RESUMEN
Systemic sclerosis (SSc) is an autoimmune disease characterised by tissue fibrosis leading to vascular injury. Nitric oxide (NO) has been implicated in the pathogenesis of autoimmune diseases. A deficiency in basal NO production by the constitutive endothelial isoform of nitric oxide synthase may promote vasoconstriction and vascular wall thickening. In January 2017, we searched the PubMed/Medline, Cochrane Library and Enbase/Medline databases for studies analysing physio-pathological correlations with lung fractional exhaled NO (FeNO) production. This review describes the rationale underlying possible applications of FeNO measurements in the management of SSc. Measuring NO levels at multiple expiratory flow rates makes it possible to distinguish airway NO production and distal airway/alveolar NO concentration (ANOC), and there is increasing evidence indicating that it may be useful in many non-respiratory conditions. FeNO levels are increased in SSc patients with fibrosing lung disease, whereas those with pulmonary hypertension have relatively low FeNO levels, thus suggesting that NO plays an important role in regulating pulmonary vascular resistance in SSc. However, a number of studies have shown increased ANOC in SSc patients without increased FeNO levels. The relationship between lung diffusing capacity for carbon monoxide and ANOC may be related to increased alveolar membrane thickness impeding NO diffusion or alveolar inflammation in SSc lung disease. The findings concerning the usefulness of FeNO measurements in SSc patients are discordant, but the available papers suggest that ANOC is a more accurate indicator of progressive lung dysfunction and an increase in ANOC could assess the extent of interstitial lung disease non-invasively.
Asunto(s)
Pruebas Respiratorias/métodos , Enfermedades Pulmonares Intersticiales , Óxido Nítrico/análisis , Esclerodermia Sistémica , Espiración , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/metabolismo , Enfermedades Pulmonares Intersticiales/patología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnósticoRESUMEN
The 6-minute walk test (6MWT) is a standardised, feasible and reliable measure of sub-maximal exercise capacity that has never been fully validated in systemic sclerosis (SSc). A variety of data suggest that many non-pulmonary aspects of SSc contribute to the test results, thus blunting the ability of the 6MWT to measure changes in lung function. Sources of variability are a training effect, technician experience, subject encouragement, medication, other activities on day of testing, deconditioning and the effects of musculoskeletal conditions and pain. Another cause of variability is the anatomical site the probe is attached to: a forehead probe is preferable to a finger or earlobe sensor. The indiscriminate use of the 6MWT for all SSc patients is not useful. It should be used in patients with pulmonary involvement, combined with diffusion capacity of the lung for carbon monoxide (DLCO) and its components (membrane diffusion and capillary volume) or the Sclerodermia Health Assessment Questionnaire Disability Index. The use of these combined parameters may indicate the onset of pulmonary hypertension. Recent studies suggest two alternatives to the 6MWT: maximal cardiopulmonary exercise testing and DLCO testing during effort. However, their use must still be validated.
Asunto(s)
Tolerancia al Ejercicio , Hipertensión Pulmonar/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Esclerodermia Sistémica/diagnóstico , Prueba de Paso , Caminata , Capacidad Cardiovascular , Estado de Salud , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/fisiopatologíaRESUMEN
BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.
