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1.
Sci Rep ; 13(1): 6013, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-37045983

RESUMEN

Two successive COVID-19 flares occurred in Switzerland in spring and autumn 2020. During these periods, therapeutic strategies have been constantly adapted based on emerging evidence. We aimed to describe these adaptations and evaluate their association with patient outcomes in a cohort of COVID-19 patients admitted to the hospital. Consecutive patients admitted to the Geneva Hospitals during two successive COVID-19 flares were included. Characteristics of patients admitted during these two periods were compared as well as therapeutic management including medications, respiratory support strategies and admission to the ICU and intermediate care unit (IMCU). A mutivariable model was computed to compare outcomes across the two successive waves adjusted for demographic characteristics, co-morbidities and severity at baseline. The main outcome was in-hospital mortality. Secondary outcomes included ICU admission, Intermediate care (IMCU) admission, and length of hospital stay. A total of 2'983 patients were included. Of these, 165 patients (16.3%, n = 1014) died during the first wave and 314 (16.0%, n = 1969) during the second (p = 0.819). The proportion of patients admitted to the ICU was lower in second wave compared to first (7.4 vs. 13.9%, p < 0.001) but their mortality was increased (33.6% vs. 25.5%, p < 0.001). Conversely, a greater proportion of patients was admitted to the IMCU in second wave compared to first (26.6% vs. 22.3%, p = 0.011). A third of patients received lopinavir (30.7%) or hydroxychloroquine (33.1%) during the first wave and none during second wave, while corticosteroids were mainly prescribed during second wave (58.1% vs. 9.1%, p < 0.001). In the multivariable analysis, a 25% reduction of mortality was observed during the second wave (HR 0.75; 95% confidence interval 0.59 to 0.96). Among deceased patients, 82.3% (78.2% during first wave and 84.4% during second wave) died without beeing admitted to the ICU. The proportion of patients with therapeutic limitations regarding ICU admission increased during the second wave (48.6% vs. 38.7%, p < 0.001). Adaptation of therapeutic strategies including corticosteroids therapy and higher admission to the IMCU to receive non-invasive respiratory support was associated with a reduction of hospital mortality in multivariable analysis, ICU admission and LOS during the second wave of COVID-19 despite an increased number of admitted patients. More patients had medical decisions restraining ICU admission during the second wave which may reflect better patient selection or implicit triaging.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/terapia , Centros de Atención Terciaria , Suiza/epidemiología , Hospitalización , Tiempo de Internación , Unidades de Cuidados Intensivos , Mortalidad Hospitalaria , Estudios Retrospectivos
2.
BMJ Case Rep ; 15(2)2022 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-35217557

RESUMEN

Mesalazine is often used as first-line therapy for ulcerative colitis. Several reports have pointed to systemic adverse reactions associated with this drug. Most have evoked a drug-induced hypersensitivity syndrome, while some have described lupus syndromes but with limited clinical and varied biological features. A 75-year-old man presented with fever, dyspnoea, chest pain, polyarthralgia, and myalgia, following mesalazine introduction. Clinical symptoms and low-titre positive antihistone antibodies disappeared after mesalazine withdrawal without recourse to steroids. Pericardial effusion and 8F-fluorodeoxyglucose uptake on positron emission tomography/CT scan, and glomerular haematuria and proteinuria also disappeared. Cytokine-lymphocyte transformation tests showed a strong sensitisation pattern with interleukin-5 production. This case advances our knowledge of the mechanism of mesalazine-induced adverse effects, namely via drug-induced hypersensitivity with lupus manifestations, which we are the first to report.


Asunto(s)
Colitis Ulcerosa , Síndrome de Hipersensibilidad a Medicamentos , Preparaciones Farmacéuticas , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Humanos , Masculino , Mesalamina/efectos adversos
3.
Geroscience ; 44(2): 573-583, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34993763

