Hypereosinophilia during dupilumab treatment in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Increased blood eosinophil count (BEC) is common in patients under dupilumab treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). This study investigated the prevalence and consequences of hypereosinophilia and to help define patients at risk. METHODS: Real-life, prospective observational cohort study of patients treated with dupilumab for severe CRSwNP. Eligible patients were adult and biological-naive (N=334). All BEC values at baseline and during treatment were reported. Patients with a follow-up of >= 1 year were included to define patients at risk for hypereosinophilia by comparing baseline BEC values (N=218). Furthermore, clinical characteristics and therapeutic consequences for patients with BEC >= 3.0 were noted. RESULTS: Hypereosinophilia developed in a minority of patients, with a peak at week 12 (16.2% with BEC >= 1.5, and 1.7% >= 3.0) in cross-sectional analysis. BEC >= 1.5 developed in 28.9% and BEC >=3.0 in 4.6% of cases with a minimal 1-year follow-up. Baseline BEC was significantly higher for patients developing BEC >= 1.5 and BEC >=3.0, with an optimal cut-off point of 0.96 to predict developing BEC >= 3.0. CONCLUSIONS: Blood eosinophil count (BEC) >= 1.5 is transient and usually abates with no therapeutic interventions and BEC >= 3.0 is rare. Hypereosinophilic syndrome did not occur and switching to a different biological was rarely employed. A baseline BEC of >=1.0 can be a reason for extra caution.

Steroid responsiveness predicts olfactory function recovery in dupilumab treated CRSwNP.

BACKGROUND: There is no known predictor for olfactory function recovery with dupilumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP). This study assessed whether patient-reported recovery of olfactory function on oral corticosteroids (OCS) is a prognostic factor. METHODS: Retrospective analysis of pre-biological OCS-responsiveness on olfactory functioning (OCS-responsive or OCS-unresponsive; OCS-r and OCR-u, respectively) as predictor for olfactory functioning after 6 months of dupilumab therapy for severe CRSwNP. RESULTS: 212 CRSwNP patients treated with dupilumab were divided between OCS-r (reported improvement of olfactory function with OCS before dupilumab treatment, n = 152), and OCS-u (OCS-unresponsive; no such improvement, n = 60). Olfactory function was tested with Sniffin's Sticks Identification Test (12 pens; SSIT-12). At baseline, both groups had a median SSIT-12 score of 3 / 12 indicating anosmia. Hyposmia and normosmia rates were also comparable (5.9% and 3.3% in OCS-r, respectively; 5.0% and 1.7% in OCS-u, respectively). After 6 months of dupilumab treatment, OCS-r showed higher olfactory scores (median SSIT-12: 8/12; 52.6% hyposmia and 17.8% normosmia) than OCS-u (median SSIT-12: 5/12; 31.7% hyposmia and 3.3% normosmia). The positive predictive value of OCS-responsiveness on scoring <7 (normosmia/hyposmia) on the SSIT-12 after 6 months of dupilumab treatment was 70.4%. Conversely, the negative predictive value of OCS-unresponsiveness on scoring <7 (anosmia) on the SSIT-12 after 6 months of dupilumab treatment was 65.0%. CONCLUSION: Patients who report olfactory function improvement on OCS have a higher chance of recovery of olfactory function during the first six months of treatment with dupilumab than patients who do not.

Eosinophils are the dominant type2 marker for the current indication of biological treatment in severe uncontrolled chronic rhinosinusitis with nasal polyps.

The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) defines markers for type2 inflammation in the context of indicating biological therapy in severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) as either a total serum immunoglobulin E (total-IgE) <100 kU/L, a blood eosinophil count (BEC, expressed as -109 cells / L) >=0.25, or a tissue eosinophil count >=10 per high power field (HPF) (1). Recently, an EPOS/EUFOREA expert panel advised to lower the threshold for BEC from >=0.25 (EPOS2020) to >=0.15 (EUFOREA2023) to align with thresholds used for biological indication in asthma patients (2). As far as we know, there is no literature supporting the cut-off value for total-IgE.

