Anaesthetic hypersensitivity reactions in France between 2011 and 2012: the 10th GERAP epidemiologic survey.

BACKGROUND: Immediate hypersensitivity reactions during anaesthesia are rare but potentially life-threatening. The epidemiology changes with time and evolving professional practice, and hence needs to be monitored. Our objective was to follow this epidemiology. METHODS: This was a retrospective, observational study in French hospital clinics, conducted by GERAP members (Groupe d'Étude des Réactions Anaphylactoïdes Périopératoires). Consecutive patients seen in allergo-anaesthesia outpatient clinics, who had experienced a hypersensitivity reaction during anaesthesia between 1 January 2011 and 31 December 2012, were included. Demographic data, allergy history, drugs received before the reaction, symptoms of the reaction, results of blood samples (histamine, tryptase, IgE-specific assays), and results of the allergy assessment were recorded. RESULTS: The most common causes of allergic reactions were (Neuromuscular Blocking Agents) NMBAs (N = 302; 60.6%), antibiotics (N = 91, 18.2%, Cephalosporin N = 49, 10%) and dyes (N = 27; 5.4%). Latex as an allergic agent was involved in 26 cases (5.2%), hypnotics in 11 cases (2.2%) and opioids in seven cases (1.4%). Of the NMBAs, Rocuronium had the highest proportion of reactions (13.8 reactions/100,000 vials sold) followed by Suxamethonium (13.3/100,000 vials sold). Cisatracurium had the lowest proportion of reactions (0.4/100,000 vials sold). Patients were sensitized to two or more NMBAs in 48.9% of cases and without testing, cross-sensitivity cannot be predicted. CONCLUSIONS: When compared with the previous GERAP studies, NMBAs are still the most frequently triggering allergens, with marked differences between individual NMBAs, but they are now followed by antibiotics (of which greater than 50% were cephalosporins) and dyes. Anaesthetists must be aware of the differences between drugs and of the pattern of emerging allergens. For the future of safe anaesthesia, allergy assessment is essential.

[Tigecycline: CMI 50/90 towards 1766 Gram-negative bacilli (3rd generation cephalosporins resistant enterobacteriaceae), Acinetobacter baumannii and Bacteroides fragilis group, University Hospital - Montpellier, 2008-2011]. / Tigécycline : CMI 50/90 vis-à-vis de 1766 bacilles à Gram-négatif (entérobactéries résistantes aux céphalosporines de troisième génération), Acinetobacter baumannii et Bacteroides du groupe fragilis, CHU - Montpellier, 2008-2011.

Tigecycline is a new glycylcyclin with a wide spectre including multi-resistant bacteria. Our laboratory tests in routine the in vitro activity of the TGC towards clinically significant isolates of 3rd generation cephalosporins resistant enterobacteriaceae (EC3R), Acinetobacter baumannii and Bacteroides fragilis group (BFG). The objective of this study is to describe the in vitro activity of TGC against these strains isolated between 2008 and 2011 in the university hospital of Montpellier. In this study period, 1070 isolates EC3R including 541 extended spectrum ß-lactamase-producers (ESBL) strains, 47 isolates of A. baumannii including 40 multi-resistant isolates and 645 isolates of BFG were tested. Minimum inhibitory concentrations (MIC) were determined using the E-test method. TGC was active against 86.2% of EC3R with a MIC 90 less or equal to 1mg/L (Escherichia coli being the most sensitive species). A. baumannii and BFG were also inhibited at low concentrations of TGC with a MIC 90 less or equal to 2mg/L respectively for 47% and 84.2% of the isolates. Our study confirms the activity of TGC against the EC3R including ESBL-producers strains. The relevance of the therapeutic use of TGC on the BFG isolates with a MIC greater than 2mg/L should be better documented. Often prescribed in therapeutic impasse, the proper use of TGC would require: clarifying the threshold of sensitivity for some species (i.e., A. baumannii, Bacteroides fragilis group); a better understanding of correlation between in vitro and in vivo activity.

Surgery versus conservative care for Rathke's cleft cyst.

