14-day Group Research Articles

Outcomes After Prolonged ICU Stays in Postoperative Cardiac Surgery Patients.

Prolonged postoperative intensive care unit (ICU) stays are common after cardiac surgery and are associated with poor outcomes. There are few studies evaluating how risk factors associated with mortality may change during prolonged ICU stays or how mortality may vary with length of stay. We evaluated operative and long-term mortality in post-cardiac surgery patients after prolonged ICU stays at 7, 14, 21, and 28 days and factors associated with mortality. We included University of Michigan Medical Center cardiac surgery patients with ≥ 7 postoperative days in the ICU. We determined factors associated with hospital mortality at 7, 14, 21, and 28 days of ICU stay using logistic regression, and among hospital survivors, we determined the factors associated with long-term mortality using Cox regression. Of 8309 ICU admissions from cardiac surgery, 1174 (14%) had ICU stays > 7 days. Operative mortality was 11%, 18%, 22%, and 35% for the 7-, 14-, 21-, and 28-day groups, respectively. Mechanical ventilation on the day of assessment was associated with increased odds ratios of operative mortality in all models. Of the 1049 (89%) hospital survivors, 420 (40%) died by late follow-up. Median (IQR) Cox model survival was 10.7 (0.7) years. Longer ICU stays, postoperative pneumonia, and elevated discharge blood urea nitrogen were associated with increased hazard of dying; whereas higher discharge platelet count and cardiac transplant were protective. Both operative and late mortality increased as the duration of a ICU stay increased after cardiac surgery.

Optimal timing of preoperative intravitreal anti-VEGF injection for proliferative diabetic retinopathy patients.

To analyze concentrations of vascular endothelial growth factor (VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy (PDR) patients pre-treated with intravitreal anti-VEGF injections (IVI) at different time periods prior to pars plana vitrectomy (PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI. The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDR-related complications (PDR group) and 21 eyes with non-diabetic ocular disease (control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3d after IVI (3-day group); 5d after IVI (5-day group); 7 or more days after IVI (≥7-day group); and no IVI. Vitreous fluid samples (0.5-1.0 mL) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor (bFGF), periostin (PN), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis. PDR eyes without IVI had significantly higher VEGF, bFGF, PN, and IL-6 concentrations than non-diabetic eyes (all P<0.05), and had a significantly higher concentration of VEGF (P<0.05) and a significantly lower concentration of IL-8 (P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, bFGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups (all P<0.05); meanwhile there was no significant difference in TNF-α among groups (P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of bFGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day (P=0.015) and 5-day group (P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of bFGF, PN, IL-6, and IL-8 (all P<0.05). Univariate ordinal logistic regression analysis showed that bFGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI. The vitreous concentrations of VEGF, bFGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angio-fibrosis switch. The results suggest that PPV should be performed 5d after IVI administration in PDR patients.

A comprehensive analysis of 30-day readmissions after emergency general surgery procedures: Are risk factors modifiable?

Modifiable risk factors associated with procedure-related 30-day readmission after emergency general surgery (EGS) have not been comprehensively studied. We set out to determine risk factors associated with EGS procedure-related 30-day unplanned readmissions. A retrospective cohort study was conducted using the National Surgical Quality Improvement Project database (2013-2019). It included nine surgical procedures encompassing 80% of the burden of EGS diseases, performed on an urgent/emergent basis. The procedures were classified as low risk (open and laparoscopic appendectomy and laparoscopic cholecystectomy) and high risk (open cholecystectomy, laparoscopic and open colectomy, lysis of adhesions, perforated ulcer repair, small bowel resection, and exploratory laparotomy). Data on patient characteristics, admission status, procedure risk, hospital length of stay, and discharge disposition were analyzed by multivariate logistic regression. A total of 312,862 patients were included (16,306 procedure-related 30-day readmissions [5.2%]). Thirty-day readmission patients were older, had higher American Association of Anesthesiology scores, were more often underweighted or markedly obese, and were more frequently presented with sepsis. Risk factors associated with EGS procedure-related 30-day unplanned readmissions included age older than 40 years (adjusted odds ratio [AOR], 1.15), American Association of Anesthesiology ≥3 (AOR, 1.41), sepsis present at the time of surgery (AOR, 1.84), body mass index <18 kg/m 2 (AOR, 1.16), body mass index ≥40 kg/m 2 (AOR, 1.12), high-risk procedures (AOR, 1.51), LOS ≥4 d (AOR, 2.04), and discharge except to home (AOR, 1.33). Thirty-day readmissions following low-risk procedures occurred at a median of 5 days (interquartile range, 2-11 days) and 6 days (interquartile range, 3-11 days) after high-risk procedures. Surgical site infections, postoperative sepsis, wound disruption, and thromboembolic events were more prevalent in the 30-day readmission group. Mortality rate was fourfold higher in the 30-day readmission group (2.4% vs. 0.6%). We identified several unmodifiable patients and EGS disease-related factors associated with 30-day unplanned readmissions. Readmissions could be potentially reduced by the implementation of a postdischarge surveillance systems between hospitals and postdischarge destination facilities, leveraging telehealth and outpatient care. Prognostic and Epidemiological; Level IV.

