When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that is responsible for coronavirus disease 2019 (COVID-19), which has rapidly spread across the world, becoming a pandemic. The "cytokine storm" (CS) in COVID-19 leads to the worst stage of illness, and its timely control through immunomodulators, corticosteroids, and cytokine antagonists may be the key to reducing mortality. After reviewing published studies, we proposed a Cytokine Storm Score (CSs) to identify patients who were in this hyperinflammation state, and at risk of progression and poorer outcomes. We retrospectively analyzed 31 patients admitted to Infectious Disease Department in "St. Maria" Hospital in Terni with confirmed SARS-CoV-2 infections, and analyzed the "CS score" (CSs) and the severity of COVID-19. Then we conducted a prospective study of COVID-19 patients admitted after the definition of the CSscore. This is the first study that proposes and applies a new score to quickly identify COVID-19 patients who are in a hyperinflammation stage, to rapidly treat them in order to reduce the risk of intubation. CSs can accurately identify COVID-19 patients in the early stages of a CS, to conduct timely, safe, and effect administration of immunomodulators, corticosteroids, and cytokine antagonists, to prevent progression and reduce mortality.

Routine drain or no drain after laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Laparoscopic cholecystectomy (LC) is considered to be the gold standard in the early management of acute cholecystitis however, recommendations for routine drain insertion in the acute setting are unavailable. STUDY DESIGN: A systematic review of literature review and metanalysis was conducted. All studies comparing drain versus no drain after LC for acute cholecystitis were included. RESULTS: Seven studies, with 1274 patients, were included. Postoperative wound infection rates (relative risk (RR) 0.30, 95% confidence interval (CI) 0.10 to 0.88; I2 = 0%) and postoperative abdominal collection requiring drainage (RR 1.20, 95% CI 0.35 to 4.12; I 2 = 0%) were lower in the no-drain group, but this was only significant for wounded infections on subgroup analysis of RCTs. Length of stay hospital (mean difference (MD) -0.49, 95% CI -0.89 to -0.09; I 2 = 69%) and operative time (MD -8.13, 95% CI -13.87 to -2.38; I 2 = 92%) were significantly shorter in the no drain group however this was in the context of significant heterogeneity. CONCLUSION: The available data suggests that acute cholecystitis is not an indication for routine drain placement after LC. However, these results must be interpreted with caution due to the limitations of the included studies. In effect, the main issue of this meta-analysis lies on the limitations of the included studies themselves, because of a considerable heterogeneity among the included works, particularly for the inclusion criteria of patients and reported severity of acute cholecystitis. Further work is required to produce evidence which will definitively alter clinical practice. LEVEL OF EVIDENCE: Level 2a (systematic review of cohort studies). Oxford CEBM levels of evidence.

Headless compression screw in the neuronavigation-guided and microscope-assisted treatment of spondylolysis / Tornillo de compresión sin cabeza en el tratamiento de la espondilolisis guiada por neuronavegación y asistida por microscopio

Since 1968, many surgical techniques used in repairing the pars defect of the vertebra have been reported. Technological advances are giving rise to new ways of obtaining the best outcome using less invasive methods, which are more accurate, simple and effective. To treat cases of spondylolysis such as pseudarthrosis, we used neuro-navigation and microscopy through a 2.5-cm skin incision to approach the pars defect, freshen the fracture and place a type of screw that, until now, has never been used for this purpose. This is a novel technique, which guarantees prolonged compression and sufficient stability to facilitate the prompt healing of the vertebra. We present 2 cases of L5 spondylolysis treated with our technique, a modification of Buck's technique. A detailed description of the screw selection, surgical technical details, follow-up and outcome are discussed

Desde 1968 se han descrito muchas técnicas quirúrgicas utilizadas para reparar el defecto en la pars de la vértebra. Los avances tecnológicos están dando lugar a nuevas formas de obtener el mejor resultado utilizando métodos menos invasivos que son más precisos, simples y eficaces. Para tratar los casos de espondilolisis como una unión en seudoartrosis, se utilizó la neuronavegación y la microscopía a través de una incisión cutánea de 2,5cm para abordar el defecto de la pars, refrescar la fractura y colocar un tipo de tornillo que no se ha utilizado previamente con ese fin. Esta es una técnica novedosa, que garantiza una compresión prolongada y suficiente estabilidad para lograr la curación oportuna de la vértebra. Presentamos 2 casos de espondilolisis de L5 tratados con nuestra técnica, una modificación de la técnica de Buck. Se realiza una descripción detallada de la selección del tornillo, detalles técnicos quirúrgicos, seguimiento y resultado

Association of long-term glycaemic control on tear break-up times and dry eye symptoms in Chinese patients with type 2 diabetes.

