Initial assessment of "Gissell's stain": A novel histopathological method for the identification of Helicobacter pylori.

INTRODUCTION AND OBJECTIVES: The histopathological identification of Helicobacter pylori using the routine method (haematoxylin-eosin) is not only very difficult but also has low sensitivity. Giemsa staining is often used in addition, but different protocols do not produce homogeneous results. Furthermore, the Gold Standard recommended by the European Helicobacter Pylori Study Group has been applied in very few studies, thus resulting in uncertain outcomes. Therefore, a new staining method is required to overcome these limitations. The aim of this study was to evaluate the diagnostic capacity and inter-observer agreement of "Gissell's stain". MATERIAL AND METHODS: A cross-sectional study evaluated 99 gastric paraffin blocks from a private laboratory. Three sections were prepared from each block, and haematoxylin-eosin (HE), Giemsa and "Gissell's stain" methods were applied. The kappa statistics, sensitivity, specificity, and predictive values were calculated. RESULTS: "Gissell's stain" obtained the highest inter-observer agreement (kappa=0.87) compared to the other two methods (HE, kappa=0.51; Giemsa, kappa=0.83). It also obtained the best sensitivity and negative predictive value (97.1% and 98.3%, respectively) compared with the other two methods (HE: 68.6% and 85.1%, respectively; Giemsa: 88.6% and 93.9%, respectively). CONCLUSIONS: Given its unique characteristics (fast, cheap, accessible, and easy to use), in addition to its statistical reliability, "Gissell's stain" has great potential for routine use in the identification of H. pylori.

Intraoperative assessment and postsurgical treatment of prostate cancer tumors using tumor-targeted nanoprobes.

Successful visualization of prostate cancer (PCa) tumor margins during surgery remains a major challenge. The visualization of these tumors during surgery via near infrared fluorescence (NIRF) imaging would greatly enhance surgical resection, minimizing tumor recurrence and improving outcome. Furthermore, chemotherapy is typically administered to patients after surgery to treat any missed tumor tissue around the surgical area, minimizing metastasis and increasing patient survival. For these reasons, a theranostics fluorescent nanoparticle could be developed to assist in the visualization of PCa tumor margins, while also delivering chemotherapeutic drug after surgery. Methods: Ferumoxytol (FMX) conjugated to the fluorescent dye and PCa targeting agent, heptamethine carbocyanine (HMC), yielded the HMC-FMX nanoprobe that was tested in vitro with various PCa cell lines and in vivo with both subcutaneous and orthotopic PCa mouse models. Visualization of these tumors via NIRF imaging after administration of HMC-FMX was performed. In addition, delivery of chemotherapeutic drug and their effect on tumor growth was also assessed. Results: HMC-FMX internalized into PCa cells, labeling these cells and PCa tumors in mice with near infrared fluorescence, facilitating tumor margin visualization. HMC-FMX was also able to deliver drugs to these tumors, reducing cell migration and slowing down tumor growth. Conclusion: HMC-FMX specifically targeted PCa tumors in mice allowing for the visualization of tumor margins by NIRF imaging. Furthermore, delivery of anticancer drugs by HMC-FMX effectively reduced prostate tumor growth and reduced cell migration in vitro. Thus, HMC-FMX can potentially translate into the clinic as a nanotheranostics agent for the intraoperative visualization of PCa tumor margins, and post-operative treatment of tumors with HMC-FMX loaded with anticancer drugs.

Effect of Using the Rapid Shallow Breathing Index as Readiness Criterion for Spontaneous Breathing Trials in a Weaning Protocol.

