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Introduction: Increasing reports of adverse effects have raised concerns about the Essure hysteroscopic sterilization method. Women suffering alleged complications of the Essure device often seek surgical removal. This study evaluated the quality of life (QoL) and postoperative outcomes in women undergoing Essure removal., Material and Methods: This observational case series included 95 women. Removal was performed by laparoscopic salpingectomy-cornuectomy, or hysterectomy with bilateral salpingectomy. QoL was assessed preoperatively and three months postoperatively by SF-36 questionnaires [correlated physical health score (PCS) and mental health scores (MCS)]. Symptoms evolution was collected at three months, and complications at one month., Results: Sixty-four laparoscopic salpingectomy-cornuectomies, 33 laparoscopic hysterectomies, and eight vaginal hysterectomies were performed. Four intraoperative complications occurred (one conversion from cornuectomy to laparoscopic hysterectomy, one skin burn, two bladder injuries). Seven postoperative complications occurred (Clavien Dindo, grade 1 or 2). All components of the preoperative QoL scores were lower than those of the general population. PCS scores were lower preoperatively than postoperatively [37.6 versus 50.7; p<0.001]. MCS scores were lower preoperatively than postoperatively [29 versus 52.4; p<0.001]. 71% of patients showed an improvement of at least 10% in both PCS and MCS scores. Systemic and gynecologic symptoms were more frequent before than after surgery (98% versus 50%; p<0.001 and 77% versus 20%; p<0.001 respectively)., Conclusions: Patients seeking Essure removal had an impaired preoperative QoL. They experienced a significant QoL improvement at three months post-operation. These findings will help clinicians to inform patients about their expected postoperative functional status and QoL., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Symptomatic isolated carotid artery occlusions (ICAO) can lead to disability, recurrent stroke, and mortality, but natural history and best therapeutic management remain poorly known. The objective of this study was to describe our cohort of ICAO patients with an initial medical management., Methods: We conducted a retrospective study including consecutive patients admitted to our Comprehensive Stroke Center for ICAO within 24 h after stroke onset between January 2016 and September 2018. Patients with immediate endovascular therapy (EVT) were excluded. Medical treatment was based on anticoagulation (delayed by 24 h if intravenous thrombolysis was performed). 'Rescue' EVT was considered if first-week neurological deterioration (FWND) occurred., Results: Fifty-six patients were included, with a median National Institutes of Health Stroke Scale (NIHSS) of 3. Eleven patients (20%) had FWND during the first week, four benefited from rescue EVT. A mismatch volume > 40 cc on initial perfusion imaging and FLAIR vascular hyperintensities were associated with FWND (p = 0.007 and p = 0.009, respectively). Thirty-eight patients (69%) had a good outcome (modified Rankin Scale mRS 0-2) at 3 months, 36 (69%) had an excellent outcome (mRS 0-1). Seventeen patients (38%) had carotid patency on 3-month control imaging. Recurrences occurred in six (13%) of the survivors (mean follow-up: 13.6 months)., Conclusion: Our results suggest that the prognosis of patients with acute ICAO was favorable with a medical strategy, albeit a substantial rate of FWND and recurrence. FWND was well predicted by a core-perfusion mismatch volume > 40 cc. Randomized controlled trials are necessary to assess the benefit of EVT in ICAO.

Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. Nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p < 0.001). Moreover, both biomarkers were higher in PPMS than in RRMS even if multivariate analysis only confirmed this difference for s-GFAP (130.3 ± 72.8 pg/ml vs 83.4 ± 41.1 pg/ml, p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis.

In patients with heart failure, some organizational and modifiable factors could be prognostic factors. We aimed to assess the association between the in-hospital care pathways during hospitalization for acute heart failure and the risk of readmission. This retrospective study included all elderly patients who were hospitalized for acute heart failure at the Universitary Hospital Lariboisière (Paris) during 2013. We collected the wards attended, length of stay, admission and discharge types, diagnostic procedures, and heart failure discharge treatment. The clinical factors were the specific medical conditions, left ventricular ejection fraction, type of heart failure syndrome, sex, smoking status, and age. Consistent groups of in-hospital care pathways were built using an ascending hierarchical clustering method based on a primary components analysis. The association between the groups and the risk of readmission at 1 month and 1 year (for heart failure or for any cause) were measured via a count data model that was adjusted for clinical factors. This study included 223 patients. Associations between the in-hospital care pathway and the 1 year-readmission status were studied in 207 patients. Five consistent groups were defined: 3 described expected in-hospital care pathways in intensive care units, cardiology and gerontology wards, 1 described deceased patients, and 1 described chaotic pathways. The chaotic pathway strongly increased the risk (p = 0.0054) of 1 year readmission for acute heart failure. The chaotic in-hospital care pathway, occurring in specialized wards, was associated with the risk of readmission. This could promote specific quality improvement actions in these wards. Follow-up research projects should aim to describe the processes causing the generation of chaotic pathways and their consequences.

