[Allogeneic haematopoietic stem cell transplantation induced remission of periarteritis nodosa associated with azacytidine-refractory myelodysplastic syndrome]. / Mise en rémission par allogreffe de cellules souches hématopoïétiques d'une péri artérite noueuse associée à un syndrome myélodysplasique réfractaire à l'azacytidine.

INTRODUCTION: Periarteritis nodosa (PAN) is a vasculitis affecting medium-vessel and may be associated with myelodysplastic syndrome. This association needs a simultaneous treatment of the vascular and the hematological disease. However limited data are available on the benefit of hematological treatment, and in particular allogeneic stem cell transplantation, in this situation. CASE REPORT: A 32-year-old patient with refractory periarteritis nodosa and simultaneous myelodysplastic syndrome, was treated with chemotherapy followed by hematopoietic stem cell allograft. The symptoms relating to PAN improved, allowing to decrease the dose of prednisone down to 5mg/d. However, a hematological relapse occurred two months later leading to the patient's death. CONCLUSION: Hematopoietic stem cell allograft may represent a therapeutic option in the management of severe or refractory autoimmune diseases when the hematological indication is retained.

Urine concentration impairment in sickle cell anemia: genuine nephrogenic diabetes insipidus or osmotic diuresis?

The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule.NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria.

A study of 28 pregnant women with sickle cell disease and COVID-19: elevated maternal and fetal morbidity rates.

Not available.

[Management of the adult with sickle cell disease]. / Prise en charge de l'adulte drépanocytaire.

Sickle cell disease is a chronic disease with multisystemic complications. Follow-up requires specialised and multidisciplinary care. The consultation allows for the screening of complications.

Sickle cell disease and COVID-19 in pregnant women.

INTRODUCTION: The effect of coronavirus disease (COVID-19) on pregnancy outcome in women with sickle cell disease (SCD) is unknown. OBJECTIVES: To analyze the severity of the SARS-CoV-2 infection in pregnant women with SCD and its impact on pregnancy. METHODS: This retrospective cohort study included SCD pregnant women tested positive for COVID-19 between March 2020 - February 2021. The primary endpoint was the severity of the COVID-19 infection. Secondary endpoints were pregnancy complications and fetal outcomes. RESULTS: During the study period among 82 pregnant women with SCD, 8 have presented symptoms suggestive of COVID-19 and were tested positive. A common mild clinical presentation was observed in 6 women (75%), one woman was asymptomatic and one required oxygen. The latter was admitted to the Intensive Care Unit and a cesarean section was performed in the context of an ongoing vaso-occlusive crisis and acute chest syndrome together with incidental preeclampsia. Labor was induced in another patient who developed a vaso-occlusive crisis after COVID-19 remission. Fetal outcomes were good with an average Apgar score of 10 and normal umbilical blood pH at birth. Two newborns were small-for-gestational-age as expected on the ultrasound follow-up before occurrence of COVID-19. CONCLUSION: COVID-19 infection in our population of pregnant women with SCD had typical presentation and rarely triggered a sickle cell crisis or other complications. Fetal outcomes were good and did not seem to be directly influenced by the SARS-CoV-2 virus. Further studies are required to confirm these observations as compared to the population of women with SCD without COVID-19 infection.

Hemodynamic and biological correlates of glomerular hyperfiltration in sickle cell patients before and under renin-angiotensin system blocker.

Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (< 700 dynes/s/cm-5) in 38% of cases. mGFR association with CI and SVR were significant at baseline (respectively ρ: 0.44, p = 0.008 and ρ: - 0.37, p = 0.02) and under ACEI (p = 0.007 and 0.01 respectively), in accordance with previous data showing that hyperfiltration was linked to an increased glomerular perfusion and a glomerulomegaly rather than increased capillary hydrostatic pressure. Of notice, after adjustment on CI, mGFR remained associated with reticulocyte count and albuminuria under ACEI (p = 0.006 and 0.02 respectively). Our results suggest that hyperfiltration is tightly linked to an increased cardiac output which may account for an increased renal blood flow. Chronic hemolysis could be a relevant factor accounting for hyperfiltration potentially acting on glomerular enlargement which appears as a key factor. Our data suggest that cardiac output assessment is a relevant tool in the routine management and monitoring of SCA nephropathy.

Score Predicting Acute Chest Syndrome During Vaso-occlusive Crises in Adult Sickle-cell Disease Patients.