Asunto(s)
Selección de Donante , Hospitales de Alto Volumen/estadística & datos numéricos , Hospitales de Bajo Volumen/estadística & datos numéricos , Trasplante de Riñón/métodos , Riñón/anatomía & histología , Donadores Vivos , Nefrectomía/métodos , Recolección de Tejidos y Órganos/métodos , Femenino , Supervivencia de Injerto , Humanos , Riñón/irrigación sanguínea , Riñón/cirugía , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
OBJECTIVES: Fibromyalgia (FM) is characterised by chronic musculoskeletal pain, autonomic nervous system (ANS) dysfunction, and disturbed sleep. The aim of this study was to evaluate the influence of ANS dysfunction on the genesis of sleep disorders. METHODS: Fifty female FM patients and 45 healthy subjects matched for age, gender and body mass index underwent a clinical, polysomnographic and autonomic profile evaluation at rest and during a tilt test in order to determine muscle sympathetic nerve activity (MSNA), plasma catecholamine levels, and the spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation computed by means of the spectrum analysis of RR during sleep. RESULTS: The FM patients had a higher heart rate (HR), more MSNA and a higher LF/HF ratio, and lower HFRR values at rest (p<0.05), and showed no increase in MSNA, a smaller decrease in HFRR, and an excessive rate of syncope (46%) during the tilt test. Their sleep was less efficient (p<0.01), and they had a higher proportion of stage 1 non-REM sleep (p<0.001), experienced many arousals and periodic limb movements (PLMs) per hour of sleep (p<0.001) and a high proportion of periodic breathing (PB%) (p<0.0001). Their cyclic alternating pattern (CAP) rate was significantly increased (p<0.001). During sleep, they had a higher HR and LF/HF ratio, and a lower HFRR (p<0.001). The number of tender points, CAP rate, PB% and PLMI correlated positively with HR and the LF/HF ratio, and negatively with HFRR during sleep. CONCLUSIONS: Our findings seem to show that sleep causes the same effects as a stressful test in FM patients. A vicious circle is created during sleep: pain increases sympathetic cardiovascular activation and reduces sleep efficiency, thus causing lighter sleep, a higher CAP rate, more arousals, a higher PLMI, and increasing the occurrence of PB, which gives rise to abnormal cardiovascular neural control and exaggerated pain sensitivity.
Asunto(s)
Fibromialgia/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Nervio Vago/fisiopatología , Adulto , Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea , Estudios de Casos y Controles , Catecolaminas/sangre , Electrocardiografía , Femenino , Fibromialgia/sangre , Fibromialgia/complicaciones , Humanos , Persona de Mediana Edad , Conducción Nerviosa , Nervio Peroneo/fisiopatología , Polisomnografía , Frecuencia Respiratoria , Trastornos del Sueño-Vigilia/sangre , Trastornos del Sueño-Vigilia/complicaciones , Análisis EspectralRESUMEN
OBJECTIVES: The aim of this study was to evaluate whether pulmonary diffusing capacity is impaired in patients with fibromyalgia (FM) as it is in those with other diseases characterised by autonomic nerve system (ANS) dysfunction such as type 1 diabetes. METHODS: Forty-five consecutive anti-nuclear antibody (ANA)-negative female Caucasian patients aged 50.1± 5.6 years with FM and compared with 45 healthy female control volunteers matched in terms of age and body mass index (BMI). The autonomic function has been evaluated by means of standard electrocardiography (ECG), finger blood pressure respiration, and muscle sympathetic nerve activity (MSNA) at rest and during a stepwise tilt test up to 75°. Their autonomic profiles were drawn up on the basis of MSNA, plasma catecholamine levels, and spectral indices of cardiac sympathetic and vagal modulation, and sympathetic vasomotor control computed by means of the spectrum analysis of RR and systolic arterial pressure (SAP) variability. Lung volumes and dynamic spirometry parameters were assessed by means of plethysmography. All of the patients were clinically evaluated and completed the FQI and COMPASS questionnaire. RESULTS: There was no difference in lung volumes between the FM patients and healthy controls, but DLCO (83±4 vs. 96±5; p<0.001), Kco (84±5 vs 98±5; p<0.001), DM (12.7±2.4 vs 13.6±1.8; p<0.05) and Vc (48±3.9 vs 65±7; p<0.001) were significantly reduced in the patients. The COMPASS-31, RCS and pain VAS scores significantly correlated with DLCO, Kco and Vc with the correlation being particularly close in the case of Vc. Furthermore, univariate Cox proportional hazard analysis showed that the three scores were all significantly associated with an increased risk of impaired DLCO (respectively, χ(2) 16.21, p<0.0005; χ(2) 7.09, p<0.005; χ(2) 6.37, p<0.01). CONCLUSIONS: FM impairs DLCO mainly as a result of a reduction in Vc, and that this defect is inversely proportional to the severity of the dysfunction suggesting a relationship between impaired DLCO and autonomic nerve dysfunction.