New-generation positional therapy in patients with positional central sleep apnea.

PURPOSE: To evaluate the effect of a sleep position trainer (SPT) in patients with positional central sleep apnea (PCSA). METHODS: A multicentre cohort study was conducted. Patients with symptomatic PCSA were included. Effectiveness, compliance and quality of life were assessed at 1- and 6-month follow-up. RESULTS: Sixteen patients were included. Median AHI dropped from 23.4/h [12.9-31.2] to 11.5/h [7.2-24.5] (p = 0.044) after 1-month SPT therapy and in patients who continued treatment, median AHI further decreased after 6 months to 9.7/h [3.4-27.6] (p = 0.075). Median percentage of supine sleep decreased significantly from 37.6 [17.2-51.8] to 6.7 [0.7-22.8] (p < 0.001), after 1 month, and to 6.8 [0.7-22.1] (p = 0.001), after 6 months. Mean compliance over 1 and 6 months was 78.6 ± 35.3 and 66.0 ± 33.3%, respectively. Epworth Sleepiness Scale at baseline was 9.5 [3.3-11.8] and did not significantly decrease after 1 month (11.0 [3.0-13.0]) and 6 months (4.0 [3.0-10.5]) follow-up. Functional Outcomes of Sleep Questionnaire remained stable within the first month. However, after 6 months, there was a significant improvement compared to baseline values, 15.9 [11.9-18.4] vs. 17.8 [14.3-19.2]; p = 0.030. CONCLUSION: This is the first study on effects of positional therapy with a new-generation smart device in patients with PCSA after 1 and 6 months of follow-up. Results of this study show that the SPT is effective in reducing AHI and central AI, feasible in PCSA, and is associated with symptomatic improvement. While the working mechanism behind this effect remains speculative, the effect is positive and considerable.

Comparison of upper airway collapse patterns and its clinical significance: drug-induced sleep endoscopy in patients without obstructive sleep apnea, positional and non-positional obstructive sleep apnea.

PURPOSE: To compare patient characteristics, upper airway (UA) collapse patterns and treatment outcome in obstructive sleep apnea (OSA) patients, including non-positional OSA patients (NPP) and positional OSA patients (PP), and non-OSA. METHODS: Cohort study of patients screened for OSA in 2012. Polysomnography was performed and UA was evaluated using the VOTE classification during drug-induced sleep endoscopy (DISE). Treatment outcome of MAD and UA surgery was evaluated. RESULTS: Eight hundred sixty patients were included. Higher BMI, larger neck circumference, and greater age were independent significant predictors for OSA. DISE was performed in 543 patients: 119 non-OSA and 424 OSA patients of whom 257 PP and 167 NPP patients. PP were younger, had smaller neck circumference, lower BMI and apnea-hypopnea index (AHI) than NPP. Collapse at velum (p < 0.001) and oropharynx (p < 0.001) significantly increased the odds for having OSA. Tongue base and epiglottis collapse were, on group level, not determinative for OSA or non-OSA. Complete concentric collapse (CCC) was observed less frequently in PP (31.5%) as compared to NPP (46.1%). After UA surgery, OSA often was cured or improved to less severe positional OSA. Lower efficacy of UA surgery was observed in PP as compared to NPP. No differences were observed in MAD treatment outcome. CONCLUSIONS: Current study provides insight in patients screened for OSA: collapse at velum and oropharynx significantly determined presence of OSA and CCC occurred less frequently in PP compared to NPP. In addition, residual positional dependency is common after UA surgery. More trials are needed to gain insight in pathophysiology and treatment outcome.

Subjective effects of the sleep position trainer on snoring outcomes in position-dependent non-apneic snorers.