RESUMEN

Platelet aggregation has been associated with COVID-19 pathogenesis. In older patients hospitalized for SARS-CoV-2 pneumonia, we aimed to investigate the association between aspirin use before admission and the risk of in-hospital all-cause mortality. We performed a retrospective international cohort study in five COVID-19 geriatric units in France and Switzerland. Among 1,357 consecutive hospitalized patients aged 75 or older and testing positive for SARS-CoV-2, we included 1,072 with radiologically confirmed pneumonia. To adjust for confounders, a propensity score for treatment was created, and stabilized inverse probability of treatment weighting (SIPTW) was applied. To assess the association between aspirin use and in-hospital 30-day mortality, SIPTW-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed. Of the 1047 patients with SARS-CoV-2 pneumonia and median age 86 years, 301 (28.7%) were taking aspirin treatment before admission. One hundred forty-seven (34.3%) patients who had taken aspirin died in hospital within 1 month vs 118 patients (30.7%) without aspirin. After SIPTW, aspirin treatment was not significantly associated with lower mortality (adjusted hazard ratio: 1.10 [0.81-1.49], P = .52). Moreover, patients on aspirin had a longer hospital stay and were more frequently transferred to the intensive care unit. In a large multicenter cohort of older inpatients with SARS-CoV-2 pneumonia, aspirin use before admission did not appear to be associated with an improved prognosis.


Asunto(s)
COVID-19 , Neumonía , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Estudios de Cohortes , Humanos , Pacientes Internos , Estudios Retrospectivos , SARS-CoV-2
4.
J Gerontol A Biol Sci Med Sci ; 77(4): e115-e123, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34272847

RESUMEN

BACKGROUND: It is uncertain whether antibiotic therapy should be started in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. We aimed to investigate the association between early antibiotic therapy and the risk of in-hospital mortality in older patients. METHODS: We performed a retrospective international cohort study (ANTIBIOVID) in 5 coronavirus disease 2019 geriatric units in France and Switzerland. Among 1357 consecutive patients aged 75 or older hospitalized and testing positive for SARS-CoV-2, 1072 had radiologically confirmed pneumonia, of which 914 patients were still alive and hospitalized at 48 hours. To adjust for confounders, a propensity score for treatment was created, and stabilized inverse probability of treatment weighting (SIPTW) was applied. To assess the association between early antibiotic therapy and in-hospital 30-day mortality, SIPTW-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS: Of the 914 patients with SARS-CoV-2 pneumonia, median age of 86, 428 (46.8%) received antibiotics in the first 48 hours after diagnosis. Among these patients, 147 (34.3%) died in hospital within 1 month versus 118 patients (24.3%) with no early antibiotic treatment. After SIPTW, early antibiotic treatment was not significantly associated with mortality (adjusted hazard ratio, 1.23; 95% confidence interval, 0.92-1.63; p = .160). Microbiologically confirmed superinfections occurred rarely in both groups (bacterial pneumonia: 2.5% vs 1.5%, p = .220; blood stream infection: 8.2% vs 5.2%, p = .120; Clostridioides difficile colitis: 2.4% vs 1.0%, p = .222). CONCLUSIONS: In a large multicenter cohort of older inpatients with SARS-CoV-2 pneumonia, early antibiotic treatment did not appear to be associated with an improved prognosis.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Anciano , Antibacterianos/uso terapéutico , Estudios de Cohortes , Mortalidad Hospitalaria , Humanos , Estudios Retrospectivos
5.
Clin Nutr ; 41(12): 3085-3088, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-33933295

RESUMEN

BACKGROUND & AIMS: To investigate the association of nutritional risk at admission with the length of hospital stay (LOS) and mortality in older patients with COVID-19. METHODS: Retrospective monocentric study in an acute geriatric hospital. Data were collected after an extensive review of medical records and the nutritional risk was assessed according to the Nutritional Risk Screening (NRS). Univariate and multivariate (adjusted for age, sex and comorbidity burden) Cox proportional-hazard and linear regression models were used to investigate the association with the above-mentioned outcomes. RESULTS: Of a total of 245 patients (86.1 ± 6.4 yrs), 50.6% had a severe nutritional risk with an NRS≥5/7 at admission. Lower BMI, cognitive impairment and swallowing disorders were more prevalent in the patients with a higher NRS. A NRS≥5 was not associated with mortality but prolonged by more than 3 days the LOS among the 173 survivors (ß 3.69; 0.71-6.67 95% CI; p = 0.016), with a discharge rate delayed by 1.8 times (HR 0.55; 0.37-0.83 95% CI; p = 0.101). CONCLUSION: Among the survivors of COVID-19 in an acute geriatric hospital, a NRS ≥5 at admission was associated with a longer LOS, but not with mortality.


