Radiomic nomogram based on bi-parametric magnetic resonance imaging to predict the International Society of Urological Pathology grading ≥ 3 prostate cancer: a multicenter study.

PURPOSE: To create a reliable radiomic nomogram for the prediction of the International Society of Urological Pathology (ISUP) grading ≥ 3 prostate cancer (PCa) patients. METHODS: patients with verified PCa were obtained from three different hospitals. The patients were divided into training, internal validation, and two external validation groups. A radiomic signature (rad-score) extracted from T2WI, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps were constructed in the training cohort. Eight clinical features were performed to develop a clinical model using univariate and multivariate logistic regression. The combined model incorporated the radiomic signature and clinical model. The model's performance was assessed by the receiver operating characteristic (ROC) curve. RESULTS: Rad-score, magnetic resonance imaging T-stage, and ADC value were significant predictors of ISUP ≥ 3 PCa. A nomogram of these three factors was shown to have greater diagnostic accuracy than using only the radiomic signature or clinical model alone. The area under the ROC curve was 0.85, 0.88, 0.81, 0.81 for the training, internal, and two external validation cohorts, respectively. In the stratified analysis based on the MR scanner model, the area under the ROC curve of predicting ISUP ≥ 3 PCa for GE, Siemens, and combined groups were 0.84, 0.83, and 0.84, respectively, in the combined training group and an internal validation group. CONCLUSIONS: The proposed nomogram has the potential to predict the differentiation degree of ISUP PCa patients.

CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K-Akt pathway and epithelial-mesenchymal transition.

BACKGROUND: Multiple studies have established a strong relationship between circRNA and cancer progression. Cervical lymph node metastasis is a key factor influencing the surgical approach and distant metastasis of papillary thyroid cancer (PTC). However, the role of circNDST1 in PTC has not been investigated. Our research focused on revealing the function and mechanism of action of circNDST1 in PTC. METHODS: High-throughput sequencing and qPCR were used to assess the expression of circRNA in PTC tissues with extensive cervical lymph node metastasis and circNDST1 in cell lines, respectively. The proliferative effects of circNDST1 in vitro and in vivo were analyzed using CCK8, clone formation assay, EdU, and nude mouse tumorigenesis assay. The transwell scratch assay was employed in the scrutiny of the effect of circNDST1 on the migration and invasion abilities of thyroid cancer cells, while circNDST1's influence on the PI3K-Akt pathway and the Epithelial-Mesenchymal Transition (EMT) key protein expression was evaluated utilizing RNA sequencing and western blot. RNA pull-down and RIP were used to examine the binding of circNDST1 to CSNK2A1. RESULTS: CircNDST1 was highly expressed in PTC cell lines, but knocking it down inhibited the proliferation, migration, and invasive abilities of TPC1 and KTC1 cell lines. CircNDST1 bonded with CSNK2A1 and promoted the interaction between CSNK2A1 and Akt, leading to the activation of the PI3K-Akt pathway and EMT. CONCLUSION: CircNDST1's high expression boosted thyroid cancer progression through the activation of the PI3K-Akt pathway and EMT in a CSNK2A1-dependent manner.

[Endovascular abdominal aortic aneurysm repair with a new stent graft:early results from a multicenter study].

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.

[Enodvascular treatment of isolated abdominal aortic dissection].

Objective: To examine the outcome of endovascular treatment in patients of isolated abdominal aortic dissection. Methods: From February 2012 to June 2020, 61 patients (44 males, 17 females) with an age of (60.2±11.4) years (range: 43 to 87 years) of isolated abdominal aortic dissection who underwent the endovascular treatment, including bifurcated and straight aortic stent graft, in the Department of Vascular Surgery, the Second Xiangya Hospital, Central South University were enrolled. There were 47 patients treated with bifurcated aortic stent grafts and 14 patients with straight aortic stent grafts. Patient demographic, preoperative, intraoperative, perioperative data were collected. Clinical follow-up data, including mortality, relative complications and aortic remodeling, were obtained. Kaplan-Meier method and Log-rank test was used to calculate and compare the rates of survival and freedom from all adverse events. Results: The operative time was (142.4±47.9) minutes (range:70 to 310 minutes) and (95.7±23.7) minutes (range: 70 to 150 minutes) in bifurcated stent group and straight stent group, respectively. The perioperative mortality was 0. One patient had partial occlusion of the left renal artery, and 3 patients had type Ⅰa endoleak post-operation. The follow-up period was (37.1±22.1) months (range: 3 to 91 months). Three patents suffered from type B aortic dissection; one of them progressed into type A aortic dissection and died, another one was treated with secondary endovascular operation, and the remaining one was treated conservatively. One patient had type A aortic dissection and was treated conservatively for 57 months without any discomfort. Stent grafts in iliac artery occlusion happened in 2 patients treated with a bifurcated graft, one of them was treated with a secondary operation because of severe symptom. Aortic remodeling was well with the treatment of bifurcated and straight grafts. There was no difference in the cumulative survival (P=0.584) and freedom from all adverse events (P=0.309) between the two different endovascular treatment strategies. Conclusion: Endovascular aortic repair is an effective and safe treatment strategy for isolated abdominal aortic dissection with reliable mid-term result and excellent aortic remodeling.

PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers.

Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. Results: We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%-49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P < 0.001, n = 78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P < 0.001, n = 62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman's rho=0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9 months (95% CI 1.7-2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. Conclusion: A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.

Kramers-Kronig detection with Brillouin-amplified virtual carrier: publisher's note.

This publisher's note corrects an error in the title in Opt. Lett.43, 1367 (2018)OPLEDP0146-959210.1364/OL.43.001367.

Subcutaneous ICD screening with the Boston Scientific ZOOM programmer versus a 12-lead ECG machine.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) requires preimplant screening to ensure appropriate sensing and reduce risk of inappropriate shocks. Screening can be performed using either an ICD programmer or a 12-lead electrocardiogram (ECG) machine. It is unclear whether differences in signal filtering and digital sampling change the screening success rate. METHODS: Subjects were recruited if they had a transvenous single-lead ICD without pacing requirements or were candidates for a new ICD. Screening was performed using both a Boston Scientific ZOOM programmer (Marlborough, MA, USA) and General Electric MAC 5000 ECG machine (Fairfield, CT, USA). A pass was defined as having at least one lead that fit within the screening template in both supine and sitting positions. RESULTS: A total of 69 subjects were included and 27 sets of ECG leads had differing screening results between the two machines (7%). Of these sets, 22 (81%) passed using the ECG machine but failed using the programmer and five (19%) passed using the ECG machine but failed using the programmer (P < 0.001). Four subjects (6%) passed screening using the ECG machine but failed using the programmer. No subject passed screening with the programmer but failed with the ECG machine. CONCLUSION: There can be occasional disagreement in S-ICD patient screening between an ICD programmer and ECG machine, all of whom passed with the ECG machine but failed using the programmer. On a per lead basis, the ECG machine passes more subjects. It is unknown what the inappropriate shock rate would be if an S-ICD was implanted. Clinical judgment should be used in borderline cases.

[Procedure selection of left subclavian artery revascularization in thoracic endovascular aortic repair].

In order to require ideal proximal landing zone and durable long-term outcome, it is necessary to reconstruct the left subclavian artery(LSA) blood supply as much as possible in thoracic aortic endovascular repair(TEVAR). With the advent and progress of diverse assisted techniques and devices, several procedures for the reconstruction of the left subclavian artery have been developed and widely utilized, including surgical LSA bypass or transposition, chimney technique, periscope technique, fenestration and branched stent-graft, which have expanded the proximal landing zone and widened the indication for original TEVAR. This article describes the advantages and pitfalls of each revascularization methods. Anatomies of aortic arch and LSA, urgency and types of pathologies, proficiency of the surgeon with different revascularization techniques and pre-operative risk score of patient should be evaluated in procedure selection. In clinical application, patient-specific evaluations and individualized considerations are essential for initialize the therapeutic strategy and decision making.

[Association between Long Working Hours and Job Stress and Depression among Employees from a State Grid Company].

