Objective:To investigate the application value of metagenomic next-genera-tion sequencing (mNGS) in pathogenic diagnosis of suspected infected severe acute pancreatitis (SAP).Methods:The prospective study was conducted. The clinical data of 25 patients with suspected infected SAP who were admitted to the Xiangya Hospital of Central South University from May to September 2023 were collected. Upper limb venous blood samples of all the patients were collected for both of mNGS and routine pathogen microbial culture. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture; (3) results of peripheral blood pathogen microbial testing and peri-pancreatic effusion microbial culture; (4) testing time and cost. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 25 patients were selected for eligibility. There were 18 males and 7 females, aged 48(40,59)years. The duration of hospital stay of 25 patients was 30(20,50)days. The etiologies of 25 patients included 14 cases of hyperlipidemic pancreatitis, 8 cases of biliary pancreatitis, 1 case of alcohol-induced acute pancreatitis, and 2 cases of pancreatitis caused by other causes. Of the 25 patients, there were 17 cases with infected pancreatic necrosis (IPN) including 7 cases of death, and 8 cases with sterile pancreatic necrosis including no death. (2) Comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture. The positive rates of mNGS and routine pathogen microbial culture in diagnosis of suspected infected SAP were 72.0%(18/25) and 32.0%(8/25), respectively, showing a significant difference between them ( χ2=8.01, P<0.05). The sensitivity and negative predic-tive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 94.1%(16/17), 35.3%(6/17) and 85.7%(6/7), 35.3%(6/17), showing significant differences between them ( χ2=12.88, 5.04, P<0.05). The specificity and positive predictive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 75.0%(6/8), 75.0%(6/8) and 88.9%(16/18), 75.0%(6/8), showing no significant difference between them ( χ2=0, 0.82, P>0.05). (3) Results of peripheral blood pathogen microbial testing and peripancreatic effusion microbial culture. Of the 17 patients with IPN, 36 strains of pathogenic bacteria were detected by mNGS, and 6 strains were detected by routine pathogen microbial culture. There were 16 of 17 patients with IPN showing positive mNGS pathogenic testing, of which 13 cases were consistent with the pathogenic testing results of peri-pancreatic effusion microbial culture, showing a consistency rate of 76.5%(13/17). There were 6 pati-ents with IPN showing positive routine pathogen microbial culture, with a consistency rate of 35.3%(6/17) to peripancreatic effusion microbial culture. (4) Testing time and cost. Testing time of mNGS and routine pathogen microbial culture were (43±17)hours and (111±36)hours, showing a signifi-cant difference between them ( t=9.31, P<0.05). Testing cost of mNGS was (2 267±0)yuan/case, accoun-ting for 1.7% of the hospitalization expenses of (133 759±120 744)yuan/case. Testing cost of routine pathogen microbial culture was (240±0)yuan/case, accounting of 0.2% of the hospitalization expenses. Conclusion:mNGS has important value for early pathogenic diagnosis of suspected infected SAP, and has a high timeliness.

Objective To analyze the relationship between the relevant imaging signs of the Bosniak classification system version 2019 and the benign or malignant of cystic renal masses(CRMs).Methods The CRMs were graded using the Bosniak classification system version 2019,and the overall inter-observer agreement,and the agreement between different subgroups were compared.In addition,the diagnostic value of benign and malignant lesions with weighted weakened imaging signs,redefined and quantified imaging signs in the Bosniak classification system after upgrading from version 2005 to version 2019 was analyzed.Results Fifty-six CRMs were enrolled,including 43 benign and 13 malignant lesions.Based on the Bosniak classification system version 2019,the overall inter-observer agreement was excellent(Kappa=0.881),while the agreement of ≤30 mm and MRI were moderate(Kappa=0.548,0.722).In the comparison of the differences between benign and malignant CRMs,there were significant differences between the groups in age,lesion maximum diameter,thick septa or cyst wall,number of septa ≥4,mural nodule,and enhancement(P＜0.05).In the logistic regression model,the mural nodule was the only imaging sign that was significantly correlated with the malignant CRMs[odds ratio(OR)=9.842,P=0.022].Conclusion The Bosniak classification system version 2019 has an excellent overall inter-observer agreement.When the lesions are small,MRI can provide more imaging details.The mural nodule is an independent risk factor for malignant CRMs.

Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

Background::The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.Methods::The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored.Results::The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3–0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, ?1.0 to ?0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) with regard to incident cases in 2019. Conclusions::Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

Objective To analyze the potential distribution and quality zoning of Gentiana farreri Balf.f.;To provide a theoretical basis for the conservation,sustainable utilization,and domestication of this Tibetan medicine resource.Methods The MaxEnt model and geographic information system software ArcGIS 10.2 were used to conduct ecological suitability zoning of Gentiana farreri Balf.f.in China through searching online specimen libraries and field investigations.SPSS25.0 software was used to construct a relationship model between indicator components and ecological factors,combined with ArcGIS software spatial analysis technology,to form a quality zoning of Gentiana farreri Balf.f.medicinal material.Results The primary environmental factors influencing the ecological suitability of Gentiana farreri Balf.f.were altitude,precipitation in May,April and December,and the mean monthly diurnal temperature range.The most suitable growth areas for Gentiana farreri Balf.f.were predominantly found at the junction of Gansu,Sichuan and Qinghai provinces,certain parts of Tibet,and selected regions of Sichuan.The southern part of Tibet and the southwestern part of Sichuan were identified as having higher comprehensive quality of Gentiana farreri Balf.f.medicinal materials.Conclusion The findings of this study can serve as a reference for the production planning and quality assessment of Gentiana farreri Balf.f.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.

Objective:To evaluate the efficacy and safety of pharyngeal spraying recombinant human interfe-ron alpha 2b (rhIFNα2b) in the treatment of herpangina in children.Method:s A prospective, multicenter, rando-mized, opened and controlled study was carried out in 11 hospitals in Anhui province from August 2018 to March 2019.According to the time of admission, 180 patients diagnosed as herpangina were prospectively and randomly divided into rhIFNα2b treatment group and Ribavirin control group.On the basis of giving both groups the heat-clearing, detoxifying and anti-infection treatment, the patients in treatment group received pharyngeal spraying rhIFNα2b 9 g/L saline solution[1 million IU/mL, 0.1 million IU/(0.1 mL·press)], and the patients in control group were treated by pharyngeal spraying Ribavirin (0.5 mg RBV/press, 150 press), 3 presses per time, 4 times per day, continuous administration for 5 days for both groups.Those who recovered in advance were no longer given medication.All patients were observed to fully recover.The clinical efficacy and the disappearing time of symptoms and signs between two groups were compared, and the safety of pharyngeal spraying rhIFNα2b for patients was evaluated.Result:s All of the 180 patients completed the study, including 90 cases in the treatment group and 90 cases in the control group.There was no statistically significant difference in terms of gender, age, weight and course of illness before treatment between the two groups (all P>0.05), which had clinical comparability.The apparent efficiency of the treatment group [63.3% (57/90 cases)] was significantly higher than that in the control group [38.9% (35/90 cases)] and the difference was statistically significant( χ2=10.934, P=0.004); no significant difference in the total efficiency between the treatment group [96.7% (87/90 cases)]and the control group [92.2% (83/90 cases)]was observed ( χ2=2.924, P=0.169). The duration of fever[(32.59±20.73) h vs.(45.72±26.96) h], hyperemia[(76.48±23.12) h vs.(92.44±24.31) h], herpes[(72.99±25.77) h vs.(85.09± 26.62) h], salivation[(45.44±24.96) h vs.(54.42±31.20) h] and anorexia[(62.70±23.99) h vs.(78.71±30.54) h] in the treatment group were significantly shorter than those in the control group, and the differences were statistically significant(all P<0.05). Before treatment, the serum levels of tumor necrosis factor α(TNF-α) [(13.02±4.41) ng/L vs.(13.57±9.27) ng/L], interleukin-6(IL-6) [(26.48±11.31) ng/L vs.(30.15±15.55) ng/L] and C-reactive protein(CRP)[(19.34±14.11) mg/L vs.(19.83±14.57) mg/L]were not significantly different between the two groups (all P>0.05). After treatment, the serum levels of TNF-α and IL-6 were(7.26±1.99) ng/L and (2.42±0.73) ng/L in the treatment group, which were significantly lower than those in the control group [(12.09±6.39) ng/L and (7.32±11.51) ng/L](all P<0.05), but no significant difference in serum levels of CRP between the two groups was observed ( P>0.05). The comparison on positive rate of virus in pharyngeal swab between the treatment group [65.3% (32/49 cases) and 40.6% (13/32 cases) respectively] and the control group[66.7%(36/54 cases) and 41.0% (16/39 cases), respectively]before and after therapy showed no significant difference (all P>0.05). During the treatment, no serious adverse reactions were observed in the two groups.The incidence of adverse reactions was 1.1% (1/90 cases) in the treatment group and 5.6% (5/90 cases) in the control group.In addition, the serum hemoglobin level of children in the control group after treatment was significantly lower than that before treatment and that in the treatment group (all P<0.05). Conclusions:Compared with pharyngeal spraying ribavirin, pharyngeal spraying rhIFNα2b can greatly improve the clinical efficiency, accelerate the disappearance of clinical symptoms and signs, and shorten the total course of disease, and is more safe and worthy of clinical application.