IMPORTANCE: Diabetes mellitus is known to be associated with dry eye syndrome (DES), but the effects of long-term glycaemic control on tear film metrics and dry eye symptoms are not known in the Chinese population. BACKGROUND: To evaluate tear film stability and dry eye symptoms and their associations with systemic risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital), Hong Kong. PARTICIPANTS: A total of 80 Chinese participants, aged 18 or above, with T2DM recruited from the specialist outpatient setting were included. METHODS: The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI). The association between OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using multiple linear regression. MAIN OUTCOME MEASURES: The associations between long-term glycaemic control and NITBUT and OSDI scores. RESULTS: Stepwise multiple linear regression analysis revealed glycated haemoglobin to be the only significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2 = 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM population. The odds of DES for increasing percentage of glycated haemoglobin was 1.49 (95% confidence interval: 1.03-2.17, P = 0.04). CONCLUSIONS AND RELEVANCE: Our findings highlight the importance of good glycaemic control as a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM.

Headless compression screw in the neuronavigation-guided and microscope-assisted treatment of spondylolysis.

Since 1968, many surgical techniques used in repairing the pars defect of the vertebra have been reported. Technological advances are giving rise to new ways of obtaining the best outcome using less invasive methods, which are more accurate, simple and effective. To treat cases of spondylolysis such as pseudarthrosis, we used neuro-navigation and microscopy through a 2.5-cm skin incision to approach the pars defect, freshen the fracture and place a type of screw that, until now, has never been used for this purpose. This is a novel technique, which guarantees prolonged compression and sufficient stability to facilitate the prompt healing of the vertebra. We present 2 cases of L5 spondylolysis treated with our technique, a modification of Buck's technique. A detailed description of the screw selection, surgical technical details, follow-up and outcome are discussed.

An Analysis of Bubble Deformation by a Sphere Relevant to the Measurements of Bubble-Particle Contact Interaction and Detachment Forces.

Atomic force microscopy makes it possible to measure the interacting forces between individual colloidal particles and air bubbles, which can provide a measure of the particle hydrophobicity. To indicate the level of hydrophobicity of the particle, the contact angle can be calculated, assuming that no interfacial deformation occurs with the bubble retaining a spherical profile. Our experimental results obtained using a modified sphere tensiometry apparatus to detach submillimeter spherical particles show that deformation of the bubble interface does occur during particle detachment. We also develop a theoretical model to describe the equilibrium shape of the bubble meniscus at any given particle position, based on the minimization of the free energy of the system. The developed model allows us to analyze high-speed video captured during detachment. In the system model deformation of the bubble profile is accounted for by the incorporation of a Lagrange multiplier into both the Young-Laplace equation and the force balance. The solution of the bubble profile matched to the high-speed video allows us to accurately calculate the contact angle and determine the total force balance as a function of the contact point of the bubble on the particle surface.

The secret of the care of the patient is in knowing and applying the evidence about effective clinical communication.

American physicians and dentists conduct approximately 140 000-160 000 patient interviews in a practice lifetime, making the interview the most frequently performed medical procedure. Over the past 75 years, a steadily growing stream of scientific research has confirmed the fact that patient-clinician communication affects the course, direction, and both biomedical and functional outcomes of care. The field of clinical communication research has matured from anecdotes and aphorisms about 'bedside manner' to sophisticated randomized control trials and evidence-based outcomes that have been translated into reliable practice guidelines. Several key skills or habits of practice have been identified and studied in terms of their efficacy and effectiveness. These include the importance of agenda-setting, eliciting patients' perspectives about the nature of their ailments, communicating caring and concern, and testing for patient comprehension and agreement with proposed treatments. In addition to being effective, interpersonal communication can be deeply satisfying as well as offering a lower probability of law suits in the event of an adverse outcome.

Housekeeping health care workers have the highest risk for tuberculin skin test conversion.

