Olfactory and taste dysfunctions caused by COVID-19: a nationwide study.

BACKGROUND: Olfactory dysfunctions (OD) and taste dysfunctions (TD) are widely recognized as characteristic symptoms of COVID-19; however, the frequency and mode of occurrence has varied depending on the viral mutation. The prevalence and characteristics of OD/TD in Japan have not been definitively investigated. The purpose of this study is to assess the prevalence of OD/TD in Japan during the Alpha variant epidemic, and measure symptom prolongation at 6 months and 1 year later following initial infection. METHODS: Patients treated for COVID-19 between February to May 2021 were evaluated for OD/TD symptoms and provided with a QOL questionnaire. Olfactory tests and taste tests were performed using Open Essence and Taste Strips, respectively. RESULTS: Among the 251 COVID-19 patients who participated, 119 underwent both olfactory and taste tests. Prevalence of subjective OD and TD at the time of survey was 57.8% and 40.2%, respectively. After 12 months, the prevalence fell to 5.8% for OD and 3.5% for TD. Among the OD/TD patients, 36.6% experienced parosmia, and 55.4% experienced parageusia. Prevalence of parosmia and parageusia was higher at 6 and 12 months than at the time of survey. Patients with long-lasting disease reported qualitative dysfunctions and scored significantly higher in food-related QOL problems. Most patients who were aware of their hyposmia had low scores on the olfactory test (83.1%). In contrast, only 26.7% of patients who were aware of their hypogeusia had low scores on the taste test. CONCLUSIONS: The prevalence of COVID-19-related OD and TD at the time of survey was 57.8% and 40.2%, respectively. Subjective symptoms of OD and TD persisted for one year in 5.8% and 3.5% of patients, respectively. More than half of the patients with OD or TD complained of qualitative dysfunction and a decrease in their QOL related to eating and drinking. Most patients with TD did not have true TD, but rather developed flavour disorders associated with OD. This conclusion is supported by the finding that patients with subjective OD had low scores on the olfactory test, whereas most patients with subjective TD had normal scores on the taste test.

Randomized clinical trial of single skin sterilization with a povidone-iodine applicator versus conventional skin sterilization in abdominal surgery.

Background: The efficacy of widely used povidone-iodine applicators for skin sterilization in abdominal surgery is unclear. The aim of this trial was to evaluate whether sterilization with a povidone-iodine applicator was not inferior to a conventional sterilization method. Methods: Patients undergoing elective abdominal surgery were assigned randomly to receive single sterilization with the applicator or conventional sterilization. The primary endpoint was wound infection rate. Secondary endpoints were rate of organ/space surgical-site infection (SSI), adverse effects of povidone-iodine, amount of povidone-iodine used and total cost of sterilization. Results: Of 498 patients eligible for the study between April 2015 and September 2017, 240 were assigned and analysed in the applicator group and 246 in the conventional group. Wound infection was detected in 16 patients (6·7 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group (absolute difference 0·0016 (90 per cent c.i. -0·037 to 0·040) per cent; P = 0·014 for non-inferiority). There was no difference between the groups in the organ/space SSI rate (11 patients (4·6 per cent) in the applicator group and 16 (6·5 per cent) in the conventional group. Both the amount of povidone-iodine used and the total cost of sterilization were higher in the conventional group than in the applicator group (median 76·7 versus 25 ml respectively, P < 0·001; median €7·0 versus €6·4, P < 0·001). Skin irritation was detected in three patients in the conventional group. Conclusion: In abdominal surgery, this povidone-iodine applicator was not inferior to conventional sterilization in terms of the wound infection rate, and it is cheaper. Registration number: UMIN000018231 (http://www.umin.ac.jp/ctr/).

Comparison between dexmedetomidine and midazolam as a sedation agent with local anesthesia in inguinal hernia repair: randomized controlled trial.

