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Islet transplantation is one of the most efficient cell therapies used in clinics and could treat a large proportion of patients with diabetes. However, it is limited by the high requirement of pancreas necessary to provide the sufficient surviving islet mass in the hepatic tissue and restore normoglycaemia. Reduction in organ procurement requirements could be achieved by extrahepatic transplantation using a biomaterial that enhances islet survival and function. We report a plasma-supplemented hydroxypropyl methylcellulose (HPMC) hydrogel, engineered specifically using a newly developed technique for intra-omental islet infusion, known as hOMING (h-Omental Matrix Islet filliNG). The HPMC hydrogel delivered islets with better performance than that of the classical intrahepatic infusion. After the validation of the HPMC suitability for islets in vivo and in vitro, plasma supplementation modified the rheological properties of HPMC without affecting its applicability with hOMING. The biomaterial association was proven to be more efficient both in vitro and in vivo, with better islet viability and function than that of the current clinical intrahepatic delivery technique. Indeed, when the islet mass was decreased by 25% or 35%, glycaemia control was observed in the group of plasma-supplemented hydrogels, whereas no regulation was observed in the hepatic group. Plasma gelation, observed immediately post infusion, decreased anoïkis and promoted vascularisation. To conclude, the threshold mass for islet transplantation could be decreased using HPMC-Plasma combined with the hOMING technique. The simplicity of the hOMING technique and the already validated use of its components could facilitate its transfer to clinics. STATEMENT OF SIGNIFICANCE: One of the major limitations for the broad deployment of current cell therapy for brittle type 1 diabetes is the islets' destruction during the transplantation process. Retrieved from their natural environment, the islets are grafted into a foreign tissue, which triggers massive cell loss. It is mandatory to provide the islets with an 3D environment specifically designed for promoting isletimplantation to improve cell therapy outcomes. For this aim, we combined HPMC and plasma. HPMC provides suitable rheological properties to the plasma to be injectable and be maintained in the omentum. Afterwards, the plasma polymerises around the graft in vivo, thereby allowing their optimal integration into their transplantation site. As a result, the islet mass required to obtain glycaemic control was reduced by 35%., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Carbonate apatites are sought as a bone substitute due to their biocompatibility and excellent resorbability. The present study deals with Cowrie's shell derived powder (CSDP) as natural biomaterial for bone regenerative medicine. Structural and physicochemical analysis showed that Cowrie's shells, presenting brick and mortar microstructures, were mainly composed of aragonite crystals, which were converted into poorly crystalline B-type carbonate apatite once soaked, at 37 °C, in simulated body fluid for 7 days, reflecting bioactive features. Cytotoxic assays showed that CSDP boosted human stem cell proliferation over the study time compared to nacre derived powder (NDP), used as positive control. Human stem cells adopted a flattened morphology and established physical contact with CSDP, signature of a good biocompatibility. Thus, these results suggested that CSDP presents a great interest for bone regenerative medicine, and could be a useful and versatile carrier/scaffold for bone tissue engineering or a raw material for 3D printed orthopedic devices., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hydroxyapatite (HA) enriched with strontium and boron ions was synthesized using two different methods: the precipitation method (Sr,B-HAw) and the dry method (Sr,B-HAd). Additionally, for the sake of comparison, the "pure" unsubstituted HA was prepared together with HAs substituted only with one type of a foreign ion. The obtained materials were subjected to physicochemical analysis with the use of various analytical methods, such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), inductively coupled plasma optical emission spectroscopy (ICP-OES), Fourier transform infrared spectroscopy (FT-IR) and solid-state proton nuclear magnetic resonance ( 1 H ssNMR). All the obtained materials were also biologically tested for their potential cytotoxicity. The obtained materials (Sr,B-HAw and Sr,B-HAd) were homogeneous and respectively showed nano- and microcrystal apatitic structures. The simultaneous introduction of Sr 2+ and BO 3 3- ions turned out to be more effective in respect of the dry method. Of importance, doped materials obtained using both synthesis routes have been demonstrated to be biocompatible, opening the way for medical applications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Weaning failure can be caused by myocardial ischaemia during the switch from mechanical to spontaneous ventilation. We report ischaemic left ventricular failure and ischaemic mitral insufficiency during weaning. Angiography showed that the coronary vessels were stenosed. Transluminal angioplasty made weaning possible. We conclude that acute ischaemic mitral insufficiency may contribute to cardiac failure during weaning and that angioplasty, by reversing it, can allow successful weaning.

