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Background@#Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment. @*Results@#The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the midcolon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such asTNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats. @*Conclusions@#These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.
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Background@#Recombination activating gene2 (Rag2) knockout (KO) mice are used widely in various research fields, including vaccine development, transplantation studies, and hematopoiesis research, but few studies have compared their phenotypes. This study examined whether there were differences in the immunophenotypes between Rag2 KO mice derived from different sources. In particular, the changes in the organ weight, histological structure, and subpopulation of T and B cells were compared in the spleen and thymus of C57BL/6-Rag2em1hwl/Korl (Rag2/Korl KO) and B6.Cg-Rag2tm1.1Cgn/J (Rag2/J KO) mice. @*Results@#The weight of the spleen and thymus similarly decreased in the Rag2/Korl and Rag2/J KO mice compared to their wild type (WT) mice, even though the other organs were kept at the same weight. A slight difference between the Rag2/Korl and Rag2/J KO group were detected in the number of white blood cells (WBC), lymphocytes (LYM), red cell distribution width (RDW), and platelets (PLT). In addition, the white pulp of the spleen and the cortex region of the thymus decreased in both Rag2 KO mice compared to WT mice. On the other hand, significant differences in the number of CD8+ T and B cell subpopulations between WT and Rag2 KO mice were observed between Rag2/Korl and Rag2/J KO group, while the CD4+ T subpopulation was maintained similarly in both groups. @*Conclusions@#These results suggest that Rag2/Korl and Rag2/J KO mice exhibit similar immunophenotypes in the spleen and thymus except for the differences in the number of CD8+ T and B cell subpopulations.
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A 13-year-old neutered male Maltese dog presented to our hospital with lethargy and anorexia. Laboratory abnormalities included severe non-regenerative anemia (hematocrit, 12.9%; reticulocyte count 12.8 K/μL). The cytology of bone marrow revealed erythroid hypercellularity with mild myelofibrosis. Therefore, late-stage precursor-targeted immune-mediated anemia (PIMA) was diagnosed. Multimodal treatment including 2 immunosuppressant drugs (prednisolone and mycophenolate mofetil), antithrombic drug (clopidogrel), and blood transfusion was performed. The dog showed complete remission from PIMA, and the total duration of follow-up was 622 days. This is the first case report of canine PIMA managed successfully with prednisolone and mycophenolate mofetil in Korea.
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Objective@#Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. @*Methods@#Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. @*Results@#Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. @*Conclusion@#This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.
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Background@#and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. @*Methods@#This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. @*Results@#Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352–2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. @*Conclusion@#Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.
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Background@#and Purpose The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs). @*Methods@#Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival. @*Results@#Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050). @*Conclusions@#This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.
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Gel bleeding following breast augmentation using silicone breast implants (SBIs) occurs when microscopic silicone droplets diffuse through the implant surface, potentially resulting in complications such as capsular contracture and immune responses related to breast implant illness. Prompt and reliable diagnostic measures are crucial, as the presentation of gel bleeding can resemble cancer, making an accurate diagnosis challenging. This report discusses a rare case of axillary silicone lymphadenopathy caused by gel bleeding in a 48-year-old woman with intact SBIs. Silicone lymphadenopathy can be suspected based on mammography, ultrasonography, and magnetic resonance imaging in patients with a history of SBI insertion, and confirmation can be obtained through a pathological examination. Excisional biopsy is generally recommended for symptomatic patients, while treatment may not be necessary for asymptomatic patients; However, removal can be considered if the patient indicates a preference for it. Patients with silicone lymphadenopathy require replacement of SBIs to examine the breast capsule and verify the integrity of the implant. This case highlights the importance of considering gel bleeding as a potential cause of silicone lymphadenopathy, even in patients with intact SBIs.
