The development and validation of the Score for the Prediction of Postoperative Respiratory Complications (SPORC-2) to predict the requirement for early postoperative tracheal re-intubation: a hospital registry study

Postoperative pulmonary complications are associated with an increase in mortality, morbidity and healthcare utilisation. The Agency for Healthcare Research and Quality recommends risk assessment for postoperative respiratory complications in patients undergoing surgery. In this hospital registry study of adult patients undergoing non-cardiac surgery between 2005 and 2017 at two independent healthcare networks, a prediction instrument for early postoperative tracheal re-intubation was developed and externally validated. This was based on the development of the Score for Prediction Of Postoperative Respiratory Complications. For predictor selection, stepwise backward logistic regression and bootstrap resampling were applied. Development and validation cohorts were represented by 90,893 patients at Partners Healthcare and 67,046 patients at Beth Israel Deaconess Medical Center, of whom 699 (0.8%) and 587 (0.9%) patients, respectively, had their tracheas re-intubated. In addition to five pre-operative predictors identified in the Score for Prediction Of Postoperative Respiratory Complications, the final model included seven additional intra-operative predictors: early post-tracheal intubation desaturation; prolonged duration of surgery; high fraction of inspired oxygen; high vasopressor dose; blood transfusion; the absence of volatile anaesthetic use; and the absence of lung-protective ventilation. The area under the receiver operating characteristic curve for the new score was significantly greater than that of the original Score for Prediction Of Postoperative Respiratory Complications (0.84 [95%CI 0.82–0.85] vs. 0.76 [95%CI 0.75–0.78], respectively; p < 0.001). This may allow clinicians to develop and implement strategies to decrease the risk of early postoperative tracheal re-intubation.     

Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity

Fas ligand (CD95L) is synthesized both on the cell surface membrane and in a soluble form. Although CD95L contributes to immune privilege in the cornea and testis, the functions of these alternatively processed proteins are not well understood. Some reports suggest that the cytotoxicity of soluble CD95L is insignificant, whereas others show potent responses in vivo, including hepatocyte apoptosis that causes liver failure. We show here that extracellular matrix proteins interact with soluble CD95L and potentiate its pro-apoptotic activity. The cytotoxicity of supernatants from CD95L-expressing cells was increased by incubation on tissue culture plates coated with these matrix proteins; this effect was mediated by trimeric soluble CD95L. With the use of immunoprecipitation, it was found that CD95L binds directly to fibronectin. In addition, immunohistochemical analysis of the cornea revealed that soluble CD95L binds primarily to extracellular matrix. The retention of soluble CD95L on extracellular matrices is likely to play an important role in the development of peripheral tolerance in immune-privileged sites.     

Cancer of the colon in an egg donor: policy repercussions for donor recruitment

This paper describes the tragic case of a young woman who died of cancer of the colon after successfully donating eggs to her younger sister. Although there is no direct link between her operation and the subsequent development of bowel carcinoma, this case imparts a feeling of unease when seen in conjunction with other cases reported during the last few years. It is a reminder that little is known of the long-term consequences of some aspects of assisted conception. Women undergoing ovarian stimulation for themselves or a matched recipient have the right to be advised, in an agreed format, that there is some concern about unproven potential risks from the stimulatory drugs. The safety of egg donors must assume priority over all other considerations, including lack of donors or any moral position. The recent decision by the Human Fertilisation and Embryology Authority (HFEA) to withdraw any form of payment or recompense to egg donors does not seem to us to be based on a balance of scientific advances, patient needs and the ethics of gamete supply. They state that the intention to withdraw payments was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum donation was uncommon and fertility drugs had not yet caused any unease. The Act provided the HFEA with discretionary powers to issue directions so that the future policies would be consistent with any emerging new medical evidence. It is imperative that the HFEA provide convincing evidence on how the current policy of payment to donors harms society, donors or recipients, and how in the UK the new policy will improve medical practice in assisted conception. Successful pilot studies must precede the implementation of any new policy. Failure to do this could cause irreversible harm to the practice of assisted conception using donor gametes, which will ultimately be against the basic aims of the 1990 HFE Act.      

A comparison of postoperative respiratory complications associated with the use of desflurane and sevoflurane: a single-centre cohort study