Pneumocystis jirovecii Pneumonia in Patients with Solid Malignancies: A Retrospective Study in Two Hospitals.

Pneumocystis jirovecii pneumonia (PJP) is a rare opportunistic infection in patients with solid malignancies. This study aimed to examine the characteristics of patients with solid cancers and PJP. We retrospectively reviewed the medical records of patients with solid tumors and PJP over an 11-year period, enrolling a total of 47 patients (30-day survival group: n = 20, 30-day mortality group: n = 27). Only 34% of patients received ≥20 mg of prednisolone for ≥2 weeks, and the 30-day mortality rate was 57.4%. The 30-day survival group included more women and patients with colon cancer than the mortality group. Furthermore, absolute lymphocyte counts (ALCs) were decreased at PJP symptom onset, as compared with the values observed 1–3 months earlier. Increased oxygen demand and low ALCs after 5–7 days of PJP treatment were also related to poor prognosis. Due to the limitations of this retrospective study, further studies that adhere to the PJP criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium will be needed to evaluate PJP in solid malignancies more clearly.

Enhancing Parental Well-being: Initial Efficacy of a 21-Day Online Self-help Mindfulness-Based Intervention for Parents

ObjectivesParental self-care is extremely important in the face of stress throughout parenthood. A 21-day online mindfulness-based intervention was developed that was aimed at enhancing parental well-being. The present study evaluated this intervention by examining its initial efficacy on parents’ mindfulness, parenting stress, subjective well-being, and symptoms of depression and anxiety.MethodsParticipants were 273 parents (90.11% mothers) who were randomly assigned to the 21-day mindfulness-based intervention group (n = 136) or waitlist control group (n = 137). Pre-intervention assessment, immediate post-intervention assessment, and 30-day follow-up assessment were conducted to assess parents’ mindfulness, parenting stress, subjective well-being, and symptoms of depression and anxiety.ResultsLinear mixed models indicated that the group × time effects on subjective well-being, anxiety symptoms, and mindfulness were significant, after controlling for sex, age, education, income, habit of mindfulness practice, hours of weekly mindfulness practice, and diagnostic history of psychiatric disorder. Follow-up analyses indicated that compared to baseline, participants from the intervention group reported significantly greater subjective well-being and mindfulness, and fewer symptoms of anxiety than did those from the waitlist control group. The group × time effects on parenting stress and depressive symptoms were non-significant. Exploratory findings further suggested practicality and perceived acceptability of the intervention.ConclusionsThis study showed initial efficacy of a 21-day online mindfulness-based intervention on parents’ subjective well-being, anxiety symptoms, and mindfulness. The findings inform researchers and practitioners about the utility of a brief mindfulness-based intervention in promotion parental well-being. Other areas of feasibility warrant future investigation.

