Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals. Data on STD were collected prospectively using an in-person survey. The severity of STD was categorized using a visual analog scale. We analyzed time to onset, recovery rate, time to recovery, hospital admission, pneumonia, comorbidities, smoking, and symptoms. RESULTS: STD was at least 2-fold more common in COVID-19-positive patients than in controls. COVID-19-positive hospitalized patients were older, with a lower frequency of STD, and recovered earlier than outpatients. Analysis stratified by severity of STD showed that more than half of COVID-19 patients presented severe loss of smell (53.7%) or taste (52.2%); both senses were impaired in >90%. In the multivariate analysis, older age (>60 years), being hospitalized, and increased C-reactive protein were associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement in smell (45.6%) and taste (46.1%) at the time of the survey; in 90.6% this was within 2 weeks of infection. CONCLUSION: STD is a common symptom in COVID-19 and presents mainly in young and nonhospitalized patients. More studies are needed to evaluate follow-up of chemosensory impairment.

Front microrheology of the non-Newtonian behaviour of blood: scaling theory of erythrocyte aggregation by aging.

We introduce a new framework to study the non-Newtonian behaviour of fluids at the microscale based on the analysis of front advancement. We apply this methodology to study the non-linear rheology of blood in microchannels. We carry out experiments in which the non-linear viscosity of blood samples is quantified at different haematocrits and ages. Under these conditions, blood exhibits a power-law dependence on the shear rate. In order to analyse our experimental data, we put forward a scaling theory which allows us to define an adhesion scaling number. This theory yields a scaling behaviour of the viscosity expressed as a function of the adhesion capillary number. By applying this scaling theory to samples of different ages, we are able to quantify how the characteristic adhesion energy varies as time progresses. This connection between microscopic and mesoscopic properties allows us to estimate quantitatively the change in the cell-cell adhesion energies as the sample ages.

Multiple-locus variable-number tandem-repeat analysis is a suitable tool for differentiation of Mycoplasma hyopneumoniae strains without cultivation.

An assay based on multiple-locus variable-number tandem-repeat analysis allowed differentiating and studying diversity and persistence of Mycoplasma hyopneumoniae strains in pig herds without prior cultivation. The test had a discriminatory index of >0.99 and was applied reliably to porcine bronchoalveolar lavage fluid and tracheal swabs.

Can positron emission tomography support the characterization of immune-mediated inner ear disease? / ¿Puede la tomografía por emisión de positrones ayudar en la caracterización de la enfermedad inmunomediada del oído interno?

INTRODUCTION: To evaluate the utility of 18F-FDG PET/TC as an imaging tool for the characterization of immune-mediated inner ear disease (IMIED), providing measurements of the inner ear region activity as well as detecting possible involvement of other organs. MATERIAL AND METHODS: The study included 28 patients with IMIED and 4 sex-matched and age-matched control subjects with no history of ear disease. Eighteen patients were considered to be suffering from primary IMIED and 10 patients from secondary. PET/CT scans with 18F-FDG were performed to assess systemic involvement as well as inner ear region activity. Interpretation of PET/CT scans was performed independently by 2nuclear medicine physicians blinded to clinical history. In order to assess inter-rater agreement before performing the analysis of the inner ear, different Bland & Altman plots and the intraclass correlation coefficients were estimated. RESULTS: Different metabolically active foci findings were reported in 13 patients. Four patients diagnosed as primary IMIED showed thyroid and aorta activity. Regarding the inner-ear semiquantitative analysis, the inter-rater agreement was not sufficiently high. Comparisons between groups, performed using Mann-Whitney test or Kruskal-Wallis tests, showed no differences. CONCLUSIONS: The study showed 18F-FDG PET/TC could be an important tool in the evaluation of IMIED as it can support the characterization of this entity providing the diagnosis of unknown or underestimated secondary IMIED. Nevertheless, we consider PET is not an adequate tool to approach the inner ear because of the small size and volume of the cochlea which makes the assessment very difficult.

Intratympanic gadolinium magnetic resonance imaging supports the role of endolymphatic hydrops in the pathogenesis of immune-mediated inner-ear disease.

