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Hyperprolinemia is a rare genetic condition due to mutations in proline metabolic pathway. Type I Hyperprolinemia (HPI) typically causes neuropsychiatric disorders, and diagnosis is usually confirmed in pediatric population with suggestive neuropsychiatric involvement by elevated serum proline levels and elevated urinary proline, hydroxyproline, and glycine levels. The possible coexistence of nephropathy in patients with HPI, often specified as malformative urinary disease, is often mentioned. However, reports of HPI diagnosis due to kidney impairment do not exist in scientific literature yet. Here we present the case of a patient presenting with chronic kidney disease secondary to obstructive nephropathy who received a HPI diagnosis in adulthood. Interestingly, the family study showed the same 22q11.21 deletion and elevated blood proline levels in the father, who had no clinical anomalies. We therefore suggest, in light of the high frequency of mutations involving 22q11 and PRODH in the general population, to consider these rare alterations in patients with congenital urinary malformations, even in the presence of nuanced neurological symptoms and negative family history.
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Acidosis , Errores Innatos del Metabolismo de los Aminoácidos , Humanos , Niño , Prolina Oxidasa/genética , Mutación , Prolina/genética , Prolina/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/genética , Riñón/metabolismoRESUMEN
ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.
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In order to fight the SARS-CoV-2 pandemic, mass-vaccination programs have been launched globally starting December 2020. The pace of COVID-19 vaccines development was impressive and although data from clinical trials and post-authorization studies showed acceptable safety profile, additional studies and long-term population-level surveillance are needed. A possible link between all type of vaccination and immunological diseases is perhaps one of the hottest topics in literature; correspondingly, there is growing concern over the small but growing number of case reports linking COVID-19 vaccines with the development of glomerular disease. Our group conducted a systematic review of such cases. Results showed that IgA nephropathy (IgAN) and Minimal Change Disease (MCD) are the most frequently associated glomerulopathies. Interestingly, IgAN cases are mostly flares occurring few hours after the second dose of RNA vaccines and have a good clinical outcome, while both de novo and recurring MCD can occur up to 28 days after the first or second dose of vaccines. RNA vaccines are the most common vaccine type to be associated with glomerulopathy. Of course, this may simply reflect the more widespread use of these vaccines. However, compared to traditional vaccines, they do seem produce a higher antibody response and a stronger CD8+ T- and CD4+ T-cell response, including higher production of chemokines and cytokines.
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COVID-19 , Glomerulonefritis por IGA , Nefrosis Lipoidea , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Femenino , Humanos , Masculino , Nefrólogos , SARS-CoV-2 , VacunaciónRESUMEN
BACKGROUND: Septic shock is characterized by breakdown of the endothelial glycocalyx and endothelial damage, contributing to fluid extravasation, organ failure and death. Albumin has shown benefit in septic shock patients. Our aims were: (1) to identify the relations between circulating levels of syndecan-1 (SYN-1), sphingosine-1-phosphate (S1P) (endothelial glycocalyx), and VE-cadherin (endothelial cell junctions), severity of the disease, and survival; (2) to evaluate the effects of albumin supplementation on endothelial dysfunction in patients with septic shock. METHODS: This was a retrospective analysis of a multicenter randomized clinical trial on albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis Trial, ALBIOS). Concentrations of SYN-1, S1P, soluble VE-cadherin and other biomarkers were measured on days 1, 2 and 7 in 375 patients with septic shock surviving up to 7 days after randomization. RESULTS: Plasma concentrations of SYN-1 and VE-cadherin rose significantly over 7 days. SYN-1 and VE-cadherin were elevated in patients with organ failure, and S1P levels were lower. SYN-1 and VE-cadherin were independently associated with renal replacement therapy requirement during ICU stay, but only SYN-1 predicted its new occurrence. Both SYN-1 and S1P, but not VE-cadherin, predicted incident coagulation failure. Only SYN-1 independently predicted 90-day mortality. Albumin significantly reduced VE-cadherin, by 9.5% (p = 0.003) at all three time points. CONCLUSION: Circulating components of the endothelial glycocalyx and of the endothelial cell junctions provide insights into severity and progression of septic shock, with special focus on incident coagulation and renal failure. Albumin supplementation lowered circulating VE-cadherin consistently over time. CLINICAL TRIAL REGISTRATION: ALBIOS ClinicalTrials.gov number NCT00707122.
