The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth.

The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.

Evaluation of OMNIgene®â€¢SPUTUM reagent for mycobacterial culture.

SETTING: National Mycobacterium Reference Laboratory, Borstel, Germany. OBJECTIVE: To evaluate the effectiveness of OMNIgene®â€¢SPUTUM (OM-S) reagent in comparison with a method using N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) with regard to mycobacterial recovery and contamination of broth and solid cultures. DESIGN: Sputum samples from patients with tuberculosis and other respiratory diseases underwent decontamination with NALC-NaOH-based (MycoDDR™) or OM-S reagent. The decontamination procedure was assigned by block randomisation. Samples were inoculated on Löwenstein-Jensen, Stonebrink and MGIT™ (Mycobacterial Growth Indicator Tubes). Mycobacterial recovery from samples spiked with Mycobacterium tuberculosis following decontamination was determined. RESULTS: Eighty-five samples were randomised to NALC-NaOH and 84 to OM-S reagent. Mycobacterial recovery was significantly lower for samples processed with OM-S reagent compared with the NALC-NaOH method across all media types. Culture contamination was lower with NALC-NaOH reagent on solid media (9.4-12.9% vs. 28.6-29.8%). Growth was not observed in MGIT among samples spiked with 10 600-16 800 colony-forming units of M. tuberculosis following decontamination with OM-S reagent. CONCLUSION: Low mycobacterial recovery, especially in MGIT, observed in the present study suggests that OM-S reagent might not be compatible with the MGIT system. More extensive field evaluations of the OM-S reagent are warranted to demonstrate a significant benefit over currently used methods.

Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer.

Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.

Factors predicting deviation from an enhanced recovery programme and delayed discharge after laparoscopic colorectal surgery.

AIM: The study aimed to identify factors that predict postoperative deviation from an enhanced recovery programme (ERP) and/or delayed discharge following colorectal surgery. METHOD: Data were prospectively collected from all patients undergoing elective laparoscopic colorectal resection between January 2006 and December 2009. They included Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) variables, body mass index (BMI), sex, preoperative serum albumin, pathology, conversion from a laparoscopic to an open approach and postoperative length of hospital stay. RESULTS: There were 176 patients (90 women) of mean age 68 years. Fifteen (9%) operations were converted from laparoscopic to open. The remainder were completed laparoscopically. Fifty-five (31%) deviated from the ERP, with most failing multiple elements. The most common reason was failure to mobilize, which often occurred in conjunction with paralytic ileus or analgesic failure. Factors independently predicting ERP deviation on multivariate analysis were pathology and intra-operative complications. The median length of stay was 5 days. Sixty-four (36%) patients had a prolonged length of stay that was predicted by age, number of procedures and ERP deviation. CONCLUSION: Pathology and intra-operative complications are independent predictors of ERP deviation. Prolonged length of stay can be predicted by age, multiple procedures and ERP deviation. Failure to mobilize should be considered as a red flag sign prompting further investigation following colorectal resection.

Impaired absorption of marked oligopeptide Glycine-I Tyrosine-Glycine after successful autologous-allotopic ileal mucosa transplantation in beagles.

PURPOSE: After establishing a method for ileal mucosa transplantation in an animal model, the authors investigated the absorptive capacity for oligopeptides of the transplanted mucosa. METHODS: In 14 beagle dogs the authors transplanted ileal mucosa in a vascularized demucosed segment of the transverse colon. The colonic wall-ileal mucosa complex then was integrated in the ileal continuity. Six animals were lost owing to operative complications. Absorptive capacity for oligopeptides was measured in the remaining 8 animals with the iodine 131 (131I)-marked tripeptide glycine-tyrosine-glycine before and 4 weeks after transplantation. The results were compared and analyzed with the Student's t test for matched pairs. Blood concentrations of the marked tripeptide with P value less than .05 were considered as a significant reduction in the absorptive capacity of the transplanted ileal mucosa. After fixation with glutaraldehyd graft, uptake of the colonic wall-ileal mucosa complex was evaluated histologically in 8 animals. RESULTS: In all 8 animals, a 100% graft uptake was verified in all sections. Fifteen minutes after application of 15 MBc Glycine-131I-Tyrosine-Glycine there was no significant difference in the absorption between normal and transplanted ileal mucosa. After 30 minutes, the absorption of the transplanted ileal mucosa showed a tendency (P < .1) for an impaired uptake of the marked tripeptide. However, 60 minutes after application the difference in the absorptive capacity of the transplanted ileal mucosa was significant (P < .05). CONCLUSIONS: Autologous allotopic ileal mucosa transplantation is feasible; however, an impaired absorption of oligopeptides of the transplanted mucosa 4 weeks after transplantation could be observed.