BACKGROUND: Rathke's cleft cysts are benign cystic lesions of the sellar region, which may cause headache, pituitary deficiencies and visual disturbances from mass effect. Their management is not standardized yet. This study is about establishing a consensus for medical care of RCC. MATERIAL AND METHODS: We performed a retrospective observational study of all patients that were diagnosed or followed for RCC between 2008 and 2018 (11 years), in the neurosurgical and the adult endocrine departments of our institution. The study's average time length of follow-up is 72.9 months (from 2 to 385 months). RESULTS: The 57 included patients were divided into 2 groups: group A, which included 39 patients that were conservatively managed and group B, which included 18 surgically treated patients. Group A showed either an improvement or a spontaneous resolution of headaches in 56.1% of the cases (P<0.01); a resolution of hyperprolactinemia in 70% of the cases (P=0.21); and of hypogonadism, ACTH deficiency, growth hormone deficiency in 100% of the cases. There was no spontaneous improvement of visual disturbances (P<0.01) or diabetes insipidus (P=0.29) during follow-up. Regarding group B, surgery allowed improvement or complete resolution of headaches in 60% of the cases; visual troubles in 100% of the cases (P<0.01); and hyperprolactinemia in 100% of the cases. Pituitary deficiencies were not improved by surgery. CONCLUSIONS: This study offers guidance in decision-making regarding the management of RCC patients. Surgery is particularly suitable for treating visual disturbances caused by RCC. Regular follow-up is more appropriate than surgery concerning headaches, hyperprolactinemia, endocrine disruptions and diabetes insipidus.

Hearing preservation and facial nerve function after microsurgery for intracanalicular vestibular schwannomas: comparison of middle fossa and retrosigmoid approaches.

PURPOSE: Therapeutic options for vestibular schwannomas (VS) include microsurgery, stereotactic radiosurgery and conservative management. Early treatment of intracanalicular vestibular schwannomas (IVS) may be advisable because their spontaneous course will show hearing loss in most cases. Advanced microsurgical techniques and continuous intraoperative monitoring of cranial nerves may allow hearing preservation (HP) without facial nerve damage. However, there are still controversies about the definition of hearing preservation, and the best surgical approach that should be used. METHODS: In this study, we reviewed the main data from the recent literature on IVS surgery and compared hearing, facial function and complication rates after the retrosigmoid (RS) and middle fossa (MF) approaches, respectively. RESULTS: The results showed that the average HP rate after IVS surgery ranged from 58% (RS) to 62% (MF). HP varied widely depending on the audiometric criteria that were used for definition of serviceable hearing. There was a trend to show that the MF approach offered a better quality of postoperative hearing (not statistically significant), whereas the RS approach offered a better facial nerve preservation and fewer complications (not statistically significant). CONCLUSIONS: We believe that the timing of treatment in the course of the disease and selection between radiosurgical versus microsurgical procedure are key issues in the management of IVS. Preservation of hearing and good facial nerve function in surgery for VS is a reasonable goal for many patients with intracanalicular tumors and serviceable hearing. Once open surgery has been decided, selection of the approach mainly depends on individual anatomical considerations and experience of the surgeon.

[Micronutrients in parenteral nutrition]. / Micronutrientes en nutrición parenteral.

At a multidisciplinary debate, and after reviewing the evidence available as well as experts' opinion, the IV Baxter-SENPE Working Panel established the indications and managemente guidelines for micronutrients (water-soluble and fat-soluble vitamins, and oligoelements or trace elements) in parenteral nutrition. It was concluded about the convenience of daily intake of micronutrients with diferent options regarding deficiente or excessive dosages, administration systems, interactions, monitoring, and cots-effectiveness.

Heart rate differences between symptomatic and asymptomatic Brugada syndrome patients at night.

OBJECTIVE: Ventricular arrhythmias in Brugada syndrome (BS) mainly occur at rest, especially during nighttime, suggesting that parasympathetic activity at night may play an important role in the arrhythmogenesis of the disease. This study examined and compared the autonomic function of symptomatic and asymptomatic BS patients overnight. APPROACH: We analyzed various heart rate variability (HRV) and heart rate complexity (HRC) markers in a clinical series including 87 BS patients, where 23 were symptomatic. MAIN RESULTS: Statistically significant differences were found in markers MIRR, SDNN, SDANN, [Formula: see text] and SampEn, suggesting that symptomatic patients may be related to lower heart rate variability and complexity values, as well as to greater circadian fluctuations overnight. SIGNIFICANCE: The results provide further evidence for the role of autonomic imbalance in the pathophysiology of BS, highlighting the relevance of nighttime analysis to the unmasking of significant ANS changes. Based on these outcomes, the role of HRV and HRC assessment at night could be a step forward towards the understanding of BS and the risk for the occurrence of symptoms in these patients, with a potential future impact on therapeutic strategies.

