Low-pressure versus standard pressure laparoscopic colorectal surgery (PAROS trial): a phase III randomized controlled trial.

TRIAL DESIGN: This is a phase III, double-blind, randomized, controlled trial. METHODS: In this trial, patients with laparoscopic colectomy were assigned to either low pressure (LP: 7 mmHg) or standard pressure (SP: 12 mmHg) at a ratio of 1 : 1. The aim of this trial was to assess the impact of low-pressure pneumoperitoneum during laparoscopic colectomy on postoperative recovery. The primary endpoint was the duration of hospital stay. The main secondary endpoints were postoperative pain, consumption of analgesics and postoperative morbidity. RESULTS: Some 138 patients were enrolled, of whom 11 were excluded and 127 were analysed: 62 with LP and 65 with SP. Duration of hospital stay (3 versus 4 days; P = 0.010), visual analog scale (0.5 versus 2.0; P = 0.008) and analgesic consumption (level II: 73 versus 88 per cent; P = 0.032; level III: 10 versus 23 per cent; P = 0.042) were lower with LP. Morbidity was not significantly different between the two groups (10 versus 17 per cent; P = 0.231). CONCLUSION: Using low-pressure pneumoperitoneum in laparoscopic colonic resection improves postoperative recovery, shortening the duration of hospitalization and decreasing postoperative pain and analgesic consumption. This suggests that low pressure should become the standard of care for laparoscopic colectomy. TRIAL REGISTRATION: NCT03813797.

The aim of this trial was to assess the impact of low-pressure pneumoperitoneum during laparoscopic colectomy. The study proved that using low pressure in laparoscopic colonic resection improves postoperative recovery, decreasing length of hospitalization, postoperative pain and analgesic consumption.

Nodal analysis of nonlinear behavior of the instability at a fluid interface.

In interface instabilities, deformations first grow exponentially, then enter a nonlinear regime affecting amplitude and symmetry. Most extant studies have focused on amplitude alone. Here, we study a 2D Rayleigh-Taylor instability for an initial sinusoidal deformation, analyzing its amplitude and asymmetry over time. For the latter, we define a metric based on the zero crossings of the interface. We develop a weakly nonlinear model and compare it to experimental data. It shows that our asymmetry metric complements the amplitude for an improved description of the instabilities' nonlinear phases.

[Prognosis of in hospital nonagenarians with acute kidney injury].

BACKGROUND: There has been little in the way of study of nonagenarians with acute kidney injury (AKI, defined in lines with KDIGO guidelines), but the rise in their life expectancy makes further study of this population necessary. The aim of this study is to assess mortality in nonagenarians with AKI during hospitalization. METHODS: In this retrospective study, patients with AKI during hospitalization between 2013-2014 were included. At baseline, epidemiological variables, comorbidities and treatments were collected. Analytics and mortality were studied during hospitalisation. Univariate analysis was carried out to evaluate mortality-associated variables. A logistic regres-sion analysis was carried out to demonstrate independent predictors for mortality. RESULTS: Two hundred and sixty-four nonagenarian patients were included. Mean age was 93±3 years, 73 (27.7?%) of whom were men. During hospitalization, 79 patients (29.9?%) died. Comorbidities related to mortality were history of heart failure (p?=?0.018), diastolic dysfunction (p?

Randomized trial comparing low-pressure versus standard-pressure pneumoperitoneum in laparoscopic colectomy: PAROS trial.

BACKGROUND: Laparoscopy, by its minimally invasive nature, has revolutionized digestive and particularly colorectal surgery by decreasing post-operative pain, morbidity, and length of hospital stay. In this trial, we aim to assess whether low pressure in laparoscopic colonic surgery (7 mm Hg instead of 12 mm Hg) could further reduce pain, analgesic consumption, and morbidity, resulting in a shorter hospital stay. METHODS AND ANALYSIS: The PAROS trial is a phase III, double-blind, randomized controlled trial. We aim to recruit 138 patients undergoing laparoscopic colectomy. Participants will be randomly assigned to either a low-pressure group (7 mm Hg) or a standard-pressure group (12 mm Hg). The primary outcome will be a comparison of length of hospital stay between the two groups. Secondary outcomes will compare post-operative pain, consumption of analgesics, morbidity within 30 days, technical and oncological quality of the surgical procedure, time to passage of flatus and stool, and ambulation. All adverse events will be recorded. Analysis will be performed on an intention-to-treat basis. TRIAL REGISTRATION: This research received the approval from the Committee for the Protection of Persons and was the subject of information to the ANSM. This search is saved in the ID-RCB database under registration number 2018-A03028-47. This research is retrospectively registered January 23, 2019, at http://clinicaltrials.gov/ed under the name "LaPAroscopic Low pRessure cOlorectal Surgery (PAROS)". This trial is ongoing.

