ABSTRACT
BACKGROUND: We investigated alterations of human microbiota under anti-TB therapies in relationship to the level of Mycobacterium tuberculosis drug response. METHODS: Stool, sputum, and oral swab samples were analysed from participants with treatment-naïve TB and participants treated for drug-susceptible TB (DS-TB), drug-resistant TB without injectable drugs (DR-TB-inj-), or with injectable drugs (DR-TB-inj+) at 27-42 days of therapy. RESULTS: From September 2018 to December 2019, 5 participants with treatment-naïve TB, 6 participants with DS-TB, 10 participants with DR-TB-inj-, and 4 participants with DR-TB-inj+ were recruited. Reduced alpha diversities in stool samples indicated more profound dysbiosis in participants treated for DR-TB than in participants treated for DS-TB (-12% (non-significant) for DS-TB, -44% (P < 0.001) for DR-TB-inj-, and -60% (P < 0.05) for DR-TB-inj+ compared to treatment-naïve participants). While reduced abundances were observed in numerous taxa, genus Lactobacillus revealed the most substantial abundance increase in sputa of participants treated for DR-TB compared to treatment-naïve ones (P < 0.05 for DR-TB-inj- and DR-TB-inj+). Notably, a group of nosocomial pneumonia-associated taxa was increased in oral swabs of the DR-TB-inj+ compared to the treatment-naïve group (P < 0.05). CONCLUSIONS: Second-line anti-TB therapy in participants with DR-TB results in altered microbiota, including reduced alpha diversity and expansion of phylogenetically diverse taxa, including pathobionts.
CONTEXTE: Nous avons étudié les altérations du microbiote humain sous traitements anti-TB en lien avec le niveau de réponse médicamenteuse de Mycobacterium tuberculosis. METHODES: Des échantillons de selles, d'expectorations et d'écouvillons buccaux ont été examinés chez des participants n'ayant jamais reçu de traitement contre la TB et des participants traités pour une TB sensible aux médicaments (DS-TB), une TB résistante aux médicaments sans médicaments injectables (DR-TB-inj), ou avec des médicaments injectables (DR-TB-inj+) après 27 à 42 jours de traitement. RESULTATS: De septembre 2018 à décembre 2019, 5 participants atteints de TB naïve, 6 participants atteints de DS-TB, 10 participants atteints de DR-TB-inj et 4 participants atteints de DR-TB-inj+ ont été sélectionnés. La diminution des diversités alpha dans les échantillons de selles indique une dysbiose plus profonde chez les participants traités pour la DR-TB que chez les participants traités pour la DS-TB (12% (non significatif) pour la DS-TB, 44% (P < 0,001) pour la DR-TB-inj, et -60% (P < 0,05) pour la DR-TB-inj+ par rapport aux participants n'ayant jamais reçu de traitement). Bien que des abondances réduites aient été observées dans de nombreux taxons, le genre Lactobacillus a montré la plus forte augmentation d'abondance dans les expectorations des participants traités pour la DR-TB par rapport aux participants non traités (P < 0,05 pour DR-TB-inj et DR-TB-inj+). En particulier, un groupe de taxons associés à la pneumonie nosocomiale était plus abondant dans les écouvillons oraux du groupe DR-TB-inj+ par rapport au groupe non traité (P < 0,05). CONCLUSIONS: Le traitement anti-TB de deuxième ligne chez les participants atteints de DR-TB entraîne des changements dans le microbiote, notamment une diminution de la diversité alpha et une expansion de taxons phylogénétiquement diversifiés, y compris les pathobiontes.
ABSTRACT
BACKGROUND: A post-authorisation safety study (PASS) on delamanid (DLM) was conducted as part of a post-approval commitment to the European Medicines Agency. The aim of this study was to evaluate the use of DLM in a real-life setting, its safety, and treatment outcomes in patients with multidrug-resistant TB (MDR-TB). METHODS: This was a prospective, multicentric, non-interventional study conducted in the European Union. MDR-TB Regimen selection and patient monitoring were conducted in accordance with existing medical practices. Data on the use of DLM, related adverse events, and treatment outcomes were collected for up to 30 months after the first DLM dose. Descriptive summary statistics were used for continuous and categorical variables. RESULTS: Out of 86 patients, one had extrapulmonary TB. Two-thirds of the patients were treated with DLM for more than 24 weeks. The most frequent adverse drug reaction to DLM was QT interval prolongation. Resistance to DLM was detected in one patient during treatment. The treatment success rate was 77%. CONCLUSION: No new safety concerns were revealed, including in patients treated with DLM for more than 24 weeks. QT interval prolongations were well managed and did not lead to any clinically significant cardiac effects. The treatment outcomes were in line with the WHO target for Europe.
