Imaging of Lemierre Syndrome in children and young adultsA case-series analysis

Background / Purpose : Lemierre Syndrome (LS) is defined by a recent oro-pharangeal infection, the clinical presence or radiological demonstration of internal jugular vein (IJV) thrombosis and documented anaerobe germ, principally Fusobacterium necrophorum (Fn) leading to septicaemia and septic embolization. It is a rare infection described since 1900 and it nearly disappeared since the beginning of the antibiotic area. Even if it is seldom described in the literature, this infection is reappearing in the last 10 years, either because of the increase of antibiotic resistance or by modification of antibiotic prescription. The aim of this study is to describe the role of medical imaging in the diagnosis, staging and follow up of Lemierre syndrome, as well as to describe the ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) findings of this rare disease. Patients and methods : Radiological and medical files of patients diagnosed with Lemierre syndrome in the past 6 years at CHUV hospital were analysed retrospectively. The CT scan, US, colour Doppler US (CDUS) and MRI examinations that were performed have been examined so as to define their specific imaging findings. Results IJV thrombosis was demonstrated in 2 cases by US, by CT in 6 cases and MRI in one case. Septic pulmonary emboli were detected by CT in 5 patients. Complications of the LS were depicted by MR in one case and by CT in 1 case. Conclusion : In the appropriate clinical settings, US, CT or MR evidence of IJV thrombosis and chest CT suggestive of septic emboli, should lead the physician to consider the diagnosis of LS. As a consequence, imaging allows a faster diagnosis and a more efficient treatment of this infection, which in case of insufficient therapy can lead to death

Palliative psychiatry in a narrow and in a broad sense: A concept clarification

Even with optimal treatment, some persons with severe and persistent mental illness do not achieve a level of mental health, psychosocial functioning and quality of life that is acceptable to them. With each unsuccessful treatment attempt, the probability of achieving symptom reduction declines while the probability of somatic and psychological side effects increases. This worsening benefit-harm ratio of treatment aiming at symptom reduction has motivated calls for implementing palliative approaches to care into psychiatry (palliative psychiatry). Palliative psychiatry accepts that some cases of severe and persistent mental illness can be irremediable and calls for a careful evaluation of goals of care in these cases. It aims at reducing harm, relieving suffering and thus improving quality of life directly, working around irremediable psychiatric symptoms. In a narrow sense, this refers to patients likely to die of their severe and persistent mental illness soon, but palliative psychiatry in a broad sense is not limited to end-of-life care. It can - and often should - be integrated with curative and rehabilitative approaches, as is the gold standard in somatic medicine. Palliative psychiatry constitutes a valuable addition to established non-curative approaches such as rehabilitative psychiatry (which focuses on psychosocial functioning instead of quality of life) and personal recovery (a journey that persons living with severe and persistent mental illness may undertake, not necessarily accompanied by mental health care professionals). Although the implementation of palliative psychiatry is met with several challenges such as difficulties regarding decision-making capacity and prognostication in severe and persistent mental illness, it is a promising new approach in caring for persons with severe and persistent mental illness, regardless of whether they are at the end of life. Keywords: Severe and persistent mental illness; end of life; futility; goals of care; irremediability; palliative psychiatry; quality of life; sufferin

Identification and Characterization of Mediators of Fluconazole Tolerance in Candida albicans.

Candida albicans is an important human pathogen and a major concern in intensive care units around the world. C. albicans infections are associated with a high mortality despite the use of antifungal treatments. One of the causes of therapeutic failures is the acquisition of antifungal resistance by mutations in the C. albicans genome. Fluconazole (FLC) is one of the most widely used antifungal and mechanisms of FLC resistance occurring by mutations have been extensively investigated. However, some clinical isolates are known to be able to survive at high FLC concentrations without acquiring resistance mutations, a phenotype known as tolerance. Mechanisms behind FLC tolerance are not well studied, mainly due to the lack of a proper way to identify and quantify tolerance in clinical isolates. We proposed here culture conditions to investigate FLC tolerance as well as an easy and efficient method to identity and quantify tolerance to FLC. The screening of C. albicans strain collections revealed that FLC tolerance is pH- and strain-dependent, suggesting the involvement of multiple mechanisms. Here, we addressed the identification of FLC tolerance mediators in C. albicans by an overexpression strategy focusing on 572 C. albicans genes. This strategy led to the identification of two transcription factors, CRZ1 and GZF3. CRZ1 is a C2H2-type transcription factor that is part of the calcineurin-dependent pathway in C. albicans, while GZF3 is a GATA-type transcription factor of unknown function in C. albicans. Overexpression of each gene resulted in an increase of FLC tolerance, however, only the deletion of CRZ1 in clinical FLC-tolerant strains consistently decreased their FLC tolerance. Transcription profiling of clinical isolates with variable levels of FLC tolerance confirmed a calcineurin-dependent signature in these isolates when exposed to FLC

