Late Phase Group Research Articles

Online Intensive Cardiac Rehabilitation Program for Japanese Patients With Coronary Artery Disease - A Pilot Study Protocol.

A comprehensive cardiac rehabilitation (CR) program is recommended for coronary artery disease (CAD). However, many facilities do not have established programs for dietary guidance and patient education, resulting in an exercise-based CR program and limited efficacy for secondary prevention. A pilot study will be conducted to develop an online Japanese-style intensive cardiac rehabilitation (J-ICR) program for Japanese patients with CAD and will examine adherence, safety, and efficacy. Twenty-four patients diagnosed with stable CAD will be randomly assigned in a 1 : 1 ratio to either an early or late-phase group. The program will comprise the following four parts: exercise sessions; dietary education centered on "the Japan diet"; mindfulness; and group support, with a frequency of 3 h per session, once a week for 12 weeks (a total of 36 h). The primary endpoint will be program feasibility, determined by examining its adherence. Physical examination and function, stress-coping skills, risk of classic CAD (e.g., lipid profile, glucose tolerance, and blood pressure), and dietary changes will be assessed as secondary endpoints. The online J-ICR program is designed as a comprehensive CR program for Japanese patients with CAD. If this program shows high adherence and an improvement in CAD risk factors, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers.

Morphological changes in the substantia nigra pars reticulata of the mice during kindling

Substantia nigra pars reticulata (SNpr) has been implicated in modulation, propagation and cessation of seizures. This study aimed to determine whether structural changes occur in SNpr during kindling.Male mice were randomly divided into four groups including early and late-phase kindled groups and their time-matched controls. Kindling was induced by every other day administration of a subconvulsive dose of PTZ (40 mg/kg, i.p.). The first occurrence of seizure behaviors was used to categorize the early and late phases of kindling.There was no significant difference in the volume of SNpr between the early- and late-phase kindled groups. The diameter of SNpr was significantly increased in the early phase group and decreased in the late phase group as compared to their matched controls (p < 0.05). Reduced neural cells and increased dead cell numbers were observed in the SNpr of the late-phase group in comparison to its control group (p < 0.05).These findings suggest that SNpr is a sensitive and vulnerable structure involving seizure propagation in the processes of epileptogenesis.

Radiomics Analysis of Computed Tomography helps predict poor prognostic outcome in COVID-19.

Rationale: Given the rapid spread of COVID-19, an updated risk-stratify prognostic tool could help clinicians identify the high-risk patients with worse prognoses. We aimed to develop a non-invasive and easy-to-use prognostic signature by chest CT to individually predict poor outcome (death, need for mechanical ventilation, or intensive care unit admission) in patients with COVID-19.Methods: From November 29, 2019 to February 19, 2020, a total of 492 patients with COVID-19 from four centers were retrospectively collected. Since different durations from symptom onsets to the first CT scanning might affect the prognostic model, we designated the 492 patients into two groups: 1) the early-phase group: CT scans were performed within one week after symptom onset (0-6 days, n = 317); and 2) the late-phase group: CT scans were performed one week later after symptom onset (≥7 days, n = 175). In each group, we divided patients into the primary cohort (n = 212 in the early-phase group, n = 139 in the late-phase group) and the external independent validation cohort (n = 105 in the early-phase group, n = 36 in the late-phase group) according to the centers. We built two separate radiomics models in the two patient groups. Firstly, we proposed an automatic segmentation method to extract lung volume for radiomics feature extraction. Secondly, we applied several image preprocessing procedures to increase the reproducibility of the radiomics features: 1) applied a low-pass Gaussian filter before voxel resampling to prevent aliasing; 2) conducted ComBat to harmonize radiomics features per scanner; 3) tested the stability of the features in the radiomics signature by several image transformations, such as rotating, translating, and growing/shrinking. Thirdly, we used least absolute shrinkage and selection operator (LASSO) to build the radiomics signature (RadScore). Afterward, we conducted a Fine-Gray competing risk regression to build the clinical model and the clinic-radiomics signature (CrrScore). Finally, performances of the three prognostic signatures (clinical model, RadScore, and CrrScore) were estimated from the two aspects: 1) cumulative poor outcome probability prediction; 2) 28-day poor outcome prediction. We also did stratified analyses to explore the potential association between the CrrScore and the poor outcomes regarding different age, type, and comorbidity subgroups.Results: In the early-phase group, the CrrScore showed the best performance in estimating poor outcome (C-index = 0.850), and predicting the probability of 28-day poor outcome (AUC = 0.862). In the late-phase group, the RadScore alone achieved similar performance to the CrrScore in predicting poor outcome (C-index = 0.885), and 28-day poor outcome probability (AUC = 0.976). Moreover, the RadScore in both groups successfully stratified patients with COVID-19 into low- or high-RadScore groups with significantly different survival time in the training and validation cohorts (all P < 0.05). The CrrScore in both groups can also significantly stratify patients with different prognoses regarding different age, type, and comorbidities subgroups in the combined cohorts (all P < 0.05).Conclusions: This research proposed a non-invasive and quantitative prognostic tool for predicting poor outcome in patients with COVID-19 based on CT imaging. Taking the insufficient medical recourse into account, our study might suggest that the chest CT radiomics signature of COVID-19 is more effective and ideal to predict poor outcome in the late-phase COVID-19 patients. For the early-phase patients, integrating radiomics signature with clinical risk factors can achieve a more accurate prediction of individual poor prognostic outcome, which enables appropriate management and surveillance of COVID-19.