Treatment of erythema migrans with doxycycline for 7 days versus 14 days in Slovenia: a randomised open-label non-inferiority trial

Lyme borreliosis is the most prevalent vector-borne disease in Europe and the USA. Doxycycline for 10 days is the primary treatment recommendation for erythema migrans. To reduce potentially harmful antibiotic overuse by identifying shorter effective treatments, we aimed to assess whether oral doxycycline for 7 days is non-inferior to 14 days in adults with solitary erythema migrans. In this randomised open-label non-inferiority trial, we enrolled patients with a solitary erythema at the University Medical Centre in Ljubljana, Slovenia. Patients were excluded if they were pregnant or lactating, immunosuppressed, allergic to doxycycline, or had received antibiotics with anti-borrelial activity within 10 days preceding enrolment or had additional manifestations of Lyme borreliosis Adults were randomly allocated 1:1 to receive oral doxycycline 100 mg twice a day for 7 days or 14 days. The primary efficacy endpoint was the difference in proportion of patients with treatment failure, defined as persistent erythema, new objective signs of Lyme borreliosis, or borrelial isolation on skin re-biopsy at 2 months, in a per-protocol analysis (the population that completed the assigned doxycycline regimen according to the study protocol and did not receive any other antibiotics with anti-borrelial activity until the 2-month visit). The non-inferiority margin was 6 percentage points. Safety was assessed in all randomly assigned patients who followed the study protocol and were evaluable at the 14-day visit. This study is registered with ClinicalTrials.gov, NCT03153267. Between July 3, 2017, and Oct 2, 2018, we enrolled 300 patients (150 per group: median age 56 years [IQR 47-65]; 126 [45%] of 300 male; skin culture positive 72 [30%] of 239 assessed). 295 patients completed antibiotic therapy as per protocol and 294 (98%) patients were evaluable 2 months post-enrolment. Five (3%) of 147 patients from the 7-day group versus 3 (2%) of 147 patients from the 14-day group (one patient did not attend the 2-month visit and was unreachable by telephone) had treatment failure manifesting as persistence of erythema (difference 1·4 percentage points; upper limit of one-sided 95% CI 5·2 percentage points; p=0·64). No patients developed new objective manifestations of Lyme borreliosis during follow-up or had positive repeat skin biopsies. Two (1%) of 150 patients in the 7-day and one (1%) of 150 patients in the 14-day group discontinued therapy due to adverse events. Our data support 7 days of oral doxycycline for adult European patients with solitary erythema migrans, permitting less antibiotic exposure than current guideline-driven therapy. Slovenian Research Agency and the University Medical Centre Ljubljana.

Conversion of External Fixator to Intramedullary Nail in Tibial fractures.

Conversion of provisional external fixation to intramedullary nail (IMN) in femur fractures has been reported to be safe within 14 days of initial surgery. However, there is no current literature guiding this practice in tibial fractures. The purpose of this study was to identify the time period when conversion of external fixation to nail in tibial fractures is safe. After obtaining IRB approval, tibial fractures (OTA 41A, 42, 43A) that received provisional ex-fix and were converted to IMN from 2009 to 2019 were retrospectively reviewed. Skeletally mature patients with minimum 6 months of follow-up were included. The primary outcome was deep infection. External fixation days were categorized as less than 7, 8 to 14, and 15+ days. Risk ratios of infection were estimated using generalized linear regression with a Poisson distribution. A separate regression model evaluated risk factors for infection using both the external fixation and non-external fixation tibial cohorts. Twenty-eight patients (32%) were treated for deep infection. The infection rate for closed fractures was 28% (11 of 39 patients) and for open fractures was 35% (17 of 49 patients) ( P = 0.56). Examining both tibial cohorts, external fixation (odds ratio [OR] = 2.39, P = 0.017), open fracture (OR = 3.13, P = 0.002), and compartment syndrome (OR = 2.58, P = 0.01) were all associated with infection in regression modeling. Median external fixation days for patients with deep infection was 8 days (Inter-quartile range, 3 to 18 days) as compared with 4 days (IQR, 2 to 9 days) in patients without infection ( P = 0.06). While controlling for open fractures, the 8- to 14-day group had RR = 1.81 ( P = 0.2), and the 15+-day group had RR = 2.67 ( P = 0.003) as compared with the <7-day group. Infection rates of tibial fracture patients treated with external fixation and converted to IMN were high. Surgeons should strongly consider the necessity of external fixation for these fractures. Earlier conversion of external fixation to definitive fixation reduced infection rates. Level IV-case series.