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Antígenos CD/análisis , Cadherinas/análisis , Endotelio/lesiones , Lisofosfolípidos/análisis , Choque Séptico/sangre , Esfingosina/análogos & derivados , Sindecano-1/análisis , Anciano , Anciano de 80 o más Años , Antígenos CD/sangre , Biomarcadores/análisis , Biomarcadores/sangre , Cadherinas/sangre , Endotelio/irrigación sanguínea , Endotelio/fisiopatología , Femenino , Humanos , Italia , Lisofosfolípidos/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Choque Séptico/complicaciones , Esfingosina/análisis , Esfingosina/sangre , Sindecano-1/sangreRESUMEN
COVID 19 pandemic represents an emergency for public health services and containment measures to reduce the risk of infection have been promptly activated worldwide. The healthcare systems reorganization has had a major impact on the management of cancer patients who are considered at high risk of infection. Recommendations and guidelines on how to manage cancer patients during COVID 19 pandemic have been published. Oral administration of chemotherapy is recommended to limit the access of cancer patients to hospital facilities and in some cases to guarantee the continuum of care. Low-dose metronomic administration of chemotherapy with different drugs and schedules has emerged in the last years as a possible alternative to conventional chemotherapy, due to its promising tumor control rates and excellent safety profiles. Moreover, given that many metronomic schedules use the oral route administration, it could represent a therapeutic strategy to ensure continuum of cancer care during COVID 19 pandemic. In this review we have selected all the clinical studies that have used the metronomic strategy, especially with oral drugs, in order to identify the subgroups of cancer patients who can benefit most from a metronomic approach even during COVID 19 pandemic.
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COVID-19 , Neoplasias , Administración Metronómica , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Pandemias , SARS-CoV-2RESUMEN
BACKGROUND: Chemotherapy plus targeted therapy is the established treatment for human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer (BC). Limited data regarding the safety and activity of the combination of eribulin and trastuzumab (E/T) in pretreated HER2-positive advanced BC (ABC) are available. The aim of this observational, retrospective, multicenter study was to examine the tolerability and the clinical activity of E/T in this setting. METHODS: Patients treated with eribulin mesylate plus standard dose of trastuzumab were included. Data on overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were reported. RESULTS: Between October 2012 and November 2015, 24 consecutive patients with HER2-positive ABC were included. All patients were heavily pretreated: the median number of prior chemotherapy regimens for ABC was 3 (range 2-9). The median number of cycles with E/T was 11.5 (range 2-26). The ORR was 41.7%. Median PFS was 5.4 months, median postprogression survival was 5.4 months, and median OS was 8 months. Neutropenia was the most common grade 3/4 clinical adverse event (16.7%). CONCLUSIONS: Tolerability and clinical activity of the E/T combination schedule are encouraging. The results of this study indicate that this combination might be considered for treatment of pretreated HER2 ABC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Trastuzumab/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Furanos/efectos adversos , Humanos , Italia/epidemiología , Cetonas/efectos adversos , Persona de Mediana Edad , Estadificación de Neoplasias , Supervivencia sin Progresión , Receptor ErbB-2/genética , Estudios Retrospectivos , Trastuzumab/efectos adversosRESUMEN
OBJECTIVES: Acute respiratory distress syndrome is a clinical syndrome characterized by a refractory hypoxemia due to an inflammatory and high permeability pulmonary edema secondary to direct or indirect lung insult (pulmonary and extrapulmonary form). Aim of this study was to evaluate in a large database of acute respiratory distress syndrome patients, the pulmonary versus extrapulmonary form in terms of respiratory mechanics, lung recruitment, gas exchange, and positive end-expiratory pressure response. DESIGN: A secondary analysis of previously published data. PATIENTS: One-hundred eighty-one sedated and paralyzed acute respiratory distress syndrome patients (age 60 yr [46-72 yr], body mass index 25 kg/m [22-28 kg/m], and PaO2/FIO2 184 ± 66). INTERVENTIONS: Lung CT scan performed at 5 and 45 cm H2O. Two levels of positive end-expiratory pressure (5 and 15 cm H2O) were