Asunto(s)
Fibromialgia , Mediciones del Volumen Pulmonar/métodos , Pulmón/fisiopatología , Sistema Nervioso Simpático , Presión Sanguínea/fisiología , Catecolaminas/sangre , Electrocardiografía/métodos , Femenino , Fibromialgia/sangre , Fibromialgia/diagnóstico , Fibromialgia/fisiopatología , Humanos , Persona de Mediana Edad , Pletismografía/métodos , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
OBJECTIVES: To identify factors indicating exercise-induced oxygen desaturation during the 6-minute walk test (6MWT) in patients with diffuse systemic sclerosis (SSc) and initial interstitial lung disease (ILD). METHODS: The study involved 121 consecutive adult anti-Scl 70 autoantibody-positive SSc patients with initial ILD, 93 of whom were followed up for five years. Before enrolment and then annually, the patients underwent high-resolution computed tomography (HRCT), functional lung tests, with carbon monoxide diffusion capacity of the lung (DLCO) and its components (alveolar-capillary membrane [Dm] and pulmonary blood volume [Vc]), the evaluation of dyspnea before and after the 6MWT using the Borg scale, and transthoracic echocardiography. A decrease in peripheral capillary oxygen saturation (SpO2) of ≥4% during the 6MWT was used to define desaturation, the appearance of which led to the patient being withdrawn from follow-up. RESULTS: There were no significant differences in HRCT score during the follow-up, but 32 patients (35%) desaturated during the 6MWT, including 12 (37%) who experienced a severe decrease SpO2 to ≤88%, indicating a high risk of mortality. At baseline, there was no statistically significant difference in any considered clinical characteristics between the desaturating and non-desaturating patients but, at the time of desaturation, the desaturators had lower minimum SpO2% levels during the 6MWT (p<0.0001), and lower DLCO (p<0.0001) and Dm (p<0.0001). Comparison of the desaturators defined on the basis of a reduction in SpO2 to ≤88% and those defined on the basis of a decrease in SpO2 of ≥4% showed that, at baseline, the former had lower minimum SpO2% levels during 6MWT (p<0.001), lower DLCO (p=0.01), a lower DLCO/VA ratio (p=0.05), lower Dm (p<0.005) and Vc values (p<0.5), and higher RVsystP (p=0.01). At the time of desaturation, the desaturators' minimum SpO2 levels during the 6MWT correlated with their DLCO (r=0.78; p<0.001), Dm (r=0.65; p<0.01), Vc (r=0.52;p<0.05) and RV-systP values (r = -0.53; p<0.05). CONCLUSIONS: Our data seem to confirm the close interdependence between pulmonary diffusion and oxygen desaturation during exercise. In SSc combined 6MWT, DLCO and its components may indicate patients at increased risk of developing pulmonary hypertension.
Asunto(s)
Disnea/diagnóstico , Prueba de Esfuerzo/métodos , Tolerancia al Ejercicio , Enfermedades Pulmonares Intersticiales/diagnóstico , Pulmón/fisiopatología , Esclerodermia Difusa/complicaciones , Caminata , Anciano , Biomarcadores/sangre , Monóxido de Carbono/sangre , Disnea/sangre , Disnea/etiología , Disnea/fisiopatología , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Valor Predictivo de las Pruebas , Capacidad de Difusión Pulmonar , Pruebas de Función Respiratoria , Factores de Riesgo , Esclerodermia Difusa/diagnóstico , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Interstitial lung involvement is common and potentially limits the quality of life in patients with systemic limited sclerosis (SScl). OBJECTIVES: To study the lung carbon monoxide diffusion (DLCO) measured during effort in order to identify a possible subclinical impairment. METHODS: We enrolled 20 SScl patients without interstitial lung involement and 20 healthy controls. At enrolment all subjetcs underwent plethysmography, DLCO by single-breath technique, and evaluation of pulmonary blood flow (Qc) with the rebreathing CO2 method. Skin involvement in the SScl patients was rated using the modified Rodman skin score (mRSS). During exercise on a cycle ergometer, DLCO, DLCO/ alveolar volume (Kco) and Qc were calculated at 25% and 50% of predicted maximum workload (25% pmw and 50% pmw). RESULTS: At baseline two groups did not differ in age, body mass index, lung function or Qc. In the controls, DLCO, Kco and DLCO/Qc measured at 25% pmw and 50% pmw were significantly higher than in SScl patients, while Qc was not different. Based on response to effort, SScl patients were divided into two groups: responders, with an increase of DLCO(25%pmw) and DLCO(50%pmw) at least 5% and 10% respectively, and non-responders. The non-responders showed greater skin involvement and significantly reduced DLCO, Kco and DLCO/Qc values at rest than responders. CONCLUSIONS: Moderate effort in SScl patients may reveal a latent impairment in gas diffusion through the alveolar/capillary membrane, thus confirmig that exertional DLCO can identify lung damage at an earlier stage than DLCO at rest.