Aims: Intra-aortic balloon pump (IABP) utilization was expected to be quickly abandoned following the IABP-shock trial and its class III, level B recommendation in the 2016 European Society of Cardiology (ESC) guidelines. The aim of this study was to evaluate the use of IABP compared with other mechanical support devices in a nationwide approach., Methods and Results: We conducted a retrospective study based on the French national hospital discharge database. All patients undergoing assist device implantation by IABP, extracorporeal membrane oxygenation (ECMO), or IMPELLA® from 2014 to 2018 (2 years before/2 years after the 2016 guidelines) were included. The primary endpoint was the incidence of IABP implantation over the years. Secondary endpoints were incidence of total assist device, ECMO, and IMPELLA® implantations. From 2014 to 2018, a total of 18 940 patients benefited from mechanical support by IABP (n = 6657, 35.2%), ECMO (n = 11 881, 62.7%), or IMPELLA® (n = 402, 2.1%) in France. The incidence of total mechanical support implantations (ECMO and IABP) was constant over the years. IABP implantations decreased progressively from 1725 implantations in 2014 to 996 in 2018 (-42%). By contrast, ECMO implantations increased progressively from 1919 implantations in 2014 to 2763 implantations in 2018 (+44%). IMPELLA® implantations remained stable over the years from 63 (1.7%) implantations in 2014 to 83 (2.1%) in 2018., Conclusions: In this nationwide real-life study, despite a significant decline in IABP implantations over the years since the ESC guidelines, this device remained used in clinical practice with around 1000 implantations in 2018. The size of centres was not strictly correlated with this use, suggesting differential uses depending on the local background., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Coronavirus disease 2019 (COVID-19) is likely to have significant implications for the cardiovascular care of patients. In most countries, containment has already started (on 17 March 2020 in France), and self-quarantine and social distancing are reducing viral contamination and saving lives. However, these considerations may only be the tip of the iceberg; most resources are dedicated to the struggle against COVID-19, and this unprecedented situation may compromise the management of patients admitted with cardiovascular conditions., Aim: We aimed to assess the effect of COVID-19 containment measures on cardiovascular admissions in France., Methods: We asked nine major cardiology centres to give us an overview of admissions to their nine intensive cardiac care units for acute myocardial infarction or acute heart failure, before and after containment measures., Results: Before containment (02-16 March 2020), the nine participating intensive cardiac care units admitted 4.8±1.6 patients per day, versus 2.6±1.5 after containment (17-22 March 2020) (rank-sum test P=0.0006)., Conclusions: We confirm here, for the first time, a dramatic drop in the number of cardiovascular admissions after the establishment of containment. Many hypotheses might explain this phenomenon, but we feel it is time raise the alarm about the risk for patients presenting with acute cardiovascular disease, who may suffer from lack of attention, leading to severe consequences (an increase in the number of ambulatory myocardial infarctions, mechanical complications of myocardial infarction leading to an increase in the number of cardiac arrests, unexplained deaths, heart failure, etc.). Similar consequences can be feared for all acute situations, beyond the cardiovascular disease setting., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Potentially avoidable hospitalizations are an indirect measure of access to primary care. However, the role and quality of primary care might vary by geographical location. The main objective was to assess the impact of primary care on geographic variations of potentially avoidable hospitalizations in Occitanie, France., Methods: We conducted a retrospective analysis of claims and socio-economic data for the French Occitanie region in 2014. In order to account for spatial heterogeneity, the region was split into two zones based on socio-economic traits: median pre-tax income and unemployment rate. Age- and sex-adjusted hospital discharge potentially avoidable hospitalization rates were calculated at the ZIP-code level. Demographic, socio-economic, and epidemiological determinants were retrieved, as well as data on supply of, access to and utilization of primary care., Results: 72% of PAH are attributable to two chronic conditions: chronic obstructive pulmonary disease and heart failure. In Zone 1, the potentially avoidable hospitalization rate was positively associated with premature mortality and with the number of specialist encounters by patients. It was negatively associated with the density of nurses. In Zone 2, the potentially avoidable hospitalization rate was positively associated with premature mortality, with access to general practitioners, and with the number of nurse encounters by patients. It was negatively associated with the proportion of the population having at least one general practitioner encounter and with the density of nurses., Conclusions: This study suggests that the role of primary care in potentially avoidable hospitalizations might be geography dependent.

Kabuki syndrome (KS, KS1: OMIM 147920 and KS2: OMIM 300867) is caused by pathogenic variations in KMT2D or KDM6A. KS is characterized by multiple congenital anomalies and neurodevelopmental disorders. Growth restriction is frequently reported. Here we aimed to create specific growth charts for individuals with KS1, identify parameters used for size prognosis and investigate the impact of growth hormone therapy on adult height. Growth parameters and parental size were obtained for 95 KS1 individuals (41 females). Growth charts for height, weight, body mass index (BMI) and occipitofrontal circumference were generated in standard deviation values for the first time in KS1. Statural growth of KS1 individuals was compared to parental target size. According to the charts, height, weight, BMI, and occipitofrontal circumference were lower for KS1 individuals than the normative French population. For males and females, the mean growth of KS1 individuals was -2 and -1.8 SD of their parental target size, respectively. Growth hormone therapy did not increase size beyond the predicted size. This study, from the largest cohort available, proposes growth charts for widespread use in the management of KS1, especially for size prognosis and screening of other diseases responsible for growth impairment beyond a calculated specific target size., (© 2019 Wiley Periodicals, Inc.)

Background: Essure is an effective method for hysteroscopic sterilization. Reports of adverse effects, the underlying mechanisms of which are unknown, have increased in recent years., Objective: The aim of the study was to determine whether there is a relationship between adverse events attributed to Essure and nickel sensitization., Methods: Patients presenting alleged adverse reactions to Essure were referred for nickel patch testing before removal. Data regarding medical history of nickel sensitization and symptoms attributed to Essure were collected. Dimethylglyoxime spot tests were performed on the explanted Essure. There was a follow-up at 3 months to evaluate whether there is improvement of the symptoms after Essure removal., Conclusions: Nickel sensitization via the classic delayed hypersensitivity pathway did not seem to be responsible for adverse events attributed to Essure. Among systemic symptoms reported, extracutaneous symptoms had the highest prevalence. Systemic contact dermatitis to nickel could not be ruled out in one case.