Objective: To observe the changes in nutrition indicators and the effect on chemotherapy complications as well as the safety of enteral nutrition by way of providing enteral nutrition support for children with acute lymphoblastic leukemia (ALL) at the stage of induction chemotherapy. Methods: From November 2016 to September 2017, 60 children with newly diagnosed ALL at the Hematology Oncology Center of Beijing Children′s Hospital were enrolled in this study.They were randomly divided into an experimental group and a control group, 30 cases for each group.The experimental group was given a high-calorie diet, high-quality protein, and high-medium-chain trigly-ceride enteral nutrition on the basis of a conventional low-fat diet, and the duration lasted the whole induction treatment of ALL children; while the control group was given a low-fat diet routinely.By analyzing relevant indicators before induction chemotherapy (D0), chemotherapy day 15 (D15), and after chemotherapy (D33), the changes in nutritional status and the effect on chemotherapy complications in 2 groups were investigated. Results: There was no significant difference in the body mass index (BMI) and the thickness of triceps skinfold between 2 groups before and after chemotherapy (all P>0.05). The upper arm circumference increased after chemotherapy in the experimental group[before treatment: (15.80±2.63) cm, after treatment: (16.27±2.57) cm], while that of the control group decreased slightly[before chemotherapy: (17.19±3.71) cm, after chemotherapy: (17.15±3.64) cm], and the difference between 2 groups was statistically significant (P<0.05). After chemotherapy, the total protein levels in two groups decreased[the experimental group: (64.52±4.85) g/L, the control group: (61.97±4.65) g/L] which was significantly different from that before chemotherapy [the experimental group: (68.17±6.37) g/L, the control group: (68.08±5.14) g/L] (P<0.01). The total protein level of the experimental group after chemotherapy was significant higher than that in the control group (P<0.05). Both albumin levels in 2 groups increased after chemotherapy [(42.45±4.32) g/L in the experimental group and (41.15±3.73) g/L in the control group], and there was a significant difference between 2 groups before chemotherapy [(39.54±3.26) g/L in the experimental group and (40.01±4.37) g/L in the control group] (P<0.05). The level of prealbumin increased after chemotherapy in both groups [(324.57±64.328) mg/L in the experimental group and (293.07±69.09) mg/L in the control group] compared with that before chemotherapy [(121.10±35.13) mg/L in the experimental group and(131.20±52.77) mg/L in the control group]. The change was statistically significant (P<0.01). The albumin level in the experimental group before chemotherapy was lower than that in the control group after chemotherapy, but it was higher than that in the control group after chemotherapy.Protein differences were statistically significant (P<0.05). The reduction rate of elemental iron in the experimental group after chemotherapy was lower than that in the control group, but it was not statistically significant (P>0.05). Elemental zinc was not significantly different compared with the control group.The incidence of neutropenia after chemotherapy in ALL children was higher (37/60 cases, 61.67%). The recovery of neutropenia after chemotherapy in the experimental group was better than that in the control group.After chemotherapy, the severity of anemia in the experimental group was lighter than that in the control group.The amount of blood transfusion required and amount of transfusion per capita were less than those in the control group (54 person-times vs.74 person-times, 2.45 times vs.3.08 times). The total number of transfused blood products was less than that of the control group (78 person-times vs.101 person-times), but none of the findings above were statistically significant (all P>0.05). The degree of hepatic damage in the experimental group decreased after chemotherapy, but there was no significant change in the control group.The initial activated partial thromboplastin time(APTT) prolongation in the trial group was more than that in the control group (5 cases vs.3 cases), and less than the control group (0 case vs.1 case) after chemotherapy.The frequency of fever in the experimental group during chemotherapy was less than that in the control group (6 cases vs.8 cases), and the average time of fever was shorter than that in the control group (2.8 d vs.4.1 d). None of the above findings were statistically significant (all P>0.05). During the course of chemotherapy, 0 pancreatitis occurred in the experimental group, and 1 pancreatitis occurred in the control group.There was no difference in remission rates between 2 groups of chemotherapy for 15 days and chemotherapy for 33 days. Conclusions The nutritional status of children with ALL was reduced after initial induction chemotherapy.Enteral nutrition support was helpful to maintain the nutritional status for children at the initial stage of chemotherapy, high-calorie diet, high-quality protein, and high-medium-chain triglyceride enteral nutrition support improves blood system tolerance to chemotherapy and reduces chemotherapy complications.

