Post COVID-19 condition of the Omicron variant of SARS-CoV-2.

OBJECTIVES: To investigate the prevalence of post coronavirus disease (COVID-19) condition of the Omicron variant in comparison to other strains. STUDY DESIGN: A single-center cross-sectional study. METHODS: Patients who recovered from Omicron COVID-19 infection (Omicron group) were interviewed via telephone, and patients infected with other strains (control group) were surveyed via a self-reporting questionnaire. Data on patients' characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted for at least 2 months, within 3 months of COVID-19 onset. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching. RESULTS: We conducted interviews for 53 out of 128 patients with Omicron and obtained 502 responses in the control group. After matching cases with controls, 18 patients from both groups had improved covariate balance of the factors: older adult, female sex, obesity, and vaccination status. There were no significant differences in the prevalence of each post COVID-19 condition between the two groups. The number of patients with at least one post COVID-19 condition in the Omicron and control groups were 1 (5.6%) and 10 (55.6%) (p = 0.003), respectively. CONCLUSIONS: The prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with a larger sample size is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.

Difference in efficacy of proton pump inhibitor between new-onset and recurrent gastroesophageal reflux disease: Result from a study of on-demand versus continuous maintenance therapy in Japan.

BACKGROUND-OBJECTIVE: No study has focused on the difference in efficacy of maintenance therapy between patients with new-onset and recurrent gastroesophageal reflux disease (GERD). The aim of this study is to reveal this point. METHODS: Endoscopically proven GERD patients who had completed 8-week initial therapy were sequentially randomized to continuous arm (Omeprazole 20mg od) or on-demand arm (Omeprazole 20mg on-demand). Patients filled in daily symptoms and tablet usages for 24 weeks. Patients underwent upper GI endoscopy at 24 weeks. Symptom relief was defined as no symptoms for>6 days during a week. The numbers of patients who achieved symptom relief and mucosal healing were compared between the new-onset and recurrent groups in the continuous arm and in the on-demand arm, respectively. RESULTS: Among new-onset GERD [n=82 (continuous: 42 patients, on-demand: 40)], continuous arm achieved significant symptom-relief than in on-demand arm at 4*,5*,6** and 17*week. Among recurrent GERD [n=36(continuous: 17 patients, on-demand: 19)], continuous arm achieved significant symptom-relief at 1**,2*,3*,4*,5**,7**,8**,17* and 18* week, respectively (*<0.05,**<0.01). The number of healed patients was significantly higher in new-onset group (60/68, 88.2%) than in recurrent group (17/30, 56.7%) (<0.01). CONCLUSION: Since therapeutic response during maintenance therapy was poor in recurrent GERD, continuous therapy is recommended in order to maintain symptom-relief and mucosal healing. Hippokratia 2015, 19 (1): 53-56.

Exploration and characterization of genes involved in the synthesis of diterpene defence secretion in nasute termite soldiers.

Nasutitermes takasagoensis soldiers defend their colonies using characteristic diterpenes. Diterpenes are thought to be synthesized in the frontal gland cells surrounding the gland reservoir. To identify the genes involved in diterpene synthesis, a cDNA library was prepared from the frontal gland cells and exhaustively sequenced using a 454 pyrosequencer (GS Junior; Roche, Branford, CT, USA). A total of 50,290 clean sequences were assembled into 1111 contigs, which were grouped into 774 genes (isogroups). Based on sequence similarity with known proteins, we identified seven genes encoding the following four enzymes associated with diterpene synthesis: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase (HMGS), HMG-CoA reductase (HMGR), farnesyl diphosphate synthase, and geranylgeranyl diphosphate synthases. The expression levels of two enzymes, HMGS and HMGR, involved in the mevalonate pathway were examined, assuming that the site of the defensive terpenoid synthesis strongly activates the mevalonate pathway, which produces a precursor of terpenoids. Real-time quantitative reverse-transcriptase PCR confirmed significantly higher expression of HMGS and HMGR in the heads of soldiers. We then divided the head into three parts and found that the expression levels of HMGS and HMGR were significantly higher in the part containing class 1 secretory cells of the frontal gland. Overall, the results suggested that the mevalonate pathway for diterpene synthesis occurs in class 1 cells around the frontal gland reservoir.

Efficacy of the 5-HT1A agonist tandospirone citrate in improving symptoms of patients with functional dyspepsia: a randomized controlled trial.