CONTEXTE: Une étude de sécurité post-autorisation (PASS) sur le délamanide (DLM) a été menée dans le cadre d'un engagement post-approbation auprès de l'Agence européenne des médicaments. L'objectif de cette étude était d'évaluer l'utilisation du DLM dans un contexte réel, son innocuité et les résultats du traitement chez les patients atteints de TB multirésistante (MDR-TB). MÉTHODES: Il s'agissait d'une étude prospective, multicentrique et non interventionnelle menée dans l'Union européenne. La sélection du schéma thérapeutique de la MDR-TB et le suivi des patients ont été effectués conformément aux pratiques médicales existantes. Les données sur l'utilisation du DLM, les effets indésirables connexes et les résultats du traitement ont été recueillies jusqu'à 30 mois après la première dose de DLM. Des statistiques sommaires descriptives ont été utilisées pour les variables continues et catégorielles. RÉSULTATS: Sur 86 patients, un avait une TB extrapulmonaire. Les deux tiers des patients ont été traités avec du DLM pendant plus de 24 semaines. L'effet indésirable le plus fréquent du DLM était l'allongement de l'intervalle QT. Une résistance au DLM a été détectée chez un patient pendant le traitement. Le taux de réussite du traitement était de 77%. CONCLUSION: Aucun nouveau problème de sécurité n'a été révélé, y compris chez les patients traités par le DLM pendant plus de 24 semaines. Les allongements de l'intervalle QT ont été bien gérés et n'ont pas entraîné d'effets cardiaques cliniquement significatifs. Les résultats du traitement étaient conformes à l'objectif de l'OMS pour l'Europe.
Subject(s)
Refugees , Humans , Ukraine/epidemiology , Antitubercular Agents/therapeutic use , Mass ScreeningABSTRACT
INTRODUCTION: Gyrate atrophy (GA) is a rare retinal dystrophy due to biallelic pathogenic variants in the ornithine aminotransferase (OAT) gene, causing a 10-fold increase in plasma ornithine levels. It is characterized by circular patches of chorioretinal atrophy. However, a GA-like retinal phenotype (GALRP) without elevated ornithine levels has also been reported. The aim of this study is to compare the clinical characteristics of GA and GALRP and to identify possible discriminators. METHODS: A multicenter, retrospective chart review was performed at three German referral centres on patient records between 01/01/2009 and 31/12/2021. Records were screened for patients affected by GA or GALRP. Only patients with examination results for plasma ornithine levels and / or genetic testing of the OAT gene were included. Further clinical data was gathered where available. RESULTS: Ten patients (5 female) were included in the analysis. Three suffered from GA, while seven had a GALRP. Mean age (± SD) at onset of symptoms was 12.3 (± 3.5) years for GA compared with 46.7 (± 14.0) years for GALRP patients (p = 0.002). Mean degree of myopia was higher in GA (-8.0 dpt. ± 3.6) compared to GALRP patients (-3.8 dpt. ± 4.8, p = 0.04). Interestingly, all GA patients showed macular oedema, while only one GALRP patient did. Only one patient with GALRP had a positive family history, while two were immunosuppressed. DISCUSSION: Age of onset, refraction and presence of macular cystoid cavities appear to be discriminators between GA and GALRP. GALRP may encompass both genetic and non-genetic subtypes.
