Long-term Follow-up Evaluation Research Articles

#2374 Long-term clinical outcomes in pediatric patients with primary nephrogenic insipidus

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, and there is a paucity of studies assessing long-term clinical outcomes in affected individuals. This study aims to evaluate the long-term clinical outcomes, encompassing growth and kidney function, in pediatric patients with NDI. Method This multicenter retrospective study included forty-nine children diagnosed with NDI. The medical records of these patients were retrospectively reviewed, and a linear mixed model was employed to analyze variations in growth and kidney function with increasing age. Results Mutations in the AVPR2 and AQP2 genes were identified in 40 (81.6%) and 4 (8.2%) patients, retrospectively, while pathogenic variants were either not found or not tested in 5 (10.2%) patients. The median ages at diagnosis and the last follow-up were 0.41 (interquartile ranges (IQR) 0.12−0.64) years and 9.97 (IQR 2.42−18.66) years, respectively. Thiazide treatment was administered to all patients, with 43 (87.8%) and 14 (28.6%) patients also receiving amiloride and indomethacin, respectively, in conjunction with thiazide. Our analysis using linear mixed models revealed significant changes in growth including height, weight, and body mass index (BMI) with increasing age. The estimated marginal means (EMM) for height Z score decreased from −0.114 (95% confidence interval (CI) −0.507 to 0.279) at diagnosis to −1.464 (95% CI −1.880 to −1.048) at 2 years of age, subsequently increasing to −0.706 (95% CI −1.186 to −0.225) at 14 years of age (P < 0.001). The height Z score at 19 year of age is −0.899 (95% CI −1.434 to −0.365), significantly lower than those at diagnosis (P = 0.038). The EMM for weight Z score increased from −1.580 (95% CI −2.009 to −1.149) at one year of age to 0.760 (95% CI 0.170 to 1.350) at 19 years of age, exhibiting a steady increase (P < 0.001). The EMM for BMI Z score demonstrated a consistent increase after age of 2 years (P < 0.001), which were −0.326 (95% CI −0.835 to 0.182) at 2 years of age and 1.210 (95% CI 0.602 to 1.817) at 19 years of age. The proportion of obesity increased from 3.2% at 3 years of age to 33.3% at 19 years of age. The EMM for estimated glomerular filtration rate (eGFR) consistently increased from 82.8 (95% CI 75.2 to 90.3) mL/min/m2 to 100.8 (95% CI 88.9 to 112.7) mL/min/m2. Although eGFR less than 60 mL/min/m2 is not present, the eGFR less than 90 mL/min/m2 is 47.5% at last follow up. Conclusion At the end of growth, the height Z score is low, and the proportion of obesity is high. To improve the growth pattern, clinicians need to monitor nutritional status and establish nutritional support during follow-up in patients with NDI. Since mild decreased kidney function developed in half, patients with NDI need long-term follow-up evaluation for kidney function.

Early outcomes of total hip arthroplasty using point-of-care manufactured patient-specific instruments: a single university hospital’s initial experience