[Augmentation therapy with alpha-1 antitrypsin: 20 year- follow-up of a deficient patient]. / Traitement substitutif par alpha-1 antitrypsine: suivi sur 20 ans d'un patient déficitaire.

INTRODUCTION: Alpha one antitrypsin deficiency is a rare genetic disorder occurring principally in patients with the PiZZ phenotype. This deficiency can lead to pulmonary emphysema which impairs quality of life and which may progress to respiratory failure. The diagnosis is based on the presence of emphysema typically with a basal preponderance and airflow obstruction and is confirmed by measuring A1AT levels. A1AT replacement is the only specific therapy for this condition. OBSERVATION: We describe the 1st patient with A1AT deficiency treated in this way in France. The patient was 52 years old at the start of treatment with A1AT replacement, initially in hospital and then at their place of residence. Treatment was initiated in the context of progressive breathlessness, the presence of emphysema and confirmation of the biochemical deficit. The patient received 4 g of AIAT per week in combination with inhaled corticosteroids and ongoing physical rehabilitation. Follow up over 20 years has revealed a slowing in the decline in spirometric measurements. No problems with tolerating the treatment have been reported. CONCLUSION: In this clinical case replacement therapy appeared to show clinical benefits and was well tolerated.

[Characteristics of the patients included in the French cohort of patients with emphysema caused by alpha-1 antitrypsin deficiency]. / Caractéristiques des patients inclus dans la cohorte française de patients emphysémateux déficitaires en alpha-1 antitrypsine.

INTRODUCTION: Alpha-1 antitrypsin deficiency is associated with the occurrence of pulmonary emphysema. The aim of this study is to describe the characteristics of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema. METHODS: We describe a prospective cohort study including adult patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema confirmed by CT scan living in France. Patients' clinical and functional characteristics, quality of life measures and management were recorded every 6 months during a five-year period. RESULTS: 201 patients were included from 56 centres between 2005 and 2008. The characteristics of 110 patients have been analysed. Mean age was 50 years (SD:11.8), 62.7% were males, 90% were tobacco smokers. The main functional results (% predicted) were: FEV1: 42.8 (19.6), CPT: 128.3 (21.7), CRF: 167.0 (46.0), 6 minute walking distance (meters): 413 (130). 51 (46.4%) patients received augmentation therapy. Augmentation therapy was administered weekly (37.5%), twice a month (35.4%) or monthly (25.5%). Study centre was the only factor associated with the likelihood to received augmentation therapy. CONCLUSIONS: The clinical and functional characteristics as well as management of these patients varied markedly. There is a need for a standardization of the management of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema.

Clinical pharmacokinetics of alpha 1-antitrypsin in homozygous PiZ deficient patients.

A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3-compartment model. The intravenously administered protein diffused quickly to the extravascular compartment where some retention occurred. No significant difference in AAT metabolism was observed between the 3 groups. The half-life of the injected protein is slightly longer than 2.5 days. The AAT protein was not stored. These results confirm the observations collected during the clinical trials. That is, a weekly infusion is necessary to obtain stable serum AAT concentrations. Monthly infusions are unable to maintain a 'plateau' phase. The periodicity may be limited to every 2 weeks.

Plasma DNA as a marker of cancerous cell death. Investigations in patients suffering from lung cancer and in nude mice bearing human tumours.

