Tracheostomies after SARS-CoV-2 intubation, performed by academic otorhinolaryngologists in the Paris area of France: Preliminary results.

OBJECTIVE: To analyse tracheostomies after intubation for SARS-Cov-2 infection performed by otorhinolaryngologists in 7 university hospitals in the Paris area of France during the month March 24 to April 23, 2020. MATERIAL AND METHODS: A multicentre retrospective observational study included 59 consecutive patients. The main goals were to evaluate the number, characteristics and practical conditions of tracheostomies, and the COVID-19 status of the otorhinolaryngologists. Secondary goals were to analyse tracheostomy time, decannulation rate, immediate postoperative complications and laryngotracheal axis status. RESULTS: Tracheostomy indications were for ventilatory weaning and extubation failure in 86% and 14% of cases, respectively. The technique was surgical, percutaneous or hybrid in 91.5%, 3.4% and 5.1% of cases, respectively. None of the operators developed symptoms consistent with COVID-19. Postoperative complications occurred in 15% of cases, with no significant difference between surgical and percutaneous/hybrid techniques (P=0.33), although no complications occurred after percutaneous or hybrid tracheostomies. No procedures or complications resulted in death. The decannulation rate was 74.5% with a mean tracheostomy time of 20±12 days. In 55% of the patients evaluated by flexible endoscopy after decannulation, a laryngeal abnormality was found. On univariate analysis, no clinical features had a significant influence on tracheostomy time, decannulation rate or occurrence of laryngeal lesions. CONCLUSION: The main findings of the present retrospective study were: absence of contamination of the surgeons, heterogeneity of practices between centres, a high rate of complications and laryngeal lesions whatever the technique, and the specificities of the patients.

The effects of TMS over dorsolateral prefrontal cortex on trans-saccadic memory of multiple objects.

Humans typically make several rapid eye movements (saccades) per second. It is thought that visual working memory can retain and spatially integrate three to four objects or features across each saccade but little is known about this neural mechanism. Previously we showed that transcranial magnetic stimulation (TMS) to the posterior parietal cortex and frontal eye fields degrade trans-saccadic memory of multiple object features (Prime, Vesia, & Crawford, 2008, Journal of Neuroscience, 28(27), 6938-6949; Prime, Vesia, & Crawford, 2010, Cerebral Cortex, 20(4), 759-772.). Here, we used a similar protocol to investigate whether dorsolateral prefrontal cortex (DLPFC), an area involved in spatial working memory, is also involved in trans-saccadic memory. Subjects were required to report changes in stimulus orientation with (saccade task) or without (fixation task) an eye movement in the intervening memory interval. We applied single-pulse TMS to left and right DLPFC during the memory delay, timed at three intervals to arrive approximately 100 ms before, 100 ms after, or at saccade onset. In the fixation task, left DLPFC TMS produced inconsistent results, whereas right DLPFC TMS disrupted performance at all three intervals (significantly for presaccadic TMS). In contrast, in the saccade task, TMS consistently facilitated performance (significantly for left DLPFC/perisaccadic TMS and right DLPFC/postsaccadic TMS) suggesting a dis-inhibition of trans-saccadic processing. These results are consistent with a neural circuit of trans-saccadic memory that overlaps and interacts with, but is partially separate from the circuit for visual working memory during sustained fixation.

Sequential result refinement for searching the biomedical literature.

Information overload is a problem for users of MEDLINE, the database of biomedical literature that indexes over 17 million articles. Various techniques have been developed to retrieve high quality or important articles. Some techniques rely on using the number of citations as a measurement of an article's importance. Unfortunately, citation information is proprietary, expensive, and suffers from "citation lag." MEDLINE users have a variety of information needs. Although some users require high recall, many users are looking for a "few good articles" on a topic. For these users, precision is more important than recall. We present and evaluate a method for identifying articles likely to be highly cited by using information available at the time of listing in MEDLINE. The method uses a score based on Medical Subject Headings (MeSH) terms, journal impact factor (JIF), and number of authors. This method can filter large MEDLINE result sets (>1000 articles) returned by actual user queries to produce small, highly cited result sets.

Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial.

Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients enrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for advanced colorectal cancer. Patients completed QOL questionnaires at randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and hand/foot sensitivity); physical functioning; and emotional functioning. Patient compliance with the QOL assessment schedule was good, supporting the feasibility of including QOL measures in cooperative group trials. However, death and deteriorating health produced substantial missing data. Cross-sectional analyses indicated that the seven therapeutic arms did not differ in their impact on QOL. Unfortunately, longitudinal analyses of the QOL data were inappropriate given non-random missing data. Graphical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treatment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random missing data can lead to serious overestimates of patient QOL over time.

IgE antibody response to vertebrate meat proteins including tropomyosin.