Asunto(s)
COVID-19 , Desnutrición , Humanos , Anciano , Tiempo de Internación , Evaluación Nutricional , Desnutrición/diagnóstico , Estado Nutricional , Estudios Retrospectivos , COVID-19/epidemiología , Hospitales
6.
J Clin Med ; 10(23)2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34884199

RESUMEN

BACKGROUND: We investigated the prognostic significance of visceral and subcutaneous adiposity in octogenarians with COVID-19. METHODS: This paper presents a monocentric retrospective study that was conducted in acute geriatric wards with 64 hospitalized patients aged 80+ who had a diagnosis of COVID-19 and who underwent a chest CT scan. A quantification of the subcutaneous, visceral, and total fat areas was performed after segmentations on the first abdominal slice caudal to the deepest pleural recess on a soft-tissue window setting. Logistic regression models were applied to investigate the association with in-hospital mortality and the extent of COVID-19 pneumonia. RESULTS: The patients had a mean age of 86.4 ± 6.0 years, and 46.9% were male, with a mean BMI of 24.1 ± 4.4Kg/m2 and mortality rate of 32.8%. A higher subcutaneous fat area had a protective effect against mortality (OR 0.416; 0.183-0.944 95% CI; p = 0.036), which remained significant after adjustments for age, sex, and BMI (OR 0.231; 0.071-0.751 95% CI; p = 0.015). Inversely, higher abdominal circumference, total fat area, subcutaneous fat area, and visceral fat were associated with worse COVID-19 pneumonia, with the latter presenting the strongest association after adjustments for age, sex, and BMI (OR 2.862; 1.523-5.379 95% CI; p = 0.001). CONCLUSION: Subcutaneous and visceral fat areas measured on chest CT scans were associated with prognosis in octogenarians with COVID-19.

7.
J Clin Med ; 10(7)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33804890

RESUMEN

BACKGROUND: Mechanisms and causes of death in older patients with SARS-CoV-2 infection are still poorly understood. METHODS: We conducted in a retrospective monocentric study, a clinical chart review and post-mortem examination of patients aged 75 years and older hospitalized in acute care and positive for SARS-CoV-2. Full body autopsy and correlation with clinical findings and suspected causes of death were done. RESULTS: Autopsies were performed in 12 patients (median age 85 years; median of 4 comorbidities, mainly hypertension and cardiovascular disease). All cases showed exudative or proliferative phases of alveolar damage and/or a pattern of organizing pneumonia. Causes of death were concordant in 6 cases (50%), and undetected diagnoses were found in 6. Five patients died from hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), five had another associated diagnosis and two died from alternative causes. Deaths that occurred in the second week were related to SARS-CoV-2 pneumonia whereas those occurring earlier were related mainly to heart failure and those occurring later to complications. CONCLUSIONS: Although COVID-19 hypoxemic respiratory failure was the most common cause of death, post-mortem pathological examination revealed that acute decompensation from chronic comorbidities during the first week of COVID-19 and complications in the third week contributed to mortality.

8.
Medicine (Baltimore) ; 100(11): e25060, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725981

RESUMEN

RATIONALE: The phrenic nerve stimulation (PNS) is a rare complication after pacemaker setting. We report a case report that describes this complication and how it can be resolved. PATIENT CONCERNS: An 88-year-old man presented himself to the emergency geriatric unit with intermittent painless abdominal contraction due to phrenic nerve stimulation. He has a history of transcatheter aortic valve implantation with cardiac resynchronization therapy pacemaker due to persistent left bundle branch block. DIAGNOSES: All the usual causes for abdominal spasms were eliminated and the possibility of a link with the pacemaker was considered. The phrenic nerve stimulation is a rare complication of a pacemaker implantation. It can be clinically nonrelevant but challenging to diagnose for those not familiar with cardiac devices technology. INTERVENTIONS: Initial setting was an axis of stimulation between distal left ventricular (LV) and right ventricular. It was changed to LV and D1-M2. OUTCOMES: This noninvasive procedure managed to eradicate the involuntary abdominal spasms. LESSONS: PNS could be challenging to diagnose for those not familiar with cardiac devices technology but easy to manage with noninvasive methods.