Asunto(s)
Monóxido de Carbono/metabolismo , Enfermedades Pulmonares Intersticiales/etiología , Calidad de Vida , Esclerodermia Sistémica/fisiopatología , Biomarcadores/metabolismo , Estudios de Casos y Controles , Prueba de Esfuerzo/métodos , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: Inactivating mutations of the calcium-sensing receptor (CaSR), of the G-protein subunit α11 (GNA11) and of the adaptor-related protein complex 2, sigma 1 subunit (AP2S1) genes are responsible for familial hypocalciuric hypercalcaemia (FHH). The aim of this study was to analyse prevalence and pathogenicity of CaSR, GNA11 and AP2S1 mutations in patients with an FHH phenotype and to compare them with a sample of patients with primary hyperparathyroidism (PHPT) in order to identify the most useful laboratory parameter for a differential diagnosis. METHODS: Patients with an FHH phenotype were studied with polymerase chain reaction amplification and direct sequencing of the entire CaSR, GNA11 and AP2S1 coding sequences. Novel mutations were introduced in a Myc-tagged human wild-type (WT) CaSR cDNA-expressing vector, and functional assay was performed on human embryonic kidney cells evaluating expression and function of mutated proteins. RESULTS: Among 16 FHH patients, none had an inactivating GNA11 or AP2S1 mutation while 3 (18.8%) carried a CaSR mutation and 10 (62.5%) at least one CaSR polymorphism. Within the latter group, 7 of 10 patients had more than one polymorphism (4.1 ± 2.1 per patient). Two novel CaSR mutations [c.2120A>T (E707V) and c.2320G>A (G774S)] were identified: the E707V mutation prevented CaSR expression (western blot), whereas the G774S mutation determined a reduced receptor sensitivity to calcium (IP3 assay). PHPT patients showed significantly (P < 0.001) higher serum calcium, parathyroid hormone, urinary calcium and calcium-creatinine clearance ratio (CCCR) and significantly lower serum phosphate than FHH ones. CONCLUSIONS: FHH should be clearly differentiated by PHPT to avoid unnecessary surgery: CCCR could be a useful screening tool while genetic analysis should include the two novel CaSR mutations herein described. The role of multiple polymorphisms deserves further investigation in patients with an FHH phenotype.