BACKGROUND: Vaso-occlusive crisis (VOC), hallmark of sickle-cell disease (SCD), is the first cause of patients' Emergency-Room admissions and hospitalizations. Acute chest syndrome (ACS), a life-threatening complication, can occur during VOC, be fatal and prolong hospitalization. No predictive factor identifies VOC patients who will develop secondary ACS. METHODS: This prospective, monocenter, observational study on SS/S-ß0thalassemia SCD adults aimed to identify parameters predicting ACS at Emergency-Department arrival. The primary endpoint was ACS onset within 15days of admission. Secondary endpoints were hospitalization duration, morphine consumption, pain evaluation, blood transfusion(s) (BT(s)), requiring intensive care and mortality. FINDINGS: Among 250 VOCs included, 247 were analyzed. Forty-four (17.8%) ACSs occurred within 15 (median [IQR] 3 [2, 3]) days post-admission based on auscultation abnormalities; missing chest radiographs excluded three patients. Comparing ACS to VOC, respectively, median hospital stay was longer 9 [7-11] vs 4 [3-7] days (p<0.0001), 7/41 (17%) vs 1/203 (0.5%) required intensive care (p<0.0001), and 20/41 (48.7%) vs 6/203 (3%) required BTs (p<0.0001). No patient died. The multivariate model retained reticulocyte and leukocyte counts, and spine and/or pelvis pain as being independently associated with ACS; the resulting ACS-predictive score's area under the ROC was 0.840 [95% CI 0.780-0.900], 98.8% negative-predictive value and 39.5% positive-predictive value for the real ACS incidence. INTERPRETATION: The ACS-predictive score is simple, easily applied and could change VOC management and therapeutic perspectives. Assessed ACS risk could lead to earlier discharges or close monitoring and rapid medical intensification to prevent ACS.

S100B blood level measurement to exclude cerebral lesions after minor head injury: the multicenter STIC-S100 French study.

BACKGROUND: S100B protein measurement in blood is proposed to exclude the presence of computed tomography (CT) lesions after minor head injury (MHI). We aimed to validate S100B as an accurate and valuable screening tool for MHI diagnosis in a large multicenter study, as well as: 1) to evaluate whether a second S100B blood level determination 3 h after the first one would be informative; 2) to compare the bioclinical performances of the two commercially available automated methods of measurement of S100B for the screening of patients. METHODS: Four thousand and thirty MHI subjects were enrolled in a prospective observational multicenter study; results for serum S100B measurement determined within 3 h after the clinical event (H0) then at H3 were compared to that of cranial CT scans performed with 6 h following the presentation to emergency department. Both the Diasorin and the Roche Diagnostics assays were systematically performed. RESULTS: Cerebral lesions on CT scan were identified with sensitivity and negative-predictive value (NPV) of 96.3% and 99.4% (Diasorin, 1 dissonant case), and of 100% and 100% (Roche Diagnostics, no dissonant case). Sensitivity and NPV at H3 appeared lower than those at H0, due to the rapid decrease in S100B levels. CONCLUSIONS: Serum S100B level on admission of patients with MHI is an accurate and useful screening tool to exclude intracranial lesions. Performing a second late S100B level determination is not informative. The two automated immunoassays appear usable in a similar manner, although the two methods are not interchangeable.

Outcomes of early, late, and no admission to the intensive care unit for patients hospitalized with community-acquired pneumonia.

OBJECTIVES: The objective was to compare outcomes associated with early, late, and no admission to the intensive care unit (ICU) for patients hospitalized with community-acquired pneumonia (CAP). METHODS: This was a post hoc analysis of the original data from the Emergency Department Community-Acquired Pneumonia (EDCAP) and Pneumocom-1 prospective multicenter cohort studies of adult patients hospitalized with CAP. Propensity score-adjusted analysis was used to compare 28-day mortality and hospital length of stay (LOS) for 199, 144, and 2,215 patients with early (i.e., ICU admission on the day of emergency department [ED] presentation), late, and no ICU admission. RESULTS: Unadjusted 28-day mortality rates were 13.1, 19.4, and 5.7% for early, late, and no ICU admissions, respectively (p < 0.001). After adjusting for quintile of propensity score, the odds of 28-day mortality were higher for late ICU admissions relative to early ICU admissions (odds ratio [OR] = 2.63; 95% confidence interval [CI] = 1.42 to 4.90), and no ICU admissions (OR = 3.40; 95% CI = 2.11 to 5.48), but did not differ between early and no ICU admissions (OR = 1.29; 95% CI = 0.79 to 2.09). The median hospital LOS was 10 days for early (interquartile range [IQR] = 7 to 18), 15 days for late (IQR 9 to 23), and 6 days (IQR 4 to 9) for no ICU admissions (p < 0.001). CONCLUSIONS: This study suggests that late but not early admission to the ICU is associated with higher 28-day mortality for patients hospitalized with CAP. Patients admitted to the ICU have longer hospital LOS in comparison to those managed on the wards, particularly if they are admitted late to the ICU.