Asunto(s)
Bloqueo de Rama/cirugía , Terapia de Resincronización Cardíaca/efectos adversos , Marcapaso Artificial/efectos adversos , Nervio Frénico/lesiones , Anciano de 80 o más Años , Humanos , Masculino , Reemplazo de la Válvula Aórtica Transcatéter
9.
BMC Geriatr ; 21(1): 52, 2021 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-33446113

RESUMEN

BACKGROUND: Stroke in the course of coronavirus disease (COVID-19) has been shown to be associated with more severe respiratory symptoms and higher mortality, but little knowledge in this regard exists on older populations. We aimed to investigate the incidence, characteristics, and prognosis of acute stroke in geriatric patients hospitalized with COVID-19. METHODS: A monocentric cross-sectional retrospective study of 265 older patients hospitalized with COVID-19 on acute geriatric wards. 11/265 presented a stroke episode during hospitalization. Mortality rates and two-group comparisons (stroke vs non-stroke patients) were calculated and significant variables added in logistic regression models to investigate stroke risk factors. RESULTS: Combined ischemic and hemorrhagic stroke incidence was 4.15%. 72.7% of events occurred during acute care. Strokes presented with altered state of consciousness and/or delirium in 81.8%, followed by a focal neurological deficit in 45.5%. Ischemic stroke was more frequently unilateral (88.8%) and localized in the middle cerebral artery territory (55.5%). Smoking and a history of previous stroke increased by more than seven (OR 7.44; 95% CI 1.75-31.64; p = 0.007) and five times (OR 5.19; 95% CI 1.50-17.92; p = 0.009), respectively, the risk of stroke. Each additional point in body mass index (BMI) reduced the risk of stroke by 14% (OR 0.86; 95% CI 0.74-0.98; p = 0.03). In-hospital mortality (32.1% vs. 27.3%; p > 0.999) and institutionalization at discharge (36.4% vs. 21.1%; p = 0.258) were similar between patients with and without stroke. CONCLUSION: Incident stroke complicating COVID-19 in old patients was associated with active smoking, previous history of stroke, and low BMI. Acute stroke did not influence early mortality or institutionalization rate at discharge.


Asunto(s)
COVID-19 , Coronavirus , Accidente Cerebrovascular , Anciano , Estudios Transversales , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología
10.
J Am Med Dir Assoc ; 21(11): 1546-1554.e3, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33138936

RESUMEN

OBJECTIVE: To determine predictors of in-hospital mortality related to COVID-19 in older patients. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients aged 65 years and older hospitalized for a diagnosis of COVID-19. METHODS: Data from hospital admission were collected from the electronic medical records. Logistic regression and Cox proportional hazard models were used to predict mortality, our primary outcome. Variables at hospital admission were categorized according to the following domains: demographics, clinical history, comorbidities, previous treatment, clinical status, vital signs, clinical scales and scores, routine laboratory analysis, and imaging results. RESULTS: Of a total of 235 Caucasian patients, 43% were male, with a mean age of 86 ± 6.5 years. Seventy-six patients (32%) died. Nonsurvivors had a shorter number of days from initial symptoms to hospitalization (P = .007) and the length of stay in acute wards than survivors (P < .001). Similarly, they had a higher prevalence of heart failure (P = .044), peripheral artery disease (P = .009), crackles at clinical status (P < .001), respiratory rate (P = .005), oxygen support needs (P < .001), C-reactive protein (P < .001), bilateral and peripheral infiltrates on chest radiographs (P = .001), and a lower prevalence of headache (P = .009). Furthermore, nonsurvivors were more often frail (P < .001), with worse functional status (P < .001), higher comorbidity burden (P < .001), and delirium at admission (P = .007). A multivariable Cox model showed that male sex (HR 4.00, 95% CI 2.08-7.71, P < .001), increased fraction of inspired oxygen (HR 1.06, 95% CI 1.03-1.09, P < .001), and crackles (HR 2.42, 95% CI 1.15-6.06, P = .019) were the best predictors of mortality, while better functional status was protective (HR 0.98, 95% CI 0.97-0.99, P = .001). CONCLUSIONS AND IMPLICATIONS: In older patients hospitalized for COVID-19, male sex, crackles, a higher fraction of inspired oxygen, and functionality were independent risk factors of mortality. These routine parameters, and not differences in age, should be used to evaluate prognosis in older patients.


Asunto(s)
Infecciones por Coronavirus/mortalidad , Mortalidad Hospitalaria/tendencias , Neumonía Viral/mortalidad , Anciano , Anciano de 80 o más Años , Betacoronavirus , COVID-19 , Comorbilidad , Femenino , Predicción , Geriatría , Humanos , Masculino , Pandemias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , SARS-CoV-2
11.
Rev Med Suisse ; 16(714): 2153-2155, 2020 Nov 11.
Artículo en Francés | MEDLINE | ID: mdl-33174695

RESUMEN

The older patients have been the most affected by the SARS-CoV-2 pandemic. In addition, this infection has been responsible for high mortality rate in this population. In this article we wanted to describe the clinical findings we encountered in older people with COVID-19 and share some of the issues and challenges we faced during the COVID-19 pandemic.