BACKGROUND: Not all health care workers (HCWs) are at the same risk for tuberculin skin test (TST) conversion, indicating latent tuberculosis (TB) infection. OBJECTIVE: To identify risk factors for TST conversion among HCWs. METHODS: A retrospective cohort study conducted at a tertiary university medical centre included every HCW who had had a negative two-step TST at work entry and at least one consecutive TST in the period 2005-2009 (mean follow-up period 55 months). Binomic logistic regression analysis was used to identify risk factors for TST conversion. Potential risk factors such as age, health care profession, patient exposure profile, workplace division and history of bacille Calmette-Guérin vaccination were entered in the model. RESULTS: A total of 450 subjects met the inclusion criteria, of whom 93 had TST conversion. The highest annual rates of TST conversion occurred in workers who worked as housekeeping staff (6.9%). Older age, a work environment with high patient turnover and employment in maintenance departments were significant risk factors (adjusted odds ratios 2.05, 5.2 and 8.4 respectively). CONCLUSION: Housekeeping staff, older age workers and health care professionals working in an environment of high patient turnover are at increased risk for latent TB infection.

Spontaneous caloric restriction associated with increased leptin levels in obesity-resistant αMUPA mice.

BACKGROUND: αMUPA mice carry as a transgene the cDNA encoding urokinase-type plasminogen activator, a member of the plasminogen/plasmin system that functions in fibrinolysis and extracellular proteolysis. These mice spontaneously consume less food when fed ad libitum and live longer compared with wild-type (WT) control mice. αMUPA mice are obesity resistant and they share many similarities with calorically restricted animals. However, extensive metabolic characterization of this unique transgenic model has never been performed. METHOD: Metabolism of αMUPA mice was analyzed by measuring hormone, lipid and glucose levels in the serum, as well as gene and protein expression levels in the liver, hypothalamus and brainstem. RESULTS: αMUPA mice were found to be leaner than WT mice mainly because of reduced fat depots. Serum analyses showed that αMUPA mice have high levels of the anorexigenic hormones insulin and leptin, and low levels of the orexigenic hormone ghrelin. Analyses of brain neuropeptides showed that the transcript of the anorexigenic neuropeptide Pomc is highly expressed in the brainstem, whereas the expression of the orexigenic neuropeptides Npy, Orexin and Mch is blunted in the hypothalamus of αMUPA mice. In addition, adenosine monophosphate (AMP)-activated protein kinase (AMPK) levels were higher in the liver and lower in the hypothalamus, thus promoting simultaneously central reduction in appetite and peripheral loss of fat. The levels of SIRT1 were low in the liver, but high in the hypothalamus, a feature that αMUPA mice share with calorically restricted animals. CONCLUSION: Taken together, αMUPA mice exhibit a unique metabolic phenotype of low-calorie intake and high leptin levels, and could serve as a model for both spontaneous calorie restriction and resistance to obesity.

Target preparation for DNA microarray hybridization.

DNA microarrays are widely used to analyze genome-wide gene expression patterns and to study genotypic variations. They are miniaturized collections of thousands of DNA fragments arrayed on a surface. Based on nucleic acid complementary binding, they serve as a tool to interrogate complex populations of nucleic acids for abundance or binding affinity of particular sequences. Before a nucleic acid (target) can be used for hybridization to the probes of a microarray, it needs to be extracted from the tissue and labeled. Frequently, it also needs to be amplified to increase detection sensitivity. During a hybridization process, labeled target molecules with sequences complementary to the probes are captured quantitatively. Subsequently, a reader measures the amount of label on each probe. To generate accurate and informative data, one of the most critical aspects of these experiments is the quality of both the isolated and the labeled nucleic acid samples. This chapter describes detailed procedures for the preparation of labeled RNA samples for DNA microarray analysis.

Environmental whole-genome amplification to access microbial populations in contaminated sediments.

Low-biomass samples from nitrate and heavy metal contaminated soils yield DNA amounts that have limited use for direct, native analysis and screening. Multiple displacement amplification (MDA) using phi29 DNA polymerase was used to amplify whole genomes from environmental, contaminated, subsurface sediments. By first amplifying the genomic DNA (gDNA), biodiversity analysis and gDNA library construction of microbes found in contaminated soils were made possible. The MDA method was validated by analyzing amplified genome coverage from approximately five Escherichia coli cells, resulting in 99.2% genome coverage. The method was further validated by confirming overall representative species coverage and also an amplification bias when amplifying from a mix of eight known bacterial strains. We extracted DNA from samples with extremely low cell densities from a U.S. Department of Energy contaminated site. After amplification, small-subunit rRNA analysis revealed relatively even distribution of species across several major phyla. Clone libraries were constructed from the amplified gDNA, and a small subset of clones was used for shotgun sequencing. BLAST analysis of the library clone sequences showed that 64.9% of the sequences had significant similarities to known proteins, and "clusters of orthologous groups" (COG) analysis revealed that more than half of the sequences from each library contained sequence similarity to known proteins. The libraries can be readily screened for native genes or any target of interest. Whole-genome amplification of metagenomic DNA from very minute microbial sources, while introducing an amplification bias, will allow access to genomic information that was not previously accessible. The reported SSU rRNA sequences and library clone end sequences are listed with their respective GenBank accession numbers, DQ 404590 to DQ 404652, DQ 404654 to DQ 404938, and DX 385314 to DX 389173.