BACKGROUND: Although meat is a main source of proteins in western diets, little information is available regarding allergy to vertebrate meats or the allergens implicated in these reactions. OBJECTIVE: To evaluate the in vitro IgE antibody response to different vertebrate meats in suspected meat-allergic subjects, as well as the possible role of tropomyosin in meat allergy and to analyze the cross-reactivity between vertebrate meats and the effect of heating on the IgE-binding to meat proteins. METHODS: Fifty-seven sera from suspected meat-allergic subjects were tested by grid blot to extracts of beef, lamb, pork, venison, chicken, and turkey and to four mammalian tropomyosins of different origins. RESULTS: Meat-allergic subjects have IgE antibodies to proteins in different mammalian meats (43/57 subjects); cross-reactivity with avian meat was limited: less than 50% (19/43) of meat positive sera reacted to chicken. In contrast, most of the poultry-positive sera also reacted to different mammalian meats. In general, there was stronger IgE reactivity to raw meats in comparison to cooked meats; an exception was six cases in which IgE reactivity to cooked poultry was stronger. Weak IgE reactivity to tropomyosin was detected in only 2/57 sera tested. CONCLUSIONS: Suspected meat-allergic subjects have serum IgE directed to meat proteins. In vitro cross-reactivity among mammalian meats appears to be important, while cross-reactivity to poultry is limited indicating mammalian-specific proteins. Although cooking in general denatures meat proteins rendering them less allergenic, in some cases the process of cooking may result in the formation of new allergenic moieties. The muscle protein tropomyosin is not an important vertebrate meat allergen.

Identification of Genes Predisposing to Clinically Severe Obesity: An Approach.

BACKGROUND: Familial correlations, twin studies and adoption studies have all indicated that human obesity has a substantial genetic component. To date, obesity genes have only been identified using mouse models. METHODS: In an attempt to identify human obesity genes large numbers of multigenerational families, in whom extreme obesity segregates, are currently being collected. RESULTS AND CONCLUSIONS: Relative risk estimates and models of genetic heterogeneity indicate that at least 500 affected sibling pairs will need to be collected to identify major genes.

Partial characterization of Serratia marcescens nosocomial strains.

A nosocomial infection outbreak occurred in the Intensive Care Unit (ICU) of the Instituto Nacional de Pediatría (INP) in México City, during the months of March, April and May in 1988 Serratia marcescens was isolated as the etiological agent for this epidemic. Up to date, the source of contamination, the spreading and the pathogenic mechanisms which were involved in this outbreak remain unknown. In order to study the dynamics of the bacterial population involved in this outbreak, all strains of nosocomial S. marcescens isolated during 1988 were collected and studied. Eighty nosocomial strains were analysed. For this purpose we used four different markers: antibiotic susceptibility, presence of plasmids, exoenzyme production and pigment synthesis from a precursor. Using these markers, we were able to establish that five subpopulations of bacteria were present during the ICU outbreak, and that one of these subpopulations, VIII-A, was the most frequently isolated. A short time after this outbreak, we obtained S. marcescens isolates with similar properties which proceeded from other hospital units, suggesting intrahospital dissemination of the strain in question. We believe that, eventually, this study will allow us to establish bacterial spreading models within our institution.

A phase II study of cisplatin and cytosine arabinoside for recurrent squamous cell carcinoma of the head and neck.

Based on experimental data suggesting synergy between cisplatin and cytosine arabinoside, 17 patients with recurrent squamous cancer of the head and neck were treated with this combination. The response rate was 18% with no complete responses, and the partial responses were of brief duration. There were moderate hematologic and gastrointestinal toxicities and two therapy-related deaths. The study was stopped early because of low response. When compared to results reported for cisplatin alone, the combination of cisplatin and cytosine arabinoside offered no clear advantage.

Daunomycin administered by continuous intravenous infusion is effective in the treatment of acute nonlymphocytic leukaemia.

Anthracyclines given by continuous infusion, as opposed to bolus administration, are associated with a reduced incidence of cardiac and gastrointestinal toxicity. Our study was developed to test the antileukaemic effect of anthracyclines given as a continuous infusion. Nineteen sequential patients admitted for treatment of acute nonlymphocytic leukaemia (ANLL) were managed with a regimen utilizing a 3 d continuous intravenous infusion of daunomycin (DNM), and the complete response rate was similar to this institution's past experience with antileukaemic regimens employing 3 d bolus DNM. In our studies, infusion DNM was at least as myelotoxic and antileukaemic as bolus DNM; thus this method of administration should be explored further in remission-induction regimens for ANLL.

Thyroid function during the spontaneous course of subacute thyroiditis.

