Visualizing disintegration of 3D printed tablets in humans using MRI and comparison with in vitro data.

Three-dimensional (3D) printing is revolutionising the way that medicines are manufactured today, paving the way towards more personalised medicine. However, there is limited in vivo data on 3D printed dosage forms, and no studies to date have been performed investigating the intestinal behaviour of these drug products in humans, hindering the complete translation of 3D printed medications into clinical practice. Furthermore, it is unknown whether conventional in vitro release tests can accurately predict the in vivo performance of 3D printed formulations in humans. In this study, selective laser sintering (SLS) 3D printing technology has been used to produce two placebo torus-shaped tablets (printlets) using different laser scanning speeds. The printlets were administered to 6 human volunteers, and in vivo disintegration times were assessed using magnetic resonance imaging (MRI). In vitro disintegration tests were performed using a standard USP disintegration apparatus, as well as an alternative method based on the use of reduced media volume and minimal agitation. Printlets fabricated at a laser scanning speed of 90 mm/s exhibited an average in vitro disintegration time of 7.2 ± 1 min (measured using the USP apparatus) and 25.5 ± 4.1 min (measured using the alternative method). In contrast, printlets manufactured at a higher laser scanning speed of 130 mm/s had an in vitro disintegration time of 2.8 ± 0.8 min (USP apparatus) and 18.8 ± 1.9 min (alternative method). When tested in humans, printlets fabricated at a laser scanning speed of 90 mm/s showed an average disintegration time of 17.3 ± 7.2 min, while those manufactured at a laser scanning speed of 130 mm/s exhibited a shorter disintegration time of 12.7 ± 6.8 min. Although the disintegration times obtained using the alternative method more closely resembled those obtained in vivo, no clear correlation was observed between the in vitro and in vivo disintegration times, highlighting the need to develop better in vitro methodology for 3D printed drug products.

Predicting axillary response to neoadjuvant chemotherapy: the role of diffusion weighted imaging.

OBJECTIVE: The aim of this study is to investigate whether the primary tumour response to neoadjuvant chemotherapy (NAC), based on the increase in the ADC-values (apparent diffusion coefficient) within the breast lesion, could help to predict axillary complete response. METHODS: We retrospectively included 74 patients who were treated with NAC followed by surgery at Lucus Augusti Hospital between January 2015 and September 2020. Simple logistic regression was used to evaluate the factors associated with axillary pathological complete response, including the changes in breast tumour ADC-values due to the treatment. RESULTS: Axillary complete response was correlated with negative oestrogen receptor status, Her2 positivity and response of primary tumour. It was achieved in 31% of the patients. In addition, the increase in the tumour ADC-values with NAC was higher for responders. Among the tumours that demonstrated an increase in ADC-value >0.92 ×10-3 mm2/s, 42.8% (15/35) showed axillary complete response. Eight (20.5%) breast cancers with an increase in ADC below the cut-off value were found to have no metastatic nodes after treatment (p = 0.038). CONCLUSION: Our results suggest that the performance of models predicting axillary response to NAC can be improved by adding the tumour response determined also using diffusion-weighted imaging. ADVANCES IN KNOWLEDGE: For the fist time, we investigate the relation between tumour response to NAC, assessed using diffusion-weighted imaging, and axillary pathologic complete response.

Can dedicated breast PET help to reduce overdiagnosis and overtreatment by differentiating between indolent and potentially aggressive ductal carcinoma in situ?