Les personnes âgées ont été les plus touchées par la pandémie de SARS-CoV-2. De plus, cette infection a été responsable d'une mortalité élevée au sein de cette population. Dans cet article, nous avons souhaité décrire les particularités cliniques du Covid-19 que nous avons constatées chez les patients âgés et faire part de plusieurs enjeux et défis auxquels nous avons été confrontés au cours de la pandémie de Covid-19.


Asunto(s)
Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Evaluación Geriátrica , Geriatría , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Anciano , Betacoronavirus/patogenicidad , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , SARS-CoV-2 , Suiza/epidemiología
12.
J Clin Med ; 9(8)2020 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-32708003

RESUMEN

Patients with type 1 Gaucher disease (GD1) present thrombocytopenia, anemia, organomegaly, and bone complications. Most experts consider that the less aggressive forms do not require specific treatment. However, little is known about the disease course of these forms. The objective of this cross-sectional retrospective study was to compare the clinical, radiological, and laboratory characteristics of patients with less severe GD1 at diagnosis and at the last evaluation to identify features that might lead to potential complications. Non-splenectomized and never-treated patients (19 women and 17 men) were identified in the French Gaucher Disease Registry (FGDR). Their median age was 36.6 years (2.4-75.1), and their median follow-up was 7.8 years (0.4-32.4). Moreover, 38.7% were heterozygous for the GBA1 N370S variant, and 22.6% for the GBA1 L444P variant. From diagnosis to the last evaluation, GD1 did not worsen in 75% of these patients. Some parameters improved (fatigue and hemoglobin concentration), whereas platelet count and chitotriosidase level remained stable. In one patient (2.7%), Lewy body dementia was diagnosed at 46 years of age. Bone lesion onset was late and usually a single event in most patients. This analysis highlights the genotypic heterogeneity of this subgroup, in which disease could remain stable and even improve spontaneously. It also draws attention to the possible risk of Lewy body disease and late onset of bone complications, even if isolated, to be confirmed in larger series and with longer follow-up.

13.
Age Ageing ; 49(5): 883-884, 2020 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-32147707

RESUMEN

Statins are widely prescribed in the treatment of hypercholesterolemia. While their efficacy in the secondary prevention of vascular events is proven, their safety profile in older patients with multiple co-morbidities and polypharmacy remains questionable. Although rare, antihydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is a severe adverse effect of statins, manifesting as myalgias, proximal muscle weakness, muscle cell necrosis and rhabdomyolysis. We report an uncommon case of an autopsy-proven anti-HMGCR necrotising myopathy predominately affecting pharyngeal muscles in an older patient, leading to dysphagia, pneumonia and death within 3 weeks from onset. Clinicians should screen for dysphagia in any patient with suspected anti-HMGCR myopathy, order an anti-HMGCR antibody titre and consider prompt immunosupressive therapy.


Asunto(s)
Enfermedades Autoinmunes , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedades Musculares , Miositis , Anciano , Autoanticuerpos , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/diagnóstico , Músculos Faríngeos
14.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-32069933

RESUMEN

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40-9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.


Asunto(s)
Enfermedad de Gaucher/sangre , Inmunoglobulinas/sangre , Paraproteinemias/sangre , Adulto , Estudios de Cohortes , Femenino , Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad de Gaucher/patología , Humanos , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/complicaciones , Mieloma Múltiple/patología , Paraproteinemias/complicaciones , Paraproteinemias/tratamiento farmacológico , Paraproteinemias/patología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , gammaglobulinas/administración & dosificación
15.
J Clin Med ; 8(4)2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-30991716