Subject(s)
Gyrate Atrophy , Humans , Female , Child , Adolescent , Gyrate Atrophy/diagnosis , Gyrate Atrophy/genetics , Retrospective Studies , Retina/pathology , Phenotype , Ornithine , Atrophy/pathologyABSTRACT
BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
Subject(s)
Tuberculosis , Humans , Biological Specimen Banks , Tuberculosis/drug therapy , Clinical Trials as TopicABSTRACT
BACKGROUND: Photodynamic therapy (PDT) was originally approved for the treatment of neovascular age-related macular degeneration (nAMD) and secondary choroidal neovascularization in myopia (mCNV). In addition, it is used as an off-label treatment in patients with choroidal hemangioma, polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). OBJECTIVE: To track the development of PDT treatment numbers in Germany between 2006 and 2021 and to investigate the composition of the therapeutic indications. METHODS: In this retrospective study the quality reports of German hospitals were evaluated in the period from 2006 to 2019 and the number of PDTs performed was recorded. In addition, the range of indications for PDT was determined exemplarily for the Eye Center at Medical Center, University of Freiburg and the Eye Center at St. Franziskus Hospital in Münster between 2006 and 2021. Finally, the estimated prevalence of CSC and an estimate of cases requiring treatment were used to calculate the number of patients in need of PDT treatment in Germany. RESULTS: The number of PDTs performed in Germany decreased from 1072 in 2006 to 202 in 2019. While PDT was used in 86% of cases in patients with nAMD and in 7% of cases with mCNV in 2006, it was mainly performed in patients with CSC (70%) and choroidal hemangiomas (21%) from 2016 to 2021. With an estimated incidence of CSC of 1:10,000 and assuming that 16% of patients develop chronic CCS requiring treatment, approximately 1330 PDTs would need to be performed per year in Germany for patients with newly diagnosed chronic CSC alone. CONCLUSION: The decreasing numbers of PDT treatment performed in Germany is mainly due to a change to intravitreal injections as the preferred treatment for nAMD and mCNV. As PDT is currently the recommended treatment of choice for chronic CSC, an underprovision of PDT in Germany can be assumed. To enable an appropriate treatment for patients, a reliable verteporfin production, a simplified approval process by health insurance companies and a close cooperation between ophthalmologists in private practice and larger centers are urgently needed.
Subject(s)
Choroid Neoplasms , Choroidal Neovascularization , Photochemotherapy , Humans , Photosensitizing Agents/therapeutic use , Photochemotherapy/adverse effects , Retrospective Studies , Verteporfin/therapeutic use , Choroidal Neovascularization/drug therapy , Choroid Neoplasms/complicationsABSTRACT
After several years with no real therapeutic alternatives, the management of obesity is entering a new era with the development of new surgical and endoscopic bariatric techniques, digital therapeutics and the arrival of new classes of drugs. New medication treatments aim to reduce food intake, targeting the hypothalamic regulation of food intake and satiety. The mechanism of their action remains poorly understood but, combines weight reduction and amelioration of cardiometabolic risk factors with a favorable benefit-risk balance and known side effects, mainly digestive. The future will tell us how these drugs will find their place in the management of this chronic disease that is obesity.
Subject(s)
Leptin , Obesity , Humans , Leptin/metabolism , Leptin/pharmacology , Obesity/drug therapy , Hypothalamus/metabolismABSTRACT
The Berlin Grading System assesses clinical severity of moyamoya angiopathy (MMA) by combining MRI, DSA, and cerebrovascular reserve capacity (CVRC). Our aim was to validate this grading system using [15O]H2O PET for CVRC. We retrospectively identified bilateral MMA patients who underwent [15O]H2O PET examination and were treated surgically at our department. Each hemisphere was classified using the Suzuki and Berlin Grading System. Preoperative symptoms and perioperative ischemias were collected, and a logistic regression analysis was performed. A total of 100 hemispheres in 50 MMA patients (36 women, 14 men) were included. Using the Berlin Grading System, 2 (2.8%) of 71 symptomatic hemispheres were categorized as grade I, 14 (19.7%) as grade II, and 55 (77.5%) as grade III. The 29 asymptomatic hemispheres were characterized as grade I in 7 (24.1%) hemispheres, grade II in 12 (41.4%), and grade III in 10 (34.5%) hemispheres. Berlin grades were independent factors for identifying hemispheres as symptomatic and higher grades correlated with increasing proportion of symptomatic hemispheres (p < 0.01). The Suzuki grading did not correlate with preoperative symptoms (p = 0.26). Perioperative ischemic complications occurred in 8 of 88 operated hemispheres. Overall, complications did not occur in any of the grade I hemispheres, but in 9.1% (n = 2 of 22) and 9.8% (n = 6 of 61) of grade II and III hemispheres, respectively. In this study, we validated the Berlin Grading System with the use of [15O]H2O PET for CVRC as it could stratify preoperative symptomatology. Furthermore, we highlighted its relevance for predicting perioperative ischemic complications.