BackgroundThe use of 3D-printed Patient-Specific Instruments (PSI) has been investigated to enhance the postoperative functional results in total hip arthroplasty (THA) and has been recognized as an innovative approach for the optimal alignment of hip implant components. Point-of-care production is gradually becoming the norm for PSI manufacturing. The purpose of this article is to assess the accuracy and safety of PSI for total hip arthroplasty performed at the point-of-care in Vietnam.Methods34 THA cases were assessed in this prospective study. A template for the size and orientation of the implant and the design of the PSI was generated using data from preoperative 3D computed tomography (CT) scanning of the lower limb. The principal surgeon determined the implants’ position and PSI design directly using the software. The PSI is then produced using a 3D-compatible resin printer in our manufacturing hospital. The PSI, consisting of an acetabulum and a femoral component placed press-fit on the bony surface, guided surgeons to precisely ream the acetabulum and cut the femoral neck according to the pre-planned plane. Postoperative CT scanning was obtained and superimposed onto the 3D model of the implant to evaluate the accuracy of the procedure by comparing the orientation values of the cup and the alignment of the stem between the planned and the actual results. Intra- and postoperative clinical parameters of surgery, including surgical time, intra-operative blood loss, complications, and the first ambulation, were also recorded to evaluate the safety of the surgery.ResultsThe preparation for PSI required an average of 3 days. 94% of cup size and 91% of stem size were correctly selected. The mean values of postoperative inclination and anteversion were 44.2° ± 4.1° and 19.2° ± 5.6°, respectively. 64.7% of cases deviated from planned within the ± 50 range and 94.1% within the ± 10° range. There was no significant statistical difference between the planned and the achieved values of stem anteversion, osteotomy height, and leg length discrepancy (p > 0.05). The average surgical time was 82.5° ± 10.8 min, and the intraoperative blood loss was estimated at 317.7° ± 57.6 ml. 64.7% of patients could walk on the day of surgery. There were no complications reported.ConclusionsThe point-of-care manufactured PSI is a useful solution for improving the accuracy of total hip arthroplasty surgery, especially in restoring implant orientation and reducing leg length discrepancy. However, long-term clinical follow-up evaluation is needed to confirm the efficacy and safety of this approach.

Echocardiographic Findings in Children with Multisystem Inflammatory Syndrome from Initial Presentation to the First Years after Discharge.

We aimed to evaluate clinical and echocardiographic features of the children diag- nosed with multisystem inflammatory syndrome related to severe acute respiratory syndrome coronavirus-2 infection and determine early and mid-term cardiovascular outcomes. We retrospectively evaluated 38 children who were diagnosed with multisystem inflammatory syndrome in our hospital between November 2020 and November 2021. Cardiovascular evaluations were performed during hospitalization, at the first, the second, and the third months after discharge, and then cardiac evaluation was repeated at 3-month intervals until a median of 24 weeks (range: 9-56 weeks). The mean age of patients was 9.6 years and 25 patients had cardiovascular involve- ment. Echocardiography showed that there was left ventricular dysfunction in 11 cases and any coronary abnormalities in 11 cases on admission. Cardiovascular involvement was most fre- quently seen in patients older than 10 years and of male sex. Severe clinical courses occurred in half of them. The mortality rate was 2.6% during hospitalization. At discharge, complete recovery was achieved in 30 cases and partial recovery was seen in 6 cases; there were 1 case with ventricular dysfunction and 5 cases with coronary abnormalities. At the last polyclinic visit, there was no case with symptoms or myocardial dysfunction, there was only 1 case with persist- ing coronary aneurysms. Cardiovascular abnormalities in patients with multisystem inflammatory syndrome show rapid resolution within the first month. We recommend long-term follow-up evaluation for coronary arteries.

Spinal intradural extramedullary tumors: microscopic keyhole resection with the focus on intraoperative neurophysiological monitoring and long-term outcome

ObjectiveSpinal schwannomas (SS) and spinal meningiomas (SM) account for most intradural extramedullary (IDEM) tumors. These tumors are usually benign lesions, which generally respond favorably to surgical excision. Few studies up to now tried to determine the long-term outcome after minimally invasive surgery (MIS) with multimodal intraoperative neurophysiological monitoring (IONM) for IDEM tumors. The aim of this study was to present one of the largest case series with special regard to IONM findings and long-term outcome after MIS-keyhole surgery with a tubular retractor system.MethodsBetween January 2013 and August 2018, 87 patients with IDEM tumors who underwent tumor removal surgery via MIS-keyhole approach under multimodal IONM were retrospectively reviewed. The neurological status was assessed using a modified McCormick grading scale pre- and postoperatively. Multimodal IONM consisted of motor evoked potentials (MEP), somatosensory evoked potentials (SEP), and electromyography (EMG). Both short-term and long-term clinical evaluations as well as patients’ medical files were retrospectively analyzed.ResultsSurgeries were performed for resection of SS in 49 patients and SM in 38 patients. Tumor locations were cervical in 16.1%, thoracic in 48.3%, thoracolumbar in 4.6%, lumbar 31%. Critical IONM changes were detected in 9 operations (10.3%) in which there were 2 SEPs, 5 MEPs, and 2 EMG events. Three IONM changes (2 MEPs, 1 EMG) were turned out to be transient change in nature since they were resolved in a short time when immediate corrective actions were initiated. Six patients with permanent IONM changes (2SEPs, 3MEPs, 1EMG event), all deficits had resolved during hospitalization or on short -term follow-up evaluation. Sensitivity, specificity, and positive and negative predicted values of IONM were 100, 96, 67, and 100%, respectively. Gross total resection rate was 100%, and a stable or improved McCormick grade exhibited in all patients. No tumor recurrence and no spinal instability were found in the long-term follow-up evaluation (mean 5.2 ± 2.9 years postoperatively). Overall, 94% of patients were either satisfied or very satisfied with their operation, and 93% patients reported excellent or good general clinical outcome according to Odom’s criteria.ConclusionMIS-keyhole surgery with multimodal IONM for IDEM tumors enables a high level of satisfaction and a satisfying long-term clinical and surgical outcome.

Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study

To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Assessment of Computed Tomography Imaging for Isolated Type 1 Bicuspid Aortic Valve Repair: A Comparison between Internal and External Suture Annuloplasty Techniques.

The ideal position of suture annuloplasty relative to the aortic annulus (internal or external) remains unclear. This study aimed to investigate the effectiveness of internal and external suture annuloplasty for isolated type 1 bicuspid aortic valve (BAV) repair. Electrocardiogram (ECG)-gated computed tomography (CT) was used to compare the two techniques and analyze their impact on the aortic annulus. We retrospectively analyzed 20 patients who underwent isolated type 1 BAV repair with either internal or external suture annuloplasty. Each group included 10 patients with comparable clinical features. Preoperative and postoperative ECG-gated CT scans were performed to assess the anatomical relationship between the ventricular-aortic junction (VAJ) and virtual basal ring (VBR), and to measure the height of annuloplasty from the VBR at predefined landmarks in both groups. Perioperative annular geometries, including annular area and perimeter, were measured to quantify the impact of annuloplasty on annular expansibility. The discrepancy between the postoperative annular dimension and size of the Hegar dilator were compared between groups to evaluate the effectiveness of annuloplasty. In both groups, VAJ was higher than VBR at the right coronary (RC) ostium (7.7 3.3 mm) and the raphe (7.9 1.5 mm). The height from the VBR to the external suture annuloplasty shared a similar pattern at the RC ostium and raphe (5.3 1.1 mm and 4.8 1.0 mm, respectively). In contrast, the height differences were minimal for these landmarks in the internal group. Postoperative annular area expansibility decreased in the internal group compared to preoperative levels (4.9 2.3% vs. 8.9 5.5%, p = 0.038), while no significant change was found in the external group (7.6 4.1% vs. 6.5 2.8%, p = 0.473). The internal group showed less area discrepancy between the VBR and the Hegar dilator both at systole (10.1 3.7% vs. 30.1 16.6%, p = 0.004) and diastole (5.7 4.9% vs. 20.9 14.5%, p = 0.009) compared to the external group. Internal suture annuloplasty results in better positioning relative to the VBR than external suture annuloplasty due to the absence of VAJ interference. While this results in more precise annular reduction and less expansibility in the short term, a long-term follow-up evaluation is necessary to assess its effectiveness.

Pressure cooker technique in cerebral AVMs and DAVFs: different treatment strategies.