PURPOSE: In Japan, inguinal hernia repair is widely performed with local anesthesia. The objective of this study was to evaluate safety and efficacy of intravenous dexmedetomidine as a sedation agent with local anesthesia in inguinal hernia repair. METHODS: We performed this randomized, single-blind study for 200 patients who were scheduled to undergo inguinal hernia repair with local anesthesia. Patients were randomly divided into two groups (dexmedetomidine group: Group D, midazolam group: Group M). The primary outcome was to evaluate the safety of intravenous dexmedetomidine. Secondary outcomes were to analyze results of operators' surveys and patients' questionnaires and evaluate implementation of conscious sedation. RESULTS: Incidence of respiratory depression was significantly higher in Group M than Group D (p = 0.03). Other adverse events examined did not differ significantly. All three operators' questionnaires indicated that results were better in Group D than Group M. More than 70% of patients in both groups were satisfied with the surgery. More than 80% of Group D patients and 74% of Group M patients achieved a state of conscious sedation. CONCLUSION: This study demonstrated that intravenous dexmedetomidine during hernia repair with local anesthesia is safe and the results were satisfactory to both operators and patients.

Observation of a large reaction cross section in the drip-line nucleus 22C.

Reaction cross sections (sigma(R)) for 19C, 20C and the drip-line nucleus 22C on a liquid hydrogen target have been measured at around 40A MeV by a transmission method. A large enhancement of sigma(R) for 22C compared to those for neighboring C isotopes was observed. Using a finite-range Glauber calculation under an optical-limit approximation the rms matter radius of 22C was deduced to be 5.4+/-0.9 fm. It does not follow the systematic behavior of radii in carbon isotopes with N < or = 14, suggesting a neutron halo. It was found by an analysis based on a few-body Glauber calculation that the two-valence neutrons in 22C preferentially occupy the 1s(1/2) orbital.

Poor applicability of estimation method for adults to calculate unbound serum concentrations of valproic acid in epileptic neonates and infants.

OBJECTIVE: To characterize the relationship between total and unbound concentrations of valproic acid (VPA) in epileptic neonates and infants, the clinical examination records of those patients archived via therapeutic drug monitoring (TDM) activities were retrospectively analyzed. METHODS: The screening encompassed 249 records of 114 epileptic patients aged 0-19 years old, who were treated with VPA monotherapy and whose total and unbound VPA concentrations were determined. These data were divided into groups according to the patients' age. In each group, the relationship between total and unbound VPA concentrations was compared to a reference profile, and the deviation from the reference was evaluated. The reference profile was calculated using the Langmuir equation, in which two parameters Kd and Bm were set to 7.8 and 130 microg/mL, respectively, according to our previous findings. RESULTS: The relationship between total and unbound VPA concentrations of patients of 0 years old considerably deviated from the reference, and their unbound VPA concentrations were generally higher compared to the corresponding reference values. It is suggested that the large deviation is related to the fact that the serum albumin concentrations of patients younger than 1 year old tend to be lower than those of patients in other age groups. CONCLUSION: Since the relationship between the VPA concentrations of epileptic neonates and infants is noticeably different from the reference, the unbound serum VPA concentrations of these patients are not adequately estimated using the same method as that for grown-ups. The unbound VPA concentrations of neonates and infants should be explicitly determined via TDM activities.

Characterization of non-linear relationship between total and unbound serum concentrations of valproic acid in epileptic children.