Absorption of D(+)-xylose, cobalamin, and folic acid after autologic-allotopic ileum mucosa transplantation in beagles.

BACKGROUND/PURPOSE: Ileum mucosa transplantation in a demucosed colon coat was developed as a new method for small bowel elongation. In an animal model, the authors investigated the absorptive capacity of the transplanted mucosa for D(+)-xylose, cobalamin (vitamin B12), and folic acid. METHODS: Ileum mucosa was transplanted in a vascularized demucosed segment of transverse colon in 18 beagle dogs. The colon coat-ileum mucosa complex then was integrated in the ileal continuity. Absorptive capacity for D(+)-xylose, cobalamin, and folic acid was measured before and 4 weeks after transplantation. The results were compared and analyzed with the Students' t test for matched pairs. All determined blood values with P values less than.05 were considered to show a significant reduction in the absorptive capacity of the transplanted ileum mucosa. RESULTS: Fifteen minutes after application there was no significant difference in the absorption of D(+)-Xylose and cobalamin between normal and transplanted ileum mucosa (P >.1). Absorption of folic acid in the transplanted segment was lower but not significant (P <.1). After 30 minutes D(+)-xylose and cobalamin again showed no difference between the absorptive capacity of normal and transplanted ileum mucosa (P >.1), whereas folic acid continued with the tendency toward an impaired absorption (P <.1). However, after 60 minutes, the difference of the absorptive capacity of the transplanted ileum mucosa was significant (P <.05) for folic acid. D(+)-xylose showed a tendency for an impaired uptake (P <.1), whereas absorption of cobalamin did not differ significantly after transplantation (P >.1). CONCLUSIONS: Experimental autologic-allotopic ileum mucosa transplantation is a feasible new method for small bowel elongation in an animal model. Examination of the absorptive capacity of the transplanted ileum mucosa showed a normal uptake for cobalamin, while there was an impaired absorption of D(+)-xylose and folic acid.

The urinary corticoid:creatinine ratio (UCCR) in healthy cats undergoing hospitalisation.

Thirty-one healthy pet cats had voided urine samples collected prior to, during and after a brief period of hospitalisation. Urinary corticoids were measured, both prior to and following an extraction technique, and the urinary corticoid:creatinine ratio (UCCR) was calculated. Associations between the UCCR and age, sex, breed and time of urine collection were investigated. There was no significant relationship established between age, sex and breed and the UCCR. A significant increase in the UCCR, however, did occur between the first home collected and first hospitalised urine sample, but only when comparing extracted corticoid results. A normal range for feline UCCR is established for the chemiluminescent immunoassay used in this study.

The detection of HPV DNA improves the recognition of cervical intraepithelial lesions.

UNLABELLED: Reasons that influence the efficacy of cervical cancer screening are failure to screen all women at risk, as well as inherent technical limitations of the conventional cervical smear. HPV DNA testing is a supplementary, objective test less independent on sampling failure. The aim of this study was to compare results of HPV DNA screening to cytological smears (CS) and histological diagnosis. From January 1995 to January 1999, cytological smears, cells for HPV DNA analysis and cervical biopsies were obtained from 280 women included in this study. STATISTICAL METHODS: Fisher's exact test (2x2 contingency tables, P<0.01), Pearson Chi-square, P< 0.05, Spearman's rank correlation R. Sixty patients (21.4%) tested positive for low-risk (LR-HPV), 227 (81.1%) positive for high-risk HPV (HR-HPV). The CS proved to be a strong predictor for the histological diagnosis, reaching a sensitivity of 93.4%, a specificity of 65.8% and a positive predictive value (PPV) of 77.4%. By combining cytology and HPV DNA testing, the sensitivity could be considerably enhanced (99.0%), though at a price of loss in specificity (30.1%). HPV DNA testing, available as a commercially standardized product, leads to a significant rise in sensitivity when used as an additional diagnostic tool to cytological screening methods and thus contributes to reduce the incidence of cervical carcinomas.

Circulating breast cancer cells are frequently apoptotic.