Subject(s)
Cerebral Revascularization , Moyamoya Disease , Male , Humans , Female , Retrospective Studies , Moyamoya Disease/diagnostic imaging , Moyamoya Disease/surgery , Magnetic Resonance Imaging , Cerebral Revascularization/adverse effects , Positron-Emission TomographyABSTRACT
OBJECTIVE: Anti-tuberculosis (antiTB) drugs are characterized by an important inter-interindividual pharmacokinetic variability poorly predictable from individual patients' characteristics. Therapeutic drug monitoring (TDM) may therefore be beneficial for patients with Mycobacterium tuberculosis infection, especially for the management of multidrug/extensively drug resistant- (MDR/XDR)-TB. Our objective was to develop robust HPLC-MS/MS methods for plasma quantification of 15 antiTB drugs and 2 metabolites, namely rifampicin, isoniazid plus N-acetyl-isoniazid, pyrazinamide, ethambutol (the conventional quadritherapy for susceptible TB) as well as combination of agents against MDR/XDR-TB: bedaquiline, clofazimine, delamanid and its metabolite M1, levofloxacin, linezolid, moxifloxacin, pretomanid, rifabutin, rifapentine, sutezolid, and cycloserine. METHODS: Plasma protein precipitation was used for all analytes except cycloserine, which was analyzed separately after derivatization with benzoyl chloride. AntiTB quadritherapy drugs (Pool1) were separated by Hydrophilic Interaction Liquid Chromatography (column Xbridge BEH Amide, 2.1 × 150 mm, 2.5 µm, Waters®) while MDR/XDR-TB agents (Pool 2) and cycloserine (as benzoyl derivative) were analyzed by reverse phase chromatography on a column XSelect HSS T3, 2.1 × 75 mm, 3.5 µm (Waters®). All runs last <7 min. Quantification was performed by selected reaction monitoring electrospray tandem mass spectrometry, using stable isotopically labelled internal standards. RESULTS: The method covers the clinically relevant plasma levels and was extensively validated based on FDA recommendations, with intra- and inter-assay precision (CV) < 15% over the validated ranges. Application of the method is illustrated by examples of TDM for two patients treated for drug-susceptible- and MDR-TB. CONCLUSION: Such convenient extraction methods and the use of stable isotope-labelled drugs as internal standards provide an accurate and precise quantification of plasma concentrations of all major clinically-used antiTB drugs regimens and is optimally suited for clinically efficient TDM against tuberculosis.
Subject(s)
Extensively Drug-Resistant Tuberculosis , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Antitubercular Agents/therapeutic use , Extensively Drug-Resistant Tuberculosis/drug therapy , Tandem Mass Spectrometry/methods , Isoniazid/therapeutic use , Cycloserine/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , IsotopesABSTRACT
The ultrafast scattering dynamics of intersubband polaritons in dispersive cavities embedding GaAs/AlGaAs quantum wells are studied directly within their band structure using a noncollinear pump-probe geometry with phase-stable midinfrared pulses. Selective excitation of the lower polariton at a frequency of â¼25 THz and at a finite in-plane momentum k_{â} leads to the emergence of a narrowband maximum in the probe reflectivity at k_{â}=0. A quantum mechanical model identifies the underlying microscopic process as stimulated coherent polariton-polariton scattering. These results mark an important milestone toward quantum control and bosonic lasing in custom-tailored polaritonic systems in the mid and far infrared.
ABSTRACT
BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.
