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.

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.

[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.

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.

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.

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.

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.

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.

Association between timing of intensive care unit admission and outcomes for emergency department patients with community-acquired pneumonia.

OBJECTIVE: To compare the 28-day mortality and hospital length of stay of patients with community-acquired pneumonia who were transferred to an intensive care unit on the same day of emergency department presentation (direct-transfer patients) with those subsequently transferred within 3 days of presentation (delayed-transfer patients). DESIGN: Secondary analysis of the original data from two North American and two European prospective, multicenter, cohort studies of adult patients with community-acquired pneumonia. PATIENTS: In all, 453 non-institutionalized patients transferred within 3 days of emergency department presentation to an intensive care unit were included in the analysis. Supplementary analysis was restricted to patients without an obvious indication for immediate transfer to an intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The sample consisted of 138 delayed-transfer and 315 direct-transfer patients, among whom 150 (33.1%) were considered to have an obvious indication for immediate intensive care unit admission. After adjusting for the quintile of propensity score, delayed intensive care unit transfer was associated with an increased odds ratio for 28-day mortality (2.07; 95% confidence interval, 1.12-3.85) and a decreased odds ratio for discharge from hospital for survivors (0.53; 95% confidence interval, 0.39-0.71). In a propensity-matched analysis, delayed-transfer patients had a higher 28-day mortality rate (23.4% vs. 11.7%; p = 0.02) and a longer median hospital length of stay (13 days vs. 7 days; p < .001) than direct-transfer patients. Similar results were found after excluding the 150 patients with an obvious indication for immediate intensive care unit admission. CONCLUSIONS: Our findings suggest that some patients without major criteria for severe community-acquired pneumonia, according to the recent Infectious Diseases Society of America/American Thoracic Society consensus guideline, may benefit from direct transfer to the intensive care unit. Further studies are needed to prospectively identify patients who may benefit from direct intensive care unit admission despite a lack of major severity criteria for community-acquired pneumonia based on the current guidelines.

Risk stratification of early admission to the intensive care unit of patients with no major criteria of severe community-acquired pneumonia: development of an international prediction rule.

INTRODUCTION: To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3. METHODS: Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support). RESULTS: A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population. CONCLUSIONS: The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions.

Prediction of myocardial infarction risk in older patients with acute coronary syndrome.

PURPOSES: To identify bedside variables that aid in diagnosis of acute coronary syndrome (ACS) and might facilitate rapid triage of patients aged > or = 65 years. BASIC PROCEDURES: Prospective, observational study of consecutive patients aged > or = 65 years with suspicion of ACS presenting to our emergency department (ED). Patients' medical characteristics were collected at baseline and during a 1-month follow-up period. We identified variables independently associated with ACS by multivariate analyses and bootstrapping techniques. MAIN FINDINGS: Among 399 patients, 124 (31.1%) received a diagnosis of ACS (61 acute myocardial infarction, 63 unstable angina). We surveyed multiple clinical and ECG variables to develop a predictive model which included the following variables: male sex, history of coronary artery disease, typical chest pain, dyspnea, epigastric pain, pathological Q-wave, ST-segment elevation (area under the receiver operating characteristic curve (AUC) 0.79, 95% confidence interval 0.71 to 0.82). With the addition of cardiac troponin I to the model the AUC increased to 0.83 (0.79 to 0.88). We used these findings to create the Heart Attack Risk for aged Patient (HARP) scale. Our data suggest that patients with a low HARP score might be safely managed without further testing. PRINCIPAL CONCLUSIONS: A model based on variables easily available at ED presentation from history, physical examination, and electrocardiography, can help ED physicians to identify seniors at very low risk of ACS.

A case of POEMS syndrome treated by autologous hematopoietic stem-cell transplantation.

BACKGROUND: A 55-year-old woman with no remarkable medical history presented to a neurology ward with a 17-week history of rapidly progressive gait difficulties that confined her to a wheelchair. INVESTIGATIONS: Electroneuromyography, immunoelectrophoresis, bone radiography, lesion-targeted bone-marrow examination, blood tests. DIAGNOSIS: Neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. MANAGEMENT: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation.

Routine use of the Pneumonia Severity Index for guiding the site-of-treatment decision of patients with pneumonia in the emergency department: a multicenter, prospective, observational, controlled cohort study.

BACKGROUND: Although the Pneumonia Severity Index (PSI) has been extensively validated, little is known of the impact of its routine use as an aid to site-of-treatment decisions for patients with pneumonia who present to emergency departments (EDs). METHODS: A prospective, observational, controlled cohort study of patients with pneumonia was conducted in 8 EDs that used the PSI (PSI-user EDs) and 8 EDs that did not use the PSI (PSI-nonuser EDs) in France. The outcomes examined included the proportion of "low-risk" patients (PSI risk classes I-III) treated as outpatients, all-cause 28-day mortality, admission of inpatients to the intensive care unit, and subsequent hospitalization of outpatients. RESULTS: Of the 925 patients enrolled in the study, 472 (51.0%) were treated at PSI-user EDs, and 453 (49.0%) were treated at PSI-nonuser EDs; 449 (48.5%) of all patients were considered to be at low risk. In PSI-user EDs, 92 (42.8%) of 215 patients at low risk were treated as outpatients, compared with 56 (23.9%) of 234 patients at low risk in PSI-nonuser EDs. The adjusted odds ratios for outpatient treatment were higher for patients in PSI risk classes I and II who were treated in PSI-user EDs, compared with PSI-nonuser EDs (adjusted odds ratio, 7.0 [95% confidence interval, 2.0-25.0] and 4.6 [95% confidence interval, 1.3-16.2], respectively), whereas the adjusted odds ratio did not differ by PSI-user status among patients in risk class III or among patients at high risk. After adjusting for pneumonia severity, mortality was lower in patients who were treated in PSI-user EDs; other safety outcomes did not differ between patients treated in PSI-user and PSI-nonuser EDs. CONCLUSIONS: The routine use of the PSI was associated with a larger proportion of patients in PSI risk classes I and II who had pneumonia and who were treated in the outpatient environment without compromising their safety.

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.