sectional area, Chinese hair shows a slightly smaller inter-scale distance as well as a higher scale angle. On the other hand, Chinese hair cuticle seems to be more sensitive to chemical treatment than Caucasian hair, at least for straightening treatment taken here as an example. Such an approach can be of interest in designing cosmetic products more suited to specific needs of human hair.

Acute cytomegalovirus cholecystitis following renal transplantation.

Solid organ transplant recipients are at risk of infection from cytomegalovirus (CMV). A wide range of disease is associated with CMV infection and we report two cases of CMV cholecystitis in patients following renal transplantation. Both patients presented with severe hemorrhagic cholecystitis, which required immediate resuscitation and emergency cholecystectomy. The diagnosis of CMV infection was confirmed in both cases using CMV-specific staining of the gallbladder. The diagnosis of CMV cholecystitis must be considered in all patients with upper abdominal pain after renal transplantation.

Allele frequencies of the 15 AmpF/Str Identifiler loci in the population of Metztitlán (Estado de Hidalgo), México.

The 15 AmpF/STR Identifiler loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were analyzed in the sample of 180 unrelated autochthonous healthy adults born in Meztitlán City from the valley of Metztitlán (Estado de Hidalgo, México). The agreement with Hardy-Weinberg equilibrium was confirmed for all loci. From the forensic point of view, the heterozygosity value, power of discrimination and the a priori chance of exclusion were calculated.

F18-FDG-PET evaluation of patients for resection of colorectal liver metastases.

BACKGROUND/AIMS: Liver resection is the only treatment which offers long-term survival for patients with colorectal liver metastases. However, the significant mortality and morbidity associated with hepatectomy makes accurate patient selection paramount. Current staging by CT and MRI has limitations, with these modalities delivering a sensitivity and specificity of only 70-80%. Thus some patients may be deprived of long-term survival, and others subjected to futile surgery. METHODOLOGY: We report our experience of the influence of F18-FDG-PET scanning in the management of 31 consecutive patients with colorectal liver metastases referred for liver resection. RESULTS: F18-FDG-PET scanning detected liver and pulmonary metastases with a sensitivity of 96% and 100% respectively, in comparison to corresponding figures of 70% and 83% for CT. Furthermore, the sensitivity of F18-FDG-PET scanning in identifying extra-hepatic and extra-pulmonary disease was 100% in comparison to 20% for CT. Overall, F18-FDG-PET scanning resulted in a significant alteration of management in 29% of patients. CONCLUSIONS: F18-FDG-PET scanning has an important clinical impact on the management of patients being considered for resection of colorectal liver metastases.

[Evaluation of a computer predictive model to stratify risk and site of care in community acquired pneumonia]. / Utilidad de un modelo informatizado para estratificación de riesgo y decisión de lugar de tratamiento en la neumonía de la comunidad.

BACKGROUND: CAP is a common disorder with a great variability in clinical practice. The decision regarding the appropriate site of care is the most important for the level of treatment and costs. Recently a hospital in our region ( Hospital de Galdakao) developed a prediction rule based on the Pneumonia Severity Index (PSI) plus some additional criteria (hypoxemia <60, shock, previous correct treatment failure, social problems or inability to maintain oral intake, pleural effusion or unstable comorbidities) with an easy computer program to classify patients to be hospitalized or not. OBJECTIVE: Evaluate that computer program in the emergency department of our hospital. RESULTS: We included between December 02 and December 04,662 prospective patients with CAP admitted to our emergency department, 58 had a different final diagnosis. 285 (47%) were treated on outpatient basis. Readmission rate was 6%. There was no mortality in this group. 319 (53%) patients were hospitalized, 97 were PSI low risk patients (I-II), 61 of them were admitted to hospital because additional criteria. 45% of these "low risk patients" had significant complications. These results are similar to those obtained in Galdakao* CONCLUSIONS: The application of this computer risk stratifying program to assess admission to hospital in CAP is simple useful, secure and can be export to different settings. Additional criteria to PSI are necessary to detect low risk patients that complicate.

Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue.

Wnt gene expression was investigated by ribonuclease protection analysis in human breast cancer, nontumorous breast tissue, and a variety of human breast cell lines. We report the expression of Wnt3, Wnt4, and Wnt7b in human breast cell lines and Wnt2, Wnt3, Wnt4, and Wnt7b in human breast tissues. Wnt3a and Wnt7a were absent in the cell lines and tissues tested. The level of expression of Wnt2 and Wnt4 was 10- to 20-fold higher in fibroadenomas than it was in normal or malignant breast tissue, and in 10% of tumors Wnt7b expression was 30-fold higher than in normal or benign breast tissues. In contrast to the mouse, in which Wnt1 and Wnt3 are involved in tumorigenesis, our results suggest that Wnt2, Wnt4, and Wnt7b may be associated with abnormal proliferation in human breast tissue.

Compartment switching of WNT-2 expression in human breast tumors.

WNT-2 is a secreted polypeptide with mitogenic effects in murine mammary epithelial cells, but its role in human cancer is unknown. Using RNase protection analysis of primary cell preparations and in situ hybridization analysis, we report that WNT-2 is expressed at low levels in normal human breast fibroblasts but not in epithelial cells. WNT-2 was found to be expressed at high levels in both the epithelium and stroma of 5 of 11 infiltrating carcinomas and 2 of 6 fibroadenomas. The high level of WNT-2 expression in tumor epithelium suggests that tumorigenesis may involve the ectopic expression of WNT-2 and the creation of an autocrine Wnt signaling loop.

[Understanding the evolution of polydnaviruses]. / Vers la compréhension de l'histoire évolutive des polydnavirus.