randomly applied. MEASUREMENTS AND MAIN RESULTS: Ninety-seven and 84 patients had a pulmonary and extrapulmonary acute respiratory distress syndrome. The median time from intensive care admission to the CT scan and respiratory mechanics analysis was 4 days (interquartile range, 2-6). At both positive end-expiratory pressure levels, pulmonary acute respiratory distress syndrome presented a significantly lower PaO2/FIO2 and higher physiologic dead space compared with extrapulmonary acute respiratory distress syndrome. The lung and chest wall elastance were similar between groups. The intra-abdominal pressure was significantly higher in extrapulmonary compared with pulmonary acute respiratory distress syndrome (10 mm Hg [7-12 mm Hg] vs 7 mm Hg [5-8 mm Hg]). The lung weight and lung recruitability were significantly higher in pulmonary acute respiratory distress syndrome (1,534 g [1,286-1,835 g] vs 1,342 g [1,090-1,507 g] and 16% [9-25%] vs 9% [5-14%]). CONCLUSIONS: In the early stage, pulmonary acute respiratory distress syndrome is characterized by a greater impairment of gas exchange and higher lung recruitability. The recognition of the origin of acute respiratory distress syndrome is important for a more customized ventilatory management.
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Pulmón/fisiopatología , Intercambio Gaseoso Pulmonar , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/fisiopatología , Mecánica Respiratoria , Anciano , Femenino , Humanos , Hipertensión Intraabdominal/etiología , Hipertensión Intraabdominal/fisiopatología , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Presión Parcial , Presión , Respiración Artificial , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/terapia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Treatment with fluoropyrimidines and concomitant long-course external radiotherapy (RTE) is the standard of care in locally advanced rectal cancer (LARC) preoperative chemoradiation. A randomized phase II study (RaP/STAR-03) was conducted that aimed to evaluate the activity and safety of the monoclonal antibody anti-epidermal growth factor receptor panitumumab as a single agent in combination with radiotherapy in low-risk LARC preoperative treatment. MATERIALS AND METHODS: Patients had adenocarcinoma of the mid-low rectum, cT3N- or cT2-T3N+, KRAS wild-type status, and negative circumferential radial margin. Panitumumab was administered concomitant to RTE. Rectal surgery was performed 6-8 weeks after the end of preoperative treatment. The adjuvant chemotherapy regimen was FOLFOX. The primary endpoint was the pathologic complete response (pCR) rate. The sample size was calculated using Simon's two-stage design. A pCR of 16% was considered to qualify the experimental treatment for further testing. RESULTS: Ninety-eight patients were enrolled in 13 Italian centers from October 2012 to October 2015. Three panitumumab infusions were administered in 92 (93.4%) patients. The RTE compliance was median dose 50.4 Gy; ≥28 fractions in 82 (83.7%) patients. Surgical treatment was performed in 92 (93.9%) patients, and no severe intraoperative complications were observed. A pCR was observed in 10 (10.9%) patients (95% confidence interval, 4.72%-17.07%). Pathological downstaging occurred in 45 (45.9%) patients. Grade 3 toxicities were observed in 22 (22.3%) patients, and the common adverse events were skin rash in 16 (16.3%) patients. No grade 4 toxicities were reported. CONCLUSION: The pCR rate (our primary endpoint), at only 10.9%, did not reach the specified level considered suitable for further testing. However, the analysis showed a good toxicity profile and compliance to concomitant administration of panitumumab and RTE in preoperative treatment of LARC. The pCR evaluation in all wild-type RAS is ongoing. IMPLICATIONS FOR PRACTICE: The aim of the RaP/STAR-03 study was to evaluate the activity and safety of monoclonal antibody anti-epidermal growth factor receptor (EGFR) panitumumab as a single agent without chemotherapy in low-risk, locally advanced rectal cancer (LARC) preoperative treatment. Nevertheless, the use of panitumumab in combination with radiotherapy in preoperative treatment in patients with KRAS wild type and low-risk LARC did not reach the pathologic complete response primary endpoint. This study showed a good toxicity profile and compliance to combination treatment. Further analysis of NRAS and BRAF on tissue and circulating levels of the EGFR ligands and vascular factors (soluble vascular endothelial growth factor, E-selectin) may provide insight on the potential molecular pathways involved in the anti-EGFR response.