Heart rate complexity analysis in Brugada syndrome during physical stress testing.

Symptoms such as ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest, especially during sleep, suggesting that the autonomic nervous system (ANS) function may be relevant in the arrhythmogenesis of the disease. The aim of this work was to assess the ANS response captured by nonlinear heart rate variability (HRV) measures in 69 patients diagnosed with BS, who underwent a standardized physical stress test. Heart rate complexity (HRC) was evaluated by the power-law scaling analysis (ß slope) during rest, exercise, recovery and rest post-recovery, in order to discriminate between symptomatic and asymptomatic BS patients. Symptomatic patients showed a significant reduction in HRC in comparison to asymptomatic subjects, after exertion (p = 0.015); during the whole recovery period (p = 0.023), and in particular within the passive recovery phase (p = 0.025), as well as during rest post-recovery (p = 0.022). Based on these results, symptoms could be associated with a lower ANS complexity during the stress test stages where parasympathetic activity is predominant. Therefore, the proposed HRV indicators could be of help in the risk stratification of asymptomatic patients.

Chemical, Thermal and Spectroscopic Methods to Assess Biodegradation of Winery-Distillery Wastes during Composting.

The objective of this work was to study the co-composting process of wastes from the winery and distillery industry with animal manures, using the classical chemical methods traditionally used in composting studies together with advanced instrumental methods (thermal analysis, FT-IR and CPMAS 13C NMR techniques), to evaluate the development of the process and the quality of the end-products obtained. For this, three piles were elaborated by the turning composting system, using as raw materials winery-distillery wastes (grape marc and exhausted grape marc) and animal manures (cattle manure and poultry manure). The classical analytical methods showed a suitable development of the process in all the piles, but these techniques were ineffective to study the humification process during the composting of this type of materials. However, their combination with the advanced instrumental techniques clearly provided more information regarding the turnover of the organic matter pools during the composting process of these materials. Thermal analysis allowed to estimate the degradability of the remaining material and to assess qualitatively the rate of OM stabilization and recalcitrant C in the compost samples, based on the energy required to achieve the same mass losses. FT-IR spectra mainly showed variations between piles and time of sampling in the bands associated to complex organic compounds (mainly at 1420 and 1540 cm-1) and to nitrate and inorganic components (at 875 and 1384 cm-1, respectively), indicating composted material stability and maturity; while CPMAS 13C NMR provided semi-quantitatively partition of C compounds and structures during the process, being especially interesting their variation to evaluate the biotransformation of each C pool, especially in the comparison of recalcitrant C vs labile C pools, such as Alkyl /O-Alkyl ratio.

Clinical management of hyperglycaemic patients receiving total parenteral nutrition.

We evaluated the course of total parenteral nutrition (TPN) therapy in patients with hyperglycaemia. We studied 1) incidence of hyperglycaemia, 2) amount of glucose and insulin provided and 3) incidence of metabolic problems in patients receiving TPN who required insulin to attain metabolic control. The group included 91 patients, 38 women (64 +/- 15 years) and 53 men (64 +/- 12 years), who developed glycaemia higher than 200 mg/dl. Nine patients had a previous diagnosis of IDDM, 36 NIDDM and 46 secondary hyperglycaemia.. Total caloric requirements were initially supplied at 132 +/- 20% the basal energy expenditure (Harris-Benedict formula), and 1.4 +/- 0.3 g/kg of amino-acids. Initially, TPN provided 150-200 g/day of glucose (2.1 mg/kg/min). Regular insulin was added to the bag. The annual incidence of hyperglycaemia was estimated to be 121 per 1000 patients. Mean insulin requirements were 50 U/day (25 to 150 U/day), 0.7 +/- 0.3 U/kg. Comparing with prehospitalization insulin dose, 22% needed similar doses, and 11% lower doses. IDDM patients needed 1.7 times their pre-admission dose (1-4.5 times). The ratio of insulin:glucose in TPN was 0.3 +/- 0.1 U/g (0.1-1.2 U/g). Patients with renal failure had similar insulin requirements (56 +/- 26 U/day) than patients with normal renal function (49 +/- 19 U/day). None of the patients developed glycemic complications. In conclusion, diabetic patients receiving TPN have an acceptable metabolic control if individualized prescriptions and supplemental insulin are used.