Asunto(s)
Hipercalcemia/congénito , Hiperparatiroidismo Primario/genética , Mutación/genética , Polimorfismo Genético/genética , Receptores Sensibles al Calcio/genética , Complejo 2 de Proteína Adaptadora/genética , Subunidades sigma de Complejo de Proteína Adaptadora/genética , Adulto , Anciano , Western Blotting , Estudios de Cohortes , ADN/genética , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Femenino , Subunidades alfa de la Proteína de Unión al GTP/genética , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/genética , Hiperparatiroidismo Primario/diagnóstico , Italia/epidemiología , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Sensibles al Calcio/metabolismoRESUMEN
BACKGROUND: Patients with a rare genetic disease may receive renal transplantation (KTx) without a correct diagnosis of causal nephropathy and therefore develop unexpected and even severe complications. The aim of the study was to describe the cases of rare genetic disorders diagnosed after KTx, in order to draw clinical lessons for the transplant physician. METHODS: We retrospectively assessed all patients who had received a diagnosis of a rare genetic disorder after KTx. RESULTS: In our center, more than 30% (278/911) of kidney transplant (KTx) recipients were diagnosed with a causal nephropathy: Prevalence of rare genetic disorders in this group was 4.32% (12/278), including 2,8-dihydroxyadeninuria (2,8-DHA) disease (n = 2), HNF-1B-associated nephropathy (n = 2), UMOD-related nephropathy (n = 5), Fabry disease (n = 1), INF2 focal segmental glomerulosclerosis (n = 1), and Senior-Løken syndrome (n = 1). 2,8-DHA nephropathy relapsed in both patients causing an acute renal failure and jeopardizing the graft. CONCLUSIONS: Kidney transplant recipients without a diagnosis of causal nephropathy appear to be a selected population in which rare genetic diseases might be more common than expected. As even a belated diagnosis after KTx can have a significant impact on graft and patient survival and on other family members, this possibility should be evaluated in KTx recipients without a known causal nephropathy.
Asunto(s)
Enfermedades Genéticas Congénitas/epidemiología , Enfermedades Renales/epidemiología , Trasplante de Riñón , Enfermedades Raras/epidemiología , Receptores de Trasplantes , Adulto , Anciano , Femenino , Estudios de Seguimiento , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: To assess prospectively the safety and efficacy of transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) in patients who have undergone renal transplantation (RT). To assess the impact of TURP on renal graft function. PATIENTS AND METHODS: Urological and renal functional outcomes of TURP performed in RT recipients for treatment of lower urinary tract obstruction attributable to BPH were prospectively assessed in a series of 32 consecutive patients with follow-up of ≥48 months. Maximum urinary flow rate (Qmax ) at uroflowmetry, International Prostate Symptom Score (IPSS), post-void residual urine volume (PVR), haemoglobin and serum creatinine (sCr) levels were recorded before TURP and 1, 6, 24 and 48 months after the procedure. The trends in these variables after TURP were evaluated. Early and delayed complications were assessed and graded according to the Clavien classification system. RESULTS: TURP was performed at a mean of 6 months after RT. No intraoperative complications occurred. Seven postoperative complications were observed (21.9%): two Clavien grade II and five Clavien grade IIIa. Qmax , IPSS and PVR improved significantly after surgery and the improvement was maintained until 48 months. No patient required a repeat TURP during follow-up. SCr levels significantly decreased 1 and 6 months after TURP and did not significantly increase at long-term follow-up. CONCLUSIONS: TURP for lower urinary tract obstruction attributable to BPH in RT recipients is safe and effective since it improves urinary flow, bladder emptying and related urinary symptoms. TURP allows an early significant improvement of graft function that is maintained at a follow-up of 48 months.
Asunto(s)
Trasplante de Riñón , Síntomas del Sistema Urinario Inferior/cirugía , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata , Estudios de Seguimiento , Humanos , Trasplante de Riñón/fisiología , Síntomas del Sistema Urinario Inferior/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Hiperplasia Prostática/complicaciones , Factores de Tiempo , Resección Transuretral de la Próstata/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The therapeutic approach to COVID-19 and healthcare system preparedness improved during 2020. We compared characteristics and outcomes of hospitalized COVID-19 patients during the first 28 days of the March and October pandemic waves in Milan, Italy. MATERIAL AND METHODS: A prospective, observational study enrolling adult patients hospitalized with COVID-19 pneumonia during March 7-April 4 (1st period) and October 15-November 12 (2nd period). During the 1st period hydroxychloroquine, lopinavir/ritonavir and therapeutic enoxaparin when thrombosis was confirmed were administered; systemic corticosteroids were given in case of severe pneumonia. During the 2nd period dexamethasone, methylprednisolone, remdesivir, thromboprophylaxis or anticoagulation were administered according to international recommendations. Patients with respiratory distress on oxygen masks initiated CPAP. Outcomes were: length of hospital stay, all-cause in-hospital mortality and need for intubation. RESULTS: We included 70 patients (75% males) during the 1st and 76 patients (51% males, p = 0.522) during the 2nd period. Prevalence of severe respiratory failure (30% vs. 12%, p = 0.006), and D-dimer >3000 FEU (34% vs. 15%, P = 0.012) were reduced during the 2nd period, while anticoagulation and corticosteroids were more frequently administered (both p < 0.01). Mortality and time to referral were also reduced (39.4% vs. 22.4%, p = 0.019 and 6 vs. 5 days, p = 0.014), while need for intubation didn't change. Hospitalization length was comparable, but the proportion of patients discharged home was higher during the 2nd period (28.2% vs. 55.4%, p = 0.001). CONCLUSIONS: Changing treatment paradigms and early referral might have reduced mortality in COVID-19 patients. The effects of specific therapeutic regimens needs further confirmation in future clinical studies.