Phenotypic assessment of genetic gain from selection for improved drought tolerance in semi-tropical maize populations

Most maize production across the globe is rain-fed, and production is set to be negatively impacted as duration and occurrence of droughts increases due to climate change. Development of water-deficit tolerant maize germplasm has been a major focus for most breeding programmes. Here, we sought to assess the genetic gain for grain yield in two maize populations developed for drought tolerance at CIMMYT by evaluating their cycle progeny through hybrid performance. Inbreds derived from different cycles of the Drought Tolerant Population (DTP) and La Posta Sequia (LPS) were mated to a tester (CML550), and resulting hybrids were evaluated under managed water-deficit stress and well-watered conditions. The difference in yield between water-deficit and well-watered treatments was 27% and 36% for the DTP and LPS, respectively. Genetic gain for grain yield across cycles for the two populations was confirmed in the study. Genetic gain was observed for both treatments indicating that selection for water-deficit stress tolerance simultaneously improves grain yield in well-watered conditions. The DTP population had a genetic gain of 0.07 t ha−1 cycle−1, while the LPS had 0.16 t ha−1 cycle−1 under water-deficit conditions. Significant genetic gain was also observed in the well-watered treatments for both populations. Anthesis to silking interval was significantly reduced under water-deficit stress conditions in both populations. Plant and ear height were reduced in the LPS population in both treatments, while no reductions were observed for the trait in the DTP population. Potential water-deficit stress tolerance donor lines with yields comparable to commercial check varieties were identified

Gas-Phase Cytosine and Cytosine-N 1 -Derivatives Have 0.1–1 ns Lifetimes Near the S 1 State Minimum

Ultraviolet radiative damage to DNA is inefficient because of the ultrafast S1 ⇝ S0 internal conversion of its nucleobases. Using picosecond pump–ionization delay measurements, we find that the S1(1ππ*) state vibrationless lifetime of gas-phase keto-amino cytosine (Cyt) is τ = 730 ps or ∼700 times longer than that measured by femtosecond pump–probe ionization at higher vibrational excess energy, Eexc. N1-Alkylation increases the S1 lifetime up to τ = 1030 ps for N1-ethyl-Cyt but decreases it to 100 ps for N1-isopropyl-Cyt. Increasing the vibrational energy to Eexc = 300–550 cm–1 decreases the lifetimes to 20–30 ps. The nonradiative dynamics of S1 cytosine is not solely a property of the amino-pyrimidinone chromophore but is strongly influenced by the N1-substituent. Correlated excited-state calculations predict that the gap between the S2(1nOπ*) and S1(1ππ*) states decreases along the series of N1-derivatives, thereby influencing the S1 state lifetime

Diagnostic yield and cost analysis of electrocardiographic screening in Swiss paediatric athletes

OBJECTIVES Athletes performing sports on high level are at increased risk for sudden cardiac death. This includes paediatric athletes, even though data on screening strategies in this age group remain scarce. This study aimed to assess electrocardiogram interpretation criteria in paediatric athletes and to evaluate the cost of screening. METHODS National, multicentre, retrospective, observational study on 891 athletes of paediatric age (<18 years) evaluated by history, physical examination and 12-lead electrocardiogram. The primary outcome measure was abnormal electrocardiogram findings according to the International Recommendations for Electrographic Interpretation in Athletes. The secondary outcome measure was cost of screening. RESULTS 19 athletes (2.1%) presented abnormal electrocardiogram findings requiring further investigations, mainly abnormal T-wave inversion. These 19 athletes were predominantly males, performing endurance sports with a mean volume of 10 weekly hours for a mean duration of 6 years of training. Further investigations did not identify any relevant pathology. All athletes were cleared for competition with regular follow-up. Total costs of the screening were 108,860 USD (122 USD per athlete). CONCLUSIONS Our study using the International Recommendations for Electrographic Interpretation in Athletes identified a low count of abnormal findings in paediatric athletes, yet raising substantially the cost of screening. Hence, the utility of electrocardiogram-inclusive screening of paediatric athletes remains to be elucidated by longitudinal data

Neoadjuvant treatment does not influence PD-L1 expression in stage III non-small-cell lung cancer: a retrospective analysis of tumor samples from the trials SAKK 16/96, 16/00, 16/01, and 16/14.