Serum sodium abnormalities during nonexertional heatstroke: incidence and prognostic values.

BACKGROUND: Although heatstroke is often associated with dehydration, the clinical significance of serum sodium abnormalities in patients with heat-related illness during heat wave has been poorly documented. METHOD: We evaluated 1263 patients (age, 82±15 years; body temperature, 40.1°C+1.2°C) admitted to emergency departments during the August 2003 heat wave in Paris, having a core temperature greater than 38.5°C and measurement of serum sodium concentrations. Patients were classified according to our previously described risk score of death. RESULTS: Hyponatremia (<135 mmol/L) was reported in 409 (32%) and hypernatremia (>145 mmol/L) in 220 patients (17%). One-year survival was significantly decreased in patients with hypernatremia (45%; P=.004) but not in those with hyponatremia (58%; P=.86) as compared with patients with serum sodium concentration in the reference range (57%). Using Cox regression, only hypernatremia was an independent prognostic factor (hazard ratio, 1.35; 95% confidence interval, 1.09-1.36) when risk score was taken into account. Using logistic regression, 2 variables were independently associated with hyponatremia (heatstroke severity score and blood urea nitrogen-creatinine ratio<100). Conversely, 5 variables were independently associated with hypernatremia (living in an institution, dementia, serum creatinine>120 µmol/L, a blood urea nitrogen-creatinine ratio >100, and absence of long-term diuretic intake). CONCLUSIONS: Serum sodium abnormalities are frequently observed in patients with a nonexertional heatstroke during heat wave; however, only hypernatremia should be considered as an independent risk factor of death. Rapid measurement of serum sodium concentration is mandatory to appropriately guide electrolyte resuscitation.

Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave.

INTRODUCTION: The prognostic value of cardiac troponin I (cTnI) in patients having a heat-related illness during a heat wave has been poorly documented. METHODS: In a post hoc analysis, we evaluated 514 patients admitted to emergency departments during the August 2003 heat wave in Paris, having a core temperature >38.5 degrees C and who had analysis of cTnI levels. cTnI was considered as normal, moderately elevated (abnormality threshold to 1.5 ngxmL-1), or severely elevated (>1.5 ngxmL-1). Patients were classified according to our previously described risk score (high, intermediate, and low-risk of death). RESULTS: Mean age was 84 +/- 12 years, mean body temperature 40.3 +/- 1.2 degrees C. cTnI was moderately elevated in 165 (32%) and severely elevated in 97 (19%) patients. One-year survival was significantly decreased in patients with moderate or severe increase in cTnI (24 and 46% vs 58%, all P < 0.05). Using logistic regression, four independent variables were associated with an elevated cTnI: previous coronary artery disease, Glasgow coma scale <12, serum creatinine >120 micromolxL-1, and heart rate >110 bpm. Using Cox regression, only severely elevated cTnI was an independent prognostic factor (hazard ratio 1.93, 95% confidence interval 1.35 to 2.77) when risk score was taken into account. One-year survival was decreased in patients with elevated cTnI only in high risk patients (17 vs 31%, P = 0.04). CONCLUSIONS: cTnI is frequently elevated in patients with non-exertional heat-related illnesses during a heat wave and is an independent risk factor only in high risk patients where severe increase (>1.5 ngxmL-1) indicates severe myocardial damage.

Prognostic factors in non-exertional heatstroke.

PURPOSE: To identify the prognostic factors associated with mortality in heat-related illness. METHODS: Multi-center observational cohort-study in 16 emergency departments (ED) belonging to the teaching hospital network of the Paris area. The cohort comprised all patients admitted to one of the EDs during the August 2003 heat wave in Paris and having a core temperature >38.5 degrees C. Baseline clinical and biological data in ED, patient's course and 1-year survival rate were recorded. Potential prognostic factors associated with death were assessed by Cox proportional-hazards analysis. RESULTS: A total of 1,456 patients were included. Mean age was 79 +/- 19 years. Critically ill conditions were noted in 391 patients (27%), but only 72 (5%) were admitted into an intensive care unit. The survival rate was 57% at 1 year as compared to an expected 90% (P < 0.001). Nine independent prognostic factors were identified: previous treatment with diuretics, living in an institution, age >80 years, cardiac disease, cancer, core temperature >40 degrees C, systolic arterial pressure <100 mmHg, Glasgow coma scale <12 and transportation to hospital by ambulance. We defined three risk groups: low, intermediate and high risk, with a 1-year survival rate of 85, 61 and 18%, respectively. CONCLUSIONS: We observed a low survival rate and developed a risk score based on easily obtained variables that may be useful to clinicians managing casualties from future heat waves.

A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults.

Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.