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Background@#We report our experiences with prepectoral placement breast implant surgery using Supporix (HansBioMed), a porcine acellular dermal matrix (PADM), for cosmetic and reconstructive indications. The clinical efficiency, safety, and cost-effectiveness of PADM were also discussed. @*Methods@#A single-center, retrospective study was designed from December 2017 to December 2019. The participants were Korean women who underwent PADM-assisted prepectoral breast implant surgery performed by two surgeons. All complications were registered and analyzed. A systematic review and meta-analysis of complication rates after PADM-assisted prepectoral breast implant surgery were conducted for comparison with other studies. A subgroup analysis was performed according to the operation type: the cosmetic breast surgery (CBS) group, the immediate implant-based breast reconstruction (IIBR) group, and the delayed implant-based breast reconstruction (DIBR) group. @*Results@#Twenty breasts in 16 patients were included in our study (median follow-up period, 8.25 months). In a systematic review, 20 publications with a total of 2,504 breasts in 1,921 women were quantitively analyzed. The overall complication rates in our study and other studies were 14% and 24% in the total group analysis, 0% and 12% in the CBS group, 62% and 26% in the IIBR group, and 0% and 28% in the DIBR group, respectively. @*Conclusions@#Our data support the effectiveness of PADM-assisted prepectoral breast implant surgery, which was comparable to other studies. PADM was effective for reducing seroma and hematoma in the revision CBS group and the DIBR group. In the IIBR group, it was helpful in preventing implant loss and explantation.
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Lipomas are benign soft-tissue tumors that typically progress gradually. In this case report, we describe a 77-year-old woman who presented with a mass on the left upper eyelid. An ophthalmologic examination was normal, and ultrasonography revealed a 1-cm ill-defined mass in the subcutaneous fat layer of the left upper eyelid. The tumor was completely excised surgically, and a histopathological examination showed mature fibro-adipose tissue consistent with a lipoma. The patient had an excellent postoperative prognosis. Even though eyelid lipomas are extremely rare, it is important to carefully examine the integrity of the orbital muscle, orbital septum, and levator aponeurosis. Lipoma should be distinguished from herniated orbital fat or the lacrimal glands in the differential diagnosis of an upper eyelid mass.
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Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.
Subject(s)
Female , Humans , Male , Young Adult , Adult , Middle Aged , Burns/surgery , Cicatrix , Eosine Yellowish-(YS) , Hyaluronic Acid/therapeutic use , Hyperplasia , Ki-67 Antigen , Prospective Studies , Umbilical Cord , VimentinABSTRACT
Background/Aims@#We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. @*Methods@#A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). @*Results@#Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. @*Conclusions@#Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.
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ObjectiveTo examine the current status of preschoolers' eating behaviors and investigate its correlation with family cohesion and adaptability. MethodsA cross-sectional study was conducted involving 21，954 preschoolers and their families from Pingshan District， Shenzhen， between September 2021 and December 2021. A general demographic questionnaire， the Chinese version of Family Adaptability and Cohesion Evaluation Scale Ⅱ （FACESⅡ-CV） and Chinese Preschoolers’ Eating Behavior Questionnaire （CPEBQ） were used to collect the relevant information. Multiple linear regression was used to analyze the association of family cohesion and adaptability with eating behaviors of preschoolers. ResultsTypes of family cohesion and adaptability were significantly correlated with all the 7 dimensions of preschoolers' eating behaviors， including food fussiness （R2=0.252， F=114.457， P<0.001）， food responsiveness （R2 = 0.111， F =24.973， P<0.001）， eating habit （R2= 0.304， F =139.658， P<0.001）， satiety responsiveness （R2 = 0.259， F =105.332， P<0.001）， external eating （R2 = 0.182， F =50.150， P<0.001）， emotional eating （R2 = 0.234， F =91.084， P<0.001） and initiative eating （R2 = 0.349， F =168.608， P<0.001）. After adjusting for confounding factors， our study showed that types of family cohesion and adaptability were independent predictors of preschoolers' eating behaviors （P<0.05）. ConclusionsTypes of family cohesion and adaptability have a significant predictive effect on the 7 dimensions of preschoolers' eating behaviors. Higher scores of family cohesion and adaptability imply stronger initiative eating ability and less poor dietary behaviors in preschoolers.
