Weaning from mechanical ventilation

Practice guidelines on weaning should be based on the results of several well-designed randomized studies performed over the last decade. One of those studies demonstrated that immediate extubation after successful trials of spontaneous breathing expedites weaning and reduces the duration of mechanical ventilation as compared with a more gradual discontinuation of ventilatory support. Two other studies showed that the ability to breathe spontaneously can be adequately tested by performing a trial with either T-tube or pressure support of 7 cmH₂O lasting either 30 or 120 min. In patients with unsuccessful weaning trials, a gradual withdrawal for mechanical ventilation can be attempted while factors responsible for the ventilatory dependence are corrected. Two randomized studies found that, in difficult-to-wean patients, synchronized intermittent mandatory ventilation (SIMV) is the most effective method of weaning.     

Use of (99m)Tc-sulesomab for the diagnosis of prosthesis infection after total joint arthroplasty

This study aimed to evaluate the diagnostic efficacy of antigranulocyte scintigraphy using the antibody fragment (99m)Tc-sulesomab (LeukoScan) for the diagnosis of prosthesis infection in patients with total hip or knee arthroplasty. The results from 19 patients with suspected total joint arthroplasty infection who had undergone a three-phase bone scan and a subsequent examination with (99m)Tc-sulesomab during a 1-year period were reviewed. Twelve patients were shown to have prosthesis infection on culture of aspirated synovial fluid or intra-operative samples. The overall sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for (99m)Tc-sulesomab were 75%, 86%, 90%, 66% and 79%, respectively, compared with 54%, 83%, 88%, 45% and 63%, respectively, for the three-phase bone scan. This study showed that (99m)Tc-sulesomab had good diagnostic value for the detection of prosthesis infection. The combination of (99m)Tc-sulesomab with other laboratory or imaging examinations may improve diagnostic performance in prosthesis infection and should be investigated further.     

Urinary schistosomiasis: report of case diagnosed in bladder biopsy

Background

Urinary schistosomiasis is a common parasitic disease in endemic countries.

Case presentation

We report the case of a patient who was on a working trip to Mauritania. This parasitosis, suspected in the presence of hematuria and the notion of stay in an endemic zone, was confirmed by the presence of Schistosoma heamatobium eggs during the histological examination of the bladder biopsy performed after cystoscopy, highlighting a bilharzial granuloma and of course, the diagnosis was confirmed by the presence of eggs during the direct examination of the freshly collected urine.

Conclusions

It should be pointed out that the diagnosis of schistosomiasis must be evoked with the association of hematuria and the particular inflammatory aspect of the vesical mucosa and, of course, the notion of stay in an endemic zone.

     

The ionic contrast medium ioxaglate interferes with thrombin-mediated feedback activation of factor V, factor VIII and platelets

Summary.  Clinical observation shows that radiographic contrast media (CM) may influence thrombus formation. In the search for the underlying mechanism, we have shown that the ionic CM ioxaglate is a potent inhibitor of thrombin generation in platelet-poor and platelet-rich plasma, whereas the influence of the non-ionic contrast medium iodixanol is minimal. Ioxaglate boosts the inhibitory effect of the platelet GPIIb/IIIa antagonist abciximab and the effects of ioxaglate and heparin are additive. Ioxaglate inhibits the clotting of fibrinogen and the activation of factors V and VIII, and of platelets by thrombin. It does not inhibit hydrolysis of small chromogenic thrombin substrates, nor does it influence the heparin-catalyzed inactivation of thrombin by antithrombin. We assume therefore that ioxaglate interferes with the binding of macromolecular substrates to the anionic exosite I of thrombin. The biological correlation to the observed antithrombotic effect of ioxaglate is then to be found in the inhibition of thrombin generation via inhibition of thrombin-mediated feedback activations.     