OBJECTIVE: To establish a regression equation to properly estimate the unbound serum concentration of valproic acid (VPA) from its total serum concentration; the relationship between total and unbound serum VPA concentrations was retrospectively characterized. METHODS: Data were obtained from the clinical examination records that were routinely archived during therapeutic drug monitoring. The screening encompassed 342 records of 108 paediatric patients whose total and unbound VPA concentrations had been determined. The relationship between total and unbound VPA concentrations was characterized according to the Langmuir equation by taking account of inter-individual variability with the nonmem program. RESULTS: The total VPA concentration (C(t)) in the screened patients ranged from 5.5 to 179.8 microg/mL, and the unbound VPA concentration (C(f)) increased in a non-linear manner as the total VPA concentration increased. Taking account of the effects of antiepileptics concurrently administered, the VPA dissociation constant (K(d)) and maximum binding site concentration (B(m)) were 7.8 +/- 0.7 and 130 +/- 4.5 microg/mL respectively, for the regression equation, C(t) = C(f) + B(m) x C(f)/(K(d) + C(f)). An alteration in the unbound concentration was seen in patients who were treated with the combination of VPA and ethosuximide and in those who received two additional antiepileptics. CONCLUSIONS: A regression equation for estimation of the unbound VPA concentration, based on total VPA concentration collected during routine therapeutic drug monitoring was established. Use of two additional antiepileptics and ethosuximide treatment was considered as potential factors affecting unbound VPA concentration.

High resolution optical mapping of cardiac action potentials in freely beating rabbit hearts.

UNLABELLED: Optical mapping of action potentials (APs) has become important tools for the cardiac electrophysiology. However, cardiac contraction unavoidably produces motion artifacts (MA) in optical signal. We developed a method to suppress motion artifacts without arresting the hearts. METHODS: Using a dual-wavelength optical mapping system, APs were recorded on the surface of an isolated rabbit heart. Transmembrane APs were simultaneously recorded using glass microelectrodes. We eliminated MA in a frontal plane by a motion tracking technique. Subsequently, a dual-wavelength ratiometric method was used to remove MA in a vertical direction to a frontal plane. RESULTS: MA were effectively removed from optical signals. Action potential duration measured from optical signals corresponded with those measured from microelectrodes (r2=0.9677). Our method enables us to map action potentials in freely beating hearts.

Cerebellar infarction secondary to os odontoideum.

A 43-year-old man developed cerebellar infarction due to atlantoaxial dislocation associated with os odontoideum. Cervical X-ray films confirmed os odontoideum, and conventional angiography revealed irregular narrowing of the right vertebral artery at the axis level. A correlation between the vertebral artery lesion and atlantoaxial instability was shown with 3-dimensional (3-D) computed tomographic (CT) angiography. This is the first case of atlantoaxial dislocation with vertebral artery stenosis demonstrated 3-D CT angiography. 3-D CT angiography can support the conventional angiography with respect to the diagnosis and management of vertebral artery insufficiency associated with occipitocervical deformity.

Unusual CT and MR findings of inflammatory pseudotumor in the parapharyngeal space: case report.

Unusual MR and CT findings of an inflammatory pseudotumor in the parapharyngeal space of a 73-year-old woman are reported. The mass was hypointense on T1- and T2-weighted images and demonstrated ring enhancement after contrast medium injection. Punctated calcifications were scattered at the periphery. Inflammatory pseudotumors in the parapharyngeal space are rare, and only three cases have been reported. The possible pathogenesis and varieties of inflammatory pseudotumors are discussed.

Effect of experimental renal dysfunction on bioavailability of ajmaline in rats.

The effect of renal dysfunction on the bioavailability of ajmaline has been investigated in rats, where experimental renal dysfunction was induced by subcutaneous injection of uranyl nitrate (10 mg kg(-1)). Renal dysfunction did not cause any change in the blood ajmaline concentration after intravenous administration (2 mg kg(-1)), but it increased the blood ajmaline concentration by approximately 2.8-fold after intraduodenal administration (10 mg kg(-1)). The availability of ajmaline in control rats was 16.7%, whereas the availability was increased to 41.1% in rats with renal dysfunction. The unbound fraction in the blood and the metabolic activity in the liver, was assessed with the 10000-g supernatant fraction and with isolated hepatocytes, respectively. The values were found to be similar in both groups. The blood concentration following intraportal infusion was only slightly increased in rats with renal dysfunction, but the hepatic first-pass extraction was infusion rate-dependent and saturable. The initial absorption rate of ajmaline from the small intestine in rats with renal dysfunction was significantly greater compared with control rats. These results indicated that the increased availability of ajmaline in renal dysfunction was mainly a result of partially saturated extraction in the liver, which was caused by an increased absorption rate in the intestine and non-linear extraction in the liver.