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AIM: To investigate the diagnostic value of ocular morphological parameters under different corneal diameters for early keratoconus.METHODS: A retrospective case-control study. A total of 201 patients(201 eyes)who were treated in our hospital from January 2019 to March 2022 were included. They were divided into 135 cases(135 eyes)in the control group(patients with history of refractive error)and 66 cases(66 eyes)in the subclinical keratoconus group. The Pentacam anterior segment analyzer was used to determine the horizontal central curvature of corneal posterior surface(Kf), posterior vertical central curvature of corneal posterior surface(Ks), average curvature of corneal posterior surface(Km), Posterior I-S ratio, corneal posterior surface height after the thinnest point(PE at the thinnest point), maximum posterior elevation from best fit sphere(MPE from BFS), maximum posterior elevation from best fit toric ellipsoid(MPE from BFTE), posterior asphericity asymmetry index(AAI), thinnest point thickness of the cornea(TCT), central corneal thickness(CCT), depressed corneal thickness(DCT), pachymetric progression index average(PPIavg), Ambrósio relational thickness maximum(ARTmax)and Belin D value. The differences of each parameter between the two groups were analyzed. Receiver operating characteristic(ROC)curves were analyzed to determine the best diagnosis point. The control group was further divided into groups according to the corneal diameter: corneal diameter ≤11.0mm, 11.1mm≤ corneal diameter ≤11.5mm, 11.6mm≤ corneal diameter ≤12.0mm, corneal diameter ≥12.1mm. The differences of each parameter among these groups were compared. Pearson correlation analysis was used to analyze the correlation between corneal diameter and other parameters.RESULTS: There were significant differences in posterior I-S ratio, PE at the thinnest point, MPE from BFS, MPE from BFTE, posterior AAI, TCT, DCT, PPIavg, ARTmax, Belin D value between the subclinical keratoconus group and the control group(P&#x003C;0.05). Sensitive index of Pentacam to diagnosis subclinical keratoconus were Belin D value, posterior I-S ratio, PPIavg, posterior AAI and MPE from BFTE(AUC≥0.9). In the control group, there was no significant difference in posterior I-S ratio, MPE from BFTE, posterior AAI, TCT, CCT, and DCT among different corneal diameter groups (P&#x003E;0.05), and there was no significant correlation with corneal diameter(all P&#x003E;0.05).CONCLUSION: The Belin D value, posterior I-S ratio, PPIavg, posterior AAI, MPE from BFTE obtained by Pentacam are sensitive indicators for the diagnosis of early keratoconus, among which posterior I-S ratio, posterior AAI, MPE from BFTE are less affected by corneal diameter. They play an important role in the early diagnosis of keratoconus under different corneal diameters.
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Background@#Coronavirus disease 2019 (COVID-19) is an ongoing global public health threat and different variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified. This study aimed to analyse the factors associated with negative conversion of polymerase chain reaction (PCR) and prognosis in critically ill patients according to the SARS-CoV-2 variant. @*Methods@#This study retrospectively analysed 259 critically ill patients with COVID-19 who were admitted to the intensive care unit of a tertiary medical center between January 2020 and May 2022. The Charlson comorbidity index (CCI) was used to evaluate comorbidity, and a negative PCR test result within 2 weeks was used to define negative PCR conversion. The cases were divided into the following three variant groups, according to the documented variant of SARS-CoV-2 at the time of diagnosis: non-Delta (January 20, 2020–July 6, 2021), Delta (July 7, 2021– January 1, 2022), and Omicron (January 30, 2022–April 24, 2022). @*Results@#The mean age of the 259 patients was 67.1 years and 93 (35.9%) patients were female. Fifty (19.3%) patients were smokers, and 50 (19.3%) patients were vaccinated. The CCI (hazard ratio [HR], 1.555; p<0.001), vaccination (HR, 0.492; p=0.033), and Delta variant (HR, 2.469; p=0.002) were significant factors for in-hospital mortality. The Delta variant (odds ratio, 0.288; p=0.003) was associated with fewer negative PCR conversion; however, vaccination (p=0.163) and remdesivir (p=0.124) treatments did not. @*Conclusion@#The Delta variant of SARS-CoV-2 is associated with lower survival and negative PCR conversion. Contrary to expectations, vaccination and remdesivir may not affect negative PCR conversion in critically ill patients with COVID-19.