Background and Purpose- We aimed to further investigate the long-term outcomes after reversible cerebral vasoconstriction syndrome (RCVS). Methods- A longitudinal follow-up study was conducted in 173 RCVS patients. Results- Of the 172 patients who completed a mean follow-up of 9.2±3.3 years, 10 had a recurrent RCVS that was benign in all. Independent predictors of relapse were having a history of migraine and having exercise as a trigger for thunderclap headache during initial RCVS. After new delivery, the rate of postpartum RCVS was 9%. Conclusions- Overall, long-term outcome after RCVS is excellent.

Purpose: Kabuki syndrome (KS) (OMIM 147920 and 300867) is a rare genetic disorder characterized by specific facial features, intellectual disability, and various malformations. Immunopathological manifestations seem prevalent and increase the morbimortality. To assess the frequency and severity of the manifestations, we measured the prevalence of immunopathological manifestations as well as genotype-phenotype correlations in KS individuals from a registry., Methods: Data were for 177 KS individuals with KDM6A or KMT2D pathogenic variants. Questionnaires to clinicians were used to assess the presence of immunodeficiency and autoimmune diseases both on a clinical and biological basis., Results: Overall, 44.1% (78/177) and 58.2% (46/79) of KS individuals exhibited infection susceptibility and hypogammaglobulinemia, respectively; 13.6% (24/177) had autoimmune disease (AID; 25.6% [11/43] in adults), 5.6% (10/177) with ≥2 AID manifestations. The most frequent AID manifestations were immune thrombocytopenic purpura (7.3% [13/177]) and autoimmune hemolytic anemia (4.0% [7/177]). Among nonhematological manifestations, vitiligo was frequent. Immune thrombocytopenic purpura was frequent with missense versus other types of variants (p = 0.027)., Conclusion: The high prevalence of immunopathological manifestations in KS demonstrates the importance of systematic screening and efficient preventive management of these treatable and sometimes life-threatening conditions.

Three clinical scales (the Nociception Coma Scale adapted for Intubated patients [NCS-I], its Revised version [NCS-R-I], and the Behavioral Pain Scale [BPS]) and videopupillometry were compared for measuring pain in intubated, noncommunicating, critically ill, brain-injured patients. Pain assessment was performed before, during, just after, and 5 minutes after 3 procedures: the reference non-nociceptive procedure (assessment of the Richmond Agitation Sedation Scale) and 2 nociceptive procedures (turning and tracheal suctioning). The primary endpoint was construct validity (discriminant and criterion validation), determined by comparing pain measurements between different times/procedures. Secondary endpoints were internal consistency, inter-rater reliability, and feasibility. Fifty patients (54% women, median age 63 years [56-68]) were included 13 [7-24] days after brain injury (76% hemorrhagic or ischemic strokes). All tools increased significantly more (P < 0.001) during the nociceptive procedures vs the non-nociceptive procedure. The BPS was the only pain tool that did not increase significantly during the non-nociceptive procedure (P = 0.41), suggesting that it was the most discriminant tool. The BPS, NCS-I, and NCS-R-I were good predictors of nociception with areas under the curves ≥0.96, contrary to videopupillometry (area under the curve = 0.67). The BPS, NCS-I, and NCS-I-R had high inter-rater reliabilities (weighted kappa = 0.86, 0.82 and 0.84, respectively). Internal consistency was moderate (>0.60) for all pain scales. Factor analysis represented a majority of information on a first dimension, with motor domains represented on a second dimension. Scale feasibility was better for the NCS-I and NCS-R-I than for the BPS. In conclusion, the BPS, NCS-I, and NCS-R-I are valid, reliable, and acceptable pain scales for use in intubated critically ill, brain-injured patients, unlike videopupillometry. Future research requires tool design centered on domains of observation adapted to this very specific population.