A study of changes in serum T4, T3, and Tg as well as of serum TSH response to TRH was done in ten patients with subacute thyroiditis, from the acute phase up to 56 mo. All patients had symptoms of thyrotoxicosis. The mean +/- s.e.m. serum T4 (21.6 +/- 8.2 micrograms/dl), T3 (315 +/- 191 ng/dl) and Tg (149 +/- 52 ng/ml) concentrations were significantly higher than in normal subjects (8.5 +/- 1.7 micrograms/dl, 136 +/- 34 ng/dl, and 10.5 +/- 1.0 ng/ml, respectively). The basal TSH concentrations failed to increase in response to TRH. Mean serum T3 and serum Tg levels remained higher than in normal subjects until 4 to 5 mo after the acute phase. However, normalization of clinical status and serum thyroid hormone levels did not coincide with the normalization of serum Tg levels. Thyroid autoantibodies were absent during the whole period of study. An exaggerated response of TSH to TRH in six out of seven patients was observed from a 2 to 3 mo period until the end of follow-up. All patients with T3 to T4 ratio above the normal range (7-24 ng/micrograms) showed also an exaggerated response of TSH to TRH. These data suggest that the spontaneous course of subacute thyroiditis may lead to a low thyroid reserve detectable even 5 yr following the acute phase of the disease.

Comparison of effects of high and low dosage regimens of antithyroid drugs in the management of Graves' hyperthyroidism.

We compared the effects of high and low dosages of antithyroid drugs in 113 patients with Graves' hyperthyroidism. The patients were randomly divided into 2 groups. In group A, 65 patients received either methimazole (MMI): 60 +/- 14.5 mg/day (mean +/- SD); range 40-100 mg/day, or propylthiouracil (PTU): 693 +/- 173 mg/day; range 500-1200 mg/day. These high doses were maintained throughout treatment with later addition of 50-75 micrograms T3 daily. Forty eight patients (group B) were treated with lower doses of MMI or PTU without thyroid hormone addition. The maintenance dose of MMI was 13.6 +/- 7 mg/day (range 5-25 mg/day) and that of PTU was 180 +/- 58 mg/day (range 100-300 mg/day). The treatment period was 15.1 +/- 4.2 (range 10-30) months for group A and 13.5 +/- 2.2 (range 12-20) months for group B. Remission occurred in 75.4% patients from group A and in 41.6% patients from group B (P less than 0.001). The mean follow-up was 42 +/- 14 months (17-81 months). The free T4 index (FT4I) in group A remained below the normal range during treatment. The mean FT4I, obtained during the course of treatment, of patients who went into remission from group A was significantly (P less than 0.001) lower than in relapsed patients (4.8 vs. 6.5). Moreover, there was an inverse correlation between mean FT4I and maintenance daily dose of either MMI (r = -0.567; P less than 0.001), or PTU (r = -0.379; P less than 0.01). A fall in microsomal antibody (MCHA) titer occurred mainly in remission patients, and was more significant (P less than 0.05) in group A patients. In contrast, 11 (7 from group B) of the 16 patients with an increase of microsomal antibody levels relapsed. The frequency of negative tests of thyroid-stimulating antibody was higher in group A patients (71%) than in group B (29%) at the end of therapy (P less than 0.01). No correlation was found between thyroid T3 suppressibility and either mean FT4I or thyroid-stimulatory antibody activity during treatment. Our findings show that patients treated with high doses of PTU or MMI throughout treatment have a higher remission rate when compared to those treated with a more conventional regimen. These results support the hypothesis that large antithyroid drug doses may have greater immunosuppressive effects than low dosage regimens. Furthermore, a high dosage regimen could permit the restoration of the immune surveillance mechanisms and, thus, lasting remission of Graves' disease.

Selective medium for isolation of Klebsiella pneumoniae.

Selective media for Klebsiella pneumoniae have been important in studies of hospital-acquired infections. On an agar medium which included ornithine, raffinose, and Koser citrate, K. pneumoniae strains grew as yellow mucoid colonies at 24 h and there was some increase in colony size at 48 h. Other members of Enterobacteriaceae were inhibited or produced small pink colonies on this same medium. Pseudomonas, Providencia, Acinetobacter, and Proteus species did not grow or showed very poor growth. The growth and appearance of these bacteria were not influenced by pH changes over a pH range of 5.2 to 6.4. Of 368 swabs of body sites cultured on MacConkey agar and on the test medium, 121 K. pneumoniae isolates on MacConkey agar and the same number on the test medium resulted. There were no discrepancies between the two media. Upon direct plating of stool, however, more K. pneumoniae colonies were isolated on the test medium than on MacConkey agar. Colonies on the test medium were more readily selected and identified than the colonies on MacConkey agar. There was also no inhibition of K. pneumoniae growth on the test medium compared with blood agar medium. This medium may be useful for the selective isolation of K. pneumoniae.