BACKGROUND: This study aimed to compare the effect of using versus not using the Rapid-Shallow Breathing Index (RSBI) as a readiness criterion for Spontaneous Breathing Trials (SBT) on SBT success. MATERIALS AND METHODS: Daily readiness screens were performed within a respiratory therapist-driven weaning protocol. Patients who passed these screens underwent a one-time measurement of the RSBI and then a SBT regardless of RSBI result. The proportion of passed readiness screens reaching SBT success was compared to the proportion that would have been obtained if RSBI ≤ 105 br/min/L had been used as an additional screen criterion. RESULTS: Two hundred and fifty SBTs performed on 157 patients were analyzed. The sensitivity of RSBI ≤ 105 br/min/L to predict SBT success was 94.8% (95% CI 90.6-97.5). Relative to potentially using RSBI, 14.4% additional SBTs were performed. A third of these were successful, and no complications were detected in the rest that failed. The proportion of passed readiness screens reaching SBT success would have been 4% (95% CI 1.2-6.8) (P = 0.002) lower if RSBI had been used. CONCLUSIONS: The inclusion of the RSBI in a readiness screen may not be useful in a weaning protocol.

Difference in inspiratory flow between volume and pressure control ventilation in patients with flow dyssynchrony.

PURPOSE: Flow dyssynchrony is common during volume control ventilation but minimized during pressure control. Characterizing inspiratory flow during pressure control breaths can inform adjustments of the fixed flow of volume control to address flow dyssynchrony. This study compared inspiratory flow peak and pattern between volume control and adaptive pressure control breaths. MATERIAL AND METHODS: Subjects with or at risk for ARDS were ventilated with volume control decreasing ramp flow at different tidal volumes and subsequently with adaptive pressure control targeting those same tidal volumes. Inspiratory flows of volume control breaths exhibiting flow dyssynchrony, and those of pressure control breaths at the same set tidal volumes without flow dyssynchrony were analyzed, for a total of 17 subject-tidal volume conditions. Peak flow and flows at 10, 25, 50 and 75% of inspiratory time were compared between modes. RESULTS: Group peak flows were not different between modes, but at 50 and 75% of inspiratory time flows were higher during adaptive pressure control. In 8 subject-tidal volume conditions VT were higher (>1ml/kg PBW) on adaptive pressure control than on volume control. CONCLUSIONS: In patients with flow dyssynchrony during volume control ventilation, adjustment of inspiratory flow pattern should be considered to minimize this dyssynchrony.

Distal left main trifurcation disease in a patient with porcelain aorta.

Coronary trifurcation lesions are a complex subset of lesions and are substantially more complex than bifurcations when treated with percutaneous coronary intervention (PCI) because of higher rates of acute periprocedural complications (dissection, myocardial infarction, acute vessel closure) and less effective long-term outcomes (stent thrombosis, restenosis) as compared to non-bifurcation lesions. We present the case of a 73-year-old man who was admitted to our hospital with symptomatic severe aortic stenosis who was found to have a distal left main trifurcation disease as well as porcelain aorta on work-up. Given the high risk of stroke during surgical aortic valve replacement and coronary artery bypass grafting, the patient was accepted by the heart team to proceed with percutaneous coronary intervention (PCI) and trans-catheter aortic valve replacement (TAVR). We describe a successful double mini-crush stenting technique approach for this case.

Effect of Tidal Volume Size and Its Delivery Mode on Patient-Ventilator Dyssynchrony.