Objective: This study was to understand the current situation of long working hours and identify the association of long working hours and job stress and depression among workers from one district company of state grid. Methods: The project was done with the cross-sectional survey. All questionnaires were completed by self-administered with informed consent. Employees' weekly working hours was reported by themselves; Using the PHQ-9 scale to assess depression, the JDC Model to evaluate job stress, and SPSS software to analyze data, the single factor chi-square test and multivariate Logistic analysis were performed to identify the association between long working hours and job stress, depression. Results: there were 35.3 percent employees with over 44 hours a week. The association between increasing weekly working hours and job stress and depression was statistically significant. Compared to the reference group (≤44 h) , for those who worked more than 44 hours per week, the odds ratio of job stress was 2.02 (95%CI=1.27-3.23) times increased, and the odds ratio of depression was 1.60 (95%CI=1.01-2.55) times increased, especially for those (≥60 h) , the odds ratio was 3.69 (95%CI=1.45-9.41) and 2.76 (95%CI=1.09-7.03) respectively. Conclusion: Long working hours can significantly increase the risk of job stress and depression among workers. When their weekly working hours exceeds 60, long working hours will be the independent risk factor for both job stress and depression.

[Mediating effect of work engagement between job stress and depressive symptoms in State Grid employees].

Objective: To explore the relationship between job stress, work engagement and depressive symptoms of State Grid workers, and to analyze the mediating effect of work engagement between job stress and depressive symptoms. Methods: A cross-sectional survey was conducted to investigate 845 employees from a State Grid company, using the brief job stress questionnaire, the Patient Health Questionnaire (PHQ-9) and 9-item Utrecht Work Engagement Scale (UWES-9) in March 2017. Results: The average score of work engagement was 4.49±1.42, the mean value of job stress was 1.15±0.33, the average score of depressive symptoms was 6.44±4.30, and the positive rate of depressive symptoms was 66.9%.There was a negative correlation between work engagement with both job stress and depressive symptoms (r=-0.193, -0.397, both P<0.01) , and job stress was positively correlated with depressive symptoms (r=0.260, P<0.01) . The relationship between job stress and depressive symptoms was partly mediated by work engagement, and the mediating effect accounted for 27.2% of the total effect. Conclusion: The work engagement of State Grid staff acts as the mediator between job stress and depressive symptoms, alleviating the depressive symptoms caused by job stress.

Opposing roles for JNK and Aurora A in regulating the association of WDR62 with spindle microtubules.

WD40-repeat protein 62 (WDR62) is a spindle pole protein required for normal cell division and neuroprogenitor differentiation during brain development. Microcephaly-associated mutations in WDR62 lead to mitotic mislocalization, highlighting a crucial requirement for precise WDR62 spatiotemporal distribution, although the regulatory mechanisms are unknown. Here, we demonstrate that the WD40-repeat region of WDR62 is required for microtubule association, whereas the disordered C-terminal region regulates cell-cycle-dependent compartmentalization. In agreement with a functional requirement for the WDR62­JNK1 complex during neurogenesis, WDR62 specifically recruits JNK1 (also known as MAPK8), but not JNK2 (also known as MAPK9), to the spindle pole. However, JNK-mediated phosphorylation of WDR62 T1053 negatively regulated microtubule association, and loss of JNK signaling resulted in constitutive WDR62 localization to microtubules irrespective of cell cycle stage. In contrast, we identified that Aurora A kinase (AURKA) and WDR62 were in complex and that AURKA-mediated phosphorylation was required for the spindle localization of WDR62 during mitosis. Our studies highlight complex regulation of WDR62 localization, with opposing roles for JNK and AURKA in determining its spindle association.

Incorporating an immersed boundary method to study thermal effects of vascular systems during tissue cryo-freezing.

In this paper, the three-dimensional thermal effects of a clinically-extracted vascular tissue undergoing cryo-freezing are numerically investigated. Based on the measured experimental temperature field, the numerical results of the Pennes bioheat model combined with the boundary condition-enforced immersed boundary method (IBM) agreed well with experimental data with a maximum temperature discrepancy of 2.9°C. For simulating the temperature profile of a tumor sited in a dominantly vascularized tissue, our model is able to capture with ease the thermal effects at specified junctions of the blood vessels. The vascular complexity and the ice-ball shape irregularity which cannot be easily quantified via clinical experiments are also analyzed and compared for both two-dimensional and three-dimensional settings with different vessel configurations and developments. For the three-dimensional numerical simulations, a n-furcated liver vessels model from a three-dimensional segmented volume using hole-making and subdivision methods is applied. A specific study revealed that the structure and complexity of the vascular network can markedly affect the tissue's freezing configuration with increasing ice-ball irregularity for greater blood vessel complexity.

[Progress on Determination and Analysis of Zopiclone in Biological Samples].