Association between the LACE+ index and unplanned 30-day hospital readmissions in hospitalized patients with stroke.

BackgroundThe LACE+ index is used to predict unplanned 30-day hospital readmissions, but its utility to predict 30-day readmission in hospitalized patients with stroke is unknown.MethodsWe retrospectively analyzed 1,657 consecutive patients presenting with ischemic or hemorrhagic strokes, included in an institutional stroke registry between January 2018 and August 2020. The primary outcome of interest was unplanned 30-day readmission for any reason after index hospitalization for stroke. The 30-day readmission risk was categorized by LACE+ index to high risk (≥78), medium-to-high risk (59–77), medium risk (29–58), and low risk (≤ 28). Kaplan-Meier analysis, Log rank test, and multivariable Cox regression analysis (with backward elimination) were used to determine whether the LACE+ score was an independent predictor for 30-day unplanned readmission.ResultsThe overall 30-day unplanned readmission rate was 11.7% (194/1,657). The median LACE+ score was higher in the 30-day readmission group compared to subjects that had no unplanned 30-day readmission [74 (IQR 67–79) vs. 70 (IQR 62–75); p < 0.001]. On Kaplan-Meier analysis, the high-risk group had the shortest 30-day readmission free survival time as compared to medium and medium-to-high risk groups (p < 0.01, each; statistically significant). On fully adjusted multivariable Cox-regression, the highest LACE+ risk category was independently associated with the unplanned 30-day readmission risk (per point: HR 1.67 95%CI 1.23–2.26, p = 0.001).ConclusionSubjects in the high LACE+ index category had a significantly greater unplanned 30-day readmission risk after stroke as compared to lower LACE+ risk groups. This supports the validity of the LACE+ scoring system for predicting unplanned readmission in subjects with stroke. Future studies are warranted to determine whether LACE+ score-based risk stratification can be used to devise early interventions to mitigate the risk for unplanned readmission.

14-day famciclovir treatment significantly reduces the incidence of postherpetic neuralgia in elderly patients with herpes zoster.

Pain is the main symptom of herpes zoster (HZ), whilst postherpetic neuralgia (PHN) is a long-term unbearable pain, which seriously affects the quality of life of patients and is also the most intractable problem for clinicians. Early antiviral treatment is considered as a key measure to reduce acute pain and PHN. Nevertheless, most patients still have long-term pain after 7 days of antiviral treatment, and some patients will develop PHN. This study aimed to investigate whether prolonged duration of antiviral therapy could reduce HZ acute pain and the occurrence of PHN. The outpatient data of HZ patients over 50 years old who visited the Dermatology Department from January 2016 to May 2018 were retrospectively analysed. According to the different courses of treatment of famciclovir (FCV), the patients were divided into 7-day FCV group and 14-day FCV group. The numerical rating scale (NRS) score at the first visit and on the 7th, 14th and 21st days after the start of treatment, the adverse drug reactions and the incidence of PHN were compared between the two groups. A total of 219 patients were involved in the analysis. For acute pain control, the 14-day FCV group was better than the 7-day FCV group. For patients with mild initial pain, there was no significant difference in NRS between the two treatments. For patients with moderate-to-severe initial pain, the NRS in the 14-day FCV group was significantly lower than that of the 7-day FCV group on the 14th and 21st days after starting treatment. PHN occurred in patients with moderate-to-severe initial pain, and the incidence was significantly lower in the 14-day FCV group than in the 7-day FCV group. There was no significant difference in the number of adverse reactions between the two groups. Compared with the traditional 7-day antiviral therapy, the 14-day course of FCV can reduce the acute pain and the incidence of PHN in elderly patients with HZ, especially in patients with moderate to severe initial pain. Prolonging the course of medication did not increase the side effects.

Biofilm formation is not an independent risk factor for mortality in patients with Acinetobacter baumannii bacteremia.