Shortening Hospital Stay Is Feasible and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty

BackgroundThere is no consensus on the length of hospital stay (LOHS) and post-interventional management after balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We examined temporal trends with respect to LOHS and requirement for intensive care for BPA and their relationship with the incidence of BPA-related complications. MethodsFrom November 2012 to September 2017, a total of 123 consecutive patients with CTEPH who underwent BPA were enrolled (age: 66.0 [54.0 to 74.0], World Health Organization [WHO] functional class II/III/IV; 27/88/8). Patients were divided for analysis into 3 groups according to the date of their first BPA: early-, middle-, and late-phase groups. ResultsMean pulmonary arterial pressure decreased from 36.0 (29.0 to 45.0) to 20.0 (16.0 to 22.0) mm Hg after BPA (P < 0.001). The LOHS was 41.0 (31.0 to 54.0) days in total including all sessions and 6.6 (6.0 to 7.9) days/session. Despite no significant differences in age, baseline hemodynamics, and laboratory data among the 3 groups, there was a significant reduction in LOHS (7.9 [7.0 to 9.5], 6.5 [6.1 to 7.3], 6.0 [5.3 to 6.5] days/session, P < 0.001) and use of intensive/high care unit (100%, 93%, 46%, P < 0.001). The reduction in LOHS and intensive/high care unit use did not affect the occurrence of BPA-related complications. ConclusionsIncreasing experience with BPA was associated with a reduction in LOHS and the use of intensive/high care unit, but no change was noted in the rate of BPA-related complications. These findings suggest that the reduction in both LOHS and use of the intensive care unit for BPA is feasible and does not jeopardize the safety of the procedure.

Changes to indications for tunneled cuffed catheter use in hemodialysis patients: A single-center experience.

As the number of elderly end-stage renal disease patients lacking suitable vessels for arteriovenous fistula (AVF) is increasing, indications for tunnel cuffed catheters (TCCs) may be expanding. This study aimed to clarify changes over time in the number of patients with TCC and indications for TCCs. This single-center retrospective study analyzed 143 catheters for 95 patients who inserted TCCs between July 2005 and July 2017. Patients were divided into two groups (early- and late-phase groups) based on the median observational period. Demographic data and clinical information were then compared. Fifty TCCs were inserted in the early phase group, and 93 TCCs were inserted in the late-phase group. The late-phase group was older (77 vs. 70 years; P = 0.003) and showed a higher frequency of hypertensive nephropathy (29% vs. 14%; P < 0.05) and a lower frequency of a history of cardiovascular disease (52.7% vs. 70.0%; P = 0.045). In the late-phase group, indications for bridge vascular access (0% vs. 11.8%; P < 0.05) or severe cardiac dysfunction (8.0% vs. 20.5%; P < 0.05) were increased. In addition, the late-phase group showed increases in percentage of patients with the catheter inserted in the femoral vein (10.0% vs. 23.7%; P = 0.047), nephrologists performing catheter insertion (56.0% vs. 87.1%; P < 0.001), and the patients who underwent superficialization of the brachial artery (28.0% vs. 46.2%; P = 0.034). Significant differences in catheter survival, incidence of complications, reasons for catheter removal, or incidence of catheter-related infection were not observed between groups. Patients with indications for TCC may be increasing due to an increase in elderly end-stage renal disease patients whose activities of daily living have decreased. In addition, indications for bridge vascular access were widely accepted in the late-phase group.