Asunto(s)
COVID-19/terapia , Hospitalización , Terapia Respiratoria , Adulto , Anciano , Anticoagulantes/uso terapéutico , Antivirales/uso terapéutico , COVID-19/complicaciones , COVID-19/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Italia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estaciones del Año , Tasa de SupervivenciaRESUMEN
Radiological and functional sequelae of Coronavirus Disease 2019 (COVID-19) pneumonia are still poorly understood. This was a prospective, observational, physiological, cohort study on consecutive adult patients with COVID-19 pneumonia admitted in April-May 2020 in the high dependency respiratory unit of L. Sacco University Hospital in Milan (Italy). During hospitalization, patients underwent chest computed tomography (CT), blood gas analysis, spirometry, and lung diffusion capacity for carbon monoxide (DLco), which were repeated 6 weeks post-discharge. Chest CTs were individually read by two expert radiologists, that calculated the total severity score (TSS). Twenty patients completed the study (mean age 58.2 years, 70% males). During the acute phase, mean DLco, alveolar volume (VA), and vital capacity (VC) were 56.0 (16.3), 64.8 (14.0), and 71.7 (16.9) % predicted, respectively, and were inversely associated with PaO2/FiO2 ratio. Fifty percent of patients had a restrictive ventilatory pattern; mean TSS was 7.9 (4.0). At follow up, gas exchange parameters were normalized; consolidations persisted in 10% of cases, while DLco was <80% predicted in 65% of patients and was independently predicted by Log10D-dimer at admission (ß -18.675; 95%CI, -28.373--9.076; p = 0.001). In conclusion, functional abnormalities in COVID-19 pneumonia survivors can persist during follow up and are associated with the severity of the disease.
RESUMEN
Adenine phosphoribosyltransferase (APRT) deficiency is an autosomal recessive purine enzyme defect that results in the inability to utilize adenine, which consequently is oxidized by xanthine dehydrogenase to 2,8-dihydroxyadenine (2,8-DHA), an extremely insoluble substance eventually leading to crystalluria, nephrolithiasis, and kidney injury. We describe a case of APRT deficiency not diagnosed until the evaluation of a poorly functioning kidney transplant in a 67-year-old white woman. After the transplant, there was delayed transplant function, urine specimens showed crystals with unusual appearance, and the transplant biopsy specimen showed intratubular obstruction by crystals identified as 2,8-DHA using infrared spectroscopy. APRT enzymatic activity was undetectable in red blood cell lysates, and analysis of the APRT gene showed 1 heterozygous sequence variant, a duplication of T at position 1832. The patient was treated with allopurinol, 300 mg/d, and transplant function progressively normalized. Because patients with undiagnosed APRT deficiency who undergo kidney transplant may risk losing the transplant because of an otherwise treatable disease, increased physician awareness may hasten the diagnosis and limit the morbidity associated with this disease.