Plasma DNA that circulates mainly as mononucleosomes is a cell death marker. Its significance and prognostic value in cancer as compared to other tumour markers was investigated in 68 patients hospitalised for lung cancers. Prognostic values of the various studied parameters were evaluated using the Cox's model. The cellular origin of plasma DNA was further investigated in nude mice transplanted with human lung adenocarcinoma. Plasma DNA concentrations were increased in cancer patients as compared to normal subjects (P < 0.01). They were higher in patients with extended (Stage 4) disease than in patients with limited stage disease (P < 0.05). Plasma DNA concentrations, serum lactate dehydrogenase activities and neuron-specific enolase concentrations were correlated all together in small cell lung carcinoma (SCLC) and in non-SCLC. Similar relationships were found between survival and each of these three cell death/tumour markers (P < 0.02-0.005). Plasma DNA from mice bearing human tumour hybridised with both mouse and human plasma DNA, while plasma DNA from endotoxin-injected mice hybridised only with mouse plasma DNA. In conclusion, in patients suffering from lung cancer, plasma DNA as well as LDH and NSE represent cell death markers that are correlated with survival. At a time when apoptosis pathways appear to be potential targets for cancer therapy, plasma DNA is a cell death/tumour marker that should be taken into account in studying the cancerous process in human diseases.

Distribution of lung density and mass in patients with emphysema as assessed by quantitative analysis of CT.

STUDY OBJECTIVE: To assess the effects of emphysema on the apex-to-base gradient of lung density (D) and lung mass (M) and to explore the relationship between M and lung function. METHODS: CT scans of whole lungs were performed in 12 healthy subjects and 29 patients who were breathing at functional residual capacity, after which lung function tests were performed. Whole D and M and regional D (RLD) and M (RLM) were calculated. The degree of emphysema was scored. RESULTS: The RLM for each height did not differ significantly between patients with disease and healthy subjects, while RLD was significantly lower in the patients with disease. A less marked nonlinear, increasing, craniocaudal gradient of D was observed in the group with disease, suggesting that the distension increases progressively from the apex to the base. RLD and RLM in the 40 to 90% lung height differed significantly among patients in the emphysema group with normal, high, and low M compared to the healthy subjects. M did not differ significantly between patients with centrilobular and panlobular emphysema, which was thought to stem from the marked variations in the results. Vital capacity was lower in the patients with low M. CONCLUSIONS: The lower RLD in the group with low M was due to both lung overinflation and to tissue loss, while in the groups with high or normal M, it was due only to lung overinflation.

Bronchoalveolar lavage in liquid paraffin pneumonitis.

We evaluated cells and lipids recovered in the bronchoalveolar lavage fluid from seven patients with liquid paraffin pneumonitis. For each patient, the BALF was whitish with oil droplets on the surface. Alveolar macrophages contained numerous, large vacuoles that did not react with May-Grunwald-Giemsa, Papanicolaou, or periodic acid-Schiff but were stained in black with Sudan B, orange with Sudan III and red with oil Red O. Liquid paraffin was identified on thin layer chromatography of BALF-extracted lipids as a very hydrophobic compound migrating on the solvent front as control liquid paraffin. This abnormal spot was definitely identified as liquid paraffin by infrared spectroscopy and gas liquid chromatography for the first patient. The number and percentage of AMs were largely decreased in the BALF of each patient, whereas the number of neutrophils, eosinophils and lymphocytes was increased. These findings suggest that this cell-mediated inflammatory response plays a role in the development of interstitial fibrosis at late stages of liquid paraffin pneumonitis.

Management of acute otitis media caused by resistant pneumococci in infants.