In the past decades, due to the high prevalence of the antibiotic-resistant isolates of Acinetobacter baumannii, it has emerged as one of the most troublesome pathogens threatening the global healthcare system. Furthermore, this pathogen has the ability to form biofilms, which is another effective mechanism by which it survives in the presence of antibiotics. However, the clinical impact of biofilm-forming A. baumannii isolates on patients with bacteremia is largely unknown. This retrospective study was conducted at five medical centers in Taiwan over a 9-year period. A total of 252 and 459 patients with bacteremia caused by biofilm- and non-biofilm-forming isolates of A. baumannii, respectively, were enrolled. The clinical demographics, antimicrobial susceptibility, biofilm-forming ability, and patient clinical outcomes were analyzed. The biofilm-forming ability of the isolates was assessed using a microtiter plate assay. Multivariate analysis revealed the higher APACHE II score, shock status, lack of appropriate antimicrobial therapy, and carbapenem resistance of the infected strain were independent risk factors of 28-day mortality in the patients with A. baumannii bacteremia. However, there was no significant difference between the 28-day survival and non-survival groups, in terms of the biofilm forming ability. Compared to the patients infected with non-biofilm-forming isolates, those infected with biofilm-forming isolates had a lower in-hospital mortality rate. Patients with either congestive heart failure, underlying hematological malignancy, or chemotherapy recipients were more likely to become infected with the biofilm-forming isolates. Multivariate analysis showed congestive heart failure was an independent risk factor of infection with biofilm-forming isolates, while those with arterial lines tended to be infected with non-biofilm-forming isolates. There were no significant differences in the sources of infection between the biofilm-forming and non-biofilm-forming isolate groups. Carbapenem susceptibility was also similar between these groups. In conclusion, the patients infected with the biofilm-forming isolates of the A. baumannii exhibited different clinical features than those infected with non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii may also influence the antibiotic susceptibility of its isolates. However, it was not an independent risk factor for a 28-day mortality in the patients with bacteremia.

Long-term gamma transcranial alternating current stimulation improves the memory function of mice with Alzheimer's disease.

BackgroundThe main manifestation of Alzheimer’s disease (AD) in patients and animal models is impaired memory function, characterized by amyloid-beta (Aβ) deposition and impairment of gamma oscillations that play an important role in perception and cognitive function. The therapeutic effect of gamma band stimulation in AD mouse models has been reported recently. Transcranial alternating current stimulation (tACS) is an emerging non-invasive intervention method, but at present, researchers have not completely understood the intervention effect of tACS. Thus, the intervention mechanism of tACS has not been fully elucidated, and the course of treatment in clinical selection also lacks theoretical support. Based on this issue, we investigated the effect of gamma frequency (40 Hz) tACS at different durations in a mouse model of AD.Materials and methodsWe placed stimulating electrodes on the skull surface of APP/PS1 and wild-type control mice (n = 30 and n = 5, respectively). Among them, 20 APP/PS1 mice were divided into 4 groups to receive 20 min 40 Hz tACS every day for 1–4 weeks. The other 10 APP/PS1 mice were equally divided into two groups to receive sham treatment and no treatment. No intervention was performed in the wild-type control mice. The short-term memory function of the mice was examined by the Y maze. Aβ levels and microglia in the hippocampus were measured by immunofluorescence. Spontaneous electroencephalogram gamma power was calculated by the average period method, and brain connectivity was examined by cross-frequency coupling.ResultsWe found that the long-term treatment groups (21 and 28 days) had decreased hippocampal Aβ levels, increased electroencephalogram spontaneous gamma power, and ultimately improved short-term memory function. The treatment effect of the short-term treatment group (7 days) was not significant. Moreover, the treatment effect of the 14-day treatment group was weaker than that of the 21-day treatment group.ConclusionThese results suggest that long-term gamma-frequency tACS is more effective in treating AD by reducing Aβ load and improving gamma oscillation than short-term gamma-frequency tACS.

The Predictive Value of Barthel Score, Sequential Organ Failure Assessment Score, and D-Dimer in the 28-Day Prognosis of Patients with Non-ST Elevation Myocardial Infarction: A Retrospective Study of 358 Patients.