Contribution of transcriptional regulation to natural variations in Arabidopsis.

BACKGROUND: Genetic control of gene transcription is a key component in genome evolution. To understand the transcriptional basis of natural variation, we have studied genome-wide variations in transcription and characterized the genetic variations in regulatory elements among Arabidopsis accessions. RESULTS: Among five accessions (Col-0, C24, Ler, WS-2, and NO-0) 7,508 probe sets with no detectable genomic sequence variations were identified on the basis of the comparative genomic hybridization to the Arabidopsis GeneChip microarray, and used for accession-specific transcriptome analysis. Two-way ANOVA analysis has identified 60 genes whose mRNA levels differed in different accession backgrounds in an organ-dependent manner. Most of these genes were involved in stress responses and late stages of plant development, such as seed development. Correlation analysis of expression patterns of these 7,508 genes between pairs of accessions identified a group of 65 highly plastic genes with distinct expression patterns in each accession. CONCLUSION: Genes that show substantial genetic variation in mRNA level are those with functions in signal transduction, transcription and stress response, suggesting the existence of variations in the regulatory mechanisms for these genes among different accessions. This is in contrast to those genes with significant polymorphisms in the coding regions identified by genomic hybridization, which include genes encoding transposon-related proteins, kinases and disease-resistance proteins. While relatively fewer sequence variations were detected on average in the coding regions of these genes, a number of differences were identified from the upstream regions, several of which alter potential cis-regulatory elements. Our results suggest that nucleotide polymorphisms in regulatory elements of genes encoding controlling factors could be primary targets of natural selection and a driving force behind the evolution of Arabidopsis accessions.

Expression profiling of phyB mutant demonstrates substantial contribution of other phytochromes to red-light-regulated gene expression during seedling de-etiolation.

Different Arabidopsis phytochrome (phy) family members (phyA through phyE) display differential photosensory and/or physiological functions in regulating growth and developmental responses to light signals. To identify the genes regulated by phyB in response to continuous monochromatic red light (Rc) during the induction of seedling de-etiolation, we have performed time-course, microarray-based expression profiling of wild type (WT) and phyB null mutants. Comparison of the observed expression patterns with those induced by continuous monochromatic far-red light (FRc; perceived exclusively by phyA) in WT and phyA null-mutant seedlings suggests early convergence of the FRc and Rc photosensory pathways to control a largely common transcriptional network. phyB mutant seedlings retain a surprisingly high level of responsiveness to Rc for the majority of Rc-regulated genes on the microarray, indicating that one or more other phys have a major role in regulating their expression. Combined with the robust visible morphogenic phenotype of the phyB mutant in Rc, these data suggest that different members of the phy family act in organ-specific fashion in regulating seedling de-etiolation. Specifically, phyB appears to be the dominant, if not exclusive, photoreceptor in regulating a minority population of genes involved in suppression of hypocotyl cell elongation in response to Rc signals. By contrast, this sensory function is apparently shared by one or more other phys in regulating the majority Rc-responsive gene set involved in other important facets of the de-etiolation process in the apical region, such as cotyledon cell expansion.

Delivery of pediatric after-hours care by call centers: a multicenter study of parental perceptions and compliance.