OBJECTIVES: To analyze the utility of metabolic imaging, and specifically of dedicated breast positron emission tomography (dbPET) to differentiate between indolent and potentially aggressive ductal carcinoma in situ (DCIS). METHODS: After institutional review board approval, we retrospectively reviewed the cases of pure DCIS who underwent dbPET before biopsy and surgery in Lucus Augusti Universitary Hospital (Lugo, Spain) and in Fudan Cancer Institute (Shanghai, China) between January 2016 and May 2018. Grade 1 and "non-comedo" grade 2 DCIS were considered low-risk disease, while intermediate-grade with necrosis or grade 3 cases were included in the high-risk group. DbPET sensitivity and specificity to differentiate between indolent and potentially aggressive DCIS were determined along with their respective 95% confidence intervals. RESULTS: We enrolled 139 surgery-confirmed pure DCIS cases. Fifty were high-risk neoplasms and 89 low-risk DCIS. Only seven low-risk lesions were positive at dbPET and five of potentially aggressive neoplasms did not show FDG uptake, all included into the field of view (FOV). Sensitivity and specificity of dbPET to differentiate between indolent and potentially aggressive DCIS were 90% (95% CI, 77-96%) and 92% (95% CI, 84-97%), respectively. CONCLUSION: Metabolic imaging could help to identify the subgroup of indolent lesions from those potentially aggressive ones that may be managed by active surveillance. KEY POINTS: • Low- and high-grade DCIS likely arise from two distinct evolutionary paths and when low-grade lesions progress to invasive cancer, the tumor is frequently low grade and well differentiated. • Ongoing clinical trials evaluate whether patients with low-risk DCIS could be safely managed by an active surveillance approach, with avoidance of unnecessary treatments and without impact on ipsilateral invasive breast cancer free survival time. • Dedicated breast PET may differentiate harmless from potentially hazardous DCIS, supporting active surveillance for the management of those women with low-grade DCIS, decreasing the rate of the upgrade to invasive carcinoma at surgical excision.

Percutaneous removal of benign phyllodes tumor of the breast: An alternative to surgery.

We aimed to evaluate the efficacy of vacuum assisted percutaneous excision in the treatment of benign phyllodes tumors of the breast. From 2007 to 2016, a total of 160 benign fibroepithelial nodules were percutaneously removed in our department. Ultrasonographic follow-up was performed 12 months after the procedure to assess recurrence. Out of the 160 nodules excised, 11 lesions corresponded to benign phyllodes tumors. The median patient age was 39.7 years. The average size of the lesion was 16.9 mm. Ultrasound-guided biopsy was performed before the percutaneous removal in eight of them. Six were histopathologically diagnosed as fibroadenomas, one as phyllodes tumor and in one case histological findings were inconclusive. The mean surveillance period was 27.7 months. During the follow-up period, local recurrence was detected in one patient (9%). We conclude that percutaneous excision of benign phyllodes tumors is not associated with greater risk of recurrence than surgery.

Mujeres con alta probabilidad de padecer cáncer de mama. Luces, sombras y muchos puntos oscuros / No disponible

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Long-term outcome of patients with persistent vascular obstruction on computed tomography pulmonary angiography 6 months after acute pulmonary embolism.

BACKGROUND: The incidence and clinical significance of pulmonary residual thrombosis 6 months after an acute pulmonary embolism (PE) are still not well-known. PURPOSE: To evaluate the association between residual vascular obstruction and the risk of venous thromboembolism (VTE) recurrence or death. MATERIAL AND METHODS: Computed tomography pulmonary angiography (CTPA) was repeated in 97 consecutive patients 6 months after an acute episode of hemodynamically stable pulmonary embolism. We assessed the long-term consequences of residual thrombosis on vital status and incidence of recurrent VTE. RESULTS: Six patients were lost for follow-up. The remaining 91 patients were classified according to the presence (Group 1: 18 cases) or absence (Group 2: 73 cases) of residual pulmonary vascular obstruction. After a mean ± SD of 2.91 ± 0.99 years, there were eight (8.8%) deaths and 11 (12.1%) VTE recurrences. Groups 1 and 2 did not differ in the incidence of death or VTE recurrence. CONCLUSION: Persistent pulmonary vascular obstruction on 6-month CTPA did not predict long-term adverse outcome events.

Electrocardiogram score predicts severity of pulmonary embolism in hemodynamically stable patients.