Spontaneous hemomediastinum is a rare event, occurring in association with bleeding disorders, intratumoral bleeding, or following an abrupt increase in intrathoracic pressure. We report the case of a patient with systemic lupus erythematosus, nephrotic syndrome, and renal failure, in whom mediastinal lipomatosis (ML) developed following increased corticosteroid therapy. Anticoagulant therapy likely precipitated a massive spontaneous hemomediastinum secondary to diffuse hemorrhage of mediastinal fat, which required emergency decompressive surgery. Steroid-induced ML is common and usually well tolerated, but clinicians should be aware of its potential risk of bleeding when associated with anticoagulant therapy. This case further emphasizes the bleeding complications of treatment with low-molecular-weight heparin in patients with renal failure.

Background: Hydroxyethylstarch used for volume restoration in brain-dead kidney donors has been associated with impaired kidney function in the transplant recipients. We undertook a multicentre randomised study to assess the frequency of acute renal failure (ARF) in patients with severe sepsis or septic shock treated with hydroxyethylstarch or gelatin., Methods: Adults with severe sepsis or septic shock were enrolled prospectively in three intensive-care units in France. They were randomly assigned 6% hydroxyethylstarch (200 kDa, 0.60-0.66 substitution) or 3% fluid-modified gelatin. The primary endpoint was ARF (a two-fold increase in serum creatinine from baseline or need for renal replacement therapy). Analyses were by intention to treat., Findings: 129 patients were enrolled over 18 months. Severity of illness and serum creatinine (median 143 [IQR 88-203] vs 114 [91-175] micromol/L) were similar at baseline in the hydroxyethylstarch and gelatin groups. The frequencies of ARF (27/65 [42%] vs 15/64 [23%], p=0.028) and oliguria (35/62 [56%] vs 23/63 [37%], p=0.025) and the peak serum creatinine concentration (225 [130-339] vs 169 [106-273] micromol/L, p=0.04) were significantly higher in the hydroxyethylstarch group than in the gelatin group. In a multivariate analysis, risk factors for acute renal failure included mechanical ventilation (odds ratio 4.02 [95% CI 1.37-11.8], p=0.013) and use of hydroxyethylstarch (2.57 [1.13-5.83], p=0.026)., Interpretations: The use of this preparation of hydroxyethylstarch as a plasma-volume expander is an independent risk factor for ARF in patients with severe sepsis or septic shock.

Background: In France, there are no guidelines available on withholding and withdrawal of life-sustaining treatments, and information on the frequency of such decisions is scarce., Methods: We undertook a prospective 2-month survey in 113, of a total of 220, intensive-care units (ICUs) in France to study the frequency of, and processes leading to, decisions to withhold and withdraw life-sustaining treatments., Findings: Life-supporting therapies were withheld or withdrawn in 807 (11.0%) of 7309 patients (withholding in 336 [4.6%] and withdrawal in 471 [6.4%], preceded in 358 by withholding). Of 1175 deaths in ICU, 628 (53%) were preceded by a decision to limit life-supporting therapies. Futility and poor expected quality of life were the most frequently cited reasons. Decisions were strongly correlated with the simplified acute physiological score, but an independent centre effect persisted after adjustment for this score. Decisions were mostly taken by all the ICU medical staff, with (54%) or without (34%) the nursing staff; however, a single physician made decisions in 12% of cases. The patient's family was involved in the decision-making process in 44% of cases. The patient's willingness to limit his or her own care was known in only 8% of the cases; only 0.5% of the patients were involved in decisions., Interpretation: Withholding and withdrawal of life-support therapies are widely practised in French ICUs, despite their prohibition by the French legislation. The lack of an official statement from French scientific bodies may explain several limitations on the various steps of the decision-making process.