OBJECTIVES: To assess the clinical outcome and risk of failure after oral vs. intravenous treatment in otitis media caused by penicillin-resistant pneumococci. To determine the possible correlations between pneumococcal minimal inhibitory concentration (MIC) to penicillin and clinical outcome. DESIGN: Retrospective study of 156 cases collected between 1993 and 1995. Mean follow-up: 5 months. Setting. Two tertiary academic medical centers in Paris, France. PATIENTS AND METHODS: Pneumococcus was isolated from 191 of 570 ear samples obtained from children with otitis media and shown to be penicillin-resistant in 156. Medical history, antibiotic therapy during the previous 3 months and day-care center attendance were reviewed. For the current episode microbiologic characteristics of the isolated strains, type of treatment, therapy efficacy and clinical outcome were analyzed. Patients were predominantly young (76.3% were <1 year old) and bacteriologic samples were taken mainly because of previous treatment failure. RESULTS: Among 156 children with pneumococcal penicillin-resistant otitis media, 72.2% attended day-care centers, 71.8% had been previously treated with aminopenicillin and 52.5% with cephalosporins. Failure of previous empirical oral therapy was noted in 84% (one-third of these had been receiving amoxicillin-clavulanate). Patients treated intravenously had had a more protracted otitis but no greater number of previous episodes of acute otitis media than those receiving oral therapy. Acute mastoiditis occurred in 4 infants resulting in mastoidectomy. Oral treatment (mainly with high dose amoxicillin,120 to 150 mg/kg/day) and intravenous therapy (cephalosporin or glycopeptide) had been used in 59 and 41%, respectively. Mean duration of therapy was 10.7 days. Three failures (1.9%) and 10 recurrences (6.4%, average 28 days) occurred. No statistical difference was found between intravenous and oral therapy with respect to risk of recurrence. A high penicillin MIC value was correlated with previous antibiotic treatment but not with clinical outcome. CONCLUSIONS: Oral therapy appears to be as effective as intravenous therapy for the treatment of penicillin-resistant pneumococcal otitis media. Intravenous treatment should not necessarily be dictated by the penicillin susceptibility value but should be considered in cases of failure to thrive, persistent otitis or other complications.

Multicenter randomized trial comparing cisplatin-mitomycin-vinorelbine versus cisplatin-mitomycin-vindesine in advanced non-small cell lung cancer. 'Groupe Français de Pneumo-Cancérologie'.

The study was designed to evaluate the value of vinorelbine in a cisplatin-mitomycin-vinca alkaloid regimen for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). A group of 227 patients with inoperable NSCLC in stage III (58%) or stage IV (42%) were included in this randomized multicenter trial comparing a reference regimen (VDS group, n = 113) cisplatin (120 mg/m2 on day 1, day 29 and day 71), mitomycin (8 mg/m2 on day 1, day 29 and day 71) and vindesine (3 mg/m2/week for 5 weeks and then every 2 weeks up to the 15th week) to a cisplatin-mitomycin-vinorelbine combination (VNB group, n = 114), with cisplatin and mitomycin at the same doses, and vinorelbine 25 mg/m2/week for 16 weeks. The objective response rate (evaluated at 17th week) was 17% in the VDS group and 25% in the VNB group (P = 0.15). Median survival was 33.4 weeks and 34.5 weeks in the VDS and VNB arms, respectively. Overall survival duration was not significantly different between the two arms (logrank test, P = 0.20) despite a trend to an increased survival in the VNB group. This essentially benefited the patients with stage III disease with a clear-cut lengthening of median (45.9 vs. 33.4 weeks) and 1 year survival (44.6% vs. 26.2%, P < 0.05) in favor of the VNB group. Nevertheless, there was no significant difference in overall survival (logrank, P = 0.13). Survival duration of the patients with stage IV disease was comparable in the two arms (logrank test, P = 0.90). Grade 3 or 4 neutropenia was found in 61% and 87% of the VDS and VNB groups, respectively (P < 0.01). Grade 2-4 peripheral neuropathy was observed in 23% of the patients in the VDS group and in 6% of the patients in the VNB group (P < 0.01). Replacement of vindesine by vinorelbine in a cisplatin-mitomycin-vinca alkaloid chemotherapeutic regimen did not lead to a significant improvement in objective response rate or in duration of survival. There was a reduction in neurotoxicity at the expense of an increased hematologic toxicity. However, for patients with stage III disease there was an increase in 1 year survival with the vinorelbine combination.

Free parameter, figure of merit and ionization quench in liquid scintillation counting.

A statistical study of the detection process demonstrates that the free parameter is essential to compute the counting efficiency in both CIEMAT/NIST and TDCR methods. An analysis of the computed counting efficiencies shows the uselessness of old definition of the figure of merit. A new definition is required and we adopt the idea of taking quantities related with the output of the photomultiplier. In addition, we justify the application of the chemical quenching simulation with the electronic variation of the photomultiplier gain. Finally, we describe a new procedure to determine the figure of merit and the optimum ionization-quenching factor from the pulse spectrum of different radionuclides. The robustness of the new procedure is tested with three different sets of stopping power for low-energy electrons.