PurposeTo investigate the nursing prediction value of Barthel score, sequential organ failure assessment (SOFA) score and D-dimer on non-ST-elevation myocardial infarction (NSTEMI) inpatients.MethodsThe clinical data of 358 NSTEMI patients admitted to the emergency department were analyzed using logistic regression equation and a ROC curve was drawn. The area under ROC curve (AUC) of different indicators was compared. A COX regression model was created, and a survival curve was drawn.ResultsThere were significant differences in age, D-dimer, WBC, NT-proBNP, EF (%), BI score, MEWS score, and SOFA score between the 28-day death group and the survival group (P < 0.05). The results showed that D-dimer (P = 0.002), SOFA score (P = 0.017), BI score (P < 0.001), and chest pain symptoms (P < 0.001) were independent predictors of 28-day death. When chest pain symptoms (AUC = 0.585), D-dimer (AUC = 0.945, Z = 8.00, P < 0.01), BI score (AUC = 0.145, Z = 5.36, P < 0.01), and SOFA score (AUC = 0.847, Z = 4.93, P < 0.01) were compared, the results showed that BI score (HR = 0.961, P < 0.01) and SOFA score (HR = 1.316, P < 0.001) had statistical significance on the 28-day survival time of the dead patients.ConclusionThe Barthel score, SOFA score, and D-dimer are all essential in predicting the severity of NSTEMI patients, with a high nursing evaluation value. The Barthel and SOFA scores are associated with the risk of death within 28 days.

Seven Days of Bismuth-Based Quadruple Therapy Is as Effective for the First-Line Treatment of Clarithromycin-Resistant Confirmed Helicobacter pylori Infection as 14 Days of Bismuth-Based Quadruple Therapy.

Background/Aims: Point mutations in the 23S ribosomal RNA gene have been associated with Helicobacter pylori (H. pylori) clarithromycin resistance and bismuth-based quadruple therapy (BQT) is one of the options for the treatment of clarithromycin-resistant H. pylori. Current H. pylori treatment guidelines recommend BQT for 10–14 days. This study aims to compare the eradication extents according to 7-day and 14-day BQT treatment for treatment-naïve clarithromycin-resistant confirmed H. pylori infection. Methods: We retrospectively investigated treatment-naïve H. pylori infection cases from March 2019 to December 2020, where patients were treated with BQT. Clarithromycin resistance was identified with a dual-priming oligonucleotide-based multiplex polymerase chain reaction method. We reviewed a total of 126 cases. Fifty-three subjects were treated with a 7-day BQT regimen (7-day group), and 73 subjects were treated with a 14-day BQT regimen (14-day group). We evaluated the total eradication extent of the BQT and compared the eradication extents of the two study groups. Results: Total eradication extent of H. pylori was 83.3% (105/126). The eradication extents of the two groups were as follows: 7-day group (81.1% (43/53)), 14-day group (84.9% (62/73), p = 0.572) by intention-to-treat analysis; 7-day group (95.6% (43/45)), 14-day group (92.5% (62/67), p = 0.518) by per-protocol analysis. The moderate or severe adverse event extents during the eradication were 30.2% (16/53) in the 7-day group and 19.2% (14/73) in the 14-day group (p = 0.152). Conclusions: The 7-day BQT regimen was as effective as the 14-day BQT regimen in the eradication of treatment-naïve clarithromycin-resistant H. pylori infection.

Fracture of Lithia Disilicate Ceramics under Different Environmental Conditions.

The objective of this research was to quantify the effect of surface degradation and abrasion separately and in combination on the flexural strength of lithia disilicate ceramics. Lithia disilicate disks were fabricated using the lost wax technique and pressing in vacuum. The eight groups in this pilot experiment were (i) reference, hydrated in distilled water for 24 h prior to fracture; (ii) reference, non-hydrated group; (iii) 28-day pH cycling group; (iv) 125K chewing cycle group; (v) combined pH cycling + 125K chewing cycle; (vi) constant pH 2 solution for 28 days; (vii) constant pH 7 solution for 28 days; and (viii) constant pH 10 solution for 28 days. pH cycling is a method that alternates between pH 2, 7 and 10 over 28 days. A total of 15 disks were used for each group. All the groups were tested using the biaxial piston and a three-ball flexural strength test to obtain their biaxial flexural strength. pH 2 constant immersion demonstrated the highest fracture strength and was significantly greater than all other groups (p < 0.0001). Chewing and pH cycling + chewing groups exhibited the lowest fracture strengths and were significantly lower than all other groups (p < 0.0001). The damage observed from the chewing simulator does not represent apparent clinical fractures.