BACKGROUND: Despite the rapid growth of centralized call centers to provide after-hours triage to patients of multiple providers, little is known about the perceptions of parents regarding this type of care and their compliance with triage disposition recommendations. DESIGN/METHODS: From August through September 1999, randomized samples of after-hours calls were selected each day from computerized records at 4 pediatric call centers at 1) Children's Hospital, Denver, Colorado; 2) Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; 3) Rainbow Babies and Children's Hospital, Cleveland, Ohio; and 4) All Children's Hospital, St Petersburg, Florida. All participating call centers use the same triage software. Calls were randomly selected to yield at least 250 callers with nonurgent dispositions and 100 with urgent dispositions from each site. Telephone surveys to callers were conducted by an external survey unit 3 to 7 days after the call to the call center. RESULTS: Surveys were completed for 70.5% of those sampled (N = 1561). Parents indicated they were very satisfied or satisfied with aspects of care received from 92.6% (waiting time) to 99.4% (nurse courteousness) of the time. Satisfaction did not differ by site or by recommended disposition of the index call. Most parents (65.2%) reported no preference about speaking with a physician or nonphysician for after-hours care, whereas 27.7% preferred to speak with a physician. Usually speaking with a physician during office hours (odds ratio [OR]: 1.48), feeling it was important that provider knows child's medical history (OR: 3.47), and respondent having an educational level of college graduate or higher (OR: 1.30) were significant predictors of preferring to speak with a physician. Of the 37.0% (N = 723) of parents who reported any change in their relationship with their primary provider as a result of the after-hours call center, 95.7% (N = 691) assessed the change to be positive. Reported compliance with the call center disposition recommendation was 83.3% for urgent referral, 41.0% for next day, 4.5% for visit at a later time, and 78.2% for home care. The major reason given by parents for noncompliance was reporting that they heard a different disposition (76.9% for urgent to 100% for visit at a later time). CONCLUSIONS: Parental satisfaction with pediatric call centers was uniformly high in 4 different geographic locations, and almost all parents who reported any effect on their relationship with their primary provider assessed it as positive. Compliance with recommendations for urgent evaluation or home care was relatively high but for intermediary dispositions was low. In most cases in which noncompliance occurred, parents reported hearing a different disposition. Additional study is needed to clarify whether noncompliance, especially in cases in which an urgent recommendations was made, is attributable to poor nurse communication of the recommended disposition, parental misinterpretation, or parental difference of opinion.

Tread lightly through these accounting minefields.

In the current economic climate, there is tremendous pressure--and personal incentive for managers--to report sales growth and meet investors' revenue expectations. As a result, more companies have been issuing misleading financial reports, according to the SEC, especially involving game playing around earnings. But it's shareholders who suffer from aggressive accounting strategies; they don't get a true sense of the financial health of the company, and when problems come to light, the shares they're holding can plummet in value. How can investors and their representatives on corporate boards spot trouble before it blows up in their faces? According to the authors, they should keep their eyes peeled for common abuses in six areas: revenue measurement and recognition, provisions and reserves for uncertain future costs, asset valuation, derivatives, related party transactions, and information used for bench-marking performance. If a disaster strikes, it will most likely be in one of these accounting minefields. This article examines the hazards of each minefield in turn, using examples like Metallgesellschaft, Xerox, MicroStrategy, and Lernout & Hauspie. It also provides a set of questions to ask in order to determine where a company's accounting practices might be overly aggressive. For those whose greatest interest is in fairly valuing the business--not presenting it in the best possible light--these questions are the first line of defense against creative accounting. Accounting game players are adroit, but it's both foolish and dangerous, contend the authors, to declare oneself ignorant and hence powerless against their machinations. They argue that members of corporate boards need to be financially literate.

Low risk of significant echocardiographic valvulopathy in patients treated with anorectic drugs.

BACKGROUND: Phentermine--fenfluramine and dexfenfluramine use for weight loss has been previously associated with increased prevalence of valvular heart disease. This association was initially based on small numbers of patients, limited data on dose and duration of drug therapy, and no correlation with matched controls. METHODS: Our investigation involved 343 obese subjects enrolled in a prospective, strict weight loss, research protocol from September 1994 to September 1997. All subjects underwent transthoracic echocardiography for significant valvular lesions within a mean of 121 days from the manufacturer's announcement of the voluntary withdrawal of fenfluramine and dexfenfluramine from the market. All echocardiograms were interpreted by 2 independent readers. RESULTS: The study population included 281 females and 62 males with a mean age of 46.7+/-9.1 years and mean initial body mass index of 40.1+/-8.1 kg/m(2). Using the Food and Drug Administration's criteria, only 21 subjects (6.1%) had significant valvular lesions. Aortic regurgitation was detected in 18 subjects, mitral regurgitation in 3 subjects, and both aortic and mitral regurgitation in 1 subject; no one had severe regurgitation. Significant valvular disease did not correlate with age, gender, initial/ending body mass index, the drug dose, duration of drug therapy, or serotonin reuptake inhibitors. CONCLUSIONS: Anorexigen therapy is associated with a low prevalence of significant valvular regurgitation. Late valvular abnormalities from drug treatment await long term prospective studies.