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Antineoplásicos Inmunológicos/uso terapéutico , Quimioradioterapia/métodos , Panitumumab/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Panitumumab/farmacología , Cuidados PreoperatoriosRESUMEN
Mechanical ventilation is the type of organ support most widely provided in the intensive care unit. However, this form of support does not constitute a cure for acute respiratory distress syndrome (ARDS), as it mainly works by buying time for the lungs to heal while contributing to the maintenance of vital gas exchange. Moreover, it can further damage the lung, leading to the development of a particular form of lung injury named ventilator-induced lung injury (VILI). Experimental evidence accumulated over the last 30 years highlighted the factors associated with an injurious form of mechanical ventilation. The present paper illustrates the physiological effects of delivering a tidal volume to the lungs of patients with ARDS, and suggests an approach to tidal volume selection. The relationship between tidal volume and the development of VILI, the so called volotrauma, will be reviewed. The still actual suggestion of a lung-protective ventilatory strategy based on the use of low tidal volumes scaled to the predicted body weight (PBW) will be presented, together with newer strategies such as the use of airway driving pressure as a surrogate for the amount of ventilatable lung tissue or the concept of strain, i.e., the ratio between the tidal volume delivered relative to the resting condition, that is the functional residual capacity (FRC). An ultra-low tidal volume strategy with the use of extracorporeal carbon dioxide removal (ECCO2R) will be presented and discussed. Eventually, the role of other ventilator-related parameters in the generation of VILI will be considered (namely, plateau pressure, airway driving pressure, respiratory rate (RR), inspiratory flow), and the promising unifying framework of mechanical power will be presented.
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RATIONALE: The assessment of lung recruitability in patients with acute respiratory distress syndrome (ARDS) may be important for planning recruitment maneuvers and setting positive end-expiratory pressure (PEEP). OBJECTIVES: To determine whether lung recruitment measured by respiratory mechanics is comparable with lung recruitment measured by computed tomography (CT). METHODS: In 22 patients with ARDS, lung recruitment was assessed at 5 and 15 cm H2O PEEP by using respiratory mechanics-based methods: (1) increase in gas volume between two pressure-volume curves (P-Vrs curve); (2) increase in gas volume measured and predicted on the basis of expected end-expiratory lung volume and static compliance of the respiratory system (EELV-Cst,rs); as well as by CT scan: (3) decrease in noninflated lung tissue (CT [not inflated]); and (4) decrease in noninflated and poorly inflated tissue (CT [not + poorly inflated]). MEASUREMENTS AND MAIN RESULTS: The P-Vrs curve recruitment was significantly higher than EELV-Cst,rs recruitment (423 ± 223 ml vs. 315 ± 201 ml; P < 0.001), but these measures were significantly related to each other (R(2) = 0.93; P < 0.001). CT (not inflated) recruitment was 77 ± 86 g and CT (not + poorly inflated) was 80 ± 67 g (P = 0.856), and these measures were also significantly related to each other (R(2) = 0.20; P = 0.04). Recruitment measured by respiratory mechanics was 54 ± 28% (P-Vrs curve) and 39 ± 25% (EELV-Cst,rs) of the gas volume at 5 cm H2O PEEP. Recruitment measured by CT scan was 5 ± 5% (CT [not inflated]) and 6 ± 6% (CT [not + poorly inflated]) of lung tissue. CONCLUSIONS: Respiratory mechanics and CT measure-under the same term, "recruitment"-two different entities. The respiratory mechanics-based methods include gas entering in already open pulmonary units that improve their mechanical properties at higher PEEP. Consequently, they can be used to assess the overall improvement of inflation. The CT scan measures the amount of collapsed tissue that regains inflation. Clinical trial registered with www.clinicaltrials.gov (NCT00759590).