We report a 6-year-old mildly retarded boy with trisomy 18 in 44% of peripheral lymphocytes. He had mild nonspecific dysmorphic features, microcephaly, micropenis with cryptorchidism and postnatal overgrowth. Trisomy 18 mosaicism was confirmed by a fluorescent in situ hybridization study. Ten previous reports of trisomy 18 mosaicism with normal or subnormal intelligence have been described but only one case of trisomy 18 mosaicism with high stature has been reported.

Study Objectives: To assess the respective diagnostic accuracy of transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) and their therapeutic implications in mechanically ventilated patients, in the intensive care unit (ICU)., Design: A prospective study., Settings: Intensive care units of two tertiary referral teaching hospitals., Patients: One hundred eleven ICU patients (81 men and 30 women; mean age 57 +/- 16 years). Fifty-seven percent were hospitalized for medical illnesses, 16.5 percent after thoracic surgery, 10.5 percent after other surgery, and 16.0 percent for multiple trauma. Their Simplified Acute Physiologic Score was 16 +/- 5., Interventions: The echocardiograms were performed in order to solve well-defined clinical problems. TTE was the first step of the procedure and TEE was performed only when (1) TTE did not solve the clinical problems, and (2) TTE yielded unsuspected findings requiring TEE. During each echocardiographic study, the following were noted: ventilatory mode, clinical problems, imaging quality, results, consequence on acute care, duration of the procedure, and potential complications of TEE. Diagnostic accuracy was defined as the proportion of solved problems, and therapeutic impact was defined as changes on acute care that resulted directly from the procedure., Measurements and Results: One hundred twenty-eight consecutive TTE and 96 TEE were performed. TTE solved 60 of 158 clinical problems (38 percent), whether positive end-expiratory pressure (> 4 cm H2O) was present or not (28 of 74 vs 32 of 84: p > 0.50). TTE allowed evaluation of left ventricular function in 77 percent of cases and pericardial effusion in every case, but it did not solve most of the other clinical problems. Indeed, the diagnostic accuracy of TEE was markedly superior (95/98 vs 60/158: p < 0.001), but TEE required a physician's presence longer (43 +/- 17 min vs 27 +/- 12 min: p < 0.001). When TTE and TEE were scheduled (n = 96), TEE yielded an additional diagnosis or excluded with more certitude a suspected diagnosis, except in two cases. TEE had a therapeutic impact more frequently than TTE (35/96 vs 20/128: p < 0.001). Cardiovascular surgery was prompted by echocardiographic findings in ten patients. TEE was well tolerated in all patients; there were no complications., Conclusions: TEE is a valuable well-tolerated imaging technique in mechanically ventilated patients. For the assessment of left ventricular systolic function and pericardial effusion; however, TTE continues to be an excellent diagnostic tool, even when positive end-expiratory pressure is present. Both TTE and TEE have a therapeutic impact in approximately 25 percent of cases.

The usefulness of consensus conferences has been questioned. We have assessed the impact of a 1989 consensus conference about the treatment of hypovolaemia on prescribing practice at our hospital. Data available from the blood bank enabled us to follow albumin use and costs by department between 1987 and 1991. Medical journals, direct mail, and meetings were used to disseminate the recommendations of the consensus conference, which were that the only indications for albumin are massive haemorrhage, plasmapheresis, massive hypoalbuminaemia, and volume expansion in pregnancy; for hypovolaemia caused by septic shock or vasoplegia, fluid gelatins and crystalloids should be used. In the year after the conference, and in subsequent years, albumin use and costs were 40% lower than before the conference, even though total medical expenditure continued to rise and numbers of patients admitted did not change. We believe that consensus conferences can be a useful means of improving medical practice. The features that ensured success in this programme were the small number of prescribers, the homogeneous setting, and the frequent restatement of the recommendations.

