Reply to 'Response to "The opinion of French pulmonologists and palliative care physicians on non-invasive ventilation during palliative sedation at end of life: a nationwide survey'' '.

We read with interest the letter by Twycross and al on our article recently published in BMC Palliative Care. The authors suggest that the term palliative sedation has been used inappropriately and they consider that in the situation described the sedation was a procedural one rather than a continuous deep sedation. We strongly disagree with this point of view. In an end-of-life situation, the priorities are the patient's comfort, pain and anxiety. This type of sedation does not have the characteristics of procedural sedation described in anaesthesia. The French Clayes Leonetti law makes it possible to clarify the intention of the sedation in end-of-life situations.

The opinion of French pulmonologists and palliative care physicians on non-invasive ventilation during palliative sedation at end of life: a nationwide survey.

BACKGROUND: Deciding to withdraw non-invasive ventilation (NIV) at end-of-life (EOL) in patients with chronic respiratory failure is a challenge. The European Association for Palliative Care recommends not maintaining artificial therapies that could prolong life during palliative sedation (PS) at EOL. The aim of this survey was to assess palliative care physicians' and pulmonologists' opinion on withdrawing or maintaining NIV in patients with chronic respiratory failure during PS at EOL. METHODS: From April to May 2019, we performed a prospective survey among pulmonologists (n = 1545) and palliative care physicians (n = 631) in France to determine the prevalence of opinion in favour of maintaining NIV and identify the factors associated with opinion in favour of withdrawing or maintaining NIV with multiple logistic regression. RESULTS: A total of 457 participants were enrolled comprising 202 pulmonologists and 255 palliative care physicians. An opinion in favour of maintaining NIV was found in 88 (19.3 95%CI [15.7; 23.2]) physicians comprising 57 (28.2%) pulmonologists and 31 (12.2%) palliative care physicians (p < 0.001). The factors associated with an opinion in favour of maintaining NIV were spending time looking for advanced directives (AD) in the patient's file (odds ratio (OR): 6.54, 95%CI [2.00; 21.32], p = 0.002) and personal ethics of physicians (OR: 17.97, 95%CI [9.52; 33.89], p < 0.001). The factor associated with an opinion in favour of withdrawing NIV was palliative care training (OR: 0.31, 95%CI [0.16; 0.60], p < 0.001). The three main reasons in favour of maintaining NIV among the nine identified were emotional comfort for close relatives, reducing discomfort of dyspneoa and anticipation of suffocation. CONCLUSION: In France, around 20% of pulmonologists and palliative care physicians declared an opinion in favour of maintaining NIV during PS at EOL because of their personal ethics and spending time looking for AD, if any, in the patient's file. Palliative care training can stimulate reflection help foster a change of opinion about practices, especially in the case of patients with NIV during PS at EOL.

Heterogeneity of antibody responses among clinical responders during grass pollen sublingual immunotherapy.

BACKGROUND: During allergen-specific sublingual immunotherapy (SLIT), the relevance of changes in specific IgE and IgG antibody titres to treatment efficacy remains to be evaluated at an individual patient level. OBJECTIVE: To investigate whether antibody responses can be used as biomarkers for SLIT efficacy. METHODS: Comprehensive quantitative, qualitative and functional analyses of allergen-specific IgA, IgE, IgG1-4 and IgM responses were performed using purified Phl p 1 to 12 allergens in sera, saliva and nasal secretions from 82 grass pollen allergic patients. These patients were enrolled in a randomized, double-blind placebo-controlled study and assessed in an allergen challenge chamber (ClinicalTrials.gov NCT00619827). Antibody responses were monitored in parallel to clinical responses before and after daily sublingual treatment for 4 months with either a grass pollen or a placebo tablet. RESULTS: A significant mean improvement (i.e. 33-40.6%) in rhinoconjunctivitis total symptom scores was observed in SLIT recipients, irrespective of their baseline patterns of IgE sensitization (i.e. narrow, intermediate, broad) to grass pollen allergens. SLIT did not induce any de novo IgE sensitization. Clinical responders encompassed both immunoreactive patients who exhibited strong increases in titres, affinity and/or blocking activity of grass-pollen-specific IgGs (representing 17% of treated patients), as well as patients with no detectable antibody responses distinguishing them from the placebo group. No significant changes were detected in antibody titres in saliva and nasal washes, even in clinical responders. CONCLUSIONS AND CLINICAL RELEVANCE: Sublingual immunotherapy with a grass pollen tablet is efficacious irrespective of the patients' baseline sensitization to either single or multiple grass pollen allergens. Seric IgG responses may contribute to SLIT-induced clinical tolerance in a fraction (i.e. 17%) of patients, but additional immune mechanisms are involved in most patients. Consequently, antibody responses cannot be used as a marker of SLIT efficacy at an individual patient level.

Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy.