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Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/fisiopatología , Mecánica Respiratoria/fisiología , Tomografía Computarizada por Rayos X/métodos , Anciano , Femenino , Humanos , Rendimiento Pulmonar , Mediciones del Volumen Pulmonar , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: In the cetuximab after progression in KRAS wild-type colorectal cancer patients (CAPRI) trial patients with metastatic colorectal cancer (mCRC) received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) and cetuximab in first line followed by 5-Fluorouracil, folinic acid, oxaliplatin (FOLFOX) with or without cetuximab until progression. Limited data are available on the efficacy and safety of anti-epidermal growth factor receptor (anti-EGFR) agents on elderly patients with mCRC. In the current study we evaluated the efficacy and safety of FOLFIRI plus cetuximab in age-defined subgroups. METHODS: A post-hoc analysis was performed in CAPRI trial patients; outcomes (progression-free survival (PFS), overall response rate (ORR), safety) were analysed by age-groups and stratified according to molecular characterisation. 3 age cut-offs were used to define the elderly population (≥65; ≥70 and ≥75â years). RESULTS: 340 patients with mCRC were treated in first line with FOLFIRI plus cetuximab. Among those, 154 patients were >65â years, 86 >70â years and 35 >75â years. Next-generation sequencing (NGS) was performed in 182 patients. Among them, 87 patients were >65â years, 46 >70 and 17 >75. 104 of 182 patients were wild type (WT) for KRAS, NRAS, BRAF, PIK3CA genes. In the quadruple WT group, 51 patients were ≥65â years; 29 were ≥70; 9 were ≥75. Median PFS was similar within the age-subgroups in the intention-to-treat population, NGS cohort and quadruple WT patients, respectively. Likewise, ORR was not significantly different among age-subgroups in the 3 populations. Safety profile was acceptable and similarly reported among all age-groups, with the exception of grade ≥3 diarrhoea (55% vs 25%, p=0.04) and neutropaenia (75% vs 37%, p=0.03) in patients ≥75â years and grade ≥3 fatigue (31% vs 20%, p=0.01) in patients <75â years. CONCLUSIONS: Tolerability of cetuximab plus FOLFIRI was acceptable in elderly patients. Similar ORR and PFS were observed according to age-groups. No differences in adverse events were reported among the defined subgroups with the exception of higher incidence of grade ≥3 diarrhoea and neutropaenia in patients ≥75â years and grade ≥3 fatigue in patients <75â years. TRIAL REGISTRATION NUMBER: 2009-014041-81.
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AIMS AND BACKGROUND: Few data describe the activity of panitumumab after cetuximab-irinotecan-based regimen failure in patients with KRAS wild-type metastatic colorectal cancer (WT MCRC). METHODS: The aim of this study is to assess if panitumumab has some activity in this setting. RESULTS: We retrospectively analyzed 25 patients with KRAS WT MCRC who received panitumumab from July 2009 to January 2013 after progression on cetuximab. All patients had previously received cetuximab and irinotecan (20 patients) or oxaliplatin (5 patients). We withdrew cetuximab for intolerance in 4 patients (16%). Twenty-one patients (84%) who had previously responded to cetuximab (overall response rate [ORR] plus stable disease ≥5 months) received panitumumab off-label after progression on cetuximab because they were strongly motivated to continue treatment without chemotherapy. The median number of cycles of panitumumab was 7 (range 1-54). Only 20 patients were evaluable for ORR (5 patients received 1-2 cycles and then died). We observed 1 (5%) partial response, 5 (25%) stable disease, median duration 9 months. Median progression-free survival (PFS) and overall survival (OS) were 5 (3-28) and 8 (5-41) months, respectively. All patients were evaluable for toxicity. No patients developed anemia or neutropenia. One patient (4%) developed grade 2 thrombocytopenia, 8 patients (32%) grade 2-3 dry skin or rash, and 2 patients (8%) grade 2 nausea-vomiting (Common Terminology Criteria for Adverse Events version 4.03). CONCLUSIONS: Our data, with all the limits of a retrospective analysis, show longer PFS and OS as compared to other series in the same setting, demonstrating that panitumumab has treatment effectiveness in patients with KRAS WT MCRC who progressed on prior cetuximab. Further confirmatory prospective studies with a larger series of patients are necessary.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Panitumumab , Proteínas Proto-Oncogénicas p21(ras) , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIMS: The prognostic role of BMI variation during and/or after treatments for early-stage breast cancer is still unknown. PATIENTS & METHODS: The χ(2) test was conducted to explore the correlation between breast cancer recurrence and BMI changes in 520 early-stage breast cancer patients. Cox proportional hazard models were used to analyze the association of BMI changes, baseline BMI, known prognostic factors and recurrences. RESULTS: BMI gain was significant determinant of recurrences (p = 0.0008). In multivariate analyses, BMI variation more than 5.71% was associated with higher rates of recurrences, as well as age less than 55 years, stage disease and molecular subtype. CONCLUSION: Women who experience BMI gain after breast cancer may be at increased risk of poor outcomes.