Evaluation of nonglucose carbohydrates in parenteral nutrition for diabetic patients.

OBJECTIVE: There is little information on the advantages of nonglucose carbohydrates in total parenteral nutrition (TPN) for diabetic patients. The aim of this study is to evaluate glycemic control and insulin requirements in diabetic patients who received TPN with different sources of carbohydrates, and to determine whether insulin requirements are different when septic and non-septic diabetic patients are studied. MATERIALS AND METHODS: One-hundred and thirty-eight patients were randomly divided into two groups receiving either glucose (G), n=71, or glucose-fructose-xylitol 2:1:1 (GFX), n=67. There were no differences between the demographic or anthropometric characteristics of the groups, nor between the patients with diabetes mellitus type 1 and type 2, nor the initial TPN composition. Acceptable glycemic control was considered when glycemia reached <200 mg/dl. RESULTS: Glycemic control was attained in 79.7% of patients (74.6 vs 85.1%), in the same period of treatment. At the end of treatment, insulin requirements were not different (45+/-19 vs 45+/-26 UI/day) in both groups, while similar amounts of carbohydrates (191+/-36 vs 187+/-45 g/day) were infused. The ratio insulin/body weight and insulin/carbohydrates were equal in both groups. In the GFX group nonseptic and septic patients needed less and more insulin, respectively, than their counterparts in the G group. No major adverse events related to carbohydrate infusions were observed. CONCLUSIONS: Either G or GFX could be used in TPN for diabetic patients, providing glycemic control in most cases with similar insulin requirements. GFX mixtures were slightly more beneficial to attain glycemic control in nonseptic patients, but septic diabetic patients had higher insulin needs in this group.

Analysis of abnormal signals within the QRS complex of the high-resolution electrocardiogram.

This paper presents a new, quantitative approach to measuring abnormal intra-QRS signals, using the high-resolution electrocardiogram (HRECG). These signals are conventionally known as QRS "notches and slurs." They are measured qualitatively and form the basis for the ECG identification of myocardial infarction. The HRECG is used for detection of ventricular late potentials (LP), which are linked with the presence of a reentry substrate for ventricular tachycardia (VT) after a myocardial infarction. LP's are defined as signals from areas of delayed conduction which outlast the normal QRS period. Our objective is to quantify very low-level abnormal signals that may not outlast the normal QRS period. In this work, abnormal intra-QRS potentials (AIQP) were characterized by removing the predictable, smooth part of the QRS from the original waveform. This was represented as the impulse response of an ARX parametric model, with model order selected empirically from a training data set. AIQP were estimated using the residual of the modeling procedure. Critical AIQP parameters to separate VT and non-VT subjects were obtained using discriminant functions. Results suggest that AIQP indexes are a new predictive index of the HRECG for VT. The concept of abnormal intra-QRS potentials permits the characterization of pathophysiological signals contained wholly within the normal QRS period, but related to arrhythmogenesis. The new method may have other applications, such as detection of myocardial ischemia and improved ECG identification of the site of myocardial infarction, particularly in the absence of Q waves.

[Home parenteral nutrition. A six-year combined program (adult and pediatric patients)]. / Nutrición parenteral domiciliaria. Experiencia de un programa combinado (adultos-niños) a lo largo de 6 años.

BACKGROUND: To describe the outcomes of an adult-pediatric home parenteral nutrition (HPN) program. PATIENTS AND METHODS: Retrospective protocol between 1993 and 1999. RESULTS: Sixteen adults (average 45.7 years) and eight children (3.1 years) were included in the program. Mean length of parenteral nutrition was 507 (SD: 624) and 155 (SD: 129) days respectively. Total follow-up time was 8,119 days for adults and 1,242 for children. Cancer was the main diagnosis in adults and intractable diarrhea in children. Central venous catheter related infections were the most usual complication (0.63 and 1.2 episodes/patient/year). There were no deceases due to the HPN in the period of study. CONCLUSIONS: HPN is an effective and safe technique, although prevalence and incidence in Spain are low.