OBJECTIVE: To evaluate the presence of endolymphatic hydrops in patients with immune-mediated inner-ear disease. METHODS: The presence of endolymphatic hydrops was prospectively evaluated in 17 patients clinically diagnosed with secondary (n = 5) or primary (n = 12) immune-mediated inner-ear disease, who attended the ENT department of a tertiary care centre for evaluation or treatment over the previous year. All patients underwent magnetic resonance imaging of the temporal bone. RESULTS: Intratympanic gadolinium three-dimensional magnetic resonance imaging diagnosed hydrops in 11 of 12 patients with primary immune-mediated inner-ear disease (92 per cent). Of these, seven patients (64 per cent) presented only cochlear (n = 5) or predominantly cochlear (n = 2) hydrops. A positive magnetic resonance imaging result was observed in only one of five patients with secondary immune-mediated inner-ear disease (20 per cent). CONCLUSION: This study confirms the presence of endolymphatic hydrops in immune-mediated inner-ear disease patients. The virtual absence of hydrops in patients with secondary immune-mediated inner-ear disease is remarkable, although firm conclusions cannot be drawn; this should be explored in a multicentre study with a larger sample of patients. A different immune reaction without development of endolymphatic hydrops should not be ruled out in secondary immune-mediated inner-ear disease patients.

Correlation Between Incisional Biopsy Histological Subtype and a Mohs Surgery Specimen for Nonmelanoma Skin Cancer.

BACKGROUND: Histological diagnosis of a clinically suspected nonmelanoma skin cancer (NMSC) is recommended before treatment. For NMSC, concordance between the histological subtype of the preoperative biopsy and the excision specimen of basal cell carcinoma (BCC) has been reported to range from 10% to 81%. No large study on the concordance between NMSC histology seen in a preoperative biopsy with the following tumour specimen from Mohs micrographic surgery (MMS) has been performed in a Latin American population. OBJECTIVE: The aim of this study was to analyse and compare the histological subtype of the incisional biopsies reviewed by the dermatopathologist with the histological subtype of the tumour specimen obtained during MMS interpreted by the dermatopathologist and the Mohs surgeon. METHODS: A retrospective analysis of 320 NMSC was performed. The interobserver correlation was based on kappa values. RESULTS: The mean weighted kappa value between the preoperative NMSC biopsy and intraoperative histological subtype of the tumour specimen from MMS analysed by the Mohs surgeon and the dermatopathologist was 0.22 and 0.24, respectively. The correlation in the histologic subtype of the intraoperative tumour specimen from MMS that was interpreted by the dermatopathologist and Mohs surgeon was 0.58. CONCLUSIONS: Dermatologists need to be aware of the limited value of incisional biopsies to accurately diagnose the histological subtype of a NMSC. The concordance rate in the histological diagnosis of the tumour specimens that were obtained from MMS between the Mohs surgeon and the dermatopathologist is moderate. However, the correlation is low compared with incisional biopsy subtypes.

Long-term streptozotocin-induced diabetes alters prostanoid production in rat aorta and mesenteric bed.

Vascular disease is a major cause of mortality and morbidity in chronic diabetes mellitus. Prostanoids, metabolites of arachidonic acid, include vasoactive substances produced and released from the vascular wall. Alterations in prostanoid production have been reported in the vasculature of diabetic humans and experimental animals. The aim of the present work was to study the influence of three different periods of long-term streptozotocin-induced diabetes, 30, 120 and 180 days in the production of prostanoids in the thoracic aorta and in the mesenteric vascular bed of the rat. The prostanoids released to the incubation medium by the tissues were extracted and measured by reversed-phase HPLC. In the diabetic groups, body weight was reduced and glycaemia was increased when compared with the corresponding non-diabetic controls. In the aorta, 30 days of diabetes did not modify the prostanoid release pattern, meanwhile 120 and 180 days of incubation decreased prostacyclin (PGI(2)) production. In the mesenteric bed, at 30 days the release of the vasodilators PGI(2) and prostaglandin (PGE(2)) and the vasoconstrictor thromboxane (TXA(2)) was reduced. At 120 days the vasodilators were reduced and at 180 days such reduction was joined by an increase of the release of vasoconstrictor metabolites. Thirty days of diabetes did not modify the PGI(2)/TXA(2) ratio in the aorta or mesenteric bed. On the other hand, 120 and 180 days of diabetes reduced significantly the ratio when compared with the corresponding controls. In conclusion, the mesenteric bed, a resistance vascular bed, seems to be more sensitive than the aorta, a conductance vessel, to the effects of diabetes on prostanoid production. The observed effects contribute to a displacement of the balance of prostanoid release in favour of the vasoconstrictor metabolites, a phenomenon that could be related to the vascular complications of diabetes mellitus.