Automatic search for cytokeratin/mucin-1 double immunofluorescence was performed to detect and characterize circulating epithelial tumor cells in patients with advanced breast cancer. The peripheral blood samples in 8 of 19 patients (42.1%) presented with cytokeratin-positive and epithelial-type mucin-positive (CK(+)/MUC1(+)) tumor cells. Detailed microscopic analysis, however, suggested that the majority of the double immunopositive cells was apoptotic according to an "inclusion type" cytokeratin staining pattern and nuclear condensation. Furthermore, apoptosis-related DNA strand breaks could be demonstrated by applying the TdT-uridine nick end labeling assay in these cells. In 3 of 8 positive samples all of the CK(+)/MUC1(+) cells displayed apoptotic features. We conclude that apoptotic cells significantly contribute to the circulating tumor cell fraction in breast cancer patients. As the predictive value of such cells for the outcome of the disease is unclear, they should be considered separately when analyzing tumor cell dissemination.

Carcinogen-induced Mitochondrial DNA Damage in the In Ovo Model.

After experimental exposure of turkey eggs in an in ovo model, the induction of preneoplastic liver lesions (Enzmann et al., 1992and 1995a) and alterations of the mitochondrial (mt) DNA of embryonic turkey livers (Enzmann et al., 1995b) could be demonstrated, showing the sensitivity and usefulness of this short-termed and inexpensive system for carcinogenicity testing. Chemically induced modification of mtDNA may be an important indicator of the carcinogenic potential of substances, as the mt genome may display a higher sensitivity to DNA damaging effects compared to nuclear DNA. To characterize mtDNA damages in ovo, application of diethylnitrosamine (DEN) was performed onto the chorioallantoic membrane (CAM) of the avian embryo. First, the distribution of a model substance after CAM application was measured by autoradiography. MtDNA damage after DEN exposure was demonstrated by gel electrophoresis of isolated mtDNA. Nitrosamine treatment induced a dose-dependent change of mtDNA conformation from supercoiled to relaxed shape, pointing to a possible induction of single-strand breaks.

The legal and scientific basis for FDA's assertion of jurisdiction over cigarettes and smokeless tobacco.

On August 28, 1996, the US Food and Drug Administration (FDA) asserted jurisdiction over cigarettes and smokeless tobacco under the Federal Food, Drug, and Cosmetic Act. Under this Act, a product is a "drug" or "device" subject to FDA jurisdiction if it is "intended to affect the structure or any function of the body." The FDA determined that nicotine in cigarettes and smokeless tobacco does "affect the structure or any function of the body" because nicotine causes addiction and other pharmacological effects. The FDA then determined that these pharmacological effects are "intended" because (1) a scientific consensus has emerged that nicotine is addictive; (2) recent studies have shown that most consumers use cigarettes and smokeless tobacco for pharmacological purposes, including satisfying their addiction to nicotine; and (3) newly disclosed evidence from the tobacco manufacturers has revealed that the manufacturers know that nicotine causes pharmacological effects, including addiction, and design their products to provide pharmacologically active doses of nicotine. The FDA thus concluded that cigarettes and smokeless tobacco are subject to FDA jurisdiction because they contain a "drug," nicotine, and a "device" for delivering this drug to the body.

EGFR and steroid receptors in ovarian carcinoma: comparison with prognostic parameters and outcome of patients.

Epidermal growth factor receptor (EGFR), progesterone receptor (PR) and estrogen receptor (ER) status were analyzed in 108 primary ovarian epithelial carcinoma specimens. Receptor concentration was determined with radioligand binding assays. 61% of the carcinomas investigated were positive for EGFR, 29% for PR and 57% for ER. EGFR status was not correlated with histological grading of tumors and no difference in EGFR positivity was found between subgroups of ovarian carcinomas. On the other hand, 50% of the tumors with FIGO stage III and IV and tumors which could not be operated to be free of residual tumor mass were EGFR positive, whereas only 30% were positive within the group of tumors with FIGO stage I and II and no residual tumor mass. The outcome of the carcinoma patients was followed up for a maximum of 100 months. A significant correlation between EGFR positivity and a shorter progressive-free period as well as shorter overall survival was found. For PR and ER status no relation to patient survival became evident. The response to chemotherapy was significantly correlated to EGFR status. After 5 years 63% of the patients with negative versus 25% with positive EGFR were still alive indicating the impaired response of EGFR positive carcinomas to chemotherapy containing platinum compounds.

High-resolution CT of the temporal bone in dysplasia of the auricle and external auditory canal.