The risk of skin cancer induced by photosensiting drugs is well known. An association between hydrochlorothiazide use and skin cancer has been recently published in some epidemiological studies. A systematic review of case-control or prospectives cohorts showed an increased risk of cutaneous squamous cell carcinoma even if some confusing factors such as tobacco smoking was not analysed. Results are more conflicting for basal cell carcinoma or melanoma. These results do not modify the benefit/risk ratio but should lead to propose preventive mesures: identification of high risk population, avoidance of this drug if possible in immunocompromised patients or with previous skin cancer, regular skin examination in case of long term use of hydrochlorothiazide., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)., Methods: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria., Results: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93% and 69%, respectively. Nodular enhancement ( ≥ 3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone ≥ 30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma., Conclusions: Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is ≥ 30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) emerged has a less invasive treatment than surgery for patients with degenerated bioprosthesis. However, few data are currently available regarding results of ViV versus TAVI in native aortic valve. We aimed to compare hemodynamic performances and 1-year outcomes between patients who underwent ViV procedure and patients who underwent non-ViV TAVI. This bicentric study included all patients who underwent aortic ViV procedure for surgical bioprosthetic aortic failure between 2013 and 2017. All patients who underwent TAVI were included in the analysis during the same period. ViV and non-ViV patients were matched with 1:2 ratio according to size, type of TAVI device, age (±5 years), sex, and STS score. Primary end point was hemodynamic performance including mean aortic gradient and aortic regurgitation at 1-year follow-up. A total of 132 patients were included, 49 in the ViV group and 83 in the non-ViV group. Mean age was 82.8 ± 5.9 years, 55.3% were female. Mean STS score was 5.2% ± 3.1%. Self-expandable valves were implanted in 78.8% of patients. At 1-year follow-up, aortic mean gradient was significantly higher in ViV group (18.1 ± 9.4 mm Hg vs 11.4 ± 5.4 mm Hg; p < 0.0001) and 17 (38.6%) patients had a mean aortic gradient ≥20 mm Hg vs 6 (7.8%) in the non-ViV group (p = 0.0001). Aortic regurgitation > grade 2 were similar in both groups (p = 0.71). In the ViV group, new pacemaker implantation was less frequent (p = 0.01) and coronary occlusions occurred only in ViV group (n = 2 [4.1%]). At 1-year follow-up, 3 patients (2.3%) died from cardiac cause, 1 (2.1%) in the ViV group vs 2 (2.4%) in the non-ViV group (p = 0.9). There was no stroke. In conclusion, compared with TAVI in native aortic stenosis, ViV appears as a safe and feasible strategy in patients with impaired bioprosthesis. As 1-year hemodynamic performances seem better in native TAVI procedure, long-term follow-up should be assessed to determinate the impact of residual stenosis on outcomes and durability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Patellofemoral (PF) degeneration plays an important role in knee function in the context of osteoarthritis. A specific evaluation of PF symptoms is needed to better understand the initial functional status of the knee before surgery. The aim of this study was to assess the validity of patient-related outcome measures (PROMs) for knee scores and PF scores in knee osteoarthritis., Hypothesis: PF scores are more reliable for evaluating anterior knee pain than global knee scores in the context of PF degeneration in osteoarthritis., Material and Methods: We performed a prospective single-center study of continuous patients included between January 2017 and January 2018 in our surgical department for total knee arthroplasty (TKA) for primary knee osteoarthritis. The analysis used global knee PROMs (KOOS and new IKS) and PF-specific PROMs (HSS Patella score, Kujala score and Lille score). Floor and ceiling effects were determined for each score based on tibiofemoral and PF degeneration on radiographic views; it was considered significant when greater than 15%., Results: We included 114 TKA procedures in 113 consecutive patients. According to the Iwano classification, no significant floor or ceiling effect was found for the PF preoperative scores (0-12%). The KOOS ADL and QOL scores were particularly affected by the ceiling and floor effects, whatever the patellofemoral degeneration (23-88%). In cases of severe PF degeneration (Iwano grade 3 and 4), no significant differences in the distribution of the functional scores were found., Discussion: Modern knee outcome scores used to evaluate knee function do not monitor PF degeneration and related symptoms in the context of knee osteoarthritis according to the Iwano classification. PF scores do not have a floor and ceiling effects even if the severity of the PF degeneration is difficult to identify preoperatively. Physicians should be aware of this effect on the preoperative functional evaluation before TKA., Level of Evidence: III, comparative prospective study., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri)., Methods: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed., Results: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death., Conclusion: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement., (© 2019 S. Karger AG, Basel.)

Background: The links between diet and the risk of dementia have never been studied considering the possibility of protopathic bias (i.e., reverse causation)., Objective: We aimed to examine the relationship between consumption frequency of meat, fish, fruits, and vegetables and long-term risk of dementia and Alzheimer's disease (AD), by taking into account this possibility., Methods: We analyzed data of 5,934 volunteers aged 65 and over from the Three-city study who were followed every 2 to 4 years for 12 years. Dietary habits were assessed at inclusion using a brief food frequency questionnaire. The presence of symptoms of dementia was investigated at each follow-up visit. To limit the risk of protopathic bias, a 4-year lag window between exposure and disease assessment was implemented by excluding from the analyses all dementia cases that occurred during the first four years after inclusion. Analyses were performed using a Cox proportional hazard model and were adjusted for socio-demographic, lifestyle, and health factors., Results: The average follow-up time was 9.8 years. During this period, 662 cases of dementia, including 466 of AD, were identified. After adjustment, only low meat consumption (≤1 time/week) was associated with an increased risk of dementia and AD compared with regular consumption (≥4 times/week) (HR = 1.58 95% CI = [1.17-2.14], HR = 1.67 95% CI = [1.18-2.37], respectively). No association was found between the consumption of fish, raw fruits, or cooked fruits and vegetables and the risk of dementia or AD., Conclusion: These findings suggest very low meat consumption increases the long-term risk of dementia and AD, and that a protopathic bias could have impacted finding from previous studies.

Geographic variation in admission to the intensive cardiac care unit (ICCU) might question about the efficiency and the equity of the healthcare system. The aim was to explain geographic variation in the rate of admission to ICCU for coronary artery disease (CAD) or heart failure (HF) in France.We conducted a retrospective study based on the French national hospital discharge database. All inpatient stays for CAD or HF with an admission to an ICCU in 2014 were included. We estimated population-based age and sex-standardized ICCU admission rates at the department level. We separately modeled the department-level admission rates for HF and CAD using generalized linear models.In all, 61,010 stays for CAD and 27,828 stays for HF had at least 1 ICCU admission. The ICCU admission rates were explained by the admission rate for CAD, by the diabetes prevalence, by the proportion of the population >75 years, and by the drive time to the ICCU.This work sheds light on the finding of substantial geographic variation in the ICCU admission rates for CAD and HF in France. This variation is explained by both the age and the health status of the population and also by the drive time to the closest ICCU for HF. Moreover, ICCU admission for HF might be more prone to unwarranted variations due to medical practice patterns.