Sevoflurane and desflurane are the most commonly used volatile anaesthetics for maintenance of anaesthesia. In this study, we aimed to evaluate the relationship between choice of volatile anaesthetic and early postoperative respiratory complications, and to address a critical knowledge gap in safety outcomes between these two commonly used agents. We performed a retrospective analysis of adult (non-cardiac surgery) patients who received sevoflurane or desflurane for the maintenance of general anaesthesia at our institution between 2005 and 2018. We evaluated the association between desflurane exposure (when compared with sevoflurane) and the primary outcome of postoperative respiratory complications, defined by early post-extubation desaturation (S_pO₂ < 90%) or re-intubation within 7 days postoperatively. Multivariable regression analyses were performed and adjusted for confounding factors, including patient, anaesthetic and surgical factors. Propensity matched, interaction and sub-group analyses were performed to assess outcomes in high-risk groups: morbidly obese (BMI > 35 kg.m⁻²); elderly (age > 65 years); and high risk of respiratory complications as well as the primary outcome at 24 h. Desflurane was used for 23,830 patients and sevoflurane for 84,608 patients. Patients exposed to desflurane did not demonstrate a reduced risk of postoperative respiratory complications when compared with sevoflurane (adjusted odds ratio 0.99, 95%CI 0.94–1.04, p = 0.598). These findings were consistent across all sub-groups of high-risk patients and in the propensity score matched cohort. In summary, desflurane use was not associated with reduced postoperative respiratory complications when compared with sevoflurane. In the context of environmental and cost concerns with volatile anaesthetic agents, our study provides important data to support organisational decisions regarding the use of desflurane.     

Investigation of three new mouse mammary tumor cell lines as models for transforming growth factor (TGF)-β and Neu pathway signaling studies: identification of a novel model for TGF-β-induced epithelial-to-mesenchymal transition

Introduction  

This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line).     

Response to influenza virus vaccination in vertical HIV infection

OBJECTIVE: To assess the antibody response to influenza vaccine of children vertically infected with HIV. DESIGN: Prospective study in HIV infected children vaccinated during the winter of 1994-5. SETTING: Family HIV clinic at St Mary's Hospital, Paddington. SUBJECTS: 25 children, aged 1-11 years, vertically infected with HIV. MAIN OUTCOME MEASURES: Responses to influenza antigens (H1N1-A/Taiwan/1/86, H3N2-A/Shandong/9/93, B/Panama/45/ 90) were tested by haemagglutination inhibition. Antibody responses were assessed according to clinical symptoms and immune function, stratified according to the 1994 revised classification for HIV infection in children. RESULTS: 23 children (92%) had either very low or no detectable antibody before vaccination. New protective antibody responses were made by 10 children (40%): in seven to a single antigen, in two to two antigens, and in one to all three antigens. For each antigen there was an overall small increase in the mean geometric titre of antibody produced, but this only reached a protective level for antigen H1N1 and for children with minimal symptoms. Less symptomatic children were significantly more likely to produce a protective antibody response to influenza vaccination. No association was found between immune function, as measured by CD4 count, and vaccine response. CONCLUSIONS: Only vaccination of the least symptomatic HIV infected children against influenza is likely to be effective. This will not only protect them against influenza, but will also protect other more immunosuppressed and vulnerable members of their families.     

"Early-peak" carbon monoxide production in certain erythropoietic disorders

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.     

Catheter problems in the use of ventricular cardiovascular assist systems

The prerequisite for efficient assist-ventricles and impulses in the pulsatile pumping function are sufficiently dimensioned afflux and flowing off connections. In systematic investigations on the hydraulic circulation model the cannulas from an internal parameter of 12 mm with a total length of the connection distance to the inflow and outflow valve, respectively, at the bypass ventricle of 30 cm proved sufficient for performing a volume of output of 5-6 l/min in clinic-relevant filling pressures in a hypodynamic circulatory situation. Connection cannulas for the heart-lung machine used in routine work are not sufficient in periodic filling and ejection processes in the pulsatile pumping function for an effective decompression and effective increase of the cardiac output. In case of an ECG-triggered mode of action of the ventricular assist-system an increase of frequency up to 130/min in after that incomplete filling of the assist-ventricle does not remarkably restrict the effectiveness of the assist-system.     

A randomized placebo-controlled trial of combined early intravenous captopril and recombinant tissue-type plasminogen activator therapy in acute myocardial infarction.

The adjunctive use of intravenous captopril with tissue plasminogen activator early during acute myocardial infarction offers theoretic advantages of diminishing left ventricular volume, preventing ventricular dilation and improving patient survival. To test the safety and efficacy of combined early administration of intravenous captopril and recombinant tissue-type plasminogen activator (rt-PA), 38 patients treated with rt-PA 3 +/- 0.3 h (mean +/- SE) after the onset of myocardial infarction were randomized to intravenous followed by oral captopril or placebo therapy. They underwent cardiac catheterization with measurement of hemodynamic variables and left ventricular function and determination of serum renin, angiotensin and aldosterone levels on days 1 and 7. Oral administration of the selected agent was continued for 3 months along with other antianginal medications, including nonangiotensin-converting enzyme inhibitor vasodilators. Repeat measurements of left ventricular function were obtained before hospital discharge and at 3 months. There were no significant differences in baseline clinical characteristics between groups. One patient in the captopril-treated group became hypotensive during intravenous therapy, requiring discontinuation of treatment. Compared with the placebo-treated group, the captopril-treated group had significant reductions at day 7 in left ventricular end-diastolic pressure (22.5 +/- 1.5 versus 16.3 +/- 1.6 mm Hg, p less than 0.01) and mean systemic arterial pressure (93.6 +/- 3.3 versus 86.2 +/- 2.7 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)