RESUMEN

Diagnosing pneumonia in emergency departments is challenging because the accuracy of symptoms, signs and laboratory tests is limited. As a confirmation test, chest X-ray has significant limitations and is outperformed by CT-scan. However, obtaining a CT-scan in all cases of suspected pneumonia has significant drawbacks. We used a cohort of 200 consecutive elderly patients admitted to the hospital for suspected pneumonia to build a simple prediction score, which was used to determine indication for performing a CT-scan. The reference diagnosis was adjudicated by experts considering all available data, including evolution until discharge and CT scan in all patients. Results were externally validated in a second cohort of 319 patients. Pneumonia was confirmed in 133 patients (67%). Area under the receiver operator curve (AUROC) of physician evaluation was 0.55 (0.46-0.64). The score incorporated four variables independently predicting confirmed pneumonia: male gender, acute cough, C-reactive protein >70 mg/L, and urea <7 mmol/L. AUROC of the score was 0.68 (95% confidence interval (CI) 0.60-0.76). When a CT-scan was obtained for patients at low or intermediate predicted risk (108 patients, 54% of the cohort), AUROC was 0.71 (0.63-0.80) and 0.69 (0.64-0.74) in the derivation and validation cohort, respectively. A simple prediction score for pneumonia had moderate accuracy and could guide the performance of a CT-scan.

16.
J Clin Med ; 8(2)2019 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-30744043

RESUMEN

Type 1 Gaucher disease is a rare genetic lysosomal disorder due to acid betaglucosidase deficiency. The main features are thrombocytopenia, anemia, hepatosplenomegaly and complex skeletal disease. Complications include pulmonary hypertension, cirrhosis and splenic infarction; comorbidities, such as autoimmune phenomena, B-cell malignancies and Parkinson disease also occur. Visceral aneurysms have been only rarely noted in Gaucher disease. We report the retrospective data from patients with Gaucher disease type 1 and splenic arterial aneurysm. We describe the different outcomes of a giant splenic arterial aneurysm in five patients with type 1 Gaucher disease and discuss the main possible pathophysiological explanations. Aneurysms of the splenic artery are rare in Gaucher disease but are probably greatly under-reported.

17.
Clin Pharmacokinet ; 58(4): 469-482, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30128966

RESUMEN

BACKGROUND AND OBJECTIVES: Intravenous imiglucerase enzyme replacement therapy for Gaucher disease type 1 administered every 2 weeks is at variance with the imiglucerase plasma half-life of a few minutes. We hypothesized that studying the pharmacokinetics of imiglucerase in blood Gaucher disease type 1 monocytes would be more relevant for understanding enzyme replacement therapy responses. METHODS: Glucocerebrosidase intra-monocyte activity was studied by flow cytometry. The pharmacokinetics of imiglucerase was analyzed using a population-pharmacokinetic model from a cohort of 31 patients with Gaucher disease type 1 who either started or were receiving long-term treatment with imiglucerase. RESULTS: A pharmacokinetic analysis of imiglucerase showed a two-compartment model with a high peak followed by a two-phase exponential decay (fast phase half-life: 0.36 days; slow phase half-life: 9.7 days) leading to a median 1.4-fold increase in glucocerebrosidase intra-monocyte activity from the pre-treatment activity (p = 0.04). In patients receiving long-term treatment, for whom the imiglucerase dose per infusion was chosen on the basis of disease aggressiveness/response, imiglucerase clearance correlated with the administered dose. However, the residual glucocerebrosidase intra-monocyte activity value was dose independent, suggesting that the maintenance of imiglucerase residual activity is patient specific. Endogenous pre-treatment glucocerebrosidase intra-monocyte activity was the most informative single parameter for distinguishing patients without (n = 10) and with a clinical indication (n = 17) for starting enzyme replacement therapy (area under the receiver operating characteristic curve: 0.912; 95% confidence interval 0.8-1; p < 0.001), as confirmed also by a factorial analysis of mixed data. CONCLUSION: This study provides novel pharmacokinetic data that support current imiglucerase administration regimens and suggests the existence of a glucocerebrosidase activity threshold related to Gaucher disease type 1 aggressiveness. These findings can potentially improve Gaucher disease type 1 management algorithms and clinical decision making.


Asunto(s)
Enfermedad de Gaucher/metabolismo , Glucosilceramidasa/metabolismo , Monocitos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Terapia de Reemplazo Enzimático , Femenino , Enfermedad de Gaucher/tratamiento farmacológico , Glucosilceramidasa/farmacocinética , Glucosilceramidasa/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Medicina de Precisión , Adulto Joven
18.
J Hematol ; 8(3): 121-124, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32300455