7-day versus 14-day tegoprazan-based triple therapy to treat Helicobacter pylori infection: Real-world evidence.

Potassium-competitive acid blockers (P-CABs) can be used to eradicate Helicobacter pylori infection. We aimed to evaluate the impact of treatment duration (7 vs 14days) on successful H. pylori eradication with P-CAB-based triple therapy in Korea, where clarithromycin resistance rate is high. We retrospectively reviewed the data of patients who received first-line treatment for H. pylori infection with tegoprazan-based triple therapy (50mg tegoprazan+1000mg amoxicillin+500mg clarithromycin twice daily for 1 or 2weeks). The primary endpoint was the eradication rate in intention-to-treat (ITT) analysis. Of the 948 patients included in the study, 435 and 513 received 7-day and 14-day tegoprazan-based triple therapy, respectively. The eradication rate was higher in the 14-day therapy group than in the 7-day therapy group (ITT, 63.9%; 95% confidence interval [CI], 59.3-68.3%] vs 78.6% [95% CI, 74.9-81.9%], respectively, P<0.001; per-protocol, 70.5% [95% CI, 65.8-74.8%] vs 85.1% [81.7-88.1%], respectively, P<0.001). Overall adverse event rates did not differ between the two groups. Although six patients in the 14-day treatment group discontinued the prescribed medications due to adverse events, four of them (67%) discontinued the medication within 4days. The 14-day tegoprazan-based triple therapy showed a superior eradication rate and acceptable adverse events compared with the 7-day tegoprazan-based triple therapy. A 14-day treatment regimen may be required when H. pylori infection is treated with tegoprazan-based triple therapy in regions with high clarithromycin resistance.

Time of Resumption of Antiplatelet Drugs After Upper Gastrointestinal Hemorrhage.

BackgroundThis study aimed to investigate the optimum time to reintroduce the original antiplatelet drugs after upper gastrointestinal hemorrhage in patients as secondary prevention for cardiovascular and cerebrovascular diseases.Material/MethodsAfter the upper gastrointestinal bleeding stopped, patients were randomly divided according to the oral antiplatelet drugs administered. The aspirin group was further divided into 3-day and 7-day aspirin groups. The patients who took aspirin and clopidogrel were randomly divided into 3 groups: 0-day aspirin+3-day clopidogrel; 0-day aspirin+7-day clopidogrel; and 3-day aspirin+7-day clopidogrel. The recovery time, rebleeding rate, incidence of cardiovascular and cerebrovascular events, and death were observed.ResultsThe 3-day aspirin group had more rebleeding, reduced risk of cardiovascular and cerebrovascular events, and a similar mortality rate compared to the other groups. In the aspirin+clopidogrel group, the 0-day aspirin+3-day clopidogrel group had the highest rebleeding rate and the lowest risk of cardiovascular and cerebrovascular events. The 3-day aspirin+7-day clopidogrel group had the highest risk of cardiovascular and cerebrovascular events and increased hospitalization time. The risk of rebleeding and cardiovascular and cerebrovascular events was lower in the 0-day aspirin+7-day clopidogrel group, and the overall mortality rate was the lowest in this group.ConclusionsIn patients receiving only aspirin, this drug should be reintroduced as soon as possible after peptic ulcer hemorrhage. Aspirin and clopidogrel are dual antiplatelet drugs used for the secondary prevention of cardiovascular diseases. In patients under dual-drug therapy, aspirin should not be stopped, while clopidogrel should be restarted in about 7 days.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2−. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

Human Milk Oligosaccharides Impact Cellular and Inflammatory Gene Expression and Immune Response.