PURPOSE: To determine CT findings in the external, middle, and inner ear of patients with microtia and external auditory canal dysplasia. METHODS: We used high-resolution CT, with multiplanar or axial 1-mm continuous sections, coronal or sagittal reformations, or low-dose spiral acquisitions, to examine 184 temporal bones of children with microtia. RESULTS: In cases of minor microtia, auditory canal stenosis was the most common associated abnormality; in those with major microtia, atresia was predominant. Middle ear malformations depended on the severity of the auricular anomalies. Inner ear changes could also be noted. Ossicle dysplasias occurred in 98% of patients (stapes, 72%), absence of the oval window in 36%, labyrinthine malformations in 13%, closed round window in 6%, facial canal displacement in up to 75%, and aberrations of the vascular canal in 38% of patients with third-grade auricular deformity. CONCLUSION: A variety of external, middle, and, less frequently, inner ear changes were detected in connection with microtia.

Cloning and characterization of myr 6, an unconventional myosin of the dilute/myosin-V family.

We have isolated cDNAs encoding a second member of the dilute (myosin-V) unconventional myosin family in vertebrates, myr 6 (myosin from rat 6). Expression of myr 6 transcripts in the brain is much more limited than is the expression of dilute, with highest levels observed in choroid plexus and components of the limbic system. We have mapped the myr 6 locus to mouse chromosome 18 using an interspecific backcross. The 3' portion of the myr 6 cDNA sequence from rat is nearly identical to that of a previously published putative glutamic acid decarboxylase from mouse [Huang, W.M., Reed-Fourquet, L., Wu, E. & Wu, J.Y. (1990) Proc. Natl. Acad. Sci. USA 87, 8491-8495].

HIV colonizing peripheral blood monocytes follows lymphocytic isolates in shifting from NSI to SI genotype.

Non-syncytium inducing (NSI) and syncytium inducing (SI) variants of human immunodeficiency virus (HIV) isolated from peripheral blood mononuclear cells (PBMC) could be definitely typed by sequence analysis of the env-gene V3 region. It was thus possible to compare the genotypes of viral variants isolated from PBMC and accompanying monocyte cultures and those derived directly from the patients' blood cells prior to cultivation. Within the investigated group of patients it was shown that HIV variants colonizing monocytes displayed a similar shift from NSI to SI as observed previously for PBMC, i.e. lymphocyte derived isolates. Lymphocytic SI variants could be isolated from the blood of patients, while simultaneously the predominant provirus in both blood and monocytic isolate was NSI. Consequently, we observed a delayed switch in the predominant provirus genotype found in blood which was associated with a synchronous change in the genotype of the corresponding monocytic isolate. The results show that monocytes/macrophages can be colonized by heterogeneous HIV variants in vivo and can therefore also function as carriers for the spread of highly virulent SI variants into the tissues.

[Evaluation of specialist instructions at a hospital center based on compliance. A study of 47 patients with mild hemostatic disorders]. / Evaluation der spezialärztlichen Beratung am Spitalzentrum mittels der Compliance. Eine Untersuchung an 47 Patienten mit einer milden Hämostasestörung.

Individual with so-called mild bleeding disorders (MBD) are being investigated with increasing frequency on an outpatient basis at the Central Hematology Laboratory of the Inselspital, Berne. Following diagnosis of a given disorder the patients are informed orally, and sometimes also in writing, concerning the nature of the disorder, prophylactic and therapeutic measures prior to elective surgery, and the role of certain drugs in promoting hemorrhage. In the present study we attempt to evaluate the quality of these specialized medical services catamnestically. As a first step 67 patients with well defined bleeding disorders, and who had had no further contact with this institution since the investigation, were invited for interview. The interviewer was unknown to the patients and the patients participating in the study remained anonymous. A total of 47 patients came for interview. The goal of the enquiry was to find out how far the advice given by the physicians of our laboratory had been actually taken, or what were the possible grounds for ignoring it. Since MBD causes few symptoms in everyday life and complications may arise only as a consequence of surgery, there were particular problems in properly informing patients and thereby motivating them to act on medical advice. On the basis of the criteria selected, two thirds of patients showed adequate, and one third inadequate, compliance. Compliant patients correlated significantly with understanding of diagnosis, carrying brief written information with them for emergencies, coping with disease in general, poor perception of their own body, a "positive memory for medical advice", and their position within the family.(ABSTRACT TRUNCATED AT 250 WORDS)