RATIONALE: Although increasingly recommended, compliance with low Vt ventilation remains suboptimal. Dyssynchrony induced by low Vts may be a reason for it. OBJECTIVES: To determine the effect of Vt size, and of the ventilator mode used for its delivery (volume vs. pressure control), on the magnitude of patient-ventilator dyssynchrony in patients with or at risk for acute respiratory distress syndrome. METHODS: Nineteen mechanically ventilated patients underwent six consecutive ventilatory conditions: three on volume assist-control (VC) mode, each with set Vt of 6, 7.5, and 9 ml/kg, and three on adaptive pressure-control (APC) mode, with those same set Vts and matching inspiratory times. Triggering, cycling, and flow dyssynchronies were identified by inspection of airway flow and pressure tracings. A dyssynchrony index (DI) was calculated as the total number of dyssynchronies divided by the sum of ventilator cycles and ineffective triggering events, expressed as percentage. A severe DI was calculated including only double triggering and severe flow dyssynchronies. MEASUREMENTS AND MAIN RESULTS: Under VC mode, the median (interquartile range) DIs were 100% (22-100%) at set Vt of 6 ml/kg, and 78% (7-100) at 7.5 ml/kg, both higher than 25% (0-45%) at 9 ml/kg (P = 0.02 and 0.01, respectively). Severe DI was higher at each reduction of Vt size. Under APC mode, compared with VC, DIs were lower at set Vt of 6 and 7.5 ml/kg (P = 0.004 for both). Changing from VC to APC resulted in an increase in exhaled Vt ≥ 1 ml/kg predicted body weight in a minority of patients. CONCLUSIONS: Lower Vts during VC ventilation result in higher patient-ventilator dyssynchrony in most patients with or at risk for acute respiratory distress syndrome. The use of APC mode is an option to reduce dyssynchrony, but it requires careful monitoring to avoid larger-than-target delivered volumes.

Changes in breathing variables during a 30-minute spontaneous breathing trial.

BACKGROUND: Spontaneous breathing trials (SBTs) are increasingly performed. Significant changes in monitored breathing variables and the timing of those changes during the trial have important implications for its outcome determination and supervision. We aimed to study the magnitude and timing of change in breathing variables during the course of a 30-min SBT. METHODS: Breathing variables were continuously measured and averaged by minute during the SBT in 32 subjects with trial success and 8 subjects with trial failure from a general ICU population. Percentage changes in breathing variables during the trial and proportions of subjects showing a ≥20% change at different time points relative to the second minute of the trial were calculated. RESULTS: The commonly monitored breathing variables (frequency, tidal volume, their ratio, and minute ventilation) showed median coefficients of variation of <15% throughout the trial and a median change of less than ±20% by the end of the trial. Changes in a detrimental direction of ≥20% at the end of the trial but not already present at 10 min were noted in ≤5% of all subjects. CONCLUSIONS: During the course of a 30-min SBT, breathing variables remain relatively constant, and potentially significant changes in these variables after 10 min into the trial are uncommon. These findings should be considered when addressing aspects of duration and supervision of SBTs in weaning protocols.

Inter-observer agreement of spontaneous breathing trial outcome.

BACKGROUND: Spontaneous breathing trials (SBTs) are a very important test in the weaning process. The trial involves evaluation of multiple objective and subjective variables. These characteristics could lead to variability in interpreting outcomes with important clinical implications. We aimed to measure the inter-observer agreement between respiratory therapists when analyzing SBT outcomes. METHODS: In the context of a respiratory therapist-driven weaning protocol, 2 respiratory therapists independently interpreted the subjective variables (use of accessory muscles, agitation, and diaphoresis) and the overall outcome of SBTs (success vs failure) performed in adult subjects mechanically ventilated for any duration. Raw agreements between respiratory therapists and kappa statistics were calculated. RESULTS: One-hundred fifty-one SBTs were interpreted. The overall trial outcome raw agreement was 93.3% (95% CI 88.2-96.3) and kappa 0.63 (95% CI 0.47-0.79). Raw agreement for subjective variables ranged between 92.1% (agitation) and 99.3% (diaphoresis). The group with disagreements in overall trial outcome had higher breathing frequency, breathing-frequency-to-tidal-volume ratio, and systolic blood pressure prior to the trial. CONCLUSIONS: Within a respiratory therapist-driven weaning protocol, we found a near 90% inter-observer agreement in the interpretation of SBT outcomes. Our findings illustrate the complexity of interpreting fluctuating subjective and objective variables and their integration into one result: SBT success versus failure. Refining the definitions of variables and their limits for failure along with education might reduce this variability.