Asunto(s)
Adenina Fosforribosiltransferasa/deficiencia , Trasplante de Riñón , Túbulos Renales/metabolismo , Túbulos Renales/fisiopatología , Errores Innatos del Metabolismo/complicaciones , Complicaciones Posoperatorias/enzimología , Complicaciones Posoperatorias/etiología , Anciano , Cristalización , Femenino , Humanos , Errores Innatos del Metabolismo/diagnósticoRESUMEN
BACKGROUND: To date, the effects of COVID-19 pneumonia on health-related quality of life (HRQoL) and dyspnoea are unknown. METHODS: In a real-life observational study, 20 patients with COVID-19-related pneumonia received usual care plus erdosteine (300 mg twice daily) for 15 days after hospital discharge following local standard operating procedures. At discharge (T0) and on Day 15 (T1), participants completed the St George's Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale of dyspnoea during daily activity, the BORG scale for dyspnoea during exertion, and Visual Analogue Scale (VAS) for dyspnoea at rest. Paired t-tests compared scores at T0 and T1. RESULTS: The mean (SD) SGRQ total score decreased from 25.5 (15.5) at T0 to 16.9 (13.2) at T1 (p<0.01); 65% of patients achieved a clinically important change of ≥4 points. SGRQ domain scores (symptoms, activity, and impact) were also significantly reduced (all p<0.01). The mean (SD) VAS score decreased from 1.6 (1.7) to 1.4 (2.5); p<0.01. The mean mMRC score decreased significantly (p=0.031) and 30% of patients achieved a clinically important change of ≥1 point. The mean (SD) Borg score increased from 12.8 (4.2) to 14.3 (2.4); p<0.01. CONCLUSION: The present proof of concept study is the first to report HRQoL in patients with COVID-19. During 15 days after hospital discharge, patients reported significant improvements in HRQoL and dyspnoea at rest and during daily activities.
RESUMEN
OBJECTIVE: Patients with obstructive sleep apnea (OSA) have an altered control of breathing during wakefulness. Thus far, whether and how treatment with continuous positive airway pressure (CPAP) may restore these abnormalities has been poorly understood. The aim of this study was to investigate the long-term effects of CPAP on the breathing pattern, ventilatory drive (VDr), and chemoreceptor sensitivity in OSA patients. PATIENTS AND METHODS: This was a prospective, observational study, carried out in an academic sleep outpatient clinic. A total of 62 patients with OSA (mean age [SD], 51 [11] years) underwent polysomnography (PSG), breathing pattern assessment, mouth occlusion pressure, ventilatory response to hypoxemia (Ve/SaO2), and hypercapnia (Ve/PETCO2) before and after CPAP titration and during 12-month follow-up. A total of 48 age-matched healthy subjects served as controls. Patients with good (≥6 h/night) and poor (<6 h/night) compliance with CPAP were also compared. RESULTS: At baseline, VDr as well as thoracic and inspiratory impedances were greater in patients with OSA compared with controls and were reduced by CPAP treatment, starting from the night of titration (P < 0.01), especially in patients with good compliance with CPAP. Baseline Ve/SaO2 was higher in OSA patients (P < 0.05) and was progressively normalized during CPAP treatment (P < 0.001). The pathophysiological changes were mainly due to a reduction in tidal volume. The remaining breathing pattern parameters were unaltered by CPAP treatment and were similar between groups. CONCLUSION: In OSA patients, the mechanics of breathing are inefficient because of an imbalance of the VDr. Regular CPAP treatment improves the efficiency of the respiratory system and normalizes the hypoxemic stimulus.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Respiración , Apnea Obstructiva del Sueño/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Apnea Obstructiva del Sueño/fisiopatología , Resultado del TratamientoRESUMEN
Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies.