The pressure cooker technique (PCT) was developed to enable safer and more extensive embolization of hypervascular lesions by simultaneously minimizing backflow of liquid embolic materials and thus reduce the risk of non-target embolization of adjacent healthy vessels. We report our experience in applying the PCT to cerebral arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs) and additionally suggest our technical adjustments. We retrospectively reviewed all patients suffering from AVMs or DAVFs that were treated with the PCT between 2018 and 2020 in two university hospitals. The endpoints of the study were clinical safety and the technical efficacy. The endpoints of the study were clinical safety and the technical efficacy. Clinical safety was the absence of death, major or minor symptomatic stroke, TIA and procedure-related intracranial bleeding (SAH) in the peri-procedural period until dismission. Good clinical outcome was defined as no deterioration of the modified Rankin Scale (mRS) score (comparing the pre- and post-procedural mRS evaluated by a trained neurologist at admission and dismission). The technical efficacy was considered as the complete embolization occlusion of the target vessels of the lesion documented on the final control angiogram. Long-term follow-up evaluation was not intended for this study as it was not available for all patients. Fifteen consecutive patients (6 women; mean age 55 y; range 20-82 y) with seven AVMs and eight DAVFs met the inclusion criteria. The primary clinical safety end point was obtained in all cases as no intraprocedural complications were encountered. All patients had a good clinical outcome with no difference between the pre- and post-mRS scores. The primary efficacy end point was reached in all cases. The PCT is a safe and effective technique in the treatment of cerebral AVMs and DAVFs. Adding an easy and fast step to the procedure, namely the injection of contrast media to test the complete obstruction by the plug, the risk of reflux seems to additionally be reduced.

The Effectiveness of the Schroth Best Practice Program and Chêneau-Type Brace Treatment in Adolescent Idiopathic Scoliosis: Long-Term Follow-Up Evaluation Results

Although the number of studies showing the efficacy of conservative treatment in adolescent idiopathic scoliosis has increased, studies with long-term follow-up are very limited. The aim of this study was to present the long-term effects of a conservative management method including exercise and brace in adolescent idiopathic scoliosis patients. This retrospective cohort study included patients with idiopathic scoliosis who presented at our department and were followed up for at least 2 years after completing the treatment. The main outcome measurements were the Cobb angle and angle of trunk rotation (ATR). The cohort participants were 90.4% female, with a mean age of 11 years and the maximum Cobb angle was mean 32.1°. The mean post-treatment follow-up period was 27.8 months (range 24-71 months). The improvements after treatment in mean maximum Cobb angle (p < 0.001) and ATR (p = 0.001) were statistically significant. At the end of treatment, the maximum Cobb angle was improved in 88.1% of the patients and worsened in 11.9% compared to baseline. In the long-term follow-up evaluations, 83.3% of the curvatures remained stable. The results of this study showed that moderate idiopathic scoliosis in growing adolescents can be successfully halted with appropriate conservative treatment and that long-term improvement is largely maintained.

Long-term prognosis of out-of-hospital cardiac arrest due to idiopathic ventricular arrhythmias.

Life-threatening ventricular arrhythmias (VA) may occur in patients with unknown cardiac disease. A sizable part of them remains labeled as Idiopathic VA and limited data is available regarding their natural history. Our aim was to evaluate the long-term clinical outcomes of survivors of an idiopathic life-threatening VA. Patients who survived an idiopathic life-threatening VA referred to an ICD were included and followed for a median follow-up of 7 years. Clinical and device data were collected and a comparison between genders was made. A total of 29 patients, 41% female, mean age of 50 (19) years were studied; all were implanted with an ICD at index hospitalization. At follow-up, an etiological diagnosis was established in 38% of patients. Genetic testing improved the diagnosis and allowed the identification of a distinct clinical entity in 60% of patients (p=0.04, OR=7.0), especially in women. Regarding ICD data, 31% received appropriate therapies with a median time to first appropriate shock of 39 months (IQR 12-46 months). Men had a significantly higher prevalence of appropriated shocks (50% vs 8%, p=0.04), with a similar time to the first arrhythmic event between genders. Two of the patients died, both from non-arrhythmic causes. Etiologic diagnosis and recurrence prediction in patients with idiopathic VA is challenging, even with long-term follow-up and sophisticated diagnostic evaluation. Genetic testing significantly improved the diagnostic yield, especially in women. Arrhythmia recurrence occurred in about one-third of patients and is significantly higher in men, underscoring the importance of ICD implantation.

Thyroid function and long-term outcomes of children born to mothers with Graves' disease: A 20-year review.