PURPOSE: To evaluate the effect of a new-generation positional device, the sleep position trainer (SPT), in non-apneic position-dependent snorers. METHODS: Non-apneic position-dependent snorers with an apnea-hypopnea index (AHI) < 5 events/h were included between February 2015 and September 2016. After inclusion, study subjects used the SPT at home for 6 weeks. The Snore Outcome Survey (SOS) was filled out by the subjects at baseline and after 6 weeks, and at the same time, the Spouse/Bed Partner Survey (SBPS) was filled out by their bed partners. RESULTS: A total of 36 participants were included and 30 completed the study. SOS score improved significantly after 6 weeks from 35.0 ± 13.5 to 55.3 ± 18.6, p < 0.001. SBPS score also improved significantly after 6 weeks from 24.7 ± 16.0 versus 54.5 ± 25.2, p < 0.001. The severity of snoring assessed with a numeric visual analogue scale (VAS) by the bed partner decreased significantly from a median of 8.0 with an interquartile range (IQR) of [7.0-8.5] to 7.0 [3.8-8.0] after 6 weeks (p = 0.004). CONCLUSIONS: Results of this study indicate that positional therapy with the SPT improved several snoring-related outcome measures in non-apneic position-dependent snorers. The results of this non-controlled study demonstrate that this SPT could be considered as an alternative therapeutic option to improve sleep-related health status of snorers and their bed partners.

Positional therapy in patients with residual positional obstructive sleep apnea after upper airway surgery.

PURPOSE/BACKGROUND: A considerable portion of patients has residual positional obstructive sleep apnea (POSA) after upper airway surgery. Those patients could benefit from additional treatment with positional therapy (PT). The objective of this prospective study was to assess the additional effect of PT in patients with residual POSA after upper airway surgery for sleep apnea. METHODS: A polysomnography (PSG) was used to diagnose a patient with residual POSA after surgery. After informed consent, patients were treated with PT for 3 months and underwent a follow-up PSG while using the sleep position trainer (SPT). Changes in apnea-hypopnea index (AHI) and sleep position parameters were analyzed. Compliance rates and mean disease alleviation (MDA) were determined. RESULTS: Thirty-three patients with a median postoperative AHI of 18.3/h sleep were included. With the SPT median AHI dropped to 12.5/h sleep and the Epworth Sleepiness Scale (ESS) improved from 10.0 to 7.0. After 3 months, 37.5 % patients were considered responders of whom 31.3 % had treatment success. The compliance rate with SPT was 89.0 %. MDA was 44.7 % for SPT alone. With the combination of both surgery and SPT, MDA was 65.6 %. CONCLUSIONS: The results of this study indicate that additional PT in a complex OSA patient population with residual POSA after surgery can increase overall therapeutic effectiveness by improving the median MDA from 39.5 % (effect of surgery alone) to 65.6 % (effect of combining surgery and PT).

Organization and logistics of drug-induced sleep endoscopy in a training hospital.

Drug-induced sleep endoscopy (DISE) is a rapidly growing method to evaluate airway collapse in patients receiving non-CPAP therapies for sleep-disordered breathing (SDB). The growing number of DISEs has consequences for the organization of clinical protocols. In this paper we present our recent experiences with DISE, performed by an ENT resident, with sedation given by a nurse anesthetist, in an outpatient endoscopy setting, while the staff member/sleep surgeon discusses the findings and the recommended treatment proposal on the same day.

The effect of weight loss on OSA severity and position dependence in the bariatric population.

