Swallowing disorders in tracheostomised patients: a multidisciplinary/multiprofessional approach in decannulation protocols

Safe removal of tracheal cannula is a major goal in the rehabilitation of tracheostomised patients to achieve progressive independence from mechanical support and reduce the risk of respiratory complications. A tracheal cannula may also cause significant discomfort to the patient, making verbal communication difficult. Particularly when cuffed, tracheal cannula reduces the normal movement of the larynx which can further compromise the basic swallowing defect. A close connection between respiratory, phonating, swallowing and feeding abilities to be recovered, implies a strict integration among different professionals of the rehabilitation team. An appropriate management of tracheostomy cannula is closely connected with assessment and treatment of swallowing disorders in order to limit the development of severe pulmonary and nutritional complications, but at present there are no uniform protocols in the scientific literature. Furthermore, several studies report as an essential criterion for decannulation the presence of good patient consciousness, which is often altered in patients with tracheostomy, but a general agreement is lacking

Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures.

Purpose CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15. Methods Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2–10. Results This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a ‘classical’ tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton. Conclusion Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening

Structural Study of the Micellar Aggregates of Sodium Taurodeoxycholate

Previously, fibers of sodium and rubidium salts of glycodeoxycholic and taurodeoxycholic acids have been drawn from aqueous micellar solutions. Their X-ray patterns have been interpreted by means of very similar unit cell parameters and helical structures, formed by trimers, having a 3-fold rotation axis, arranged in 7/1 helices. Micellar aggregates with an aggregation number N less than or equal to 12 and greater than or equal to 15, having oblate and cylindrical (7/1 helix) shape, respectively, have been proposed for sodium taurodeoxycholate (NaTDC) and satisfactorily verified by means of electromotive force and quasi-elastic light-scattering (QELS) measurements. The aim of this paper is to further check this two-structure model by means of QELS, circular dichroism (CD), and dielectric measurements on NaTDC aqueous solutions within concentration and temperature ranges 10-100 mM and 5-45 degrees C. The average intensity scattered by the NaTDC samples does not depend on the temperature and can be fitted by two straight lines, which intersect at a concentration about 40 mM. Two structures seem to be present, one prevailing above and the other below this concentration. The change of structure, which occurs during the growth of the aggregates, has been monitored by means of CD spectra increasing the ionic strength. The CD data agree with the two-structure model assuming that the cylindrical aggregates have an enantioselective ability toward bilirubin-IX alpha lower than that of the oblate aggregates. The average electric dipole moment mu of a NaTDC monomer has been calculated from dielectric data. The mu values, plotted as a function of NaTDC concentration within the temperature range 5-45 degrees C, can be fitted by two straight lines and show a break at a concentration that is, once more, about 40 mM. The mu values vary from 33 to 68 D, depending on the temperature and NaTDC concentration. These high values can be justified by a remarkable hydration of the NaTDC aggregates. The moderate decrease of mu when the populations of the aggregates with N greater than or equal to 15 increase can agree with the formation of 7/1 helices, but disagrees with the formation of disordered structures, especially when they have a pseudo center of symmetry. The temperature dependence of the relaxation time follows an Arrhenius law. The molar enthalpy of activation vs NaTDC concentration for the relaxation process can be fitted by two straight lines, which show a break point at a concentration about 40 mM and could be connected with two different structures

Essential arterial hypertension and stone disease

Essential arterial hypertension and stone disease.BackgroundCross-sectional studies have shown that nephrolithiasis is more frequently found in hypertensive patients than in normotensive subjects, but the pathogenic link between hypertension and stone disease is still not clear.MethodsBetween 1984 and 1991, we studied the baseline stone risk profile, including supersaturation of lithogenic salts, in 132 patients with stable essential hypertension (diastolic blood pressure of more than 95mm Hg) without stone disease and 135 normotensive subjects (diastolic blood pressure less than 85mm Hg) without stone disease who were matched for age and sex (controls). Subsequently, both controls and hypertensives were followed up for at least five years to check on the eventual formation of kidney stones.ResultsBaseline urine levels in hypertensive males were different from that of normotensive males with regards to calcium (263 vs. 199mg/day), magnesium (100 vs. 85mg/day), uric acid (707 vs. 586mg/day), and oxalate (34.8 vs. 26.5mg/day). Moreover, the urine of hypertensive males was more supersaturated for calcium oxalate (8.9 vs. 6.1) and calcium phosphate (1.39 vs. 0.74). Baseline urine levels in hypertensive females were different from that of normotensive females with regards to calcium (212 vs. 154mg/day), phosphorus (696 vs. 614mg/day), and oxalate (26.2 vs. 21.7mg/day), and the urine of hypertensive females was more supersaturated for calcium oxalate (7.1 vs. 4.8). These urinary alterations were only partially dependent on the greater body mass index in hypertensive patients. During the follow-up, 19 out of 132 hypertensive patients and 4 out of 135 normotensive patients had stone episodes (14.3 vs. 2.9%, chi-square 11.07, P = 0.001; odds ratio 5.5, 95% CI, 1.82 to 16.66). Of the 19 stone-former hypertensive patients, 12 formed calcium calculi, 5 formed uric acid calculi, and 2 formed nondetermined calculi. Of the urinary factors for lithogenous risk, those with the greatest predictive value were supersaturation of calcium oxalate for calcium calculi and uric acid supersaturation for uric acid calculi.ConclusionsA significant percentage of hypertensive subjects has a greater risk of renal stone formation, especially when hypertension is associated with excessive body weight. Higher oxaluria and calciuria as well as supersaturation of calcium oxalate and uric acid appear to be the most important factors. Excessive weight and consumption of salt and animal proteins may also play an important role

Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed to predict survival in node-positive prostate cancer patients: External validation on a multi-institutional database

Objectives: To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer-specific mortality-free survival after surgery in pN1 prostate cancer patients through an external validation. Methods: We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram-derived probability cut-off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice. Results: External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer-specific mortality-free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none. Conclusions: In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery

Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed to predict survival in node-positive prostate cancer patients: External validation on a multi-institutional database

Objectives: To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer-specific mortality-free survival after surgery in pN1 prostate cancer patients through an external validation. Methods: We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram-derived probability cut-off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice. Results: External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer-specific mortality-free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none. Conclusions: In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery

A nomogram to predict pathologic T2 stage in candidates to robot-assisted radical prostatectomy with iT3 prostate cancer on preoperative multiparametric MRI: results from a multi-institutional collaboration

: In candidates to robot-assisted radical prostatectomy (RARP) for locally advanced (iT3) prostate cancer on preoperative MRI, the performance of MRI for local staging is demonstrably suboptimal, and currently no prediction tools that might help surgeons in preoperative planning are available. We analyzed data of 685 patients with iT3 prostate cancer (PCa) who received RARP at five participating institutions between 2012 and 2020. Multivariable logistic regression model investigated predictors of pT2 disease among variables available before surgery (i.e: preoperative PSA, biopsy ISUP group, clinical T stage on digital rectal examination-DRE, prostate volume on MRI, PIRADS score of index lesion, seminal vesicles invasion on MRI, location suspicious for T3 disease on MRI). Coefficients from such model were used to build a nomogram to predict organ-confined (i.e. pT2) disease on final pathology. Internal validation was performed using the leave-one-out cross-validation. Median (interquartile range) preoperative PSA was 7.5 (5.2, 11.9) ng/ml, and 280 (41%) and 216 (32%) had biopsy ISUP group 4-5 disease and palpable disease on DRE, respectively. Preoperative MRI was suspicious for iT3 disease on the mid-posterior part of the gland in 485 (71%) men, and 527 (77%) men had a PIRADS 5 lesion. After surgery, a total of 192 (28%) patients had organ-confined disease (i.e. pT2). All variables fitted into the model and were considered to build the nomogram. After internal validation, the AUC was 73% (95% confidence interval: 69%, 77%). Awaiting external validation, we provided data that is relevant to optimize surgical strategy in men diagnosed with iT3 PCa who are scheduled for RARP

How Can the COVID-19 Pandemic Lead to Positive Changes in Urology Residency?

The COVID-19 outbreak, in a few weeks, overloaded Italian hospitals, and the majority of medical procedures were postponed. During the pandemic, with hospital reorganization, clinical and learning activities performed by residents suffered a forced remodulation. The objective of this study is to investigate how urology training in Italy has been affected during the COVID-19 era. In this multi-academic study, we compared residents' training during the highest outbreak level with their previous activity. Overall 387 (67.1%) of the 577 Italian Urology residents participated in a 72-h anonymous online survey with 36 items sent via email. The main outcomes were clinical/surgical activities, social distancing, distance learning, and telemedicine. Clinical and learning activity was significantly reduced for the overall group, and after categorizing residents as those working only in COVID hospitals, both "junior" and "senior" residents, and those working in any of three geographical areas created (Italian regions were clustered in three major zones according to the prevalence of COVID-19). A significant decrease in outpatient activity, invasive diagnostic procedures, and endoscopic and major surgeries was reported. Through multivariate analysis, the specific year of residency has been found to be an independent predictor for all response modification. Being in zone 3 and zone 2 and having "senior" resident status were independent predictors associated with a lower reduction of the clinical and learning activity. Working in a COVID hospital and having "senior" resident status were independent predictors associated with higher reduction of the outpatient activity. Working in zone 3 and having "senior" resident status were independent predictors of lower and higher outpatient surgical activity, respectively. Working in a COVID hospital was an independent predictor associated with robotic surgical activity. The majority of residents reported that distance teaching and multidisciplinary virtual meetings are still not used, and 44.8% reported that their relationships with colleagues decreased. The COVID-19 pandemic presents an unprecedented challenge, including changes in the training and education of urology residents. The COVID era can offer an opportunity to balance and implement innovative solutions that can bridge the educational gap and can be part of future urology training