Asunto(s)
Óxido Nítrico/metabolismo , Psoriasis/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Pruebas Respiratorias/métodos , Comorbilidad , Humanos , Inflamación/epidemiología , Inflamación/metabolismo , Monitoreo Fisiológico/métodos , Psoriasis/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiologíaRESUMEN
We describe factors associated to renal infarction, clinical, instrumental and laboratoristic features, and therapeutic strategies too. This is an observational, review and polycentric study of cases in Nephrologic Units in Piedmont during 2013-2015, with diagnosis of renal infarction by Computed Tomography Angiography (CTA). We collected 48 cases (25 M, age 57±16i; 23 F age 70±18, p = 0.007), subdivided in 3 groups based on etiology: group 1: cardio-embolic (n=19) ; group 2: coagulation abnormalities (n= 9); group 3: other causes or idiopathic (n=20). Median time from symptoms to diagnosis, known only in 38 cases, was 2 days (range 2 hours- 8 days). Symptoms of clinical presentation were: fever (67%), arterial hypertension (58%), abdominal o lumbar pain (54%), nausea/vomiting (58%), neurological symptoms (12%), gross hematuria (10%). LDH were increased (>530 UI/ml) in 96% of cases (45 cases out of 47), PCR (>0.5 mg/dl) in 94% of cases (45 out of 48), and eGFR <60 ml/min in 56% of cases (27 out of 48). Comparison of the various characteristics of the three groups shows: significantly older age (p=0.0001) in group 1 (76±12 years) vs group 2 (54±17 years) and group 3 (56±17 years); significantly more frequent cigarette smoking (p = 0.01) in group 2 (67%; 5 cases out of 9) and group 3 (60%; 12 cases out of 20) than group 1 (17%). No case has been subjected to endovascular thrombolysis. In 40 out of 48 cases, anticoagulant therapy was performed after diagnosis: in 12 (32%) cases no treatment, in 12 cases (30%) heparin, in 8 cases (20%) low molecular weight heparin, in 4 cases (10%) oral anticoagulants, in 3 cases fondaparinux (7%), in 1 case (2%) dermatan sulfate. CONCLUSIONS: Although some characteristics may guide the diagnosis, latency between onset and diagnosis is still moderately high and is likely to affect timely therapy.
Asunto(s)
Infarto/epidemiología , Riñón/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Diagnóstico Tardío , Embolia/etiología , Femenino , Estudios de Seguimiento , Humanos , Infarto/etiología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombofilia/complicacionesAsunto(s)
Cadenas Ligeras de Inmunoglobulina/sangre , Enfermedades Renales/diagnóstico , Paraproteinemias/complicaciones , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/inmunología , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/complicacionesRESUMEN
BACKGROUND: COPD is a heterogeneous disease composed by two main phenotypes: bronchitis (COPDb) and emphysema (COPDe) with different clinical presentation, physiology, imaging, response to therapy and decline in lung function. The aim of this study is to evaluate whether nocturnal hypoxemic COPDb and COPDe have a different behaviour during sleep and the effect of nocturnal oxygen supplementation (nO2LT). MATERIALS AND METHODS: 75 COPDb and 120 COPDe were enrolled. All patients performed polysomnography, Pittsburgh and Maugeri Foundation Respiratory Failure questionnaire, and pulmonary function before and after six months of nO2LT. RESULTS: At baseline, compared to COPDb, COPDe have decreased sleep efficiency (SE) (67.5±6% vs. 76.9±3% p<0.05) and higher arousals (A/I) (18.1±3 event/h vs. 8.7±1 event/h p<0.05). Oxygen desaturation index (ODI) was increased during REM (7.1±1 event/h vs. 2.3±0.5 event/h p<0.05). nO2LT in COPDe improves SE (77±4% vs. 67.5±6% p<0.05) and decreases A/I (9±5 event/h vs. 18.1±3 event/h p<0.05). ODI during REM (3.5±2 event/h vs. 7.1±1 p<0.05) decreases and quality of life (QoL) improves (MFR-28 total 56±22 vs 45±20 p<0.05), due to an improvement in cognitive abilities (45±30 vs 33±31 p<0.05) and daily activities (61±29 vs 53±21 p>0.05). In COPDb nO2LT reduces ST90 (15±6% vs. 43±8% p<0.05) less than in COPDe (15±6% vs. 8±4% p<0.05); improves A/I (10±2 event/h vs. 8.7±1 p<0.05) and there is no evidence of an improvement in QoL. CONCLUSIONS: Six months of nO2LT improve quality of life in COPDe, not in COPDb. We found a difference in sleep quality between COPDe and COPDb.