BACKGROUND: The aims of this study were to determine the prevalence of positional obstructive sleep apnea (POSA) in patients undergoing bariatric surgery and to evaluate the effect of weight loss brought about by bariatric surgery on POSA. Furthermore, the authors investigated whether body mass index (BMI), neck circumference, apnea-hypopnea index (AHI), and age are predictors for POSA. METHOD: A retrospective cohort study was conducted with data collected from patients who were screened for OSA pre-bariatric surgery and completed a follow-up polysomnography post bariatric surgery from August 2008 to November 2012. Descriptive statistics were used to characterize the prevalence of POSA patients, and the Mann-Whitney and Wilcoxon signed-rank tests were used to examine differences between the POSA and non-POSA groups. A logistic regression model was used to determine predictors for POSA. RESULTS: Thirty-four percent of patients had POSA, which is significantly lower (p<0.001) than in the general population. BMI, neck circumference, and AHI were significantly lower in POSA patients. AHI was the only significant independent predictor for POSA. Of the 91 patients analyzed following bariatric surgery, 35.2% (n=32) no longer had OSA. CONCLUSION: The prevalence of POSA in patients undergoing bariatric surgery is significantly lower than the prevalence noted in the general population. A low AHI was shown to be the only significant independent predictor for the presence of POSA.

Evaluation of position dependency in non-apneic snorers.

The aims of this study are to determine the prevalence of position dependency in non-apneic snorers, as defined by the American Academy of Sleep Medicine (AASM) guidelines, and to investigate the influence of various factors such as BMI, neck circumference, age, gender, and sleep efficiency on sleeping position. A cohort of consecutive patients was screened for complaints of excessive snoring or symptoms suspicious for sleep disordered breathing. Overnight polysomnographic data were collected and non-apneic snorers who met all the inclusion criteria were selected for statistical analysis. To assess position-dependent snoring, the snore index (total snores/h) was used. Supine-dependent patients were defined as having a supine snore index higher than their total non-supine snore index. 76 patients were eligible for statistical analysis. Prevalence of position dependency in non-apneic snorers was 65.8% (p < 0.008). A stepwise regression showed that only BMI had a significant effect (p < 0.003) on the supine snore index. This is the first study that uses the AASM guidelines to accurately define non-apneic snorers (AHI < 5) and provides scientific evidence that the majority of non-apneic snorers are supine dependent. Furthermore, these results show that non-apneic snorers with a higher BMI snore more frequently in supine position. The use of sleep position therapy therefore, has the potential to play a significant role in improving snoring and its associated physical and psychosocial health outcomes in this population.

Aseptic meningitis and ischaemic stroke in Fabry disease.

BACKGROUND: Fabry disease (OMIM 301 500) is an X-linked lysosomal storage disease. Neurological symptoms in Fabry disease mainly include stroke, acroparesthesia, cranial nerve palsies and autonomic dysfunction. We report on aseptic meningitis in Fabry patients. METHODS: Clinical analysis, brain magnetic resonance imaging, cerebrospinal fluid analysis, treatment and outcome data were analysed in three cases of meningitis associated with Fabry disease. FINDINGS: Mean age at meningitis onset was 26.6 (24-28) years. Headache was present in all cases and fever in two cases. Meningitis was always diagnosed before Fabry disease. A familial history of Fabry disease was present in two cases. Non-neurological symptoms caused by Fabry disease were present in all cases. All patients also suffered stroke and sensorineural hearing loss. Cerebrospinal fluid (CSF) analysis showed pleocytosis (mean, 36; range: 8-76 cells/mm(3)) and a high protein level (mean, 63; range, 47-70 mg/dl). C-reactive protein blood levels and erythrocyte sedimentation rate were raised. Diagnosis was assessed by low alpha-galactosidase A dosage and/or gene mutation analysis in all cases. All patients were treated with enzyme replacement therapy (ERT). In two cases, lumbar puncture was repeatedly performed and there was no normalisation of CSF under ERT alone, at 9 and 24 months of follow-up, respectively. One patient who suffered intracranial hypertension was treated efficiently with steroids, associated with azathioprine. The fact that Fabry disease could be an auto-inflammatory disorder is discussed. INTERPRETATION: Fabry disease may cause aseptic meningitis.

Behavior of Antimicrobial Peptide K4 in a Marine Environment.