Contralateral Cochlear Labyrinthine Concussion without Temporal Bone Fracture: Unusual Posttraumatic Consequence.

Introduction. Labyrinthine concussion is a term used to describe a rare cause of sensorineural hearing loss with or without vestibular symptoms occurring after head trauma. Isolated damage to the inner ear without involving the vestibular organ would be designated as a cochlear labyrinthine concussion. Hearing loss is not a rare finding in head trauma that involves petrous bone fractures. Nevertheless it generally occurs ipsilateral to the side of the head injury and extraordinarily in the contralateral side and moreover without the presence of a fracture. Case Report. The present case describes a 37-year-old patient with sensorineural hearing loss and tinnitus in his right ear after a blunt head trauma of the left-sided temporal bone (contralateral). Otoscopy and radiological images showed no fractures or any abnormalities. A severe sensorineural hearing loss was found in his right ear with a normal hearing of the left side. Conclusion. The temporal bone trauma requires a complete diagnostic battery which includes a neurotologic examination and a high resolution computed tomography scan in the first place. Hearing loss after a head injury extraordinarily occurs in the contralateral side of the trauma as what happened in our case. In addition, the absence of fractures makes this phenomenon even more unusual.

Capillary Filling at the Microscale: Control of Fluid Front Using Geometry.

We propose an experimental and theoretical framework for the study of capillary filling at the micro-scale. Our methodology enables us to control the fluid flow regime so that we can characterise properties of Newtonian fluids such as their viscosity. In particular, we study a viscous, non-inertial, non-Washburn regime in which the position of the fluid front increases linearly with time for the whole duration of the experiment. The operating shear-rate range of our apparatus extends over nearly two orders of magnitude. Further, we analyse the advancement of a fluid front within a microcapillary in a system of two immiscible Newtonian liquids. We observe a non-Washburn regime in which the front can accelerate or decelerate depending on the viscosity contrast between the two liquids. We then propose a theoretical model which enables us to study and explain both non-Washburn regimes. Furthermore, our theoretical model allows us to put forward ways to control the emergence of these regimes by means of geometrical parameters of the experimental set-up. Our methodology allows us to design and calibrate a micro-viscosimetre which works at constant pressure.

[Agitation in head injury. II. Treatment with antidepressant, sympathomimetic, beta blocker , dopaminergic and other drugs]. / Agitación en el traumatismo craneoencefálico. II. Tratamiento con antidepresivos, simpaticomiméticos, betabloqueantes, dopaminérgicos y otros fármacos.

OBJECTIVE: To review the literature of the past 20 years, using the articles indexed in MEDLINE, on the drug treatment of agitation in traumatic head injury. DEVELOPMENT: The treatment of agitation in traumatic head injury should be based on well-designed, randomised, placebo-controlled studies which justify any particular decision regarding drug use. However, care of the agitated traumatic head injury patient is based on the management of other related disorders, on the response of similar patient populations and clinical experience based on empirical observation. Amongst the drugs available, carbamazepine is the most widely used for post-traumatic agitation, followed by antidepressants and as a third option propranolol. We discuss other drugs which are used less frequently in post-traumatic agitation. CONCLUSIONS: Many drugs are used and there is little agreement on the subject. However, with regard to certain characteristics of the agitation, different pharmacological treatments may be recommended.

[Agitation in head injury. I. Definition and treatment with anxiolytic neuroleptics and antiepileptic drugs]. / Agitación en el traumatismo craneoencefálico. I. Definición y tratamiento con neurolépticos, ansiolíticos y antiepilépticos.

OBJECTIVE: To carry out a bibliographic review of articles indexed in MEDLINE over the past 20 years concerning the pharmacological treatment of agitation in head injury. DEVELOPMENT: Head injury may cause different behaviour changes, of which agitation is the most dramatic. The incidence of agitation after severe head injury varies from 11% to 50% depending on the study involved. This incidence is high enough to warrant specific management. Drug treatment has variable results. When there is imminent danger of harm to the patient himself or to others, or when aggressive behaviour makes medical management difficult, the benzodiazepines have been found useful. Antipsychotic drugs are only indicated in head injury when the agitation causes a clinical emergency, and in such a case the more potent drugs such as haloperidol are best, since they have less sedative effect. They are also effective when the clinical features are similar to those of classical schizophrenia. Antiepileptic drugs have been used successfully for treating agitation-aggressiveness, specially in paroxystic behaviour disorders. We also consider other treatments used for posttraumatic agitation. CONCLUSION: There is no general agreement amongst doctors as to the best treatment for posttraumatic agitation in head injury. However, with regard to certain characteristics of agitation different drugs may be recommended for treatment.