OBJECTIVES: Functional dyspepsia (FD) is a common condition in the general population; however, its treatment remains a challenge. The aim of this study was to examine the efficacy of tandospirone citrate, a new partial agonist of the 5-hydroxytryptamine 1A (5-HT1A) receptor, in improving the symptoms of patients with FD. METHODS: In this double-blind, placebo-controlled, multicenter study, FD patients were randomized to treatment with 10 mg t.i.d. tandospirone citrate or to placebo for 4 weeks. The primary end point was change in abdominal symptom scores. The difference in the proportion of responders (a total abdominal symptom score of 0 or 1) was also assessed. The quality-of-life questionnaire, the SF-8, and a psychological test questionnaire, the State-Trait Anxiety Inventory (STAI), were completed at baseline and at weekly intervals. RESULTS: Data were available for 144 patients: 73 for tandospirone and 71 for placebo. Improvements in total abdominal scores were significantly larger with tandospirone than placebo at weeks 1, 2, and 4. Significantly greater improvements in the tandospirone group were observed in upper abdominal pain (P=0.02) and discomfort (P=0.002) at week 4. The proportion of responders was significantly greater in the active treatment arm at weeks 3 (P=0.017) and 4 (P=0.0016). Significant improvements in STAI (P<0.0001) were reported in both arms, as well as in the majority of questions in the SF-8 (P=0.04). No serious adverse events were reported, with similar rates in both study arms. CONCLUSIONS: Despite a considerable placebo effect, the benefits of tandospirone were shown in terms of improvement in abdominal symptom scores.

Plical resection in pre-temporal approach for basilar bifurcation aneurysms: preliminary surgical experience and cadaveric study.

OBJECT: Although a pre-temporal approach (PA) can provide a wide space for preservation of thalamoperforating atrteries in direct surgery for basilar bifurcation aneurysms (BBAs), it cannot always secure adequate proximal control. The authors described the advantages of plical resection added to PA for BBAs. METHODS: Between October 1998 and April 2000, eight consecutive patients with BBAs were treated in the neurosurgical department of Kurashiki Central Hospital. Among them, five patients received direct clipping using this method. There were four females and one male, ages ranging from 61 to 77 (mean 70.8 years). Mean aneurysmal size and distance between the in"terclinoidal line and the aneurysmal neck was 4.5 and 9.5 mm, respectively. The operative procedures consisted of the following components; 1) fronto-temporal craniotomy with translocation of orbito-zygomatico-malar bone for PA, 2) preservation of lateral branches of the superficial sylvian veins, 3) resection of plica dural folds to increase the operative field up to the oculomotor nerve (OMN). RESULTS: Complete clipping was achieved without thalamic infarction or temporal contusion in all patients. Three of the five patients suffered from transient right OMN palsy which recovered within two months after surgery. CONCLUSION: Plical resection in the pre-temporal approach might be beneficial in the surgical treatment of BBAs when proximal control seems difficult.

Characterization of carotid atherosclerosis and detection of soft plaque with use of black-blood MR imaging.

BACKGROUND AND PURPOSE: In the treatment of carotid atherosclerosis, the rate of stenosis and characteristics of plaque should be assessed to diagnose vulnerable plaques that increase the risk for cerebral infarction. We performed carotid black-blood (BB) MR imaging to diagnose plaque components and assess plaque hardness based on MR signals. MATERIALS AND METHODS: Three images of BB-MR imaging per plaque were obtained from 70 consecutive patients who underwent carotid endarterectomy (CEA) to generate T1- and T2-weighted images. To evaluate the relative signal intensity (rSI) of plaque components and the relationship between histologic findings and symptoms, we prepared sections at 2-mm intervals from 34 intact plaques. We then calculated the relative overall signal intensity (roSI) of 70 plaques to assess the relationship between MR signal intensity and plaque hardness and symptoms. RESULTS: The characteristics of rSI values on T1- and T2-weighted images of fibrous cap (FC), fibrosis, calcification, myxomatous tissue, lipid core (LC) with intraplaque hemorrhage (IPH), and LC without IPH differed. Symptomatic plaques were associated with FC disruption (P < .001) and LC with IPH (P < .05). The roSI on T1-weighted images was significantly higher for soft than nonsoft plaques. When the roSI cutoff value was set at 1.25 (mean of the roSI), soft plaques were diagnosed with 79.4% sensitivity and 84.4% specificity. The roSI was also significantly higher for symptomatic than for asymptomatic plaques. Soft and nonsoft plaques as well as symptomatic and asymptomatic plaques did not significantly differ on T2-weighted images. CONCLUSION: BB-MR imaging can diagnose plaque components and predict plaque hardness. This procedure provides useful information for planning therapeutic strategies of carotid atherosclerosis.

Caste-specific cytochrome P450 in the damp-wood termite Hodotermopsis sjostedti (Isoptera, Termopsidae).