K4 is a de novo peptide with antibacterial activity on human pathogens. It has a short sequence (14 amino acids), with a cationic N-terminal moiety and an amphipathic ɑ-helix structure. The present paper demonstrates its activity on Vibrio bacteria in a marine environment. It was found non-toxic on marine organisms including Artemia salina, Dicentrarchus labrax, and Magallana gigas at different developmental stages, but influenced the growth of unicellular organisms like microalgae, depending on the algal strain and on K4 concentration. Furthermore, an original approach coupling liquid chromatography (RP-HPLC) and mass spectrometry (MS/MS) allowed us to monitor the degradation time course of the peptide for the first time in conditions close to a hatchery environment, i.e., in the presence of oyster spat. We detected truncated forms over time, and the full K4 was gradually no longer found in these filter-feeder oysters. Finally, using an automated optical density meter, we monitored the growth of several aquatic bacteria identified as pathogenic on animals. K4 had a bactericidal effect on Aeromonas salmonicida and Vibrio splendidus LGP32 at concentrations below 45 µg mL-1. Our results show that K4 could be an environment-friendly alternative to antibiotics, non-toxic to several marine organisms. The use of K4 would be particularly useful to decrease the bacterial load associated with food intake in the early developmental stages of marine animals reared in hatcheries.

Evaluation of human thyroid tumors by proton nuclear magnetic resonance.

Proton nuclear magnetic resonance (NMR) was used in a study of 40 patients with thyroid tumors following partial or total thyroidectomy. Three patient groups were considered: those with nodules showing increased uptake, those with solitary nodules with decreased uptake, and those with multinodular goiters. Spin-lattice and spin-spin relaxation times (T1 and T2) were measured on samples of nodular and extranodular tissue from each patient. Increased T1 and T2 were observed for benign cold nodules, an increase in T1 alone for nodules with increased uptake, and a wide fluctuation in T1 and T2 for multinodular goiters. The four cancers in the series did not show a distinctive proton NMR pattern in comparison with the other nodular structures studied. The results point to the feasibility of applying NMR techniques to the detection of thyroid disease.

Proton nuclear magnetic resonance of regenerating rat liver after partial hepatectomy.

Spin-lattice (T1) and spin-spin (T2) proton nuclear magnetic resonance relaxation times were measured over a 48-hours period of experimental liver regeneration in Wistar rats. T2 showed an early significant increase reaching a plateau 30% above baseline from the 10th hrs onwards. Laparotomized control animals showed no change in T2 values. The increase in T1 occurred at a later stage but was no different from that in laparotomized controls. T1 reached a peak, 20% above baseline, around the 30th hr. The changes observed were far less marked than those previously described for cancer tissue, which showed about a 60% increase in T1. Liver T1 fluctuations followed a circadian pattern, with a minimum at night's end and a maximum around mid-day. No circadian rhythm was seen for T2. The observed T1 and T2 changes were discussed with respect o mitotic and metabolic events known to occur during regeneration of the liver.

Proton NMR spectroscopy of plasma lipoproteins in the experimental Lewis lung carcinoma.

Plasma and fractionated lipoproteins from 40 Lewis Lung Carcinoma grafted mice were tested from the first day up to the fatal issue by biochemical analyses and water suppressed 1H NMR spectroscopy. We have confirmed first, that the 1H NMR spectra of plasma lipoproteins are modified by the tumoral state and could provide a useful marker of the disease as long as they are used for individual follow-up with appropriate spectral parameters. Using fractionated lipoproteins we have demonstrated secondly, that the observed spectral modifications do not result from a specific cancer lipoprotein but from quantitatively modified ratio between Very Light Density Lipoproteins and High Density Lipoproteins.

[Prospects for the application of 31-phosphorus NMR to the surveillance of anticancer treatment]. / Perspectives d'application de la RMN du phosphore 31 à la surveillance des traitements anticancéreux.

The use of surface coils has allowed the extend of 31P NMR spectroscopy applications to in vivo studies. This technique is particularly interesting in following the energy metabolism of subcutaneously transplanted tumors in animals and in supervising their treatments. The results already published in this domain, if not all homogeneous, show that some 31P NMR spectral changes give informations about the metabolic state, so on the therapeutic action. Thus radiations, hyperthermia and chemotherapeutic agents effects can be precociously revealed because spectral changes occur before the tumoral mass decreases. This non-invasive method enables a regular treatment follow-up.