Effect of vaccination of pigs against experimental infection with high and low virulence Mycoplasma hyopneumoniae strains.

This study investigated the infection pattern and lung lesion development in pigs caused by a low and highly virulent Mycoplasma hyopneumoniae strain at 4 and 8 weeks (w) post infection (PI). It also determined the efficacy of a commercial inactivated whole-cell vaccine against infection with each one of these M. hyopneumoniae strains. Ninety piglets free of M. hyopneumoniae were selected, and 40 of them were randomly vaccinated during their first week of life. At weaning, all piglets were allocated to 10 different groups and housed in pens with absolute filters. At 4 weeks of age, pigs were inoculated intratracheally with either a highly virulent M. hyopneumoniae strain, a low virulent strain or with sterile culture medium. Half of all animals were euthanized at 4 w PI, while the remaining half was euthanized at 8 w PI. Coughing was assessed daily, and lung lesions, immunofluorescence (IF), bacteriological analysis and nested PCR were assessed after necropsy. It was demonstrated that contrary to the highly virulent strain, the low virulent strain required more than 4 weeks PI (commonly accepted as the standard infection model) to reach maximum clinical symptoms. Vaccination significantly reduced clinical symptoms, macroscopic and microscopic lung lesions in pigs infected with the highly virulent strain. This effect was more pronounced at 4 than at 8 weeks PI. Protective efficacy was also observed in pigs infected with the low virulent strain, but the effect was less pronounced than on the highly virulent strain.

The effect of vaccination on the transmission of Mycoplasma hyopneumoniae in pigs under field conditions.

This study investigated the effect of vaccination against Mycoplasma hyopneumoniae on its transmission in nursery pigs under field conditions. Seventy-two pigs were randomly allocated at weaning into vaccinated (V) and non-vaccinated (NV) groups. Animals in the V group were vaccinated at 3 weeks of age with a commercial M. hyopneumoniae bacterin vaccine. Broncho-alveolar lavage fluid taken at weaning and at the end of the nursery period was assessed for the presence of M. hyopneumoniae by nested PCR, and the reproduction ratio of infection (R(n)) was calculated. The percentage of positive pigs in the V and NV groups was 14% and 36% at weaning, and 31% and 64% at the end of the nursery period, respectively. The R(n)-values for the V and NV groups were 0.71 and 0.56, respectively (P>0.05). The study indicates that vaccination does not significantly reduce the transmission of this respiratory pathogen.

[Clinical and biochemical characteristics of predialysis patients in terms of 25 hydroxy vitamin D levels]. / Características clínicas y bioquímicas de pacientes en prediálisis con respecto a los niveles de 25 hidroxivitamina D.

INTRODUCTION: Decreased levels of 25 hydroxyvitamin D (25[OH]D) have been reported in patients with chronic kidney disease (CKD). The pleiotropic effects of vitamin D are known to go beyond mineral metabolism. OBJECTIVES: The aims of this study were to: 1) Determine the 25(OH)D levels in predialysis outpatients. 2) Find out the clinical and biochemical characteristics of patients with 25(OH)D deficiency, and predictive factors for the deficiency. PATIENTS AND METHODS: An observational study in 79 predialysis outpatients was performed. Clinical and biochemical parameters were analysed in terms of nutrition, inflammation and mineral metabolism in relation to serum levels of 25(OH)D. Levels of 25(OH)D lower than 15ng/ml were considered to be deficient. RESULTS: Serum levels of 25(OH)D were deficient in 41 patients (52%). The comparative study regarding levels of vitamin 25(OH)D showed the group of patients with a deficiency, i.e. those with less than 15ng/ml, were older (70 ± 11.97 vs. 61 ± 14.5; p = 0.005), had a greater body mass index, BMI, (30±4.06 vs. 27.1 ± 5.08; p = 0.003) and increased proteinuria (1.42g/24h (0.53-2.96) vs. 0.51 (0.20-1.48), p = 0.009). This group included a greater number of diabetic patients: 20 (76.9%) vs. 6 (23%), p = 0.002. They had a higher level of parathyroid hormone (PTH): 359 (239-658) vs. 233 (129-323), p = 0.000; and more patients were under treatment with Calcitriol: 28 (62.2%) vs. 17 (37.8%), p = 0.024. In the multivariate analysis, high levels of PTH (OR 13.38; CI 95% [2.94-60.89]; p=0.001), increased proteinuria (OR 4.41; CI 95% [1.12-17.25]; p = 0.033); and being diabetic (OR 5.713; CI 95% [1.43-22.77]; p = 0.014) were independent predictor factors for patients with 25(OH)D deficiency. CONCLUSIONS: In our study, we observed a high prevalence of 25(OH)D deficiency among patients with CKD. The increased levels of PTH, the increase of proteinuria and the presence of diabetes were independent predictors for 25(OH)D deficiency.