Clinical usefulness of a multielectrode basket catheter for idiopathic ventricular tachycardia originating from right ventricular outflow tract.

INTRODUCTION: It often is difficult to determine the optimal ablation site for idiopathic ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT) when the VT or premature ventricular complex (PVC) does not occur frequently. The aim of our study was to evaluate the usefulness of a multielectrode basket catheter for ablation of idiopathic VT originating from the RVOT. METHODS AND RESULTS: Radiofrequency (RF) catheter ablation was performed using a 4-mm tip, quadripolar catheter in 50 consecutive patients with 81 VTs originating from the RVOT with (basket group = 25 patients with 45 VTs) or without (control group = 25 patients with 36 VTs) predeployment of a multielectrode basket catheter composed of 64 electrodes. Deployment of the multielectrode basket catheter was possible and safe in all 25 patients in the basket group. Ablation was successful in 25 (100%) of 25 patients in the basket group and in 22 (88%) of 25 patients in the control group. The total number of RF applications and the number of RF applications per PVC morphology did not differ between the two groups. However, both the fluoroscopic and ablation procedure times per PVC morphology were shorter in the basket group than in the control group (36.8+/-14.1 min vs 52.0+/-32.5 min, P = 0.04; 60.0+/-14.6 vs 81.5+/-51.2 min, P = 0.05). This difference was more pronounced in the 29 patients in whom VT or PVC was not frequently observed. CONCLUSION: The multielectrode basket catheter is safe and useful for determining the optimal ablation site in patients with idiopathic VT originating from the RVOT, especially in those without frequent VT or PVC.

The role of Purkinje and pre-Purkinje potentials in the reentrant circuit of verapamil-sensitive idiopathic LV tachycardia.

Although the mechanism of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) is usually reentry, the actual reentrant circuit is not clearly understood. This study examined the relationship between the Purkinje potential (PP) and a dull potential preceding PP (pre-PP) during ILVT to elucidate the roles of these potentials in the reentrant circuit of ILVT. Electrophysiological studies and radiofrequency catheter ablation were performed in ten patients (7 men, 3 women, mean age 29 years) who had an ILVT with a right bundle branch block configuration and left-axis deviation. Left ventricular endocardial mapping using an octapolar catheter and entrainment and resetting studies during VT was performed by pacing from the right ventricular outflow tract (RVOT) and each site of the left ventricular mapping catheter. PP and pre-PP were recorded simultaneously during VT in all patients. The earliest PP during VT was recorded at the inferoposterior septum, and PP was activated bidirectionally toward the proximal (basal) and distal (apical) sites along the left posterior fascicle. In contrast, pre-PP was recorded at sites slightly proximal to the earliest PP recording site, and was activated toward the earliest PP site. Pacing from RVOT confirmed manifest entrainment, and the stimulus to pre-PP interval was prolonged with a shorter pacing cycle length. Concealed entrainment was demonstrated by capture of the PPs of the left ventricular mapping catheter in six patients, and the postpacing interval at each PP site was equal to the tachycardia cycle length. The pre-PP was orthodromically activated from the proximal to the distal site during pacing. More rapid pacing also produced delay in activation from PP to pre-PP, indicating slow conduction in ILVT. Catheter ablation was performed at the pre-PP recording site during VT, and was successful in all patients. The reentrant circuit of ILVT could be constructed based on the pre-PP, PP, and slow conduction between the PP and pre-PP. Catheter ablation of ILVT was successful at the pre-PP recording site.

Appropriate indications for the use of a percutaneous cardiopulmonary support system in cases with cardiogenic shock complicating acute myocardial infarction.