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Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Índice de Masa Corporal , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tamoxifeno/uso terapéutico , Resultado del Tratamiento , Aumento de PesoRESUMEN
RATIONALE: Pressures and volumes needed to induce ventilator-induced lung injury in healthy lungs are far greater than those applied in diseased lungs. A possible explanation may be the presence of local inhomogeneities acting as pressure multipliers (stress raisers). OBJECTIVES: To quantify lung inhomogeneities in patients with acute respiratory distress syndrome (ARDS). METHODS: Retrospective quantitative analysis of CT scan images of 148 patients with ARDS and 100 control subjects. An ideally homogeneous lung would have the same expansion in all regions; lung expansion was measured by CT scan as gas/tissue ratio and lung inhomogeneities were measured as lung regions with lower gas/tissue ratio than their neighboring lung regions. We defined as the extent of lung inhomogeneities the fraction of the lung showing an inflation ratio greater than 95th percentile of the control group (1.61). MEASUREMENTS AND MAIN RESULTS: The extent of lung inhomogeneities increased with the severity of ARDS (14 ± 5, 18 ± 8, and 23 ± 10% of lung volume in mild, moderate, and severe ARDS; P < 0.001) and correlated with the physiologic dead space (r(2) = 0.34; P < 0.0001). The application of positive end-expiratory pressure reduced the extent of lung inhomogeneities from 18 ± 8 to 12 ± 7% (P < 0.0001) going from 5 to 45 cm H2O airway pressure. Lung inhomogeneities were greater in nonsurvivor patients than in survivor patients (20 ± 9 vs. 17 ± 7% of lung volume; P = 0.01) and were the only CT scan variable independently associated with mortality at backward logistic regression. CONCLUSIONS: Lung inhomogeneities are associated with overall disease severity and mortality. Increasing the airway pressures decreased but did not abolish the extent of lung inhomogeneities.
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Pulmón/patología , Síndrome de Dificultad Respiratoria/patología , Lesión Pulmonar Inducida por Ventilación Mecánica/patología , Femenino , Humanos , Modelos Logísticos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Respiración con Presión Positiva/métodos , Intercambio Gaseoso Pulmonar , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Mecánica Respiratoria , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Lesión Pulmonar Inducida por Ventilación Mecánica/diagnóstico por imagenRESUMEN
OBJECTIVE: Positive end-expiratory pressure exerts its effects keeping open at end-expiration previously collapsed areas of the lung; consequently, higher positive end-expiratory pressure should be limited to patients with high recruitability. We aimed to determine which bedside method would provide positive end-expiratory pressure better related to lung recruitability. DESIGN: Prospective study performed between 2008 and 2011. SETTING: Two university hospitals (Italy and Germany). PATIENTS: Fifty-one patients with acute respiratory distress syndrome. INTERVENTIONS: Whole lung CT scans were taken in static conditions at 5 and 45 cm H2O during an end-expiratory/end-inspiratory pause to measure lung recruitability. To select individual positive end-expiratory pressure, we applied bedside methods based on lung mechanics (ExPress, stress index), esophageal pressure, and oxygenation (higher positive end-expiratory pressure table of lung open ventilation study). MEASUREMENTS AND MAIN RESULTS: Patients were classified in mild, moderate and severe acute respiratory distress syndrome. Positive end-expiratory pressure levels selected by the ExPress, stress index, and absolute esophageal pressures methods were unrelated with lung recruitability, whereas positive end-expiratory pressure levels selected by the lung open ventilation method showed a weak relationship with lung recruitability (r = 0.29; p < 0.0001). When patients were classified according to the acute respiratory distress syndrome Berlin definition, the lung open ventilation method was the only one which gave lower positive end-expiratory pressure levels in mild and moderate acute respiratory distress syndrome compared with severe acute respiratory distress syndrome (8 ± 2 and 11 ± 3 cm H2O vs 15 ± 3 cm H2O; p < 0.05), whereas ExPress, stress index, and esophageal pressure methods gave similar positive end-expiratory pressure values in mild, moderate, and severe acute respiratory distress syndrome. The positive end-expiratory pressure selected by the different methods were unrelated to each other with the exception of the two methods based on lung mechanics (ExPress and stress index). CONCLUSIONS: Bedside positive end-expiratory pressure selection methods based on lung mechanics or absolute esophageal pressures provide positive end-expiratory pressure levels unrelated to lung recruitability and similar in mild, moderate, and severe acute respiratory distress syndrome, whereas the oxygenation-based method provided positive end-expiratory pressure levels related with lung recruitability progressively increasing from mild to moderate and severe acute respiratory distress syndrome.