As a new hypnotic, zopiclone is widely used in clinical treatment. There are many methods for determination of zopiclone, including spectrophotometry, chromatography and chromatography mass spectrum, etc. Present paper reviews different kinds of biological samples associated with zopiclone, extraction and purification methods, and determination and analysis methods, which aims to provide references for the relevant research and practice.

Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc.

The aim of this study was to immunolocalise type VI collagen and perlecan and determine their interactive properties in the intervertebral disc (IVD). Confocal laser scanning microscopy co-localised perlecan with type VI collagen as pericellular components of IVD cells and translamellar cross-bridges in ovine and murine IVDs. These cross-bridges were significantly less abundant in the heparin sulphate deficient Hspg2 exon 3 null mouse IVD than in wild type. This association of type VI collagen with elastic components provides clues as to its roles in conveying elastic recoil properties to annular tissues. Perlecan and type VI collagen were highly interactive in plasmon resonance studies. Pericellular colocalisation of perlecan and type VI collagen provides matrix stabilisation and cell-matrix communication which allows IVD cells to perceive and respond to perturbations in their biomechanical microenvironment. Perlecan, at the cell surface, provides an adhesive interface between the cell and its surrounding extracellular matrix. Elastic microfibrillar structures regulate tensional connective tissue development and function. The 2010 Global Burden of Disease study examined 291 disorders and identified disc degeneration and associated low back pain as the leading global musculoskeletal disorder emphasising its massive socioeconomic impact and the need for more effective treatment strategies. A greater understanding of how the IVD achieves its unique biomechanical functional properties is of great importance in the development of such therapeutic measures.

Association between age at first sexual intercourse and knowledge, attitudes and practices regarding reproductive health and unplanned pregnancy: a cross-sectional study.

BACKGROUND: Age at first sexual intercourse (AFSI) is decreasing among adolescents in developed nations. An early sexual debut has been associated, to some extent, with multiple sexual partners, infrequent use of condoms, unplanned pregnancy, unsafe abortion, and sexually transmitted disease and human immunodeficiency virus infection. Unplanned pregnancy among adolescents has both physical and social adverse effects. METHODS: In total, 78,400 self-administered anonymous questionnaires were distributed to college students in seven cities in China to determine the age at which Chinese college students first engage in sexual activity, and the association between AFSI and knowledge, attitudes and practices (KAP) regarding reproductive health and unplanned pregnancy. RESULTS: Approximately 10,164 students reported that they were sexually active, and most reported that they had engaged in sexual intercourse for the first time during college. The average AFSI was 20.14 [standard deviation (SD) 2.98] years, and the average AFSI by gender was 19.97 (SD 2.97) years for males and 20.41 (SD 2.97) years for females. The unplanned pregnancy rate among the participants was 34.03%. Participants lacked knowledge about contraception and reproductive health, although most believed that it is necessary to have this knowledge. Participants' attitudes towards premarital sex were varied. Factors that were found to be associated with unplanned pregnancy were AFSI, contraceptive methods used for first sexual act, and whether contraceptive methods were used for every sexual act. CONCLUSIONS: The college period is a key time for Chinese students in terms of becoming sexually active. As such, comprehensive and informative reproductive health education should be provided before and during the college period. Furthermore, reproductive health education should include appropriate sexual morality education and comprehensive sex education. Gender traits and needs should be considered in sex education.

[Association between sense of coherence and occupational stress of workers in modern service industry in Shanghai, China].

Objective: To investigate understand the current status of the sense of coherence and occupational stress in modern service workers, and to analyze the association between occupational stress and the sense of coherence. Methods: From March to April, 2016, 834 modern service workers from 3 companies in Shanghai, China (in air transportation industry, marketing industry, and travel industry) were surveyed by non-ran-dom sampling. The self-completion questionnaires were filled out anonymously given the informed consent of the workers. The occupational stress questionnaire was used to evaluate occupational stress, and the Chinese version of the Sense of Coherence Scale (SOC-13) was used to assess the mental health. Results: The mean score for the sense of coherence of the respondents was 61.54±10.46, and 50.1% of them were self-rated as having occupational stress. There were significant differences in SOC score between groups with different ages, marital status, positions, lengths of service, family per capita monthly income, and weekly work hours (P<0.05). The occupational stress score differed significantly across groups with different marital status, lengths of service, and weekly work hours (P<0.05). The scores for working autonomy, social support, and occupational stress differed significantly between groups with different SOC levels (P<0.05). There were significant differences in SOC score and the distribution of low-SOC respondents between groups with different levels of working autonomy, social support, and occupational stress. High SOC is a protective factor for occupational stress (OR=0.39, 95%CI 0.26~ 0.59). Conclusion: Modern service workers in Shanghai have high SOC and moderate occupational stress. Therefore, improving SOC may reduce occupational stress.