Fiberoptic bronchoscopy and bronchoalveolar lavage are major tools in the diagnosis of acute pneumonia in immunocompromised patients. We conducted a prospective study to assess the morbidity associated with this procedure in 14 patients with AIDS and 16 patients with drug-induced immunosuppression. No patient had a PaO2 lower than 70 mm Hg with additional oxygen. Clinical data, chest roentgenogram, pulmonary function test, forced vital capacity, forced expiratory volume in one second, and arterial blood gases were recorded before and after bronchoscopy. Arterial oxygen saturation was monitored during the procedure, and initial, lowest, and final saturation values were noted. The patients were separated into three groups on the basis of chest roentgenographic findings. No procedure-induced pneumonia or need for tracheal intubation occurred. Minor clinical symptoms induced by the lavage in seven patients resolved spontaneously. By contrast, mean SaO2 decreased markedly during the procedure from 94 +/- 3 to 87 +/- 5 percent (p less than 0.0001) and returned to only 89 +/- 5 percent at the end of the procedure. Lowest SaO2 during the procedure and final SaO2 correlated poorly with initial SaO2 but correlated well with initial FVC and FEV1 (p less than 0.01). The PFT values were lower following bronchoscopy. O2 desaturation was more pronounced in patients with severe roentgenographic abnormalities. No significant differences were found between the three groups of patients, or between the AIDS and DII patients in terms of changes in PFT values. We conclude that in immunocompromised patients, bronchoscopy with BAL induces severe arterial oxygen desaturation which is correlated with initial PFT and chest roentgenographic findings, and most of these abnormalities are transient and do not lead to major complications.

Most patients with severe, acute pulmonary embolism (PE) have arterial hypoxemia. To further define the respective roles of ventilation to perfusion (VA/Q) mismatch and intrapulmonary shunt in the mechanism of hypoxemia, we used both right heart catheterization and the six inert gas elimination technique in seven patients with severe, acute PE (mean vascular obstruction, 55 percent) and hypoxemia (mean PaO2, 67 +/- 11 mm Hg). None had previous cardiopulmonary disease, and all were studied within the first ten days of initial symptoms. Increased calculated venous admixture (mean QVA/QT 16.6 +/- 5.1 percent) was present in all patients. The relative contributions of VA/Q mismatching and shunt to this venous admixture varied, however, according to pulmonary radiographic abnormalities and the time elapsed from initial symptoms to the gas exchange study. Although all patients had some degree of VA/Q mismatch, the two patients studied early (ie, less than 48 hours following acute PE) had normal chest x-ray film findings and no significant shunt; VA/Q mismatching accounted for most of the hypoxemia. In the others a shunt (3 to 17 percent of cardiac output) was recorded along with radiographic evidence of atelectasis or infiltrates and accounted for most of the venous admixture in one. In all patients, a low mixed venous oxygen tension (27 +/- 5 mm Hg) additionally contributed to the hypoxemia. Our findings suggest that the initial hypoxemia of acute PE is caused by an altered distribution of ventilation to perfusion. Intrapulmonary shunting contributes significantly to hypoxemia only when atelectasis or another cause of lung volume loss develops.

A 55 year old man presented an acute massive primary aortic endocarditis, with blood cultures showing the presence of Actinobacillus actinomycetem comitans. The rapidly worsening character of this endocarditis, which required an emergency valve replacement, was the hallmark of this case. The clinical and haemodynamic signs of the often missed massive acute aortic incompetence are recalled.

Mandatory minute volume ventilation has been proposed as a method for weaning patients from ventilators. The purpose of this study was to delineate the influence of caloric intake on spontaneous ventilation in patients receiving mandatory minute volume ventilation. While the value of such ventilation remained unchanged, eight patients were studied at the following three different levels of daily caloric intake: (1) level A, mean of 223 kcal/sq m; (2) level B, mean of 1,380 kcal/sq m; and (3) level C, mean of 2,100 kcal/sq m. We performed gas exchange measurements and a 24-hour recording of ventilation with a monitoring system providing distinction between spontaneous and mechanical cycles. We found that the ventilatory mode was markedly dependent upon the nutritional intake; the percentage of spontaneous ventilation over 24 hours increased from 11 +/- 7 percent (+/- SE) during diet A to 50 +/- 9 percent during diet B and 79 +/- 8 percent during diet C. This increment paralleled the increase in production of carbon dioxide with caloric intake. We suggest therefore that the patient's ability to breathe spontaneously when receiving mandatory minute volume ventilation should be interpreted according to caloric intake.

