Regional mucociliary clearance in patients with cystic fibrosis.

This paper reports on a large retrospective analysis of mucociliary clearance (MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age-matched healthy subjects. As many of the CF patients were studied on multiple occasions, a total of 184 patient studies are presented. MCC was measured using a radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC was measured from the central, intermediate, peripheral, basal, mid and apical regions of the lung. MCC was markedly decreased in the CF patient group. Not only was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7 +/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid (14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors that may have influenced MCC in both the normal subjects and CF patients. Age, gender, body mass index, patient genotype, penetration index, spontaneous cough, and various lung function parameters were entered into a stepwise multiple regression model, but none of the factors proved to be statistically important in determining MCC. Both intrasubject repeatability and intersubject variability estimates are presented for the patients and normal subjects that had multiple studies. The values were found to be remarkably similar for both CF patients and normal subjects and for both intra- and intersubject repeatability. With marked deviation from normal ranges and good repeatability, the measurement of MCC in CF patients would seem to be a valuable outcome measure for clinical trials involving new pharmaceuticals and physical therapy designed to improve removal of secretions from the airways.     

Machine learning methods for perioperative anesthetic management in cardiac surgery patients: a scoping review

BackgroundMachine learning (ML) is developing fast with promising prospects within medicine and already has several applications in perioperative care. We conducted a scoping review to examine the extent and potential limitations of ML implementation in perioperative anesthetic care, specifically in cardiac surgery patients.MethodsWe mapped the current literature by searching three databases: MEDLINE (Ovid), EMBASE (Ovid), and Cochrane Library. Articles were eligible if they reported on perioperative ML use in the field of cardiac surgery with relevance to anesthetic practices. Data on the applicability of ML and comparability to conventional statistical methods were extracted.ResultsForty-six articles on ML relevant to the work of the anesthesiologist in cardiac surgery were identified. Three main categories emerged: (I) event and risk prediction, (II) hemodynamic monitoring, and (III) automation of echocardiography. Prediction models based on ML tend to behave similarly to conventional statistical methods. Using dynamic hemodynamic or ultrasound data in ML models, however, shifts the potential to promising results.ConclusionsML in cardiac surgery is increasingly used in perioperative anesthetic management. The majority is used for prediction purposes similar to conventional clinical scores. Remarkable ML model performances are achieved when using real-time dynamic parameters. However, beneficial clinical outcomes of ML integration have yet to be determined. Nonetheless, the first steps introducing ML in perioperative anesthetic care for cardiac surgery have been taken.     

RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota

Lymphoid cells that express the nuclear hormone receptor RORγt are involved in containment of the large intestinal microbiota and defense against pathogens through the production of interleukin 17 (IL-17) and IL-22. They include adaptive IL-17-producing helper T cells (T(H)17 cells), as well as innate lymphoid cells (ILCs) such as lymphoid tissue-inducer (LTi) cells and IL-22-producing NKp46+ cells. Here we show that in contrast to T(H)17 cells, both types of RORγt+ ILCs constitutively produced most of the intestinal IL-22 and that the symbiotic microbiota repressed this function through epithelial expression of IL-25. This function was greater in the absence of adaptive immunity and was fully restored and required after epithelial damage, which demonstrates a central role for RORγt+ ILCs in intestinal homeostasis. Our data identify a finely tuned equilibrium among intestinal symbionts, adaptive immunity and RORγt+ ILCs.     

Fast track method for the identification of multi–drug resistant tuberculosis on direct clinical specimen using combined drug media

ObjectiveTo combine isoniazid (INH) and rifampicin (RIF) in a single media to detect and evaluate multi-drug resistant Mycobacterium tuberculosis (MDR-TB) strains using clinical specimens by direct and indirect drug susceptibility testing (DST).MethodsDrug susceptibility testing for INH and RIF using individual and combined drug media was performed by minimum inhibitory concentration (MIC) method on direct clinical specimens.ResultsThe combined drug media showed complete concordance with individual drug media in the detection of MDR-TB by direct DST method and 89% efficiency with indirect DST method. Susceptibility results were available by 3 weeks after the receipt of clinical specimen using direct DST on combined drug media.ConclusionsCombined drug media can be used as a fast track method in large scale studies warranting detection of MDR-TB.     

Post-traumatic coxa vara in children following screw fixation of the femoral neck

Background and purpose

The rare displaced fractures of the femoral neck in children need accurate reduction and rigid fixation. The implants commonly used for internal fixation in children are pins or screws. We evaluated the long-term outcome in children who sustained fractures of the proximal femur that were treated by screw fixation.

Patients and methods

All 22 children (mean age 12 (5–16) years) with fractures of the femoral neck that were treated with screw fixation (mean 2.4 (1–3) screws) at our department between 1990 and 2006 were evaluated. For measurement of outcome, the Harris hip score (HHS) was used and the development of post-traumatic coxa vara was assessed from the difference in the neck-shaft angle postoperatively and at the latest follow-up examination, after mean 4 (2–15) years.

Results

A loss of reduction was observed in 12 patients. There was a statistically significant correlation between the HHS and the changes in the neck-shaft angle.

Interpretation

Loss of reduction was found in more than half of the children. Screw fixation cannot be recommended for the treatment of femoral neck fractures in children due to a substantial number of post-traumatic coxa vara.     