[Stability of theophylline in mono- and multi-layer parenteral nutrition bags]. / Estabilidad de teofilina en bolsas de nutrición parenteral unicapa y multicapa.

The addition of drugs to parenteral nutrition (PN) presents a high risk of physical and chemical incompatibilities. In certain patients with water restriction or limited vein access, however, it may be necessary to add medicines to PN. Although there are numerous studies into the stability of aminophylline in PN, all of them refer to periods of less than 2 days. The purpose of the present study is to determine the stability of anhydrous theophylline over 24 hours at room temperature in 24 hours parenteral nutrition and over five days (four days stored in refrigerator and 24 hours at room temperature). In addition, to assess whether its degradation is affected by the use of single-layer or multi-layer bags. The composition of PN corresponds to a standard 1,800 Kcal diet at our hospital with a concentration of 0.164 mg/ml of anhydrous theophylline. No statistically significant differences were obtained in any of the cases studied, thus demonstrating the stability of theophylline under our study conditions both after 24 hours at room temperature and after four days of storage in the refrigerator followed by 24 hours at room temperature. Nor were differences found between storing the drug in single-layer and multi-layer bags.

["All in one" parenteral nutrition: is it that safe?]. / Nutrición parenteral "todo en uno": es tan segura?

The use of "all in one" admixtures is supported by an extensive number of studies and by many years of experience. However, we detected stability problems in some mixtures whose stability was previously reported. We made modifications in one of these mixtures [composed of 1.000 ml Freamine 8.5%, 100 ml 10% dextrose, 500 ml water, 500 ml Intralipid 20%, 75 ml electrolyte solution (Na 75 mEq, K 60 mEq, Ca 15 mEg, Mg 15 mEq, Cl 90 mEq, acetate 75 mEq)] in order to see how the different components affect the emulsion stability. All the admixtures were visually inspected after storage during 24 hour at room temperature. It was observed that admixtures with low glucose concentration, high electrolyte levels and high volume were less stable than admixtures containing high glucose, low electrolyte and low volume. Amino acid concentration did not increased the stability as expected. MCT/LCT emulsions were more stable than LCT emulsions. More studies are needed to explain the stability problems of these TPN solutions.

[Interest and feasibility of a modified supine position for posterior cranial fossa surgical procedures]. / Chirurgie de la fosse postérieure en décubitus dorsal modifié: faisabilité et intérêt.

The sitting position is considered as a gold standard for posterior fossa surgical procedures. However, in order to decrease the incidence rate of cerebral venous air embolisms, we presently described a modified supine position allowing performance of posterior fossa surgical procedures. Such position is easy and quickly performed with light variations of blood pressure: patients are placed supine with paddings inserted under ipsilateral shoulder and buttock, and head turned to other side of surgical site. Dural tension estimated by the surgeon was always considered as good. We performed more than 100 surgical procedures in this position without any complication for 10 years.

[Intraoperative posture in the surgery of lumbar disk hernia]. / Etude des positions opératoires pour la chirurgie de la hernie discale lombaire.

For surgery of the lumbar disc, with a posterior route, the patient is placed either in a prone, or a knee-chest, or a lateral position. They aim at facilitating the surgical access in decreasing local bleeding and collapsing the dural sheath. This benefit, as a result of the maintenance of the pressure in the epidural venous system at a low level, is obtained through the absence of any abdominal compression as well as the posture. In the prone position, the abdominal compression and the increase of the physiologic lordosis impair the systemic venous return and carry the risk of cardiac arrest. In addition to these adverse effects, the conventional knee-chest position increases the haemodynamic repercussions in modifying the distribution of blood volume and increasing the potential risk of mediastinal compression and air embolism. The lateral position generates only minor haemodynamic modifications, except in the obese. However it is difficult to stabilize the patients' position and to maintain the alignment of the spine. Therefore it is used the less one. The postural risks of all three positions are numerous and include mainly the compression of nerves, vessels and skin. Finally the selection of the position depends basically on morphological criteria and the adaptative capacities of the patient. The optimal position is the one offering a low pressure level in the spinal venous system, while maintaining the venous return.

[Blood volume changes caused by position under general anesthesia]. / Modifications volémiques induites par la position sous anesthésie générale.