Defining sepsis on the wards: results of a multi‐centre point‐prevalence study comparing two sepsis definitions

Our aim was to prospectively determine the predictive capabilities of SEPSIS‐1 and SEPSIS‐3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24‐h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS‐1 definition, 212 patients had sepsis. When using the SEPSIS‐3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS‐1 criteria had a sensitivity (95%CI) of 65% (54–75%) and specificity of 47% (41–53%); SEPSIS‐3 criteria had a sensitivity of 86% (76–92%) and specificity of 32% (27–38%). SEPSIS‐3 and SEPSIS‐1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5–5.6) and 1.6 (1.3–2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63–0.76)), followed by NEWS (0.58 (0.51–0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49–0.61)) and quickSOFA score (0.56 (0.49–0.64)) could not predict outcome. The SEPSIS‐3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis‐induced organ dysfunction.     

The Transplantation of hBM-MSCs Increases Bone Neo-Formation and Preserves Hearing Function in the Treatment of Temporal Bone Defects – on the Experience of Two Month Follow Up

Temporal bone reconstruction is a persisting problem following middle ear cholesteatoma surgery. Seeking to advance the clinical transfer of stem cell therapy we attempted the reconstruction of temporal bone using a composite bioartificial graft based on a hydroxyapatite bone scaffold combined with human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The aim of this study was to evaluate the effect of the combined biomaterial on the healing of postoperative temporal bone defects and the preservation of physiological hearing functions in a guinea pig model. The treatment’s effect could be observed at 1 and 2 months after implantation of the biomaterial, as opposed to the control group. The clinical evaluation of our results included animal survival, clinical signs of an inflammatory response, and exploration of the tympanic bulla. Osteogenesis, angiogenesis, and inflammation were evaluated by histopathological analyses, whereas hBM-MSCs survival was evaluated by immunofluorescence assays. Hearing capacity was evaluated by objective audiometric methods, i.e. auditory brainstem responses and otoacoustic emission. Our study shows that hBM-MSCs, in combination with hydroxyapatite scaffolds, improves the repair of bone defects providing a safe and effective alternative in their treatment following middle ear surgery due to cholesteatoma.     

Melphalan-Based Reduced-Intensity Conditioning is Associated with Favorable Disease Control and Acceptable Toxicities in Patients Older Than 70 with Hematologic Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent alloHCT with melphalan-based reduced-intensity conditioning (RIC) at City of Hope. Engraftment was prompt, with median time to neutrophil engraftment of 15 days. More than 95% of patients achieved complete donor chimerism within 6 weeks from HCT, consistent with the “semiablative” nature of this regimen. With a median follow-up of 31.1 months, the 2-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) were 68.9%, 63.8%, and 17.0%, respectively. Cumulative incidence of relapse at 1 and 2 years was 17.0% and 19.3%, respectively. One hundred–day cumulative incidence of grades II to IV acute graft-versus-host disease was 37.7% (grades III to IV, 18.9%), and 2-year cumulative incidence of chronic graft-versus-host disease was 61.9% (extensive, 45.9%). The only significant predictor for poor OS was high/very high disease risk index. Transplant-related complications and morbidities observed here did not differ from the commonly expected in younger patients treated with RIC. In conclusion, alloHCT with a melphalan-based conditioning regimen is associated with acceptable toxicities and NRM, lower incidence of relapse, and favorable OS and PFS in patients aged 70 years or older.     

Circadian variation in number and affinity of beta 2-adrenoceptors in lymphocytes of asthmatic patients

To determine whether circadian variation in adrenoceptor function might underlie the 'morning dip' in peak expiratory flow (PEF) rate and its abolition by salbutamol we measured indices of beta-adrenoceptor function (Bmax. and Kd), the ratio FEV1/FVC, and plasma cortisol at 08.00 and 18.00 hours on and off salbutamol (4 mg given orally every 4 h) in five extrinsic asthmatic patients and five normal volunteers. There was a significant circadian variation in receptor numbers (Bmax.) in both the control and asthmatic groups which was not abolished on treatment with salbutamol. Both groups appeared to compensate for loss of receptor number induced by salbutamol administration by increasing receptor affinity. For comparable combinations of drug/time, there was no significant difference between the control and asthmatic groups. We conclude that the 'morning dip' observed in asthmatic patients cannot simply be explained by changes in cell receptor number or affinity, as our results suggest that both groups have intact beta-adrenoceptor function. Nevertheless, our observations of the normal circadian rhythm has important implications for future studies of beta-adrenoceptors in asthmatic patients.