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Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria/terapia , Femenino , Humanos , Masculino , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Although computed tomography (CT) is widely used to investigate different pathologies, quantitative data from normal populations are scarce. Reference values may be useful to estimate the anatomical or physiological changes induced by various diseases. METHODS: We analyzed 100 helical CT scans taken for clinical purposes and referred as nonpathological by the radiologist. Profiles were manually outlined on each CT scan slice and each voxel was classified according to its gas/tissue ratio. For regional analysis, the lungs were divided into 10 sterno-vertebral levels. RESULTS: We studied 53 males and 47 females (age 64 ± 13 years); males had a greater total lung volume, lung gas volume and lung tissue. Noninflated tissue averaged 7 ± 4% of the total lung weight, poorly inflated tissue averaged 18 ± 3%, normally inflated tissue averaged 65 ± 8% and overinflated tissue averaged 11 ± 7%. We found a significant correlation between lung weight and subject's height (P <0.0001, r2 = 0.49); the total lung capacity in a supine position was 4,066 ± 1,190 ml, ~1,800 ml less than the predicted total lung capacity in a sitting position. Superimposed pressure averaged 2.6 ± 0.5 cmH2O. CONCLUSION: Subjects without lung disease present significant amounts of poorly inflated and overinflated tissue. Normal lung weight can be predicted from patient's height with reasonable confidence.
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Mediciones del Volumen Pulmonar/métodos , Pulmón/anatomía & histología , Tomografía Computarizada por Rayos X/métodos , Anciano , Estatura , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Valores de Referencia , Estudios RetrospectivosRESUMEN
OBJECTIVES: Pleural effusion is a frequent finding in patients with acute respiratory distress syndrome. To assess the effects of pleural effusion in patients with acute lung injury on lung volume, respiratory mechanics, gas exchange, lung recruitability, and response to positive end-expiratory pressure. DESIGN, SETTING, AND PATIENTS: A total of 129 acute lung injury or acute respiratory distress syndrome patients, 68 analyzed retrospectively and 61 prospectively, studied at two University Hospitals. INTERVENTIONS: Whole-lung CT was performed during two breath-holding pressures (5 and 45 cm H2O). Two levels of positive end-expiratory pressure (5 and 15 cm H2O) were randomly applied. MEASUREMENTS: Pleural effusion volume was determined on each CT scan section; respiratory system mechanics, gas exchange, and hemodynamics were measured at 5 and 15 cm H2O positive end-expiratory pressure. In 60 patients, elastances of lung and chest wall were computed, and lung and chest wall displacements were estimated. RESULTS: Patients were divided into higher and lower pleural effusion groups according to the median value (287 mL). Patients with higher pleural effusion were older (62±16 yr vs. 54±17 yr, p<0.01) with a lower minute ventilation (8.8±2.2 L/min vs. 10.1±2.9 L/min, p<0.01) and respiratory rate (16±5 bpm vs. 19±6 bpm, p<0.01) than those with lower pleural effusion. Both at 5 and 15 cm H2O of positive end-expiratory pressure PaO2/FIO2, respiratory system elastance, lung weight, normally aerated tissue, collapsed tissue, and lung and chest wall elastances were similar between the two groups. The thoracic cage expansion (405±172 mL vs. 80±87 mL, p<0.0001, for higher pleural effusion group vs. lower pleural effusion group) was greater than the estimated lung compression (178±124 mL vs. 23±29 mL, p<0.0001 for higher pleural effusion group vs. lower pleural effusion group, respectively). CONCLUSIONS: Pleural effusion in acute lung injury or acute respiratory distress syndrome patients is of modest entity and leads to a greater chest wall expansion than lung reduction, without affecting gas exchange or respiratory mechanics.