Buttress pinning in the unstable distal radial fracture. A modification of the Kapandji technique.

Between 1989 and 1993, 20 patients with distal radial fractures were treated with a buttressing technique felt to be safe, effective and simple. Out of the initial 20 patients, 16 have been followed-up and are reported. The technique uses an intramedullary styloid pin and a combined extramedullary-intramedullary dorsal buttress pin. The insertion technique and the use of a medial corner pin are illustrated. Results are evaluated from both final X-ray appearance as well as return of function using the five X-ray parameters of Abbasazadegan et al (1989) and the Mayo modification of the Green and O'Brien wrist score (Cooney et al, 1987). The average score on return of function was 78 (two excellent, eight good, six fair). Final axial shortening averaged -1.4 mm (+5 mm--4 mm), radial displacement averaged 0.68 mm (0 mm-5 mm), radial angle averaged 24.75 degrees (18 degrees-34 degrees), dorsal angle averaged +8.25 degrees (-5 degrees-25 degrees) and dorsal displacement averaged +1.31 (0 mm(-)+12 mm). From this study we recognize the need for a posterior medial pin, and that routine stress views after pinning can yield information concerning carpal instability, palmar instability and the need for bone grafting.

Open reduction and internal fixation method for fractures at the proximal interphalangeal joint.

When fragment size and mineralization permit, unstable and displaced proximal interphalangeal joint fractures can be secured in an anatomic position by any one of a number of direct (through the fragments) or indirect (buttress) pinning or screw fixation techniques. Transcutaneous or limited open reduction and fixation techniques are preferred in an effort to minimize additional soft tissue trauma and scarring. Plating is reserved for fractures otherwise difficult, if not impossible, to retain. The objectives of these internal fixation techniques are pain control and early active functional restoration.

[Epidemiologic and clinical study of leptospirosis in Bourail (New Caledonia)]. / Etude épidémiologique et clinique de la leptospirose à Bourail (Nouvelle Calédonie).

Leptospirosis is a frequent zoonosis in New Caledonia, mostly in the Bourail area, with an incidence of 9.5/1000 inhabitants. This town is an important cross-roads between the main town, Noumea, and the bush. An agricultural show takes place every year in this town, concentrating a great number of domestic animals and several thousand people coming from all over the island. A study was carried out on 78 patients with leptospirosis. The patients were mostly men (70%) of all ages of Melanesian and European origin. People who were living in the bush were more often attacked by leptospirosis than people living in towns. There were two annual peak values (March-April and July-August). Three symptoms (fever, headache, myalgia) were frequent (56%). Leucocytosis increased in 45% of cases. The serogroup icterohaemorrhagiae was the more common (38%). After treatment by penicillin, patients recovered in 83% of cases, but a fatal outcome occurred in 4 patients. An information campaign was necessary in order that people seek medical care as soon as the first symptoms appeared. At present, vaccination does not seem to be possible in such a context.

[Nuclear magnetic resonance study of the thyroid tissue according to its histology]. / Etude par résonance magnétique nucléaire du tissu thyroïdien en fonction de son histologie.

To date, T1 and T2 proton relaxation times in Nuclear Magnetic Resonance have not been widely studied in thyroid disorders. In an earlier study, we compared 99mTc and histological data with T1 and T2 relaxation times. We found that nodules heterogeneity affect NMR results. This should therefore be taken into account when interpreting magnetic resonance images. The purpose of the present study was to compare T1 and T2 in thyroid tissues according to the diagnosis and the different histological components which had been quantitative defined by histomorphometric methods. 71 samples from 43 patients were examines: 35 euthyroid multiheteronodular goitres, 5 hot nodules, 2 papillary carcinomas, 1 Basedow's disease. The results show that image interpretation according to histology is difficult.