Human milk harbors complex carbohydrates, including human milk oligosaccharides (HMOs), the third most abundant component after lactose and lipids. HMOs have been shown to impact intestinal microbiota, modulate the intestinal immune response, and prevent pathogenic bacterial binding by serving as decoy receptors. However, the direct effect of HMOs on intestinal function and immunity remains to be elucidated. To address this knowledge gap, 21-day-old germ-free mice (C57BI/6) were orally gavaged with 15 mg/day of pooled HMOs for 7 or 14 days and euthanized at day 28 or 35. A set of mice was maintained until day 50 to determine the persistent effects of HMOs. Control groups were maintained in the isolators for 28, 35, or 50 days of age. At the respective endpoints, intestinal tissues were subjected to histomorphometric and transcriptomic analyses, while the spleen and mesenteric lymph nodes (MLNs) were subjected to flow cytometric analysis. The small intestine (SI) crypt was reduced after HMO treatment relative to control at days 28 and 35, while the SI villus height and large intestine (LI) gland depth were decreased in the HMO-treated mice relative to the control at day 35. We report significant HMO-induced and location-specific gene expression changes in host intestinal tissues. HMO treatment significantly upregulated genes involved in extracellular matrix, protein ubiquitination, nuclear transport, and mononuclear cell differentiation. CD4+ T cells were increased in both MLNs and the spleen, while CD8+ T cells were increased in the spleen at day 50 in the HMO group in comparison to controls. In MLNs, plasma cells were increased in HMO group at days 28 and 35, while in the spleen, only at day 28 relative to controls. Macrophages/monocytes and neutrophils were lower in the spleen of the HMO group at days 28, 35, and 50, while in MLNs, only neutrophils were lower at day 50 in the 14-day HMO group. In addition, diphtheria toxoid and tetanus toxoid antibody–secreting cells were higher in HMO-supplemented group compared to controls. Our data suggest that HMOs have a direct effect on gastrointestinal tract metabolism and the immune system even in the absence of host microbiota.

OPG and RANKL Signal Transduction in Osteoblast Regulation Post Application Extract Collagen in Osteogenesis

Background and Aim: The current goal of periodontal therapy is to achieve periodontal regeneration. Important factor for periodontal regeneration is to promote bone formation, nowadays used bone replacement. The used of xenograft materials as gold standard for periodontal tissue regeneration using type I collagen bone graft has been widely developed. The main organic component in fish scales is type I fibril collagen, which are same as with component in bones. Specific markers of bone formation are the expression of osteoblast, osteoclast, osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligands (RANKL). The purpose of this study is to assess the expression of OPG and RANKL after application of extract collagen from gourami (Osphronemus gouramy) scales. Materials and Methods: Thirty-two experimental 3-month-old male Wistar albino rats (150g and 200g) were randomly divided into four groups: 7-day control group, 7-day fish collagen group, 14-day control group and 14-day fish collagen group. The sockets were filled with blood (control group), whereas 10 mg to 30 mg extract collagen was added until the sockets were fully occupied (treatment group). Results: The ANOVA test showed a significance level of 0.000 (p &lt;0.05). Conclusion: Expression of OPG enhanced and expression of RANKL lowered after application of type I collagen from gourami scales, accelerating osteogenesis.

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in children aged 6–17 years: a preliminary report of COV006, a phase 2 single-blind, randomised, controlled trial

BackgroundVaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults.MethodsCOV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6–17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 1010 viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12–17 years were enrolled before those aged 6–11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12–17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344).FindingsBetween Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12–17 years and 112 [43%] aged 6–11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6–11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12–17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685–91 733] and 299 half-maximal inhibitory concentration [IC50; 95% CI 230–390]) compared with those aged 12–17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852–52 246] and 150 IC50 [95% CI 116–194]). Humoral responses were higher in those aged 6–11 years than in those aged 12–17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 [95% CI 1·07–2·07] for anti-SARS-CoV-2 IgG and 2·96 [1·89–4·62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination.InterpretationChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6–17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial.FundingAstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research.