BACKGROUND: It has been found that the distribution and diffusion degree of bone cement are the main factors influencing the clinical effect of percutaneous vertebroplasty. OBJECTIVE: To explore the feasibility of analyzing bone cement distribution form and diffusion degree based on Mimics software, and to evaluate the relationship of clinical efficacy with bone cement distribution form and diffusion degree. METHODS: A total of 170 cases of osteoporotic vertebral compression fracture admitted to Zigong No. 4 People's Hospital from January 2017 to March 2018 were included, including 41 cases of males and 129 cases of females aged 60-97 years. All of them were treated with percutaneous vertebroplasty. X-ray and CT examination were done at postoperative 2 days, and the bone cement distribution was classified into five types based on the distribution of bone cement in X-ray images, including type Ⅰ (most cement continuously and evenly distributed in the vertebral body), type Ⅱ (most cement distributed in the central vertebral bodies), type Ⅲ (most cement distributed on both sides of vertebral body), type Ⅳ (most cement distribution at the side of the vertebral bodies and the central), type Ⅴ (most cement distribution at the side of the vertebral body). Mimics project files were created based on CT image data to calculate bone cement volume and diffusion volume. After 6 months of follow-up, visual analogue scale score, Oswestry disability index and Cobb angle were compared among groups to analyze the relationship between bone cement distribution, bone cement diffusion volume, bone cement diffusion volume ratio and clinical efficacy. RESULTS AND CONCLUSION: (1) The visual analogue scale score and Oswestry disability index of the five types of bone cements were significantly improved at 2 days and 6 months after surgery compared with preoperative data (P < 0.05), the Cobb angle of the type Ⅰ group was significantly improved compared with preoperative data (P < 0.05), and the Cobb angles of the type Ⅱ-Ⅴ groups showed no difference from the preoperative data (P> 0.05). (2) The diffusion volume of bone cement was (6.69±1.19) mL, and the diffusion volume ratio of bone cement was (20.93±3.13) ％. There was no correlation between the volume of bone cement injection and the visual analogue scale score, Oswestry disability index and Cobb angle at 2 days and 6 months after surgery. There was a negative correlation between the bone cement dispersion volume and the visual analogue scale score at 6 months after surgery, and the Oswestry disability index score at 2 days and 6 months after surgery (P < 0.05), but the correlation was weak. The diffusion volume ratio of bone cement was negatively correlated with the visual analogue scale score and Oswestry disability index score at 2 days and 6 months after surgery (P < 0.05), showing a strong correlation. These findings show that, based on the three-dimensional reconstruction function of Mimics software, the diffusion volume and diffusion volume ratio of bone cement can be accurately calculated. The bone cement evenly distributed can alleviate the local kyphosis. The diffusion volume ratio of bone cement is positively correlated with clinical efficacy, which is more valuable than the volume of bone cement.