Deficiency of adenosine deaminase 2 (DADA2) is a recently described autoinflammatory disorder. Genetic analysis is required to confirm the diagnosis. We aimed to describe the identifying symptoms and genotypes of patients referred to our reference centres and to improve the indications for genetic testing. DNA from 66 patients with clinically suspected DADA2 were sequenced by Sanger or next-generation sequencing. Detailed epidemiological, clinical and biological features were collected by use of a questionnaire and were compared between patients with and without genetic confirmation of DADA2. We identified 13 patients (19.6%) carrying recessively inherited mutations in ADA2 that were predicted to be deleterious. Eight patients were compound heterozygous for mutations. Seven mutations were novel (4 missense variants, 2 predicted to affect mRNA splicing and 1 frameshift). The mean age of the 13 patients with genetic confirmation was 12.7 years at disease onset and 20.8 years at diagnosis. Phenotypic manifestations included fever (85%), vasculitis (85%) and neurological disorders (54%). Features best associated with a confirmatory genotype included fever with neurologic or cutaneous attacks (odds ratio [OR] 10.71, p = 0.003 and OR 10.9, p < 0.001), fever alone (OR 8.1, p = 0.01), and elevated C-reactive protein (CRP) level with neurologic involvement (OR 6.63, p = 0.017). Our proposed decision tree may help improve obtaining genetic confirmation of DADA2 in the context of autoinflammatory symptoms. Prerequisites for quick and low-cost Sanger analysis include one typical cutaneous or neurological sign, one marker of inflammation (fever or elevated CRP level), and recurrent or chronic attacks in adults.

Purpose: Referrals to the Emergency Department can be distressing to patients with advanced cancer and may be a non-optimizing health care service. We aimed to describe the appropriateness and potential avoidability of Emergency Department referrals in a tertiary cancer care center where only physician referrals are allowed., Methods: We prospectively reviewed the electronic medical charts of patients consecutively checked into the Emergency Department in August 2015. The appropriateness of referrals was assessed using a nationally validated classification (Classification Clinique des Malades aux Urgences) and local criteria. Potentially avoidable referrals were assessed using international classifications (Institute for Healthcare Improvement State Action on Avoidable Rehospitalizations diagnostic tool according to Kosecoff's criteria) and local criteria., Results: We included 500 referrals related to 423 patients. The mean age was 59 years, and 74% of cancers were progressive. The referrals were appropriate in 61% of cases. They were deemed potentially avoidable "with a high likelihood" in 33.4% (CI95% [29.3-37.5]) of cases, potentially avoidable "with a moderate likelihood" in 14.4% (CI95% [11.3-17.5]) of cases, and "non-avoidable" in 52% (CI95% [47.6-56.4]) of cases. Opportunities to avoid referrals after an index stay involved this hospital stay or discharge process in 66 cases (28%), the follow-up period in 59 cases (25%), or both in 66 cases (28%)., Conclusions: Potentially avoidable ED referrals are common in patients with cancer. These potentially avoidable ED referrals underline the importance of several domains of care coordination.

Background: Defining individual educational, or learning, targets is part of the initial educational assessment in rehabilitation programs, but no data are available on how to achieve these goals., Objective: We aimed to evaluate whether educational objectives established with the patient as part of a functional spine restoration program integrating self-care sessions were met after the program and associated therapy outcomes., Methods: This retrospective study involved 104 patients with chronic low-back pain who participated in a self-care rehabilitation program between 2008 and 2012. The program included both physical and educational approaches to dealing with the condition. The main evaluation criterion was achieving the educational objectives established with the patient at 6 months. Secondary criteria were a return to work, pain intensity and impact on function, satisfaction with the program and implementation of physical activity and self-rehabilitation at 6 months., Results: At 6 months, 55% of the established educational objectives were fully achieved and satisfaction was close to 90%. Significantly, more patients were involved in a physical activity at 6 and 12 months and self-rehabilitation exercises at 6 months as compared with at inclusion. Overall, 43.4% were working at inclusion, 64.2% at 6 months and 58.2% at 12 months (P<0.05 compared with inclusion). Pain intensity and scores from the Quebec, Dallas and FABQ questionnaires had significantly decreased at 6 months., Conclusion: For more than half of the patients in this self-care rehabilitation program, educational objectives established with the patient were achieved, with a positive effect on returning to work and both professional and physical activities at 6 and 12 months., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background and Study Aims: Fistula is the main complication of laparoscopic sleeve gastrectomy (LSG), for which healing is difficult to achieve. The aims of the study were to evaluate the efficacy of interventional endoscopy for post-LSG fistula treatment, to evaluate various endoscopic techniques used and identify their complications, and to identify predictive factors of healing following endoscopic treatment., Patients and Methods: This retrospective multicenter study included patients with post-LSG fistula. Therapeutic procedures were evaluated, taking into account complications and healing times. Endoscopic procedures were considered to have promoted healing if no other surgical procedure was performed. Predictive factors of healing were identified by univariate and multivariate analysis., Results: A total of 110 patients were included, of whom 6 (5.5 %) healed spontaneously, 81 (73.6 %) healed following endoscopic treatment, and 19 (17.3 %) healed following surgery. Healing rates following endoscopic treatment were 84.4 % in the first 6 months of treatment (65/77), 52.4 % for treatment lasting 6 - 12 months (11/21), and 41.7 % after 12 months of treatment (5/12). A drainage procedure (surgical, endoscopic, or percutaneous) was performed in 92 patients (83.6 %). A total of 177 esogastric stents were placed in 88 patients (80.0 %). Surgical debridement, clip placement, glue sealing, and plug placement were also performed. Multivariate analysis identified four predictive factors of healing following endoscopic treatment: interval < 21 days between fistula diagnosis and first endoscopy (P = 0.003), small fistula (P = 0.01), interval between LSG and fistula ≤ 3 days (P = 0.01), no history of gastric banding (P = 0.04)., Conclusion: Endoscopic treatment facilitated healing of post-LSG fistula in 74 % of patients. Early endoscopic treatment increased the likelihood of success, and was most effective during the first 6 months of management. After this point, surgical treatment should be considered., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To evaluate the performance of functional MRI (FMRI) performed by general radiologists (GR) in detection of side-specific extracapsular extension (SSECE) prostate cancer (PCa)., Methods: We retrospectively analyzed 79 patients who underwent FMRI with pelvic phased array coil before radical prostatectomy (RP) performed at University Hospital (UH) of Nîmes. Twelve GR (including three from UH) interpreted the images during their daily practice. FMRI results were dichotomized as positive or negative and confronted to pathological reports for SSECE and side-specific seminal vesicle invasion (SSSVI), with calculation of diagnostic values. The influence of interval between biopsy and FMRI, diffusion-weighted sequence (DWS) and intensity of FMRI, on the diagnostic performance were assessed by Fisher's exact test., Results: A SSECE and a SSSVI were observed at FMRI and pathology respectively on 14 (8.8%) and 38 (24.1%) prostate lobes, and on six (3.8%) and seven (4.4%) prostate lobes. The sensitivity, specificity, positive and negative predictive values of FMRI for SSECE were respectively 24%, 96%, 64% and 80%; and for SSSVI were 14%, 97%, 17% and 96% respectively. The time between biopsy and FMRI, intensity of FMRI and DWS, did not influence the sensitivity and specificity of fMRI at Fisher test., Conclusion: This study found that preoperative prostate FMRI performed by GR has good specificity but poor sensitivity in predicting SSECE on pathological reports., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease., Objective: To describe the disease course of CLIPPERS., Design: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS., Setting: Academic research., Patients: Twelve patients with CLIPPERS., Main Outcome Measures: The therapeutic management of CLIPPERS was evaluated., Results: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy., Conclusions: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.