Described in thousands of parasitoid wasp species polydnaviruses (PDVs) are unique viruses having both a segmented DNA genome in viral particles and an integrated form that persists as a provirus in the wasp genome. Parasitoid wasps inject their eggs in another insect host and along with them, the virus particles that are essential to ensure parasitism success. Two phylogenetically unrelated genera of polydnaviruses exist, the bracoviruses (BVs) and the ichnoviruses (IVs) associated with braconid and ichneumonid wasps respectively. New data on the genomes of two bracoviruses (Microplitis demolitor BV and Cotesia congregata BV) and an ichnovirus associated with Campoletis sonorensis (CsIV) offers us new elements to discuss the central questions concerning the origin and the evolution of these viral entities. The results indicate that the tens of millions of years of mutualistic associations between PDVs and wasps has had a strong impact on PDV genomes that now ressemble an eukaryotic region.

A novel human Wnt gene, WNT10B, maps to 12q13 and is expressed in human breast carcinomas.

Several members of the Wnt gene family have been shown to cause mammary tumors in mouse. Using degenerate primer polymerase chain reaction (PCR) on human genomic DNA, and specific PCR of cDNA libraries, we have isolated a WNT gene which has not previously been described in human. The gene is the human homologue of mouse Wnt10b, recently shown to be one of the oncogenes cooperating with FGF3 in the development of mouse mammary tumour virus (MMTV) induced mouse mammary carcinomas. The human WNT10B sequence was 88% and 95% identical to the murine gene at nucleotide and amino acid levels, respectively. YAC FISH mapping localises the gene to 12q13, a chromosomal region frequently rearranged in human tumours and also containing the WNT1 gene. In normal and benign proliferations of human breast tissue, WNT10B expression was not detected by ribonuclease protection assays but was found at low levels in RT-PCR experiments. In contrast, using both methods, WNT10B expression was found to be elevated in 3 of 50 primary breast carcinomas. Southern blot analysis of the carcinoma expressing the highest levels of WNT10B showed no amplification or rearrangement of the gene. The WNT10B gene was also expressed in some cancer and non cancerous breast cell lines. These findings suggest that the WNT10B gene may be involved in human breast cancer, and show that there is differential expression of the WNT10B gene in benign and malignant disease.

A RhoGAP protein as a main immune suppressive factor in the Leptopilina boulardi (Hymenoptera, Figitidae)-Drosophila melanogaster interaction.

To protect its eggs, the endoparasitoid wasp Leptopilina boulardi injects immune suppressive factors into Drosophila melanogaster host larvae. These factors are localized in the female long gland and reservoir. We analyzed the protein content of these tissues and found that it strongly differed between virulent and avirulent parasitoid strains. Four protein bands present in virulent long glands were eluted and their immune suppressive effect was assessed in vivo, allowing demonstrating a major effect of one of these proteins. The corresponding cDNA encodes a predicted 30 kDa subunit containing a Ras homologous GTPase Activating Protein (RhoGAP) domain, suggesting a possible involvement in the regulation of actin cytoskeleton changes. Using Western-blot experiments, we showed that this protein is abundant in virulent female long glands but is undetectable in virulent females deprived of long glands or in long glands from avirulent wasps. Its potential role in modifying the morphology and the adhesive properties of the host lamellocytes, involved in Drosophila cellular immune responses, is discussed.

Wnt5a cloning, expression, and up-regulation in human primary breast cancers.

Wnt genes are involved in mouse mammary cancer, but their role in human cancer is unknown. Human Wnt5a was cloned from a placental cDNA library and used to assess expression by ribonuclease protection and in situ hybridization in human breast cell lines and in normal, benign, and malignant breast tissues. Human Wnt5a shows over 99% homology at amino acid level with mouse Wnt5a, and 90% with Xenopus Wnt5a. It was expressed only at low levels in breast cell lines and normal breast tissue. Benign proliferations and invasive cancer respectively showed 10-fold and 4-fold higher Wnt5a than normal breast tissues. The greater up-regulation in benign conditions suggests a role in aberrant differentiation. In situ hybridization localized the signal to the epithelial component. Wnt5a is the first member of the Wnt family to demonstrate overexpression in human breast cancer. It was not associated with factors known to affect breast cancer prognosis such as lymph node status or epidermal growth factor receptor status.

Adherence to fesoterodine in women with overactive bladder in routine clinical practice.

OBJECTIVES: To assess the short-term compliance with fesoterodine treatment and to identify the reasons for lack of adherence and discontinuation in routine clinical practice. The secondary aim was to estimate the patient-reported outcomes. METHODS: This was an observational retrospective, multicenter study conducted in a sample of women with overactive bladder on fesoterodine treatment for at least three months. Adherence to medication was assessed using the Morisky-Green test. Patient-reported outcomes were assessed using the Incontinence Questionnaire Short Form (ICIQ-SF), Overactive Bladder Questionnaire Short Form (OAB-qSF), and Treatment Benefit Scale (TBS). RESULTS: One hundred and twenty women with a mean age [standard deviation (SD)] of 62.2 (12.0) years with severe OAB [mean (SD) ICIQ-SF score 13.2 (4.0)] were included. 42.1% of the patients were considered compliant with fesoterodine treatment. The main causes for non-compliance/discontinuation stated by the remaining 57.9% of the patients were adverse events (62.2%) and lack of clinical benefits (20.0%). The illness status as well as the patient-perceived bother occasioned by the OAB symptoms and their impact on the quality of life improved significantly after three months on fesoterodine treatment (p<0.0001). Most of the patients stated that the current state of their urinary problems had greatly improved/ improved. CONCLUSION: In routine clinical practice, a high percentage of patients were adherent to fesoterodine and perceived the benefit that the treatment provided them three months after starting treatment. However, more than half of the study population failed to comply or discontinued the treatment mainly due to intolerance or lack of efficacy.