MicroRNA-155 may be involved in the pathogenesis of atopic dermatitis by modulating the differentiation and function of T helper type 17 (Th17) cells.

Our aims were to identify the differential expression of microRNA (miR)-155, as well as to explore the possible regulatory effects of miR-155 on the differentiation and function of T helper type 17 (Th17) cells in atopic dermatitis (AD). The Th17 cell percentage and expression levels of miR-155, retinoic acid-related orphan receptor (ROR)γt, interleukin (IL)-17 and suppressor of cytokine signalling-1 (SOCS1) in peripheral CD4(+) T cells, plasma and skin specimens were detected and compared in AD patients and healthy subjects. A miR-155 mimic and an inhibitor were transfected separately into AD CD4(+) T cells to confirm the in-vivo data. The Th17 cell percentage, miR-155 expression, RORγt mRNA expression, IL-17 mRNA expression and plasma concentration were increased significantly in AD patients compared with healthy subjects. Conversely, SOCS1 mRNA expression and plasma concentration were decreased significantly. Similar results were detected in cultured CD4(+) T cells transfected with the miR-155 mimic compared with a miR-155 inhibitor or a negative control. Additionally, there was a sequential decrease in miR-155 expression, as well as RORγt and IL-17 mRNA expression, but an increase in SOCS1 mRNA expression, from AD lesional skin and perilesional skin to normal skin. Positive correlations were found between miR-155 expression and AD severity, Th17 cell percentage, RORγt mRNA expression and IL-17 mRNA expression and plasma concentration, while negative correlations were observed between miR-155 expression and SOCS1 mRNA expression and plasma concentration in AD peripheral circulation and skin lesions. In conclusion, miR-155 is over-expressed and may be involved in AD pathogenesis by modulating the differentiation and function of Th17 cells.

Modified Petticoat Technique with Pre-placement of a Distal Bare Stent Improves Early Aortic Remodeling after Complicated Acute Stanford Type B Aortic Dissection.

OBJECTIVE: This study evaluates the safety and efficacy of pre-placement of a distal bare stent as an adjunct to thoracic endovascular aortic repair (TEVAR) in the setting of complicated acute Stanford type B aortic dissection (cTBAD). METHODS: The records of all patients diagnosed with cTBAD at the institution between 2010 and 2013 were reviewed. Indications for the pre-placement of a distal bare stent included symptomatic malperfusion and/or radiological evidence of true lumen collapse. Computed tomography angiography was performed post-operatively to assess aortic remodeling. RESULTS: 148 patients were treated for cTBAD: 113 patients (76.4%) were treated with standard TEVAR and 35 (23.6%) were treated by combined proximal TEVAR with pre-placement of an adjunctive distal bare stent. Primary technical success was 95.9%. The 30 day mortality rate was 4.1% and was not different between groups. The 30 day morbidity included transient renal failure (10.1%), endoleak (7.4%), and paraplegia (2.7%), and was not different between groups. The mean follow up was 10 months (range 2-12 months). No late stent complications were observed; patients with an adjunctive bare stent had less distal re-dissection (0% vs. 15%; p = .01) and fewer endovascular re-interventions (5.7% vs. 20.4%; p = .04). At 1 year, patients treated with TEVAR and an adjunctive distal bare stent had increased true lumen volume (166 vs. 110 mL; p = .022), decreased false lumen volume (60 vs. 90 mL; p = .043), and increased complete false lumen thrombosis in the thoracic (76.5% vs. 29.5%; p < .001) and abdominal (20.6% vs. 3.8%; p = .002) segments. CONCLUSIONS: Combined pre-placement of a distal bare stent as an adjunct to proximal TEVAR to treat cTBAD restricts oversizing of the distal stent graft, reducing the potential for distal true lumen collapse and visceral malperfusion, and improving remodeling of the dissected thoracic aorta. Long-term follow up and prospective studies are needed to assess the overall effectiveness of this treatment strategy.