Fibroadenomas and breast growth disorders are the most common breast diseases in adolescent women. Assessment of breast disorders in this age group generally involves clinical evaluation through history and physical examination and when is needed ultrasonography. Due to the absence of breast cancer in adolescent women, it is easy to reassure women at the first consultation. Breast growth disorders can lead great psychological and physical embarrassment. Treatment consists of surgical procedures when the cosmetic defect is severe. According to the ANDI classification, small fibroadenomas are normal, clinical fibroadenomas are a mild aberration of the normal processes, and giant or multiple fibroadenomas are placed to the disease end of the spectrum. Fibroadenomas can be treated conservatively provided diagnosis is confident. Giant fibroadenomas are treated by surgical enucleation. Breast abscess is mainly due to the duct ectasia. In adolescence, ectasia has been described as an exaggeration of sinus duct development and can be considered as a variant of normality. Diseases of the adolescent breast are usually benign and their management are simple using medical strategy and more rarely surgical therapy., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To describe four cases of hepatic adenoma in adolescents and women with severe inherited bleeding disorders treated with norethisterone., Design: Case reports., Setting: Necker-Enfants Malades University Hospital, Paris, Department of Pediatric Endocrinology, Gynecology and Diabetes., Patient(s): Two adolescents and two young women with inherited platelet disorders, treated with high-dose norethisterone (10 to 20 mg/day) to induce amenorrhea., Intervention(s): Immediate cessation of norethisterone., Main Outcome Measure(s): Spontaneous regression of hepatic adenoma., Result(s): In four patients with inherited platelet disorders, hepatic adenoma developed at 14, 18, 22, and 24 years of age, respectively, during continuous norethisterone therapy started at 1.5, 2.5, 10.0, and 13.0 years of age, respectively. Life-threatening bleeding occurred in two patients. Immediate norethisterone discontinuation was followed by complete or nearly complete tumor regression within a few months., Conclusion(s): Our four cases strongly support a causal link between norethisterone treatment and hepatic adenoma. Continuous high-dose (10 to 20 mg/day) continuous norethisterone to treat menorrhagia in adolescents and young women with bleeding disorders is inadvisable. If other nortestosterone derivatives are needed, the patient should be closely monitored for the development of hepatic adenoma., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

FOXL2 mutations cause the autosomal dominant Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) that may be associated with premature ovarian failure (POF). However, little is known about the molecular mechanisms of FOXL2 actions in the human ovary. We conducted an extensive clinical, hormonal and ovarian histological study in two patients carrying a FOXL2 mutation associated with the typical eyelid malformations and infertility. This observational study was conducted at referral centres for POF. Histological and immunohistological studies were conducted on ovarian biopsies from two women with POF carrying a FOXL2 mutation resulting in putative polyalanine expansions of the protein. Abnormalities similar to those observed in mice with FOXL2 gene inactivation were present in the first patient's ovary, although the ovarian histology of the second patient was apparently normal. Different ovarian phenotypes, follicular defects and distribution of FOXL2 protein were observed in two patients carrying a FOXL2 mutation.

Objective: The efficacy and safety of height-limiting therapy with high-dose 17beta-oestradiol in girls with constitutionally tall stature (CTS) are controversial. We evaluated the effectiveness of high-dose 17beta-oestradiol in premenarchal girls with CTS treated until their bone age reached 14 years., Design: We retrospectively reviewed the medical records of the girls managed between 1989 and 2000 with high-dose 17beta-estradiol for CTS with a predicted final height greater than +3SDs., Patients: Twenty-six girls met our inclusion criteria. At baseline, mean chronological age was 12.06 +/- 1.51 years and mean height was 171.1 +/- 6.5 cm with a height standard deviation score of 4.5 +/- 0.24, and mean predicted final height was 183.0 +/- 4.2 cm. Treatment was stopped when bone age reached 14 years; mean treatment duration was 1.62 +/- 0.76 years., Measurements: The following were obtained at 6-month intervals: height, body weight, Tanner stage, bone age, plasma cholesterol and triglycerides, plasma glucose and side effects. A mailed questionnaire on final height and satisfaction was sent 2 years after treatment discontinuation (response rate, 24/26). Results Final height was significantly (P < 0.001) reduced, by 2.4 +/- 3.2 cm, as compared to predictions. High-dose 17beta-estradiol therapy decreased growth velocity and significantly increased skeletal maturation (P < 0.001). Linear growth after treatment discontinuation was 3.3 +/- 1.9 cm. No serious side effects were recorded. Most of the patients were satisfied with the treatment., Conclusion: High-dose 17beta-estradiol was moderately effective in reducing final height and should probably be reserved for selected patients, particularly as knowledge on potential long-term side effects is lacking.