Effect of "accordion" technique on bone consolidation during distraction osteogenesis

To investigate the effect, right timing, and mechanism of "accordion" technique on bone regeneration in rat distraction osteogenesis model. Fifty-four 12-week-old male Sprague Dawley rats underwent right tibial distraction osteogenesis procedure. After a 5-day latency, the distraction was performed for 7 days followed by 6-week consolidation. All animals were randomly divided into 4 groups based on different periods of "accordion" maneuvers in consolidation phase: control group ( n=18) with no manipulation, and three experimental groups including early-phase group ( n=18), mid-phase group ( n=12), and late-phase group ( n=6) with "accordion" maneuvers applied at 1, 3, and 5 weeks, respectively. The duration of the "accordion" maneuver was 7 days consisting of a 3.5-day compression and 3.5-day distraction. Rats in control group and early-phase group were sacrificed at 2, 4, and 6 weeks of the consolidation phase; rats in mid-phase group were sacrificed at 4 and 6 weeks of the consolidation phase; and rats in late-phase group were sacrificed at 6 weeks of the consolidation phase. Bilateral tibias from 6 rats in each group at each time point were obtained. Callus formation was monitored by X-ray radiography every week; new bone was reconstructed by Micro-CT three-dimensional reconstruction. The change of bone structure was evaluated, and parameters containing bone volume (BV)/tissue volume (TV) ratio (BV/TV) and bone mineral density (BMD) in three thresholds (158-211, 211-1 000, 158-1 000) were recorded and calculated at 6 weeks. Mechanical test consisting of ultimate load, modulus of elasticity, and energy to failure was performed. Histological analysis, such as Von Kossa staining, Safranin O staining, and HE staining, was done. Immunohistochemical staining using markers of osterix (OSX), osteocalcin (OCN), and vascular endothelial growth factor (VEGF) was analyzed. Images of X-ray showed that callus formation increased significantly in the mid-phase group. Micro-CT three-dimensional reconstruction demonstrated the mid-phase group owned fastest reconstructed speed among 4 groups, the cortical bone was continual at 6 weeks. At 6 weeks, the BMD and BV/TV in thresholds 158-1 000 and 211-1 000 in mid-phase group were higher than those in other groups. The results of mechanical test showed that ultimate load, modulus of elasticity, and energy to failure in mid-phase group were significantly higher than those in other groups ( P<0.05). Histological testing showed that the continuity of bone marrow cavity in mid-phase group was evident at 6 weeks after distraction. Immunohistochemical analyses confirmed the expression levels of osteogenesis (OCN, OSX) and angiogenesis (VEGF) elevated remarkably and then returned to normal in mid-phase group. The "accordion" technique is beneficial for new callus formation in distraction area. Applying the maneuver during the middle phase of the consolidation period was effective to accelerate new bone formation in rat distraction osteogenesis model.

Feasibility and Safety of Urgent Laparoscopic Cholecystectomy for Acute Cholecystitis After 4 Days from Symptom Onset

BackgroundIt is preferable to perform laparoscopic cholecystectomy for acute cholecystitis in the acute phase, within 72 h of symptom onset. The feasibility and safety of performing urgent laparoscopic cholecystectomy in the late phase (4–7 days after symptom onset) are unclear. The aim of this study was to clarify the feasibility and safety of late phase urgent laparoscopic cholecystectomy. MethodsBetween 2005 and 2014, 233 patients underwent urgent laparoscopic cholecystectomy for acute cholecystitis within 7 days. We compared clinical features and perioperative outcomes between patients who underwent laparoscopic cholecystectomy within 3 days (early phase group) and 4–7 days after symptom onset (late phase group). ResultsThere were 193 patients in the early phase group and 40 patients in the late-phase group. Performing laparoscopic cholecystectomy in the late phase did not influence operation time, postoperative complications, or postoperative hospital stay. The rate of conversion to open surgery and blood loss were slightly higher in the late-phase group (8 % and 140 ml) compared with the early phase group (3 % and 69 ml) but were still acceptable. ConclusionsLate phase urgent laparoscopic cholecystectomy for acute cholecystitis was feasible and safe.

Comparison of mechanisms of allodynia induced by acromelic acid A between early and late phases