Termites are eusocial insects with a well-defined caste system, which is an example of polyphenism. This polyphenism is based on hormonally controlled differential gene expression. In the damp-wood termite Hodotermopsis sjostedti, we induced differentiation into the soldier caste by using juvenile hormone analogue treatment. We then investigated specific gene expression, which appeared during the hormonal response and triggered caste differentiation, using fluorescent differential display. A candidate cDNA sequence with similarity to cytochromes P450, CYP6AM1, was characterized and its transcript shown to be repressed between 1 and 3 days after hormone treatment. CYP6AM1 was specifically expressed in the fat body of pseudergates and soldiers. The putative function of this P450 is discussed with respect to the caste differentiation system.

A phase I/II trial of irinotecan-cisplatin combined with an anti-late-diarrhoeal programme to evaluate the safety and antitumour response of this combination therapy in patients with advanced non-small-cell lung cancer.

We conducted a phase I/II study in patients with advanced non-small-cell lung cancer (NSCLC) to increase the therapeutic index of the cisplatin-irinotecan combination by institution of an anti-late-diarrhoeal program (ADP). A total of 77 chemotherapy-naive patients with advanced NSCLC were enrolled. The cisplatin dose was fixed at 60 mg m(-2) (Day 1). Irinotecan was escalated in 5 mg m(-2) increments, starting from 60 mg m(-2) (Days 1 and 8). ADP consisted of oral sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid, and was administered orally for 4 days with each dose of irinotecan. In the phase I portion, irinotecan pharmacokinetics was also examined. After the recommended dose of irinotecan with ADP was determined, a phase II study was conducted to evaluate the response. Maximum tolerated dose was reached at an irinotecan dose of 80 mg m(-2) (Grade 4 diarrhoea and neutropenia). Pharmacokinetic studies show that the maximum concentration and the area under the curve of both irinotecan and SN38 (active metabolite of irinotecan) tend to increase in the dose-dependent manner of irinotecan. The phase II portion of the study included 48 patients, who were treated with 75 mg m(-2) of irinotecan. Grade 3/4 toxicities included neutropenia in 65%, leucopenia in 33%, and late diarrhoea in 6% of the patients. During this treatment, PS did not change in 65% of patients. At the end of the chemotherapy, PS did not decline in 90% of patients. In the phase II portion, a response occurred in 63% (95% confidential interval (CI), 47-76%) of patients. Median time to progression was 19 weeks (95% CI, 15-22 weeks), and median survival was 52 weeks (95% CI, 39-64 weeks). This regimen of irinotecan and cisplatin with ADP resulted in promising efficacy with acceptable toxicity for patients with advanced NSCLC. This regimen is a candidate for the experimental arm towards future phase III studies.

Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy.

BACKGROUND: We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis. AIM: To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach. METHODS: Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3-5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed. RESULTS: After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group. CONCLUSIONS: Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.

Improvement in serum pepsinogens and gastrin in long-term monitoring after eradication of Helicobacter pylori: comparison with H. pylori-negative patients.

BACKGROUND: A decrease in pepsinogen and gastrin levels 1-3 months after Helicobacter pylori eradication is well known. However, few data are available on the long-term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori-negative patients with dyspepsia. AIM: We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori-negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio. METHODS: We enrolled 172 H. pylori-positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non-treated H. pylori-negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System. RESULTS: In the H. pylori-negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 +/- 20.8 ng/mL, 9.2 +/- 4.2 ng/mL, 6.0 +/- 1.7 and 53.5 +/- 29.2 pg/mL, respectively. In H. pylori-positive patients with long-term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 +/- 46.6 ng/mL, 25.9 +/- 17.1 ng/mL, 3.4 +/- 1.3 and 131.9 +/- 130.8 pg/mL, respectively, before treatment. At 1-3 months after eradication, serum pepsinogen I and II levels in the H. pylori-positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12-15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1-3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12-15 months. CONCLUSION: The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long-term follow-up study.

Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases.

BACKGROUND: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. AIM: To investigate oesophageal hypersensitivity in Japanese NERD patients. PATIENTS AND METHODS: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. RESULTS: The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 +/- 3.4, 4.4 +/- 3.4, 27.8 +/- 26.7, respectively) were higher than in erosive GERD (3.2 +/- 3.3, 3.0 +/- 3.2, 18.2 +/- 24.8) and Barrett patients (2.5 +/- 4.0, 1.8 +/- 3.3, 15.0 +/- 28.8), and significantly higher than in the control group (1.7 +/- 2.7, 1.1 +/- 2.0, 5.4 +/- 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). CONCLUSION: Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Is antimicrobial susceptibility testing necessary before second-line treatment for Helicobacter pylori infection?