Subject(s)
Tuberculosis, Pulmonary , Adult , Child , Humans , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiologyABSTRACT
Treatment of tuberculosis requires rapid information about Mycobacterium tuberculosis (Mtb) drug susceptibility to ensure effective therapy and optimal outcomes. At the tuberculosis referral hospital in Windhoek, Namibia, a country of high tuberculosis incidence, we evaluated the diagnostic accuracy of a line-probe-assay (LPA), GenID, for the molecular diagnosis of Mtb infection and drug resistance in patients with suspected tuberculosis (cohort 1) and confirmed rifampin (RIF)-resistant tuberculosis (cohort 2). GenID test results were compared to Xpert MTB/RIF and/or Mtb culture and antimicrobial suceptibilty testing. GenID LPA was applied to 79 and 55 samples from patients in cohort 1 and cohort 2, respectively. The overall sensitivity of GenID LPA for the detection of Mtb DNA in sputum from patients with detectable and undetectable acid-fast bacilli by sputum smear microscopy was 93.3% (56/60; 95% confidence interval = 83.8-98.2) and 22.7% (5/22; 7.8-45.4). The sensitivity/specificity for the detection of drug resistance was 84.2% (32/38; 68.7-94.0)/100% (19/19; 82.4-100.0) for RIF, 89.7% (26/29; 72.6-97.8)/91.7% (22/24; 73.0-99.0) for isoniazid, and 85.7% (6/7; 42.1-99.6)/94.7% (18/19; 74.0-99.9) for fluoroquinolones; 23.6% of tests for second-line injectable resistance were invalid despite repeat testing. The diagnosis of tuberculosis by detection of Mtb DNA in sputum by GenID LPA depends strongly on the detection of acid-fast bacilli in sputum specimen. Prediction of drug resistance by GenID did not reach the World Health Organization (WHO) target product profile. IMPORTANCE Mycobacterium tuberculosis (Mtb) drug-resistance detection is crucial for successful control of tuberculosis. Line-probe assays (LPA) are frequently used to detect resistance to rifampin, isoniazid, fluoroquinolones (FQs), and second-line injectables (SLIs). GenID RIF/isoniazid (INH), FQ, and SLI LPA have not been widely tested and used so far. This study tested the diagnostic performance of the GenID LPA in a high-incidence TB/HIV, real-world setting in Namibia. The LPA demonstrates only an acceptable diagnostic performance for Mtb and drug-resistance detection. The diagnostic sensitivity and specificity fall short of the WHO suggested target product profiles for LPA.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Lymph Node , Tuberculosis, Multidrug-Resistant , Drug Resistance , Drug Resistance, Bacterial , Fluoroquinolones/pharmacology , Humans , Isoniazid , Mycobacterium tuberculosis/genetics , Namibia , Rifampin/pharmacology , Rifampin/therapeutic use , Tuberculosis, Lymph Node/drug therapy , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
Grasshoppers are one of the most predominant insects in the grasslands of the southern Pampas. In this region, Dichroplus elongatus, Dichroplus maculipennis, Dichroplus pratensis and Borellia bruneri are the most abundant species and have the greatest economic importance. This study aimed to assess the relationship between temporal changes in the density of these species and climate variables associated with temperature and rainfall over an 11-year study period., We monitored 22 sites in different areas of Laprida county from 2005 to 2016. A total of 25 grasshopper species were collected. The most abundant species were D. maculipennis and B. bruneri which reached the highest densities from 2008-2009 to 2010-2011. The rainfall accumulated from September (RAS) to the sampling date and the number of rainy days (RD) largely explained the density variation of B. bruneri. Besides RD and RAS, winter rainfall, rainfall accumulated from October to the sampling date, and thermal amplitude of October (TAO) influenced the density of D. maculipennis. Our results indicated that seasons with less rainfall and fewer RD favored these two species' abundance. We identified that the RD and TAO contributed significantly to variations in the density of D. elongatus. In contrast to the other two species, we recorded D. elongatus in seasons with high rainfall and high RD. A better understanding of the climate influence on the life cycle of these economically important insects may identify key factors in their population dynamics which in turn may improve management options.
Subject(s)
Grasshoppers , Animals , Argentina , Climate , Population Dynamics , SeasonsABSTRACT
INTRODUCTION: For an inguinal hernia repair, meshes with a continuous memory frame made it more easy to position the mesh in the preperitoneal space by anterior approach. We present a case of a sigmoid perforation caused by a fractured nitinol ring of a Rebound HRD Shield mesh. PATIENTS AND METHODS: A 29-years old sports instructor presented to the Emergency Department (ED) with a gnawing abdominal pain in the left lower quadrant. His past medical history noted an inguinal hernia repair on this side. A computed tomography scan showed a broken metal ring of the inguinal mesh perforating the sigmoid, so a laparoscopy was performed. The sigmoid was attached to the abdominal wall partially overlying the preperitoneal mesh and a part of the broken nitinol frame was found perforating the colon. RESULTS: The memory ring of the Rebound mesh is made of nitinol. An alloy well-known in vascular surgery for stenting arteries with high bending and compression forces. In this setting, fracture due to fatigue has already been described, but it is not known in abdominal wall reconstruction. Our patients groin was subject to daily bending and compression forces resulting in breakage of the nitinol ring. CONCLUSION: Particularly in young athletic patients the nitinol ring will be subject to bending forces in the groin and prone to breakage. This can have potentially severe consequences given its location near abdominal organs and neurovascular structures. In our opinion, patients should be informed about the possibility of ring breakage and doctors should consider the risk-benefits well.