Context: Localized breast lesions have been described in lupic or diabetic patients. However, the description of breast gigantomastia in women presenting with autoimmune diseases has not been reported., Setting: The study took place within the Department of Endocrinology and Reproductive Medicine, Necker Hospital, Paris, France., Patients: We describe eight patients with inflammatory gigantomastia, occurring in a context of immune-mediated diseases: myasthenia, chronic arthritis, or thyroiditis., Main Outcome Measures: Together with hormonal, immunological, and breast magnetic resonance imaging (MRI) evaluation, breast histology enabled us to perform immunocytochemical and indirect immunofluorescence studies. Control sera were obtained from patients with (n = 10) and without (n = 7) antinuclear antibodies., Results: Six of the eight patients developed gigantomastia either at puberty or during pregnancy. Neither a hormonal oversecretion nor a specific immunological pattern was observed. All patients except one presented antinuclear antibodies. Histological study revealed a diffuse, stromal hyperplasia and a severe atrophy of the lobules. A rarefaction of adipocytes was also noted, as previously suggested on MRI. There was a perilobular lymphocytic infiltrate made of CD3+ lymphocytes. Study of sera from five of six cases of gigantomastia showed a nuclear immunofluorescence pattern in normal mammary ductal and lobular glandular epithelium, as well as in kidney and intestine epithelial cells. In control sera, a nuclear signal was observed only when antinuclear antibodies were present., Conclusions: We suggest that breast tissue may be a target tissue in autoimmune diseases, this process being favored by the hormonal milieu. However, the precise mechanism of such association is not individualized. The fact that stromal hyperplasia is the main histological feature justifies the search for the involvement of growth factors in such a process.

Unlabelled: Severe genital bleeding during adolescence can occur in the event of thrombocytopenia related to chemotherapy. Preventive hormonal treatment to induce therapeutic amenorrhea is recommended by some clinicians. Nevertheless, the adverse effects of oestroprogestative treatment, such as thromboembolic risk or hepatic toxicity, could potentialize the adverse effects of some chemotherapies., Aim of the Study: To assess retrospectively the risk of genital bleeding associated with thrombocytopenia secondary to chemotherapy in a population of adolescent girls for whom therapeutic amenorrhea was induced or not., Patients and Methods: Among 140 girls, 12 to 18 years old, who were subjected to chemotherapy between 1991 and 1998, 24 girls presented at least one thrombocytopenic event (platelet level < 20 x 10(9) l(-1)) and were included., Results: Six out of 24 adolescent girls received hormonal therapy to induce amenorrhea. Only one bleeding event was observed, in a girl who had not received preventive oestroprogestative treatment. Vital prognosis was preserved. Furthermore, spontaneous amenorrhea occurring before chemotherapy was observed in 33% of the patients and permanent secondary ovarian insufficiency in 17% of the patients., Conclusion: The risk of genital bleeding among adolescent population at risk of chemotherapy-induced thrombocytopenia is low. The high frequency of amenorrhea, secondary to weight loss or to chemotherapy toxicity, should raise questions as to the usefulness of preventive oestroprogestative treatment.

Long cycles and excessive uterine bleeding are the most common menstrual disorders in adolescents. Long cycles usually result from a benign transitory functional disorder which spontaneously resolves within two to three years after menarche; however, this diagnosis can only be retained in the absence of hirsutism or galactorrhea as revealing symptoms of functional ovarian hyperandrogenism, polycystic ovary syndrome, late form of congenital adrenal hyperplasia or hyperprolactinemia; ovarian failure will be considered in case of isolated long cycles persisting more than two years after menarche. Excessive uterine bleeding usually occurs early after menarche. Although the main cause is functional, resulting from anovulation and the related absence of progesterone, coagulation disorders must always be excluded. Management of these disorders are described.

The clinical outcomes of seven girls presenting with pseudosexual precocity caused by isolated autonomous ovarian follicular cysts are presented. Six of the seven girls, aged 11 months to 6.9 years, had a unilateral ovarian cyst detected by ultrasound at the first acute episode. Plasma oestradiol was raised in only five of the cases, but all had a low response to luteinising hormone releasing hormone stimulation. Follow up lasted for up to eight years with recurrent episodes of variable frequency and severity in all seven patients. Evidence of McCune-Albright syndrome appeared later in only three patients. It could not be predicted from the initial symptoms or the clinical course. Mutations of the G(s)alpha protein leading to activation were investigated in the lymphocytes and ovarian and bone tissues of four patients. Only one patient showed a mutation in bone tissue. Close follow up with repeated searches for skeletal lesions remains necessary since the distribution of somatic mutations cannot be assessed by molecular studies. Most patients with recurrent ovarian cysts require a conservative approach.