Influence of hematoma location on acute mortality after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: This study aimed to identify predictors of acute mortality after intracerebral hemorrhage (ICH), including voxel-wise analysis of hematoma location. METHODS: In 282 consecutive patients with acute ICH, clinical and radiological predictors of acute mortality were identified. Voxel-based lesion-symptom mapping examined spatial correlates of acute mortality, contrasting results in basal ganglia ICH and lobar ICH. RESULTS: Acute mortality was 47.9%. In bivariate analyses, one clinical (serum glucose) and two radiological (hematoma volume and intraventricular extension) measures significantly predicted mortality. The relationship was strongest for hematoma volume. Multivariable modeling identified four significant predictors of mortality (ICH volume, intraventricular extension, serum glucose, and serum hemoglobin), although this model only minimally improved the predictive value provided by ICH volume alone. Voxel-wise analysis found that for patients with lobar ICH, brain regions where acute hematoma was significantly associated with higher acute mortality included inferior parietal lobule and posterior insula; for patients with basal ganglia ICH, a large region extending from cortex to brainstem. CONCLUSIONS: For patients with lobar ICH, acute mortality is related to both hematoma size and location, with findings potentially useful for therapeutic decision making. The current findings also underscore differences between the syndromes of acute deep and lobar ICH.

Accuracy of early prediction of duration of mechanical ventilation by intensivists.

RATIONALE: Predictions of duration of mechanical ventilation are frequently made by intensivists and influence clinical decisions. OBJECTIVES: We aimed to measure the accuracy of these clinical early predictions. METHODS: One hundred fifty-five patients within 48 hours of initiation of mechanical ventilation on a general intensive care unit had clinical data prospectively collected and were followed to determine actual duration of mechanical ventilation. Intensivists, after evaluating patients in the first 2 consecutive days, predicted each duration of mechanical ventilation by selecting between less than 3, 4 to 7, 8 to 14, or more than 14 days. Accuracy of predictions was evaluated by comparisons between predicted and actual durations. MEASUREMENTS AND MAIN RESULTS: Raw agreement (95% confidence interval) between predicted and actual durations, classified into the four categories, was 37% (29-45%). Predictions of duration of more than 7 and more than 14 days showed raw agreements of 59% (51-66%) and 83% (76-88%); sensitivities of 40% (28-54%) and 29% (13-51%); specificities of 71% (61-80%) and 93% (87-97%); positive predictive values of 48% (34-63%) and 44% (20-70%); and negative predictive values of 64% (54-73%) and 87% (81-92%), respectively. CONCLUSIONS: The accuracy of intensivists' early clinical predictions of duration of mechanical ventilation is limited, particularly for identifying patients who will require prolonged mechanical ventilation.

Comparison between automatic tube compensation and continuous positive airway pressure during spontaneous breathing trials.

BACKGROUND: Various methods to perform spontaneous breathing trials (SBTs) exist, but no one method has been shown to be superior. Automatic tube compensation (ATC) is a new and potentially advantageous ventilation mode to use during SBT. We compared ATC to continuous positive airway pressure (CPAP) during SBTs, to determine their efficacy in identifying patients ready to be liberated from mechanical ventilation. METHODS: We randomized 118 adults in a general intensive care unit on mechanical ventilation for > or = 24 h who were about to undergo an SBT as part of an established respiratory-therapist-driven weaning protocol to undergo 30 min SBT with ATC or CPAP with no pressure support. We predefined the SBT-failure criteria. The primary outcome was duration of weaning (days from first SBT to extubation). Other outcomes included unsuccessful extubation within 48 h, first-SBT-pass rate, and total duration of mechanical ventilation. RESULTS: We found a trend toward less failure of first SBT with ATC, compared to CPAP (3% vs 13% respectively, P = .09), but no difference in duration of weaning, rate of unsuccessful extubation, or duration of mechanical ventilation. CONCLUSIONS: When applied as part of a respiratory-therapist-driven weaning protocol in a general intensive-care population, SBTs with ATC were safe but did not hasten liberation from mechanical ventilation, when compared to CPAP.