BACKGROUND: Risk stratification of patients with pulmonary embolism (PE) is essential to guide therapy. The presence of right ventricle dysfunction (RVD) and the anatomic extent of PE have been suggested to predict clinical course. The aim of this study was to assess the ability of an electrocardiogram (ECG) scoring system to predict RVD or the clot load score in normotensive patients with PE. METHODS: Consecutive patients presenting to the emergency room with PE and hemodynamic stability were prospectively included. ECG, echocardiography and computed tomography pulmonary angiography (CTPA) were performed on all patients. RESULTS: A total of 103 patients were studied. ECG score correlated significantly with the clot load score (r = 0.41, 95% confidence interval [CI]: 0.22-0.57, P < 0.001), systolic pulmonary artery pressure (r= 0.31, 95% CI: 0.09-0.49, P = 0.006), pulmonary artery diameter (r = 0.28, 95% CI: 0.07-0.47, P = 0.011) and right ventricle to left ventricle ratio, both measured with echocardiography (r = 0.42, 95% CI: 0.22-0.57, P < 0.001) and with CTPA (r= 0.36, 95% CI: 0.13-0.56, P = 0.004). Area under the receiver operating characteristic curve for detecting RVD was 0.82 (95% CI: 0.72-0.89). Interobserver agreement regarding ECG score was substantial (κ = 0.80). CONCLUSIONS: ECG score correlates with the severity of PE in hemodynamically stable patients. It is potentially useful for risk-stratification strategies in this setting.

The hallucinations of Frédéric Chopin.

Frédéric Chopin is the epitome of the romantic artist; he had a chronic pulmonary disease that ultimately caused his death at the age of 39. An overlooked neurological condition is discussed in this paper. We consider the possibility of a temporal lobe epilepsy, as throughout his life Chopin had hallucinatory episodes, which can accompany seizure disorders.

Relación entre presencia de comorbilidad y control del asma / Relationship Between Comorbidity and Asthma Control

Introducción. La coexistencia de procesos potencialmente agravantes es frecuente en asmáticos, especialmente en individuos con control difícil. Es objetivo primario conocer si la comorbilidad es más frecuente en los pacientes no controlados. Como objetivo secundario nos propusimos evaluar el grado de correlación entre test de control del asma (ACT) y la fracción exhalada de óxido nítrico (FENO). Pacientes y métodos. Estudio prospectivo, observacional, que comparó funcional y clínicamente dos grupos de asmáticos: controlados (ACT≥20) y no controlados (ACT<20). En todos se investigó la presencia de tabaquismo, rinosinusitis, obesidad, ansiedad, depresión, disfunción de cuerdas vocales, reflujo gastroesofágico (RGE), aspergilosis broncopulmonar alérgica (ABPA), EPOC y poliposis nasal. Resultados. Se incluyeron 56 pacientes con asma controlada y 102 con un control subóptimo. Los pacientes con un ACT≥20 tenían mejor función pulmonar, menor variabilidad del PEF, menos hiperreactividad bronquial y menores valores de FENO. Se hallaron comorbilidades en el 95% de los asmáticos controlados y en el 97% de los no controlados. Sólo la presencia de poliposis nasal, RGE y ABPA fue más frecuente en el grupo no controlado. Sin embargo, la presencia simultánea de 3 o más factores de comorbilidad fue significativamente más frecuente en los pacientes con un control subóptimo (p=0,01). No hubo correlación significativa entre los valores del FENO y los del ACT (rho=−0,08; p=0,32). Conclusiones. La suma de comorbilidades agravantes es más frecuente en pacientes con control subóptimo. No existe correlación entre los valores de ACT y de FENO (AU)

Introduction. The coexistence of potentially aggravating processes is common in asthmatics, particularly in patients with difficult control. The primary aim of this study is to ascertain whether comorbidity id more common in uncontrolled patients. As a secondary aim, we propose to evaluate the correlation between the asthma control test (ACT) and the fraction of exhaled nitric oxide (FENO). Patient and methods. A prospective, observational study comparing the function and clinical picture of two groups of asthmatics: controlled (ACT≥20) and uncontrolled (ACT<20). They were all assessed for, smoking, rhinosinusitis, obesity, anxiety, depression, vocal cord dysfunction, gastro-oesophageal reflux (GORD), allergic bronchopulmonary aspergillosis (ABPA), COPD and nasal polyps. Results. A total of 50 patients with controlled asthma and 102 with suboptimal control were included. The patients with an ACT≥20 had better lung function, less variation in PEF, less bronchial hyper-reactivity and lower FENO values. Comorbidities were found in 95% of the controlled asthmatics and in 97% of the uncontrolled. Only the presence of nasal polyps, GORD and ABPA was more frequent in the uncontrolled group. However, the simultaneous presence of 3 or more comorbidity factors was significantly more frequent in patients with sub-optimal control (P=0.01). There was no significant correlation between the FENO and the ACT values (rho=−0.08; P=0.32). Conclusions. Aggravating comorbidities are more common in patients with sub-optimal control. There was no correlation between the FENO and the ACT values (AU)

Right ventricle dysfunction and pulmonary hypertension in hemodynamically stable pulmonary embolism.