RESUMEN

BACKGROUND: Gaucher disease is a rare inborn error of lysosomal metabolism, characterized by lysosomal storage of the ß-glucosylceramide. Bleedings observed in type-1 Gaucher disease (GD1) are commonly attributed to a low platelet count, but they can also occur when the platelet count is normal or slightly low. Abnormal platelet function has been described and deficiencies in coagulation factors too, such as factors II, V, VII, VIII, IX, X, XI, XII, and von Willebrand factor. However, studies are few in number, involving few patients and having varying conclusions. The aim of this study was to analyze clotting factor deficiencies in a larger cohort of French patients with GD1. METHODS: This is an observational national study. The coagulation parameters were collected during routine GD1 monitoring and described retrospectively. RESULTS: We highlighted low levels of various coagulation factors in 46% of the patients with GD1. The most frequent coagulation abnormalities encountered were factor V, X, XI, and XII deficiencies. Deficits were usually mild and coagulation abnormalities tended to be more frequent in non-splenectomized patients. CONCLUSIONS: In conclusion, frequent and varied coagulation abnormalities were found in a high proportion of GD1 patients.

19.
Medicine (Baltimore) ; 97(42): e12871, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30335001

RESUMEN

RATIONALE: Eosinophilic pleural effusion in elderly patients is most commonly due to malignancies and infections. PATIENT CONCERNS: In rare cases, pleural eosinophilia is associated with connective tissue disease. DIAGNOSES: Presence of Hargraves cells, also called lupus erythematosus (LE) cells (polynuclear cells that have engulfed denatured nuclear material), was a key point of American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) until 1997. Now replaced by serology for autoantibodies, LE cells characterization remains useful in guiding the diagnostic strategy towards autoimmune diseases. INTERVENTIONS: An 82-year-old woman complained about anorexia, weight loss, fatigue, and mild night fever. Clinical examination disclosed a left pleural effusion without parenchymal lesion on high contrast thoraco-abdomino-pelvic computed tomography scan. A thoracocentesis revealed an exudate with eosinophilia. Direct cytological examination showed LE cells. SLE was rapidly considered. Antinuclear antibodies were subsequently found in the serum and in the pleural effusion. Anti-nucleosome antibodies were also present without antiphospholipid antibodies. Her condition rapidly improved after initiation of prednisone and hydroxychloroquine. OUTCOMES: Six months later, the patient had no particular complain, clinical examination was strictly normal biological parameter were in normal range. LESSONS: The assessment of an eosinophilic pleural effusion allowed to find LE cells, which rapidly suggested the diagnosis of SLE, and early initiation of appropriate treatment. LE cells are no longer a criterion for the diagnosis of SLE, but their presence in serosa is most helpful in guiding the diagnostic strategy, and specifically in atypical forms often seen in older patients.


Asunto(s)
Lupus Eritematoso Sistémico/diagnóstico , Neutrófilos/inmunología , Derrame Pleural/diagnóstico , Eosinofilia Pulmonar/diagnóstico , Anciano de 80 o más Años , Anticuerpos Antinucleares/sangre , Autoanticuerpos/sangre , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Neutrófilos/patología , Derrame Pleural/etiología , Derrame Pleural/inmunología , Derrame Pleural/patología , Eosinofilia Pulmonar/etiología , Eosinofilia Pulmonar/inmunología , Eosinofilia Pulmonar/patología
20.
Eur Respir J ; 51(5)2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29650558

RESUMEN

The diagnosis of pneumonia is challenging. Our objective was to assess whether low-dose computed tomography (LDCT) modified the probability of diagnosing pneumonia in elderly patients.We prospectively included patients aged over 65 years with a suspicion of pneumonia treated with antimicrobial therapy (AT). All patients had a chest radiograph and LDCT within 72 h of inclusion. The treating clinician assessed the probability of pneumonia before and after the LDCT scan using a Likert scale. An adjudication committee retrospectively rated the probability of pneumonia and was considered as the reference for diagnosis. The main outcome was the difference in the clinician's pneumonia probability estimates before and after LDCT and the proportion of modified diagnoses which matched the reference diagnosis (the net reclassification improvement (NRI)).A total of 200 patients with a median age of 84 years were included. After LDCT, the estimated probability of pneumonia changed in 90 patients (45%), of which 60 (30%) were downgraded and 30 (15%) were upgraded. The NRI was 8% (NRI event (-6%) + NRI non-event (14%)).LDCT modified the estimated probability of pneumonia in a substantial proportion of patients. It mostly helped to exclude a diagnosis of pneumonia and hence to reduce unnecessary AT.


Asunto(s)
Neumonía/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Comorbilidad , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Probabilidad , Estudios Prospectivos , Curva ROC , Suiza
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