We previously showed that intrathecal administration of acromelic acid A (ACRO-A) provoked tactile allodynia in mice. As well, recent studies have demonstrated that the activation of NMDA glutamate receptor-neuronal nitric oxide synthase (nNOS) pathway and glia play crucial roles in the development and maintenance of neuropathic pain. In order to clarify their involvement in ACRO-A-induced allodynia, we investigated the effects of various agents on two mouse models at early and late-phase allodynia. The agents employed were Ca2+ channel α2δ ligands, NMDA and AMPA receptor antagonists, nNOS, and Ca2+/calmodulin kinase II inhibitors. When injected simultaneously with ACRO-A, all of these agents blocked allodynia in the early-phase group; however, they did not block allodynia when injected 7 days after the administration of ACRO-A in the late-phase group. In order to block glial activation, astrocytic inhibitor L-α-aminoadipate (LAA) or microglial inhibitor minocycline was administrated, and allodynia was examined on day 7. Activations of nNOS and glia in the spinal cord were histochemically examined at 1h or 1 week after injection of ACRO-A. We found that nNOS activity increased 1h after ACRO-A injection; however, it did not increase 1 week after ACRO-A injection. Conversely, microglial activation was observed 1 week after ACRO-A injection and was significantly inhibited with minocycline treatment. Moreover, only LAA was found to inhibit late-phase allodynia.In this study, we demonstrate that NMDA receptor activation is involved only in ACRO-A-induced tactile allodynia in the early phase, and that spinal astrocytic activation contributes to allodynia in the late phase.

Proteomic Profiles in Acute Respiratory Distress Syndrome Differentiates Survivors from Non-Survivors

Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. Currently, there are no biomarkers that provide reliable prognostic information to guide clinical management or stratify risk among clinical trial participants. The objective of this study was to probe the bronchoalveolar lavage fluid (BALF) proteome to identify proteins that differentiate survivors from non-survivors of ARDS. Patients were divided into early-phase (1 to 7 days) and late-phase (8 to 35 days) groups based on time after initiation of mechanical ventilation for ARDS (Day 1). Isobaric tags for absolute and relative quantitation (iTRAQ) with LC MS/MS was performed on pooled BALF enriched for medium and low abundance proteins from early-phase survivors (n = 7), early-phase non-survivors (n = 8), and late-phase survivors (n = 7). Of the 724 proteins identified at a global false discovery rate of 1%, quantitative information was available for 499. In early-phase ARDS, proteins more abundant in survivors mapped to ontologies indicating a coordinated compensatory response to injury and stress. These included coagulation and fibrinolysis; immune system activation; and cation and iron homeostasis. Proteins more abundant in early-phase non-survivors participate in carbohydrate catabolism and collagen synthesis, with no activation of compensatory responses. The compensatory immune activation and ion homeostatic response seen in early-phase survivors transitioned to cell migration and actin filament based processes in late-phase survivors, revealing dynamic changes in the BALF proteome as the lung heals. Early phase proteins differentiating survivors from non-survivors are candidate biomarkers for predicting survival in ARDS.

Parentage assignment in hatchery population of brown sole Pleuronectes herzensteini by microsatellite DNA markers

Five loci (Phz2, Phz6, Phz7, Phz12, and Phz14) of microsatellite DNA markers developed in a previous study for parentage assignment in the hatchery population generated by mating among 61 broodstock fish (35 females and 26 males) in a spawning tank, were selected. After natural spawning in the same tank, larvae collected at three different times were categorized into early phase (EP), middle phase (MP), and late phase (LP) groups. In the parental broodstock, the mean number of alleles per locus was 21.8 and expected heterozygosity (H E) was 0.813. In the progeny, the mean number of alleles per locus decreased to 11.6 (EP), 14.4 (MP), and 6.4 (LP) and H E to 0.796 (EP), 0.833 (MP), and 0.681 (LP). Parental assignment determined eight dams and six sires as major parents for the EP group. In the MP group, 13 dams and ten sires genetically contributed to spawning, but only three dams and two sires were involved in LP group progeny. In the hatchery population produced from a limited number of parental fish such as the LP group, genetic variability was apparently decreased.

Response Assessments in Low-Risk and High-Risk Myelodysplastic Syndromes (MDS)

The myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders that differ with regard to etiology, pathologic and clinical features, treatment, and outcomes. MDS are chronic, progressive diseases that may be broadly categorized into early phase ("low-risk") and late-phase ("high-risk") groups based on prognostic criteria and the differential pathologic and cytogenetic features that drive the MDS phenotype in these disease phases. Consequently, the goals for treatment and management options also differ for low-risk MDS compared with high-risk MDS. Alleviation of disease-related complications, including transfusion requirements, and hematologic improvement are key treatment goals in low-risk MDS. In contrast, altering the natural history of disease, including improvements in overall survival and progression-free survival, are the most important treatment goals in high-risk MDS. To address the heterogeneity of MDS in patient populations enrolled in clinical trials and to resolve problems resulting from variability in the quality and quantity of responses to treatment, the International Working Group has developed standardized response criteria for MDS that are relevant for both low-risk and high-risk categories. The application of the standardized International Working Group response criteria in clinical trials is enabling the comparison of results from various clinical trials in MDS. Furthermore, the International Working Group response criteria provide an important framework for clinical development of new treatments options that may be particularly appropriate for specific MDS subsets.