To determine whether calbindin D9k (CaBP) is subject to posttranscriptional control, 6-wk-old Sprague Dawley-derived rats were fed one of three purified diets, 1.5% Ca and 3.0% Ca, mostly as carbonate, and 2.9% Ca, mostly as gluconate. Two weeks later, 5-cm segments of duodenum, jejunum, ileum, cecum and colon were obtained and analyzed for CaBP and CaBP-mRNA. Analysis of the steady-state distribution of CaBP-mRNA and of CaBP revealed a statistically significant (r = 0.95; P < 0.01) linear relationship between CaBP-mRNA and CaBP. When, however, animals that had been fed the 1.5% Ca diet received by intrajugular injection 1.2 nmol 1,25-dihydroxycholecalciferol [1.25-(OH)2-D3] and their CaBP-mRNA and CaBP were analyzed as a function of time after 1,25-(OH)2-D3 administration, the kinetic response of the two molecules differed. The CaBP-mRNA increased linearly by approximately 68% for 4 h after administration and then declined over the next 6 h to a concentration below the preinjection value. Thus, appearance and disappearance of CaBP-mRNA approximated 17% x h(-1). The CaBP, however, increased steeply to 80% above preinjection concentration until 2 h postinjection, i.e., at a rate of 40% x h(-1). Thereafter, CaBP decreased to 35% above the preinjection value between 5 and 10 h postinjection (2.5% x h(-1)). These findings are consistent with a 1,25-(OH)2-D3-mediated posttranscriptional regulation of CaBP concentrations, because the 1,25-(OH)2-D3-mediated increase in CaBP-mRNA is not reflected in an immediately changed CaBP level.

Objective: To determine the clinical characteristics of pubertal metrorrhagia and its treatment, depending on severity; to evaluate the frequency of etiologies and the influence of hemostatic abnormalities; and to describe severe pubertal metrorrhagia. Design, setting and participants. This retrospective study examined all the files (n = 105) of adolescents presenting for pediatric gynecology consultation at a children's hospital between January 1979 and June 1993., Results: The mean age of patients at the first consultation was 13 years. Metrorrhagia began in the year after the first menstrual period in 85% of cases. The causes were functional (83 cases), primary hemostatic disorder (14 cases), hemostatic disorder secondary to renal or hepatic disease (7 cases), or tumor (1 case). The cases were assigned to one of three groups, according to the severity of anemia; group I, mild anemia, hemoglobin Hb > 11 g%, 64 cases; group II, moderate anemia, Hb 8-11 g%, 23 cases; and group III, severe anemia, Hb < 8 g%, 18 cases. Of the 14 patients suffering from primary hemostatic disorders, 7 had been diagnosed before the onset of metrorrhagia; the disorder was revealed by the metrorrhagia in the remaining 7. Only 1 of these patients was severely anemic (known factor X deficiency). Four patients suffering from moderate von Willebrand's disease were discovered after specific tests; they were mildly or moderately anemic. The severe anemias (group III) all occurred during the first three periods. This group had functional disorders in 15 of 18 cases. Treatment continued to be required in 10 of 18 cases followed for more than 3 years. Treatment was progestin for group I and II patients or an estroprogestin, followed by a progestin, for group III. Curettage was never required., Conclusions: The most common cause of pubertal metrorrhagia is a functional disorder (80% of cases). Hemostatic disorders likely to cause severe menstrual hemorrhage were known before the age of menarche; these disorders must be controlled by hormone treatment begun before or at the time of the first menstrual period. Severe forms that arise during the initial three menstrual cycles are functional in most cases. These should be given a course of treatment lasting several years. There is a high risk of recurrence. Treatment is medical and hormonal in all cases.

To investigate the nonsaturable, paracellular pathway of intestinal Ca absorption, the luminal contents of 12-cm segments of the intestine of 8-wk-old male Sprague-Dawley rats were analyzed for pH, sojourn time and soluble and insoluble Ca over a 24-h period. The rats had been fed one of two high Ca diets for 2 wk: 1.5% Ca (diet group 3a) and 3.1% (diet group 5a). The pH of the small intestine increased from < 6.6 to > 8.0 from duodenum to ileum; transit time increased from 2.5 min in the duodenum to 58 min in the distal ileum, with the entire ileum accounting on the average for 74% of the transit time of 3 h. The amount of Ca solubilized throughout the intestine was 32 +/- 3.3 mumol in diet group 3a and 53 +/- 5.3 mumol in diet group 5a, i.e., 2.7% and 2.0% of the total luminal Ca. Because absorption by diet group 3a was 1.45 +/- 0.23 mmol/d and that by diet group 5a was 2.50 +/- 0.18 mmol/d, the amounts absorbed were 45.3 and 47.1 times greater than present in the lumen in soluble form at any one time. Thus, over a 24-h period, an average of 3.2% (46.2/1440) of the soluble Ca present in the lumen at any time was absorbed per min. Calculations involving the gradient between luminal and plasma Ca show that the rate of Ca diffusion from lumen to blood is < 2% of what it would be if the paracellular path were unrestricted. Thus, intestinal sojourn time, Ca solubility and mucosal permeability to Ca are factors that determine the rate of passive Ca absorption.

Six-week-old male rats were placed on two high calcium regimens: one with calcium carbonate and monobasic calcium phosphate, with calcium content increased via calcium carbonate; and another with calcium phosphate and calcium gluconate, with calcium gluconate the source of increased calcium. Animals fed the gluconate-containing diets absorbed 29% of the ingested calcium over the entire calcium intake range, whereas those fed the calcium carbonate diets absorbed 25% over an intake range of 225 to 450 mg Ca/d, but at calcium intakes above 450 mg Ca/d their absorption reached a plateau at approximately 109 mg/d. Active calcium transport decreased with increased calcium intake in both the calcium carbonate- and calcium gluconate-fed groups. Nonsaturable transport was unchanged as a result of increasing calcium intake and did not differ among the diet groups. Because the absorptive processes were unaffected by the calcium source, events in the lumen must have been responsible for the observed differences. Because phosphate is nearly 18 times more soluble than carbonate, very little calcium of calcium carbonate origin can have been solubilized in the presence of phosphate and this, we conclude, accounts for the limit on calcium absorption observed in diets high in calcium carbonate. Moreover, when intake is expressed as soluble calcium, absorption approaches 50%, the value expected when intestinal transit time (approximately 3 h) is multiplied by 16%/h, the experimental value of nonsaturable absorption.