BACKGROUND: Differences between major allergens from distinct grass species remain to be investigated, both in terms of structure and antigenicity. METHODS: Group 1 and 5 allergens purified from five common Pooideae species were analysed by mass spectrometry (MS). Major histocompatibility complex (MHC) class II-restricted T cell epitopes were identified using predictive algorithms and human leucocyte antigen (HLA)-binding assays. CD4+ T cell reactivity and IgE binding were assessed based on the induction of CD154 expression in peripheral blood mononuclear cells and using competitive ELISA assays, respectively. RESULTS: MS analysis of group 5 pollen allergens reveals considerable intra- and inter-species variability in amino acid sequence, with 30-50 predominant isoforms found for each species. Differences in the amino acid sequence as well as N- and O-glycosylation contribute to the variability of group 1 allergens, yielding 5-10 main isoforms, depending on the species. Out of 14 MHC class II-restricted T cell epitopes identified within group 1, only one is conserved among the five grass species. Significant differences in binding affinities for HLA-DR molecules result in variable CD4+ T cell recognition of group 1 and 5 allergens purified from the various species. Up to 38% and 85% of patients exhibit seric IgE responses to species-restricted (or semi-restricted) epitopes associated with group 1 or 5 allergens, respectively. CONCLUSION: Major pollen allergens from distinct grass species bear both shared and species-restricted T and B cell immune epitopes. When compared with single extracts, a five grass pollen extract is thus more suitable for specific immunotherapy, as it contains a broader repertoire of the IgE epitopes to which patients are sensitized.

[Hepatorenal syndrome]. / Syndrome hépatorénal.

The hepatorenal syndrome (HRS) is an acute functional renal failure due to renal arterial vasoconstriction occurring in cirrhotic patients with vascular dysfunction. The renal arterial vasoconstriction is the result of diffuse arteriole vasodilatation. There are two types of HRS, which can be differentiated according to the course and the stage of the renal failure; they have a different prognosis. Liver transplantation remains the standard treatment. Maintenance medical therapy is mainly based on vasopressin analogues. The interest of both dialysis and portosystemic intrahepatic shunt techniques remains to be determined. The prognosis of HRS is poor and in the absence of treatment, onset is usually followed by rapid fatal outcome.

Severe atypical pneumonia in critically ill patients: a retrospective multicenter study.

BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients could require intensive care unit (ICU) admission for acute respiratory failure. METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven atypical pneumonia were retrospectively described. Patients with MP were compared to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A total of 104 patients were included, 71 men and 33 women, with a median age of 56 [44-67] years. MP was the causative agent for 76 (73%) patients and CP for 28 (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%] patients). Median number of involved quadrants on chest X-ray was 2 [1-4], with alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra-pulmonary manifestations were present in 34 (33%) patients. Mechanical ventilation was required for 75 (72%) patients and vasopressors for 41 (39%) patients. ICU length of stay was 16.5 [9.5-30.5] days, and 11 (11%) patients died in the ICU. Compared with SP patients, MP patients had more extensive interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6 (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at admission could discriminate MP and SP. MP was more often associated with hemolytic anemia, abdominal manifestations, and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial pneumonia requiring ICU admission, mortality was 11%. The comparison with SP pneumonia identified clinical, laboratory, and radiographic features that may suggest MP or CP pneumonia.

Comparison of three methods of diagnosis of plasma unmeasured anions in critically ill patients.

BACKGROUND: The measurement of plasma unmeasured anions (PUA) is paramount in assessing metabolic acid base disorders. The aim of this study was to compare the accuracy of three methods in diagnosing abnormal PUA values: standard base excess (SBE), the albumin corrected anion gap (AGc), and the Stewart-Figge approach, based on unidentified anions (XAc-). METHODS: Acid-base variables were prospectively collected in ICU patients admitted January-September 2008. Whatever the method, PUA values measured two standard deviations above or below the mean of those in control subjects were considered as abnormal. RESULTS: Of the 205 consecutives patients included, 179 had an abnormal PUA value. The accuracy of AGc and XAc- in diagnosing abnormal PUA values was comparable (AUC: 0.89±0.03 and 0.89±0.03, P=0.82) but greater than that of SBE (0.67±0.06, P<0.001 and P<0.001, respectively). Of the high PUA values (n=161), 96% were diagnosed by XAc-, 88% by AGc (P<0.01) and 48% by SBE (P<0.001). Hyperlactatemia (n=111) was diagnosed equally by AGc and XAc-, (81% and 86%, P=0.37) but less by SBE (50%, P<0.001 and P<0.001, respectively). High PUA not associated with hyperlactatemia (N.=61) was more frequently diagnosed by XAc- (97%) than by AGc (84%, P=0.03). CONCLUSION: In ICU patients, AGc and the Stewart-Figge approach should be preferred over SBE for diagnosing abnormal PUA values and predicting hyperlactatemia. The Stewart-Figge approach based on unidentified anions, is the most efficient in diagnosing high PUA values not associated with hyperlactatemia.

[Hantavirus infections in Ile-de-France]. / Infections à Hantavirus en Ile-de-France.

Hantavirus infections, Puumala serotype, is a well-known disease in the northeast of France, but not in the Paris area, despite regularly diagnosed cases. A retrospective study was performed from January 1999 to December 2000 to assess the clinical and epidemiological characteristics of this disease in the "Région Ile-de-France". Fourteen cases were diagnosed. All required hospitalisation. Patients presented usually with high fever, pain, renal failure, moderate thrombocytopenia and, sometimes, transitional acute myopia witch is pathognomonic of the disease. In each case, a contact with a forest was found. Twelve patients recovered completely. One patient with pre-existing chronic renal and hepatic failure died and another developed a persistent arterial hypertension. Invasive procedures were often used before the diagnosis. Hantavirus infections does exist in the "Région Ile-de-France". Failure to recognise this disease in this area lead to unnecessary invasive procedures and hospitalizations.