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Background@#and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients.Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset.Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. @*Conclusion@#This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).
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An advantage of breast augmentation with injectable fillers is that the desired size can be determined and achieved under local anesthesia with a short recovery time. However, a high complication rate is a critical disadvantage. Some fillers are challenging to remove, resulting in breast deformity and scarring. Five patients who underwent surgery to manage a foreign body in the breasts in 2021 were enrolled in this study. Two had copolyamide filler injections, while the other three had polyacrylamide hydrogel filler injections. A physical examination was performed, and preoperative and intraoperative photographs were obtained. Two patients underwent subcutaneous mastectomy because most of the filler had infiltrated into the normal breast tissue. In contrast, the other patients underwent filler removal and debridement because most of the filler had remained separate from the normal breast tissue. All patients who had a subcutaneous mastectomy and one who underwent only filler removal underwent immediate breast reconstruction with cohesive gel implants. The other patients rejected immediate reconstruction, and only filler removal was performed. All patients recovered without complications. We propose an algorithm for diagnosis and treatment based on our cases, which we hope can help clinicians manage the complications of filler injections for breast augmentation.
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Purpose@#Near-infrared fluorescence imaging has been recently applied in the field of hepatobiliary surgery. Our objective was to apply blue-light fluorescence cholangiography during laparoscopic surgery. Therefore, we designed a preclinical study to evaluate the feasibility of using blue-light fluorescence for cholangiography in a porcine model. @*Methods@#Five millimeters of sodium fluorescein (SF) solution was administered into the gallbladder of 20 male 3-way crossbred (Landrace × Yorkshire × Duroc) pigs in laparoscopic approach. The biliary tree was observed under blue light (a peak wavelength of 450 nm) emitted from a commercialized light-emitting diode (LED) light source (XLS1 extreme, Chammed). @*Results@#In 18 of 20 porcine models, immediately after SF solution was administered into the gallbladder, it was possible to visualize the biliary tree under blue light emitted from the LED light source. @*Conclusion@#This study provided a preclinical basis for using blue-light fluorescence cholangiography using SF in laparoscopic surgery. The clinical feasibility of blue-light fluorescence imaging techniques for laparoscopic cholecystectomy remained to be demonstrated.
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The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.
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Evidence and value：impact on DEcisionMaking （EVIDEM） framework was developed by EVIDEM collaboration. Its core is the combination of multiple criteria decision analysis （MCDA） model and standardized health technology assessment （HTA） report， which aims to evaluate the overall value of medical interventions. It has been tested and implemented in the real-world evaluation environments. After more than 10 years of development， EVIDEM framework has been updated to version 10， and the relevant operation manuals have been published. More than 40 countries have joined the collaboration and more than 20 countries have carried out relevant studies. The framework is constructed with patients， population and sustainability as the overall goals， combing the evidence and value， forming a relatively complete decision-making framework system composed of 2 levels， 7 dimensions and 20 criteria. The two levels include normative universal criteria and contextual criteria. The normative universal criteria， namely EVIDEM core model， is the quantitative evaluation， consisting of 5 dimensions and 13 criteria. Contextual criteria， namely contextual tools， are qualitative evaluation， consisting of 2 dimensions and 7 criteria. The specific operation steps of EVIDEM framework include selecting and constructing criteria， assigning weights， integrating and evaluating evidence， quantitative and qualitative evaluation of value， comprehensive value estimation and ranking based on value estimation. EVIDEM framework is applicable to disease diagnosis， treatment， management and other fields. Its application scope includes medical insurance reimbursement， clinical practice decision-making， drug selection and so on， which can provide a method for more systematic， transparent and scientific healthcare decision-making. At present， the framework has been introduced into the field of traditional Chinese medicine and can provide a scientific and feasible evaluation tool and methodology system for the clinical comprehensive evaluation of Chinese patent medicine.
ABSTRACT
Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.