BACKGROUND: The main objectives of this study were to determine the incidence of echocardiography-detected right ventricle dysfunction (RVD) or pulmonary hypertension (PHT) and its correlation with computed tomography pulmonary angiography (CTPA) in hemodynamically stable patients with pulmonary embolism (PE), both at diagnosis and after 6 months follow-up. METHODS: Prospective, descriptive, single-center follow-up study. STUDY POPULATION: 103 consecutive patients, with a life expectancy of >6 months, presenting with PE and a systolic blood pressure> or =90mmHg. Echocardiography and CTPA were performed at diagnosis and after 6 months. RESULTS: At diagnosis, RVD and isolated PHT were found in 24.5% and 19.6% of patients, respectively. CTPA and echocardiography correlated significantly at diagnosis. However, CTPA could not predict accurately RVD or PHT. Persistence of RVD and isolated PHT was observed in 7.9% and 11.8% of cases, respectively, 6 months later. Intraluminal filling defects disappeared in 79%. No new filling defects were seen in any patient. Excluding cases with comorbidities that might account for PHT, CTPA was normal at the 6th month in 23.1% of patients with and in 87.8% of cases without persistent RVD or PHT, respectively (p<0.0001). CONCLUSIONS: RVD or PHT are a frequent finding at diagnosis in patients with hemodynamically stable pulmonary embolism and they persist at 6 months in a significant proportion of cases. We have observed a relationship between the persistence of residual vascular obstruction in CTPA and RVD or PHT 6 months after PE.

Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.

OBJECTIVE: To assess the outcome of 54 patients with obesity-hypoventilation syndrome (OHS) who were treated with nasal intermittent positive-pressure ventilation (NIPPV). DESIGN: Descriptive analysis of retrospectively collected clinical data. MATERIALS AND METHODS: From March 1995 to December 2002, OHS (defined as a body mass index [BMI] of > 30 kg/m2, a daytime Pa(CO2) of > or = 50 mm Hg, and a Pa(O2) of < 60 mm Hg in the absence of COPD) was diagnosed in 69 cases. Fifteen patients (21.7%) refused to be treated with NIPPV, and 20 patients were started on NIPPV therapy electively and 34 following an acute exacerbation. We employed daytime arterial blood gas values and overnight pulse oximetry to determine the initial NIPPV modes and settings. The outcome measures were survival, clinical status, and arterial blood gas levels. RESULTS: Among the 54 study patients (18 women), the mean (+/- SD) age was 56 +/- 13 years. The mean BMI was 44 +/- 8.8 kg/m2. Sleep apnea syndrome (apnea-hypopnea index, > 5) was present in 87% of the patients. At presentation, 22 of the 54 patients had experienced an acute hypercapnic respiratory failure (pH < 7.34). None of these patients required orotracheal intubation after NIPPV treatment. Initially, 2 patients were treated with volume-preset ventilation, 49 patients used pressure-preset equipment, and 3 patients employed continuous positive airway pressure (CPAP). Forty-seven patients required supplemental oxygen. At the end of the follow-up period (mean duration, 50 months), Pa(O2) had increased by 24 mm Hg from baseline (95% confidence interval [CI], 21 to 28 mm Hg; p < 0.0001) and Pa(CO2) had decreased by 17 mm Hg (95% CI, 13 to 20 mm Hg; p < 0.0001). NIPPV therapy improved subjective sleepiness (mean Epworth sleepiness scale score decrease, 16 +/- 5 to 6 +/- 2; p < 0.001), and dyspnea decreased in all but four patients. During follow-up, three patients died (one of them due to the progression of respiratory failure). NIPPV therapy could be withdrawn in 5 patients who had achieved a sufficient weight loss, and the conditions of 16 patients could be maintained without respiratory failure by the use of simple therapy with CPAP. CONCLUSIONS: NIPPV therapy is effective in the treatment of patients with OHS, providing a significant improvement in clinical status and gas exchange.