Infection with a low virulent Mycoplasma hyopneumoniae isolate does not protect piglets against subsequent infection with a highly virulent M. hyopneumoniae isolate.

The study aimed to evaluate the effect of an infection with low virulent isolates of M. hyopneumoniae (LV1 and LV2) on the subsequent infection with a highly virulent isolate (HV). Fifty-five, 3-week-old piglets free of M. hyopneumoniae were randomly allocated to 6 different groups. At 4 weeks of age (D0), groups LV1-HV and LV1 were intratracheally inoculated with LV1, groups LV2-HV and LV2 with LV2, and group HV with sterile culture medium. Four weeks later (D28), the pigs of these different groups were either intratracheally inoculated with the highly virulent isolate (groups LV1-HV, LV2-HV, HV) or with sterile culture medium (groups LV1 and LV2). A negative control group consisted of pigs inoculated with sterile culture medium on D0 and D28. All animals were necropsied at 28 days after the second inoculation (D56). Clinical symptoms were evaluated daily using a respiratory disease score (RDS). After necropsy, macroscopic and histopathological lung lesions were quantified and immunofluorescence (IF) testing on lung tissue and nested PCR on BAL fluid were performed for the detection of M. hyopneumoniae. Disease signs and lung lesions were not observed in pigs of the negative control group. In the other groups, there were no or only very mild clinical symptoms from D0 until D28. A significant increase in the average RDS values was, however, observed during D28-D56, especially in groups LV1-HV (1.48) and LV2-HV (1.49), in group HV (0.79), and to a lesser extent in groups LV1 (0.50) and LV2 (0.65) (P<0.05). The clinical symptoms during D28-D56, the lung lesions and intensity of IF staining were more pronounced in groups LV1-HV, LV2-HV and HV compared to groups LV1 and LV2. All pigs, except those from the negative control group, were positive on IF testing and PCR at D56. The present study demonstrates that pigs inoculated with low virulent isolates of M. hyopneumoniae are not protected against a subsequent infection with a highly virulent isolate 4 weeks later and may even develop more severe disease signs. This indicates that subsequent infections with different M. hyopneumoniae isolates may lead to more severe clinical disease in a pig herd.

Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.

The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain.

An effective method for the preparation of leukocyte-poor platelets.

Febrile transfusion reactions are encountered occasionally in patients receiving platelet concentrates that contain contaminating leukocytes. To remove heavier cellular elements, a 400-ml platelet pooling bg with tapered sides and a pouch at the base was designed to trap these cells after centrifugation. Two versions of this bag were tested: the initial prototype with a 3-ml pouch and a modified version with a 4-ml pouch. Platelet concentrates were pooled in batches of 6 per bag and, after sampling, were centrifuged between 186 and 600 x g for 7 to 10 minutes. The pouch on each bag was then clamped off, and samples from the primary bag were withdrawn so tht the percentage of cellular elements remaining could be determined. At optimal centrifugation conditions (390 x g for 10 minutes) with the initial prototype of the bag, average cellular decreases were: leukocytes, 75.9 percent; red cells, 84.1 percent; and platelets, 9.8 percent. Twenty-two components prepared in this manner were infused into 12 patients with histories of febrile transfusion reactions. Febrile reactions were markedly reduced or absent in ten patients, a strong febrile reaction due to incorrect component preparation occurred in one, and a marked allergic reaction occurred in one. The 4-ml pouch gave much better production results with greater than 95 percent leukocyte removal and less than 5 percent platelet loss. This system removes sufficient leukocytes from platelet concentrates that the risk of febrile transfusion reactions is reduced significantly.