OBJECTIVETo explore the appropriate operative strategy in recurrent groin hernia repair.

METHODSClinical and follow-up data of 82 patients with recurrent groin hernia undergoing operation at Department of Pancreatobiliary Surgery, Xiangya Hospital of Central South University from April 2010 to April 2017 were analyzed retrospectively. The operative approaches included laparoscopic transabdominal preperitoneal (TAPP) hernia repair, Lichtenstein repair and hybrid repair. Surgical method selection was based on the basis of European Hernia Society guidelines, combined with hernia histories, preoperative examination results and intra-operative results: (1) When an anterior approach (Lichtenstein, Bassini or Shouldice surgery) was adopted in the previous operation, TAPP was preferred for the recurrent groin hernia. (2) When the previous operation was an posterior approach [TAPP or total extraperitoneal hernioplasty (TEP)], Lichtenstein method was preferred. Moreover, Lichtenstein surgery with local anesthesia or nerve block was also selected when the patient could not tolerate general anesthesia. (3) When extensive preperitoneal adhesions were found in patients with previous anterior approach repair during laparoscopic exploration, especially in patients who had relapsed after multiple operations or had previous biochemical glues injection, hybrid surgery was preferred.

RESULTSAll 82 patients completed operations smoothly. TAPP, Lichtenstein and hybrid operation were applied in 74, 4 and 4 patients, respectively, with median operative time of 70 minutes (40-130 minutes) in TAPP, 60 minutes (40-90 minutes) in Lichtenstein and 120 minutes (70-150 minutes) in hybrid operation, respectively. The median numerical rating scales (NRS) score was 2 (0-6) on postoperative day 1. The incidences of postoperative seroma, pain and urinary retention were 4.9% (4/82), 2.4% (2/82) and 1.2% (1/82) respectively. The median postoperative hospital stay was 2 days (1-6 days). Seventy-two patients were followed-up from 11 to 87 months. The median follow-up period was 27 months. The median inguinal pain questionnaire (IPQ) score was 2 (0-8) month after operation. One recurrent case was reported 1 year after operation. No incision or mesh infection and long-term inguinal chronic pain were observed.

CONCLUSIONSFor recurrent patients with previous open anterior approach, TEP and TAPP repair are equivalent surgical techniques, and the choice should be tailored to the surgeon's expertise. For those with previous TAPP or TEP repair, Lichtenstein technique is recommended. For those with adhesions both in anterior transverse fascia and pre-peritoneum, hybrid operation may be the preferable choice according to adhesion conditions.

Groin ; Hernia, Inguinal ; surgery ; Herniorrhaphy ; Humans ; Laparoscopy ; Recurrence ; Retrospective Studies ; Surgical Mesh ; Treatment Outcome