Pulmonary complications of lymphography are usually described as radiological infiltrates without clinical symptoms. However, a case is here reported of an adult respiratory distress syndrome occurring after lymphography in a 60 year old female lymphoma patient. Pulmonary oedema developed within 48 h; haemodynamic study showed a normal capillary wedge pressure. The patient died from intractable low cardiac output within 24 h. Post-mortem examination showed pulmonary lymphocytic infiltration and multiple fat emboli. The lack of lymphatic drainage was probably responsible for the intravascular passage of lipid-soluble contrast medium, this giving endothelial lesions. In such patients with preexisting lung disease or pulmonary involvement in haematological disease, lymphography has to be considered carefully.

Information provided by computation of shunt and alveolar arterial oxygen differences have been compared in 58 episodes of acute respiratory failure. In order to demonstrate the role of hemodynamic factors on pulmonary gas exchange, we compared blood gas measurements made in 29 patients with a high cardiac output and a reduced arteriovenous oxygen difference [C(a--v-)O2 less than 3.5 ml], with 33 measurements corresponding to a low cardiac output and a widened C(a--v-)O2 (greater than 6.5 ml). When the data was pooled together, the same P(A--a)O2 corresponded to many different shunt values, depending on the level of mixed venous oxygenation (PV-O2). QS/Qtot and P(A--a)O2 were quasi linearly correlated only when they corresponded to patients with the same C(a--v-)O2. For the same value of shunt, the PaO2 was always raised when the PV-O2 was raised. As far as pulmonary gas exchange is concerned, shunt calculation in acute respiratory failure is preferable to P(A--a)O2, especially when some hemodynamic disturbance is present.

This report describes a case of paraquat poisoning, treated with continuous positive airway pressure. After an initial phase of acute respiratory failure with diffuse pulmonary edema, we observed radiologically a complete clearing of both lungs, associated with an aspect of overdistension. Surprisingly, FRC was above normal, as was total quasi static compliance. The patient died on the 15th day, with intractable hypoxemia. Pathologic analysis revealed large zones of parenchyma with overdistended airspaces, explaining the emphysematous-like aspect of the lungs. We propose that the attempts to increase lung volume with CPAP, at an early phase of diffuse epithelial disorganization, may have, partially at least, dilated the remaining distal airspaces.

Routine checking of the FIO2 of a mixture delivered by a ventilator revealed large discrepancies between the FIO2 assigned and that effectively delivered, the latter being low. Measurements of FIO2 at the wall outlets showed the O2 delivery pipeline to be contaminated by compressed air. By disconnecting all the ventilators supplied by this pipeline one after the other, one ventilator, or rather its blender, was found responsible.

Prediction of FRC using a respiratory P-V curve (2 1 syringe method) has been tested in eight patients with normal lungs and in 12 ARDS patients. FRC was measured using nitrogen dilution technique with a closed circuit. Correlation between measured and predicted FRC was excellent, especially when the expiratory limb of the P-V curve was used (r = 0.92, in patients with pulmonary edema, and r = 0,97 when patients were evaluated after a few weeks). PEEP induced increase in FRC was larger between 10 and 20 cmH2O than between 0 and 10 cmH2O. As expected, Qs/Qt decrease was correlated with the FRC augmentation.

To assess the value of measuring compliance in the adult respiratory distress syndrome, sequential pressure-volume curves were obtained in 19 patients with this syndrome. Analysis of the pressure-volume curves allowed separation of the patients into the following four groups: (1) group 1 (n = 6), normal compliance measured during deflation, little hysteresis, and no inflection in the ascending limb of the pressure-volume tracing; (2) group 2 (n = 8), normal compliance during deflation, increased hysteresis, and presence of an inflection; (3) group 3 (n = 10), decreased compliance during deflation, marked hysteresis, and presence of an inflection; and (4) group 4 (n = 10), reduced compliance during deflation, no increased hysteresis, and no inflection. These patterns were correlated with the stage of the adult respiratory distress syndrome and to the pattern of the chest x-ray film. Group 2 corresponds to the initial stage of the syndrome and to pure alveolar opacities on the chest x-ray film. Group 3 is seen later in the course of the syndrome and corresponds to mixed alveolar and interstitial opacities. Group 4 corresponds to patients with end-stage adult respiratory distress syndrome (two weeks) and a predominant interstitial pattern on the chest x-ray film. Group 1 corresponds to a nearly normal chest x-ray film and to recovery.