The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression. We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI). Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P &gt; 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar. In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival

Decreased respiratory system compliance on the sixth day of mechanical ventilation is a predictor of death in patients with established acute lung injury

<p>Abstract</p> <p>Background</p> <p>Multiple studies have identified single variables or composite scores that help risk stratify patients at the time of acute lung injury (ALI) diagnosis. However, few studies have addressed the important question of how changes in pulmonary physiologic variables might predict mortality in patients during the subacute or chronic phases of ALI. We studied pulmonary physiologic variables, including respiratory system compliance, P/F ratio and oxygenation index, in a cohort of patients with ALI who survived more than 6 days of mechanical ventilation to see if changes in these variables were predictive of death and whether they are informative about the pathophysiology of subacute ALI.</p> <p>Methods</p> <p>Ninety-three patients with ALI who were mechanically ventilated for more than 6 days were enrolled in this prospective cohort study. Patients were enrolled at two medical centers in the US, a county hospital and a large academic center. Bivariate analyses were used to identify pulmonary physiologic predictors of death during the first 6 days of mechanical ventilation. Predictors on day 1, day 6 and the changes between day 1 and day 6 were compared in a multivariate logistic regression model.</p> <p>Results</p> <p>The overall mortality was 35%. In multivariate analysis, the PaO₂/FiO₂(OR 2.09, p < 0.04) and respiratory system compliance (OR 3.61, p < 0.01) were predictive of death on the 6^thday of acute lung injury. In addition, a decrease in respiratory system compliance between days 1 and days 6 (OR 2.14, p < 0.01) was independently associated with mortality.</p> <p>Conclusions</p> <p>A low respiratory system compliance on day 6 or a decrease in the respiratory system compliance between the 1^stand 6^thday of mechanical ventilation were associated with increased mortality in multivariate analysis of this cohort of patients with ALI. We suggest that decreased respiratory system compliance may identify a subset of patients who have persistent pulmonary edema, atelectasis or the fibroproliferative sequelae of ALI and thus are less likely to survive their hospitalization.</p

Genomic and phenotypic characterization of multidrug-resistant Salmonella enterica serovar Reading isolates involved in a turkey-associated foodborne outbreak

Salmonella is a global bacterial foodborne pathogen associated with a variety of contaminated food products. Poultry products are a common source of Salmonella-associated foodborne illness, and an estimated 7% of human illnesses in the United States are attributed to turkey products. From November 2017 to March 2019, the Centers for Disease Control and Prevention reported a turkey-associated outbreak of multidrug-resistant (MDR; resistant to ≥3 antimicrobial classes) Salmonella enterica serovar Reading (S. Reading) linked to 358 human infections in 42 US states and Canada. Since S. Reading was seldom linked to human illness prior to this outbreak, the current study compared genomic sequences of S. Reading isolates prior to the outbreak (pre-outbreak) to isolates identified during the outbreak period, focusing on genes that were different between the two groups but common within a group. Following whole-genome sequence analysis of five pre-outbreak and five outbreak-associated turkey/turkey product isolates of S. Reading, 37 genes located within two distinct chromosomal regions were identified only in the pre-outbreak isolates: (1) an ~5 kb region containing four protein-coding genes including uidA which encodes beta-glucuronidase, pgdA encoding peptidoglycan deacetylase, and two hypothetical proteins and (2) an ~28 kb region comprised of 32 phage-like genes and the xerC gene, which encodes tyrosine recombinase (frequently associated with phage genes). The five outbreak isolates also had a deletional event within the cirA gene, introducing a translational frame shift and premature stop codon. The cirA gene encodes a protein with dual receptor functions: a siderophore receptor for transport of dihydroxybenzoylserine as well as a colicin Ia/b receptor. Significant differences for the identified genetic variations were also detected in 75 S. Reading human isolates. Of the 41 S. Reading isolates collected before or in 2017, 81 and 90% of the isolates contained the uidA and pgdA genes, respectively, but only 24% of the isolates collected after 2017 harbored the uidA and pgdA genes. The truncation event within the cirA gene was also significantly higher in isolates collected after 2017 (74%) compared to before or in 2017 (5%). Phenotypic analysis of the S. Reading isolates for colicin and cefiderocol sensitivities (CirA) and β-methyl-D-glucuronic acid utilization (UidA and accessory proteins) supported the genomic data. Overall, a similar genome reduction pattern was generally observed in both the turkey and human isolates of S. Reading during the outbreak period, and the genetic differences were present in genes that could potentially promote pathogen dissemination due to variation in Salmonella colonization, fitness, and/or virulence