Percutaneous cardiopulmonary support (PCPS) is now available for hemodynamic support in patients with cardiogenic shock, but there are no guidelines for its use. The present study determined the appropriate indications for the use of the PCPS in patients with cardiogenic shock complicating acute myocardial infarction (AMI). Sixty-four consecutive patients with cardiogenic shock complicating AMI had hemodynamic support with an intraaortic balloon pump (IABP; n=38) and/or PCPS (n=26). The shock score (0-15) was calculated immediately before starting these support systems to quantify the severity of shock. Multivariate logistic regression analysis determined the clinical factors affecting in-hospital mortality. The relationship between in-hospital prognosis and the shock score was also examined in the 2 groups. The most significant factor related to the in-hospital prognosis was the shock score (p=0.0007; OR 2.16, 95% CI: 1.37-3.39). Another related factor was revascularization; however, this relationship did not reach statistical significance (p=0.069; OR 0.06). Among the 13 cases whose shock score was 4-8 (moderate shock), 5 survived in the PCPS group, but only 1 of 19 patients survived in the IABP group (p<0.05). None of the patients in either group whose shock score was more than 9 survived. The severity of shock is the most reliable independent predictor of in-hospital mortality in patients with cardiogenic shock complicating AMI. Using PCPS in patients with moderate cardiogenic shock may improve their in-hospital survival, but it must be used before the shock becomes severe.

Paradoxic abbreviation of repolarization in epicardium of the right ventricular outflow tract during augmentation of Brugada-type ST segment elevation.

We report the case of a 53-year-old Japanese man with a typical Brugada-like ECG in whom epicardial and endocardial activation-recovery intervals (ARI) in the right ventricular outflow tract (RVOT) were simultaneously measured by recording unipolar electrograms from the Pathfinder catheter introduced in the great cardiac vein as well as from the multielectrode basket catheter deployed in the RVOT. Epicardial ARI in the RVOT was abbreviated paradoxically at the beat of augmented ST segment elevation in lead V2 after a long pause or after pilsicainide injection. Endocardial ARI in the RVOT and epicardial ARI in the left ventricle were prolonged or were not changed. Our data support the hypothesis that heterogenous response of repolarization across the ventricular wall in the RVOT is responsible for accentuation of ST segment elevation in the right precordial leads.

Recovery time dispersion measured from 87-lead body surface potential mapping as a predictor of sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy.

INTRODUCTION: The clinical usefulness of QT dispersion in 12-lead ECG has been controversial in identifying subjects at risk for sustained ventricular tachycardia (VT) in patients with idiopathic dilated cardiomyopathy (DCM). We hypothesized that increasing the spatial resolution of the ECG improves the accuracy of risk stratification. The purpose of this study was to test the ability of recovery time dispersion measured from 87-lead body surface potential mapping (BSPM) to identify patients at risk for sustained VT in idiopathic DCM. METHODS AND RESULTS: We obtained 87-lead BSPM and 12-lead ECG in 33 patients with idiopathic DCM (15 patients with a history of sustained VT [VT(+) group] and 18 patients without a history of sustained VT [VT(-) group]) and in 20 normal control subjects. We measured the corrected QT dispersion and corrected recovery time dispersion from 12-lead ECG (QTc-12 dispersion and RTc-12 dispersion, respectively) and 87-lead BSPM (QTc-87 dispersion and RTc-87 dispersion, respectively). Signal-averaged ECG also was recorded in 25 patients. Neither the QTc-12 nor QTc-87 dispersion discriminated between the VT(+) and VT(-) groups patients. The VT(+) group patients had a larger but insignificant RTc-12 dispersion than the VT(-) group patients. In contrast, the RTc-87 dispersion was significantly larger in the VT(+) group patients than in the VT(-) group patients (236 +/- 39 msec vs 184 +/- 28 msec, P < 0.001). Receiver operating curve analysis indicated that the RTc-87 dispersion was as good as late potentials in predicting susceptibility to sustained VT; its sensitivity, specificity, and negative predictive value were 73%, 76%, and 76%, respectively (cutoff value 200 msec). RTc-87 dispersion >200 msec combined with positive late potentials provide high sensitivity (92%) and high negative predictive value (88%) for sustained VT. CONCLUSION: The RTc-87 dispersion is a useful tool to identify subjects at risk for sustained VT in patients with idiopathic DCM.

Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms.

INTRODUCTION: Body surface distribution and magnitude of ST segment elevation and their reflection in 12-lead ECGs have not been clarified in Brugada syndrome. METHODS AND RESULTS: Eighty-seven-lead body surface potential mapping and 12-lead ECGs were recorded simultaneously in 25 patients with Brugada syndrome and 40 control patients. The amplitude of the ST segment 20 msec after the end of QRS (ST20) was measured from all 87 leads, and an ST isopotential map was constructed. The maximum ST elevation (maxST20) was distributed in an area of the right ventricular outflow tract in all Brugada patients, and it was larger than that in control patients (0.37 +/- 0.13 vs 0.12 +/- 0.04 mV; P < 0.0005). The maximum was observed on the level of the parasternal fourth intercostal space, on which the V1 and V2 leads of the standard 12-lead ECG were located, in 18 of the 25 Brugada patients in whom typical coved- or saddleback-type ST elevation was seen in leads V1 and V2. The maximum was located on the second intercostal space in the remaining seven Brugada patients in whom only a mild saddleback-type ST elevation was seen in leads V1 and V2 of the 12-lead ECG. Typical ST segment elevation was recognized in leads V1 and V2, which were recorded on the second or third intercostal space. ST elevation in Brugada patients was dramatically normalized by isoproterenol, a beta-adrenergic agonist (maxST20 = 0.17 +/- 0.08 mV; P < 0.0005 vs control conditions), and accentuated by disopyramide, an Na+ channel blocker (maxST20 = 0.50 +/- 0.15 mV; P < 0.0005 vs control conditions), without any change in the location of the maxST20. CONCLUSION: Our data indicate that recordings of leads V1-V3 of the 12-lead ECG on the parasternal second or third intercostal space would be helpful in diagnosing suspected patients with Brugada syndrome. The data suggest that Na+ channel blockers are capable of accentuating ST elevation in leads V1-V3.

[Clinical study on liver metastasis of AFP-producing gastric cancer--characteristic findings of angiography].

We studied 6 patients with liver metastasis of AFP-producing gastric cancer, especially about the angiography and treatment. The angiographic findings of liver metastasis are characteristic in 3 patients. Multiple rounded hypervascular tumor are seen in the arterial phase and its vessels are fine. In the venous phase, the tumor is homogeneous. We called the findings "Fireworks like stain". These patients were treated with TAE and responded it.

Effect of dosage form on stereoisomeric inversion of ibuprofen in volunteers.

Twelve healthy volunteers were given ibuprofen racemate in two different dosage forms, a suspension and a tablet. The plasma concentration-time profiles of S- and R-ibuprofen were determined and the R-ibuprofen inversion clearance was calculated. Although the area under the curve was almost the same in both the suspension and tablet studies, the inversion clearance was larger in the suspension study than in the tablet study (1.18+/-0.65 and 0.72+/-0.63 l/h, shown as the mean+/-S.D.). The Michaelis-Menten parameters for this inversion process were then determined in vitro with human liver microsomes (1.3+/-0.2 mM for Km and 3.1+/-0.3 nmol/min/mg protein for Vmax, shown as the mean+/-S.D.). These parameters indicated that the stereoisomeric inversion of R-ibuprofen in the liver was not likely to be saturated at the plasma concentrations measured in the volunteer study. The profile of the plasma concentration ratio between S-ibuprofen and R-ibuprofen revealed a difference in the early phase of these two studies. Therefore the inversion difference between those two studies probably resulted from the difference in the absorption phase of each dosage form. Our study demonstrated that R-ibuprofen inversion could be affected by alteration of dosage form.