Subject(s)
Hernia, Inguinal , Laparoscopy , Adult , Alloys/adverse effects , Colon, Sigmoid/diagnostic imaging , Colon, Sigmoid/surgery , Hernia, Inguinal/surgery , Herniorrhaphy/adverse effects , Humans , Surgical Mesh/adverse effectsABSTRACT
BACKGROUND & AIMS: Malnutrition following intensive care unit (ICU) stay is frequent and could be especially prominent in critically ill Coronavirus Disease 2019 (COVID-19) patients as they present prolonged inflammatory state and long length stay. We aimed to determine the prevalence of malnutrition in critically ill COVID-19 patients both at the acute and recovery phases of infection. METHODS: We conducted a prospective observational study including critically ill COVID-19 patients requiring invasive mechanical ventilation discharged alive from a medical ICU of a university hospital. We collected demographic, anthropometric and ICU stay data (SAPS2, recourse to organ support and daily energy intake). Nutritional status and nutritional support were collected at one month after ICU discharge (M1) by phone interview and at 3 months after ICU discharge (M3) during a specialized and dedicated consultation conducted by a dietitian. Malnutrition diagnosis was based on weight loss and body mass index (BMI) criteria following the Global Leadership Initiative on Malnutrition. Primary outcome was the prevalence of malnutrition at M3 and secondary outcomes were the evolution of nutritional status from ICU admission to M3 and factors associated with malnutrition at M3. RESULTS: From march 13th to may 15th, 2020, 38 patients were discharged alive from the ICU, median [IQR] age 66 [59-72] years, BMI 27.8 [25.5-30.7] kg/m2 and SAPS2 47 [35-55]. Thirty-three (86%) patients were followed up to M3. Prevalence of malnutrition increased during the ICU stay, from 18% at ICU admission to 79% at ICU discharge and then decreased to 71% at M1 and 53% at M3. Severe malnutrition prevailed at ICU discharge with a prevalence of 55% decreasing 32% at M3. At M3, the only factors associated with malnutrition in univariate analysis were the length of invasive mechanical ventilation and length of ICU stay (28 [18-44] vs. 13 [11-24] days, P = 0.011 and 32 [22-48] vs. 17 [11-21] days, P = 0.006, respectively), while no ICU preadmission and admission factors, nor energy and protein intakes distinguished the two groups. Only 35% of undernourished patients at M3 had benefited from a nutritional support. CONCLUSION: Malnutrition is frequent, protracted and probably underrecognized among critically ill Covid-19 patients requiring invasive mechanical ventilation with more than half patients still being undernourished three months after ICU discharge. A particular attention should be paid to the nutritional status of these patients not only during their ICU stay but also following ICU discharge.
Subject(s)
COVID-19 , Malnutrition , Humans , Aged , Critical Illness/therapy , COVID-19/epidemiology , COVID-19/therapy , Nutritional Status , Patient Discharge , Intensive Care Units , Length of Stay , Malnutrition/epidemiology , Malnutrition/diagnosisABSTRACT
The exploitation of ultrafast electron dynamics in quantum cascade lasers (QCLs) holds enormous potential for intense, compact mode-locked terahertz (THz) sources, squeezed THz light, frequency mixers, and comb-based metrology systems. Yet the important sub-cycle dynamics have been notoriously difficult to access in operational THz QCLs. Here, we employ high-field THz pulses to perform the first ultrafast two-dimensional spectroscopy of a free-running THz QCL. Strong incoherent and coherent nonlinearities up to eight-wave mixing are detected below and above the laser threshold. These data not only reveal extremely short gain recovery times of 2 ps at the laser threshold, they also reflect the nonlinear polarization dynamics of the QCL laser transition for the first time, where we quantify the corresponding dephasing times between 0.9 and 1.5 ps with increasing bias currents. A density-matrix approach reproducing the emergence of all nonlinearities and their ultrafast evolution, simultaneously, allows us to map the coherently induced trajectory of the Bloch vector. The observed high-order multi-wave mixing nonlinearities benefit from resonant enhancement in the absence of absorption losses and bear potential for a number of future applications, ranging from efficient intracavity frequency conversion, mode proliferation to passive mode locking.