BACKGROUND: An antimicrobial susceptibility test for Helicobacter pylori before second-line treatment is often performed, although whether the test is truly necessary remains unknown. PATIENTS AND METHODS: Eighty-two patients with H. pylori infection for whom first-line treatment with a 1-week proton pump inhibitor/amoxicillin-clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re-treatment. The cure rates for these two groups were compared. RESULTS: Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility-test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole-amoxicillin-clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole-amoxicillin-metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention-to-treat (ITT)-based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66-92%) and 92.4% (79-98%), respectively, and there was no significant difference between these two groups. CONCLUSION: Susceptibility testing is not necessarily required before second-line therapy if the first-line treatment has been performed using proton pump inhibitor/AC regimens.

Alteration of histological gastritis after cure of Helicobacter pylori infection.

BACKGROUND: It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. AIM: To clarify the histological changes after the cure of H. pylori infection through a literature survey. METHODS: Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. RESULTS: Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Four of 28 studies described significant improvement of intestinal metaplasia [corrected]. CONCLUSIONS: Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power.

[Recent advance in inhaled corticosteroid therapy].

Inhaled corticosteroid therapy against bronchial asthma has developed rapidly and remarkably during last 10 years. The significance of this therapy has been established in a lot of international guidelines for asthma management. Early intervention, which developed from the concept of step-down therapy, is new therapeutic approach to prevent the remodeling of airway walls deemed as the major cause of irreversible airflow limitation which makes patient chronic and refractory asthmatics. It is comprehensive therapeutic approach which include not only early diagnosis, early intensive corticosteroid therapy, but also environment intervention and enough patient education. In addition to this new therapeutic strategy, we will describe about add-on effect of long-acting beta-2 agonists, theophylline, and leukotriene receptor antagonist.

Pooled analysis on the efficacy of the second-line treatment regimens for Helicobacter pylori infection.

BACKGROUND: Although many of the currently available Helicobacter pylori eradication regimens fail to cure 5%-12% of patients, an optimal re-treatment therapy for eradication-failure patients has still not been established. The aim of this study was to examine all reports concerning the efficacy of re-eradication regimens for H. pylori infection, and to establish optimal re-eradication regimens. METHODS: Studies concerning re-eradication regimens were retrieved from the MEDLINE database, reference lists and major congress abstract lists up through December 1999. Data from all selected reports were pooled into several groups depending on second-line or initial therapies. Pooled eradication rates of re-treatment regimens were compared using Fisher's exact test (P < 0.05). RESULTS: Sixteen articles and 24 abstracts with 75 total treatment arms were included in this study. Pooled re-eradication rates by proton-pump inhibitor (PPI)-based dual therapy, PPI-based triple therapy, ranitidine bismuth-based triple therapy and quadruple therapy were 45.8%, 69.8%, 80.2% and 75.8%, respectively. Eradication rates from studies with two new antimicobials added were higher than rates from studies with only one new antimicrobial added (P = 0.0064). CONCLUSION: Ranitidine bismuth-based triple therapies, as well as quadruple therapies, seem to be the most effective re-treatment therapies in all currently undertaken therapies. The strategy of adding two new antimicrobials to previous regimens was also effective in re-eradication therapy.

[Magnetic resonance imaging findings of postresuscitation encephalopathy: sequential change and correlation with clinical outcome].

OBJECTIVE: The purpose of this study was to describe the findings of sequential magnetic resonance imaging (MRI) in postresuscitation encephalopathy. Although its outcome is known to be overwhelming, but its acute findings by variable imaging methods are subtle and show only limited values. The correlation of the findings of MRI with clinical outcome were also analyzed. METHODS: Twelve patients with global cerebral anoxia who underwent MRI with conventional and diffusion-weighted imaging were enrolled in this study. Compared with normal MRI images, abnormal signal regions were checked and described in cortex, basal ganglia and white matter. Also medical records were carefully reviewed to study the cause, the time necessary for resuscitation and long term clinical outcome. RESULTS: The earliest finding was obtained by diffusion-weighted image less than 24 hours (acute period) in bilateral cerebral cortex as bright high signal intensity regions. Similar abnormality of bright high signal area in FLAIR and T 2 was followed according to the time elapsed in early subacute period (1-13 days). Succeedingly, white matter was involved and laminar necrosis in cortical area was observed in late subacute period (14-20 days). Finally, diffuse brain atrophy and obtundation of gray-white matter junction were seen in chronic stage (after 21 days). These MR findings were coincided well with histopathological findings reported in literatures. The poor outcome was closely and significantly correlated with abnormality in MR images. CONCLUSION: MRI was a useful diagnostic modality to diagnose the whole brain ischemic encephalopathy and to predict the prognosis.