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Equilibrio Ácido-Base , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/epidemiología , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/epidemiología , Factores de Edad , Comorbilidad , Cuidados Críticos/métodos , Femenino , Humanos , Italia/epidemiología , Masculino , Respiración con Presión Positiva , Estudios Prospectivos , Respiración Artificial , Mecánica Respiratoria , Volumen de Ventilación Pulmonar , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: To explore clinical outcomes and cardiac safety of continuous antiHer2 therapy. PATIENTS AND METHODS: This retrospective study evaluates overall survival (OS), time to treatment failure (TTF), and cardiac safety of 80 consecutive Her2-positive metastatic breast cancer (MBC) patients that received ≥ 12 months of therapy with trastuzumab, followed by lapatinib-based or trastuzumab-based therapy. RESULTS: All patients received trastuzumab as first antiHer2 therapy; 54% received lapatinib in the second or subsequent line. Median OS was 34 months (12-120 months). Median OS was 48 months in the subgroup of 43 patients who received lapatinib and 26 months in the 37 patients who did not. Median TTF was shorter for lapatinib. There were three cardiac events and trastuzumab-based chemotherapy (CT) was interrupted in one patient because left ventricular ejection fraction (LVEF) decreased to ≤ 40%. CONCLUSION: Continuous antiHer2 therapy provides good clinical outcomes, especially in those patients who received lapatinib. Cardiac dysfunction was a rare event, reversible, associated to trastuzumab and not related to treatment duration.
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Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Corazón/efectos de los fármacos , Receptor ErbB-2/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Lapatinib , Persona de Mediana Edad , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Estudios Retrospectivos , Trastuzumab , Resultado del TratamientoRESUMEN
PURPOSE: The computation of lung recruitability in acute respiratory distress syndrome (ARDS) is advocated to set positive end-expiratory pressure (PEEP) for preventing lung collapse. The quantitative lung CT scan, obtained by manual image processing, is the reference method but it is time consuming. The aim of this study was to evaluate the accuracy of a visual anatomical analysis compared with a quantitative lung CT scan analysis in assessing lung recruitability. METHODS: Fifty sets of two complete lung CT scans of ALI/ARDS patients computing lung recruitment were analyzed. Lung recruitability computed at an airway pressure of 5 and 45 cm H(2)O was defined as the percentage decrease in the collapsed/consolidated lung parenchyma assessed by two expert radiologists using a visual anatomical analysis and as the decrease in not aerated lung regions using a quantitative analysis computed by dedicated software. RESULTS: Lung recruitability was 11.3 % (interquartile range 7.39-16.41) and 15.5 % (interquartile range 8.18-21.43) with the visual anatomical and quantitative analysis, respectively. In the Bland-Altman analysis, the bias and agreement bands between the visual anatomical and quantitative analysis were -2.9 % (-11.8 to +5.9 %). The ROC curve showed that the optimal cutoff values for the visual anatomical analysis in predicting high versus low lung recruitability was 8.9 % (area under the ROC curve 0.9248, 95 % CI 0.8550-0.9946). Considering this cutoff, the sensitivity, specificity, and diagnostic accuracy were 0.96, 0.76, and 0.86, respectively. CONCLUSIONS: Visual anatomical analysis can classify patients into those with high and low lung recruitability allowing more intensivists to get access to lung recruitability assessment.