γδ T Cells Predict Outcome in Zoledronate‐Treated Breast Cancer Patients

The biological mechanism underlying the antitumor role of zoledronate is unclear. The analysis in this letter illustrates the diagnostic and prognostic potential of a γδ T-cell-based blood test and implies a link between immune responsiveness and positive outcome with zoledronate therapy.We read with great interest the article by Valachis et al. [1], published in The Oncologist. In a comprehensive meta-analysis of 15 randomized clinical trials on adjuvant therapy for breast cancer patients with zoledronate, the authors identified a significant overall survival benefit with zoledronate treatment, in agreement with one smaller meta-analysis [2] but not another [3] conducted earlier. These new findings support the call for zoledronate to be considered as a new standard of care in adjuvant breast cancer therapy [4].The dilemma remains that the biological mechanism underlying the antitumor role of zoledronate is unclear, as Valachis et al. correctly highlight [1]. The clinical benefit may in fact stem, at least in part, from the activity of zoledronate on the patient''s immune system by specifically stimulating Vγ9/Vδ2 T cells, which compose 0.5%–5% of circulating T cells in healthy adults [5]. Targeted immunotherapy studies directly exploiting the potent non-major histocompatibility complex-restricted cytotoxicity of Vγ9/Vδ2 T cells have shown excellent safety profiles and promising clinical observations in a variety of hematological and solid cancers [6], including metastatic breast cancer [7].Studies by us and others have demonstrated that zoledronate treatment induces a rapid and long-lasting conversion of the peripheral Vγ9/Vδ2 T-cell phenotype from CD27⁺CD45RA⁻ central memory T (T_CM) cells to CD27⁻CD45RA⁻ effector memory T (T_EM) cells in many, but not all, individuals [7–9]. In Figure 1, zoledronate-treated breast cancer patients with stable disease showed elevated proportions of Vγ9/Vδ2 T_EM cells at the time of blood sampling compared with patients with progressing disease and untreated controls (Fig. 1A). No such differences were observed with regard to patient age, time on treatment, or pretreatment clinical status. We then stratified the same patient cohort according to their follow-up disease status at 3–9 months after blood sampling. This showed successful conversion from T_CM to T_EM cells (as evident by a lower frequency of T_CM cells) in patients who were stable 3–9 months after blood sampling compared with patients who went on to show progressing disease (Fig. 1B).Open in a separate windowFigure 1.γδ T-cell memory subsets in metastatic breast cancer patients in relation to clinical outcome. (A): Proportion of CD27⁻CD45RA⁻ effector memory T cells among circulating Vγ9/Vδ2 T cells in 10 zoledronate-treated patients in relation to clinical outcome at the time of sampling and in comparison to three untreated patients. (B): Proportion of CD27⁺CD45RA⁻ central memory T cells in relation to subsequent clinical outcome at 3–9 months after sampling. Patients received at least two cycles of zoledronic acid (Zometa; Novartis International, Basel, Switzerland, http://www.novartis.com) for >1 month and <8 months and had no other active malignancies within the previous year; no active or uncontrolled infections; no autoimmune disorders or serious allergic reactions; no use of immunosuppressives during the previous 3 months; and no prior chemotherapy or cytotoxic agents during the previous 6 months.Abbreviations: AUROC, area under the receiver operator curve; CI, confidence interval; PD, progressing disease; SD, stable disease; T_CM cells, central memory T cells; T_EM cells, effector memory T cells.Our analysis illustrates the diagnostic and prognostic potential of a γδ T-cell-based blood test and implies a link between immune responsiveness and positive outcome with zoledronate therapy, thereby contributing to our understanding of the as yet unexplained clinical benefit of adjuvant therapy. These findings are particularly intriguing because new treatments specifically targeting bone resorption, such as denosumab, lack this potential to act on γδ T cells and may not yield the direct antitumor benefit observed with zoledronate.     

The relationship between elastase and lactoferrin in healthy, gingivitis and periodontitis sites

OBJECTIVES: To compare the relative amounts of elastase (primary polymorphonuclear leucocyte granule constituent) and lactoferrin (secondary PMN granule constituent) in the gingival crevicular fluid (GCF) of healthy, gingivitis and periodontitis sites.
DESIGN: This cross-sectional study looked at the two GCF constituents in three categories of disease status within the same subject.
MATERIALS AND METHODS: Patients with chronic adult periodontitis were screened and those exhibiting all three types of sites ie periodontally healthy, gingivitis and periodontitis sites were recruited (n = 10) and had GCF collected from the three sites. Lactoferrin and elastase were measured in eluates of GCF by enzyme-linked immunosorbent assay.
RESULTS: The absolute amount of lactoferrin measured in ng per 30 s samples was significantly lower in healthy and gingivitis sites as compared to periodontitis sites however this difference failed to reach significance when the concentration of lactoferrin in GCF was used as the analytical unit. No significant differences were found for elastase levels at any sites when expressed as either absolute amounts or concentrations. Secondary granule release, as evidenced by lactoferrin levels, occurs during cell migration and the process is independent of primary granule release, which is thought to correlate with PMN activation. The relationship between granule constituents in the samples showed significant differences, the highest lactoferrinlelastase ratio being at periodontitis sites (P < 0.001).
CONCLUSIONS These findings imply a change in the relative amounts of elastase and lactoferrin released at different disease level sites, with an almost 10-fold increase in the proportion of lactoferrin to elastase in periodontitis sites over healthy and gingivitis sites. This variation in the release by PMNs of primary and secondary granule constituents may indicate alterations in PMN function in different disease environments.