The cardiovascular changes in response to general anaesthesia are related to several interacting mechanisms. In addition to the intrinsic effects of anaesthetic agents on the heart and vessels which depress the physiological mechanisms of adaptation, the additive independent effects of posture and mechanical ventilation on intravascular blood volume have to be considered. Physiopathologic studies show that the ultimate related mechanism is the decrease of venous return to the heart. The major effect of posture is the change in the distribution of the blood volume, as the posture modifies the influence of gravity in addition to direct vascular compression and stretching. The deterioration of the cardiac venous return results in dramatic or insidious clinical consequences which lead finally to a low cardiac output. As cardiac function is not a limiting factor of output, any decrease of blood pressure in a patient with a healthy heart must be considered as an hypovolaemic state due to an abnormal contents to container ratio, and must be managed as such.

[Problems posed by spinal anesthesia in a patient with Gélineau disease]. / Problèmes posés par une rachianesthésie chez un patient atteint de la maladie de Gélineau.

A 44-year-old patient, with narcolepsy-cataplexy, underwent surgery for lumbar disk hernia under spinal anaesthesia. Our purpose was to prevent an interaction between the patient's disease and general anaesthetic agents with the risk of postoperative hypersomnia. During surgical procedure, two narcolepsy fits occurred, without clinical consequences. The postoperative course was uneventful. However, spinal anaesthesia cannot be considered as a technique of choice because of the risk of narcolepsy-cataplexy fits with loss of consciousness and atonia, during regional anaesthesia. General anaesthesia seems to be the best choice for these patients cholinergic agents and mainly the alpha1 adrenergic blocking drugs are contra-indicated as they increase the risk of narcolepsy-cataplexy fits. Anaesthetic sleep, narcolepsy, cataplexy and epilepsy are clinically rather similar. The EEG does not allow to differentiate between narcolepsy and anaesthetic-sleep, whereas cataplexy and epilepsy result in specific EEG patterns.

[Bilateral sciatica: a predictive sign of extradural hematoma after lumbar disk herniation]. / Sciatalgies bilatérales: un signe prédictif d'hématome extradural après cure de hernie discale lombaire.

The authors analyse five cases, in order to recognize a sensitive early clinical feature of extradural haematoma following lumbar diskectomy. Neither time delay (time from surgery to the suspicion of the diagnosis) nor pain intensity (a subjective factor which might be obtunded by an analgesic drug) are valuable features. The only reliable predictive sign is bilateral sciatica, which occurred in all cases, before the diagnosis was confirmed by a sensitive and motor deficit in the lower limbs.

[Initial prognostic factors of aneurysmal subarachnoid hemorrhage]. / Facteurs pronostiques initiaux des hémorragies méningées d'origine anévrysmale.

The purpose of this retrospective study is to explain, using a total of 210 consecutive patients with aneurysmal subarachnoid hemorrhage, the survival by several prognostic factors measured at the admission time. A multivariate analysis using the Cox proportional hazards model allowed one to recognize five prognostic factors: secondary arterial hypertension (risk ratio (RR) = 1.8; p = 0.03), the Hunt and Hess grade-3 (RR = 3.3; p = 0.002), the Hunt and Hess grade-4 (RR = 7.3; p = 0.007), and the hunt and Hess grade-5 (RR = 5.8; p = 0.03), the Fisher grade-3 (RR = 2; p = 0.01), and the Fisher grade-4 (RR = 2; p = 0.001). The determination of a prognostic score for each patient (using the coefficients of selected prognostic factors) allowed one to establish 3 prognostic stages with survival probabilities significantly different (p = 0.00005); stage-1; survival rate after 150 days (SR) = 97 %, confidence interval of 95 % (CI) = [0.90; 0.99], stage-2: SR = 66 %, CI = [0.56; 0.74], stage-3; SR = 34 %, CI = [0.17; 0.54]. The relative death risk for the stage-2 was 14 times higher than that for stage-1 (p = 0.00005), and the relative death risk for the stage-3 was 36 times higher than that for stage-1 (p = 0.00005). The age, the essential arterial hypertension, the sex and the angiographic classification of George have no prognostic value. The rebleeding incidence was correlated with prognostic stages (respectively from stage-1 to the stage-3: 8 %, 14 %, 34 %).(ABSTRACT TRUNCATED AT 250 WORDS)