[Ischemic cerebrovascular complications in Rendu-Osler disease: a case]. / Accidents vasculaires cérébraux ischémiques dans le cadre de la maladie de Rendu-Osler: 1 cas.

Rendu-Osler disease is a familial disorder transmitted as an autosomal dominant trait of high penetrance. It is characterized by telengiectasias of the skin, mucous membranes and viscera, associated with recurrent bleedings. Neurological complications (brain abcesses and hemorrhagic manifestations) occur in 10% of the patients. Neurological symptoms are often associated with arteriovenous fistula of the lung (50%). Ischaemic strokes occuring in such patients with an hemorrhagic disease while unfrequent, have been described. The pathophysiology of stroke in that case remains unclear. Polycythemia causing hyperviscosity, air embolism following hemoptysis, paradoxical embolism through right-to-left shunt have been proposed. We report a new case of ischaemic strokes occuring in a caucasian forty-year-old woman, with Rendu-Osler disease (familial history, epistaxis, telengiectasias) and with an arteriovenous malformation of the right lung. She presented two strokes and one transient ischaemic attack. Her pulmonary malformation was occluded by embolization. The role of arteriovenous malformation in the pathophysiology of strokes is discussed.

[Transverse myelitis caused by Mycoplasma pneumoniae infection]. / Myélite transverse induite par une infection à Mycoplasma pneumoniae.

A twenty-six year old man was admitted for febrile atypical pneumoniae. Few hours later, he presented an acute flaccid paraplegia with dorsal pain. Cerebrospinal fluid analysis showed a high leukocyte count with raised protein level. Neuroradiological examinations (myelography and MRI) were normal. Seric immunological disorders were reported. High complement-fixing antibody titers to Mycoplasma pneumoniae were found in the serum and in the CSF. The patient was treated with antibiotic and corticosteroids. He improved dramatically within one month. Neurological complications of Mycoplasma pneumoniae infections have been described (meningoencephalitis, meningitidis, polyradiculoneuropathies, cerebellar ataxia, cranial nerve palsies). Nineteen cases of transverse myelitis induced by Mycoplasma pneumoniae have been previously reported. Pathophysiological mechanisms of nervous system complications induced by Mycoplasma pneumoniae were discussed. Vascular mechanisms, direct invasion by the pathogen, toxic, immunological causes were examined.

[Preventability of adverse effects in a medical emergency service]. / Evitabilité des effets indésirables dans un service d'admissions médicales.

The aim of this prospective pharmacovigilance study was to assess the incidence and the preventability of adverse drug reactions (ADRs) leading to hospital admissions. All patients admitted to the Toulouse University Hospital through the medical admission ward during four non-consecutive weeks were included in the study. Characteristics of patients admitted for a suspected ADR (cases) were compared with those admitted for other reasons (controls). All cases were reviewed by both a pharmacologist and an emergency medicine specialist. Among a total of 671 admissions, 44 ADRs were identified. The incidence of hospital admissions for ADRs was 6.1 per 100 admissions [4.4-8.3]. Cases were exposed to a higher number of drugs (3.6 vs. 1.7; p < 0.001). Some classes of drugs were significantly associated with a higher risk of ADRs: antineoplastic, anti-infectious or musculoskeletal drugs. Haematological, metabolic and electrolytic, liver/gastrointestinal or cutaneous disorders were causes of admissions significantly more frequently related to ADRs. Using Imbs's preventability scale, 65 per cent of ADRs were categorized as 'definitely unpreventable', 26 per cent 'potentially preventable' and 9 per cent 'definitely preventable'. These results underline the frequency of ADRs leading to hospitalization, with 35 per cent which are more than likely preventable. Further studies are needed to validate this preventability scale in order to obtain an easier, more reliable and more reproducible tool.

[Splenomegaly in sarcoidosis: clinical features and outcome. Analysis of 17 cases]. / Les splénomégalies sarcoïdosiques: caractéristiques cliniques et évolutives. A propos de 17 observations.

PURPOSE: To describe the clinical features, biological datas and outcome of patients with systemic sarcoidosis and splenomegaly. METHODS: A retrospective analysis of 17 patients presenting splenomegaly and sarcoidosis with histological proof. RESULTS: Splenomegaly was clinically perceptible in 13 patients, with a spleen size that extended 4 cm or more below the costal margin in 11 patients. It was painful in five cases. The more frequent clinical features are constitutional symptom (fever in 9 cases) and hepatomegaly (N =7). Chest X-ray showed bilateral hilar lymphadenopathy in nine patients and no abnormality in five cases. Serum angiotensin converting enzyme levels were elevated in 81% of cases. Thrombopenia (N =5) and hypersplenism (N =5) were also observed. Corticosteroid were given to 88% with a good clinical and biological response including a decrease in the spleen volume. Corticotherapy and splenectomy (performed in two patients to rule out lymphoma) didn't change outcome of disease. Sarcoidosis is often chronical (82%) and extensive. CONCLUSION: Splenomegaly may be present in sarcoidosis. Management is not standardized. Corticosteroid is indicated for symptomatic or massive splenomegaly. Splenomegaly is frequently in chronic and extensive sarcoidosis.

[Alveolar hemorrhage, glomerulonephritis and anti-cytoplasmic polynuclear antibodies]. / Hémorragie alvéolaire, glomérulonéphrite et anticorps anticytoplasme de polynucléaires.

The value of antineutrophilic cytoplasmic antibodies (ANCA) was assessed in the diagnosis and chronic treatment of 7 patients with microscopic polyarteritis or Wegener's granulomatosis. All patients had oligoimmune glomerulonephritis with segmental and focal necrosis and presented with anaemia. Five of them had alveolar haemorrhage with haemoptysis and infiltrates at radiography. ANCA were assayed by indirect immuno-fluorescence on ethanol-fixed neutrophils and were strongly positive, with a cycloplasmic aspect in 5 cases and a perinuclear aspect in 2 cases. Initial remission with fall in ANCA titres was obtained with corticosteroids, cyclophosphamide and sometimes plasmapheresis (5 patients), but frequent relapses with re-elevation of ANCA titre occurred when treatment was reduced. It is concluded that ANCA are very helpful in the diagnosis of systemic vasculitis, notably in cases with first-time alveolar haemorrhage. They also facilitate monitoring and therapeutic decisions, since relapses are frequent.

[Pneumorenal syndrome induced by d-penicillamine: Goodpasture's syndrome or microscopic polyarteritis?]. / Syndrome pneumo-rénal induit par la d-pénicillamine: syndrome de Goodpasture ou polyartérite microscopique?

Diffuse alveolar haemorrhage associated with glomerulonephritis is a rare but serious complication of d-penicillamine therapy. A case is reported which illustrates the usefulness of bronchoalveolar lavage and kidney needle biopsy for the early diagnosis of this condition. A search for antiglomerular basement membrane antibodies in serum was negative, whereas antigranulocyte cytoplasmic antibodies were present. These immunological results differentiated the disease from Goodpasture's syndrome to which it is clinically related and placed it in the same category as microscopic polyarteritis. After treatment with corticosteroids, cytostatic drugs and plasmapheresis, the outcome was favourable in contrast with the usually poor prognosis.

[An intensive survey of drug surveillance in a medical admissions department]. / Enquête intensive de pharmacovigilance dans un service d'admission médicale.

An intensive survey of pharmacovigilance was carried out in a medical admission department over a 4-month period. Out of 2,017 admissions to hospital, 23 (1,1 p. 100) were motivated by adverse reactions to drugs. Questioning brought out allergy and multiple drug therapy as important factors. Lesions of the skin and mucosae predominated, notably after treatment with antibacterial and non-steroidal anti-inflammatory agents. The categories of drugs involved were, in decreasing order of frequency: cardiovascular (6/23), anti-bacterial (5/23), neuropsychiatric (4/23) and non-steroidal anti-inflammatory drugs (4/23). The fact that the patients had taken several products rendered evaluation difficult. Using imputability scales made it possible to reduce the cause-effect relationship in 26 p. 100 of the cases.