Thyroid dysfunction in infants born to mothers with Graves' disease (GD) is influenced by maternal factors including thyroid status, thyroid-stimulating hormone (TSH) receptor antibody (TRAb) concentration and antithyroid drug use. Thyroid dysfunction during early life could affect growth and development later in life. The aim of this study is to evaluate thyroid function tests (TFTs), and long-term growth and development of children born to mothers with GD. A retrospective chart review of children born to mothers with GD at the Faculty of Medicine Ramathibodi Hospital, Mahidol University, between January 2000 and December 2019 was performed. Clinical data including age of children at enrolment, sex, gestational age, birthweight, maternal thyroid status, maternal TRAb level, maternal GD treatment during pregnancy, neonatal TSH screening and TFT results, and growth and development outcomes of children were collected. There were 262 children (148 males) enrolled. Twelve (4%) infants had neonatal GD. Five (2%) infants had hypothyroidism requiring levothyroxine treatment: four had secondary hypothyroidism and one patient had congenital primary hypothyroidism. Seven (3%) infants had transient TSH elevation, which fell to normal by 2 weeks of age. The remaining 238 children had normal TFT results. Three out of 12 children with neonatal GD had either delayed growth or development. A number of infants born to mothers with GD had abnormal TFTs requiring specific management, and some of them had abnormal growth and development. Careful evaluation of TFTs and long-term follow-up are mandatory for those children.

Nipple-Sparing Mastectomy After Neoadjuvant Chemotherapy: Definitive Results with a Long-Term Follow-Up Evaluation.

Nipple-sparing mastectomy (NSM) is increasingly used for women with breast cancer who are not candidates for conservative surgery. The authors previously reported satisfying results with NSM after neoadjuvant chemotherapy (NACT). From 2010 to 2020, 1072 women underwent mastectomy at the authors' institution. In this group, 433 NSMs were performed (40%). The only contraindications to NSM were close proximity to the nipple-areola complex (NAC), bloody discharge, and Paget disease. In 112 cases involving 111 women, NSM followed NACT (group 1), whereas it was performed as primary surgery in 321 instances involving 306 women (group 2). At 5 years, local relapse was 7% in group 1 and 2% in group 2, although in the multivariate analysis, locoregional relapses (LRRs) did not differ between the two groups. An increased incidence of local relapse was associated with higher tumor stage (stage III; p = 0.046) and age younger than 51 years (p = 0.038). For 34 (30.3%) of the 111 women in group 1 with a pathologic complete response (pCR), no LRRs were recorded. Only one NAC recurrence was observed. Overall survival with each tumor stage did not differ between the two groups. No differences in complications were observed. Cosmetic results were satisfying in 83.8% of the cases and did not get worse after NACT. The study data definitively confirm that NSM is safe even after NACT, with good cosmetic results and complications comparable with those in the primary surgery setting. Tumor stage and age were the only independent factors for local relapse. Patients with pCR enjoyed optimal locoregional control.

Safety and efficacy of dinutuximab in the treatment of neuroblastoma: A review.

Dinutuximab, which is a monoclonal antibody targeting GD2 expressed in neuroblasts, improves survival when included in the therapy regimen. This article reviews the importance of dinutuximab in managing neuroblastoma (NB). Dinutuximab targets high levels of GD2 expression in NB cells, thus increasing event-free survival when used in the maintenance therapy of high-risk patients with NB. Although several collaborative studies have set the standard of care for maintenance therapy, the long-term follow-up and continuous evaluation of the use of antibodies and the co-administration of other pharmacological or immunomodulatory drugs remain to be studied. Trials have shown that the use of dinutuximab for maintenance therapy can prolong the time before the first relapse and improve overall survival. However, there is uncertainty in the function of cytokines co-administered with dinutuximab, which may lead to increased toxicity without additional benefits. Recent studies on relapsed and refractory NB have shown the potential efficacy of dinutuximab. Further research is required to properly incorporate Dinutuximab in current treatment modalities.

Similar Survival Among All Subtypes of Mucinous Appendiceal Adenocarcinoma Except the Intermediate Subtype, Which Shows an Improved Survival.

Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported. Cytoreductive surgery with perioperative intraperitoneal chemotherapy was used to treat a cohort of patients with peritoneal dissemination of MACA. The clinical and histopathologic variables were assessed for their impact on overall survival. The study analyzed 196 patients during a median follow-up period of 8 years. The patients had a median age was 46 years, a median survival of 12 years, and a mean survival of 12.4 years. Preoperative systemic chemotherapy and a high prior surgical score had a negative impact on prognosis. Survival was better for 37 patients (18.9%) with mucinous appendiceal adenocarcinoma-Intermediate (MACA-Int) histology than for 159 patients (81.1%) with MACA grade 1, 2, or 3, or signet ring cells (S) (p = 0.0004). Although MACA-1 and MACA-2 versus MACA-3 and MACA-S had a difference in survival of 63.9 versus 43.2 years at 5 years, with long-term follow-up evaluation, the differences in survival became insignificant (p = 0.5841). The histologic subtype of MACA-Int had a 10-year survival of 81.1%, which was markedly superior to that of MACA-1, -2, -3, or -S (32.7%). With long-term follow-up evaluation, MACA-1, -2, -3, and -S did not differ significantly in survival.

MIS-TLIF or CLIF for single segmental lumbar degenerative disease.

We aimed to compare the effect of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and Crenel lateral interbody fusion (CLIF) on single segmental lumbar degenerative disease. Patients with single segmental lumbar degenerative disease undergoing MIS-TLIF (n = 28) and CLIF (n = 28) were enrolled from April to October 2017. Preoperative medical history, anthropometric data, and clinical data were recorded. Visual analogue scores and Oswestry disability index (ODI) were assessed. Radiography was performed before and after surgery. X-ray films were evaluated according to the Bridwell method, visual analogue scores and ODI scores were evaluated. There were no significant differences in the gender, age, clinical diagnosis, involved segment or preoperative ODI score between 2 groups (P > .05). During 12-month follow-up, MIS-TLIF group had less intraoperative blood loss, drainage, postoperative bedridden time, and hospital stay (P < .05), but more operation time and radiation exposure time compared with CLIF group (P < .05). CLIF group reported less pain than MIS-TLIF group (P > .05). Both groups had similar lumbar fusion rate (P > .05). Overall, CLIF has less complications, less trauma and faster recovery for the treatment of single segmental lumbar degenerate disease when compared with MIS-TLIF. Evaluation of more patients and long-term follow-up are still needed to further validate our findings.

Urban–rural human settlements in China: Objective evaluation and subjective well-being

Human settlements have an important impact on human health, livability, and the economy, which has attracted widespread concern worldwide. Few studies have, however, paid attention to a comprehensive evaluation of urban and rural areas, as well as subjective and objective aspects. This paper evaluates four dimensions of urban–rural settlements in China, including environmental health, environmental tidiness, environmental amenity, and environmental support, from both subjective and objective perspectives. The findings are summarized as follows: (1) The quality of urban–rural human settlements in China has significantly improved over the last 20 years, and it shows a significant decreasing tendency from the southeastern coastal area to the northwestern inland area spatially. (2) The national average score of subjective estimation of human settlement is at the level of “Satisfied”, and it displays significant disparities in terms of residents’ attributes, such as occupation, age, education, and habitation. (3) The subjective evaluation and subjective well-being have a positive correlation regarding the comprehensive assessment of urban–rural human settlements, but there are significant differences in objective estimation to different sub-dimensions. Long-term follow-up investigation and evaluation should be the focus of future research. Findings provide scientific guidance for the optimization and improvement mechanism of urban–rural human settlements.

Long-Term Follow-Up Evaluation of Efficacy in Alpha-Emitting Radiation Therapy on Recurrent and Locally Advanced Squamous Cell Carcinomas in Multi-Center Clinical Study

<h3>Purpose/Objective(s)</h3> Diffusing Alpha-emitter Radiation Therapy (DaRT) represents a novel method to deliver alpha particles intratumorally via the decay of Radium-224. Early results demonstrated the feasibility, safety, and efficacy of DaRT with an associated 100% overall response rate at six weeks and a favorable toxicity profile. The purpose of the study was to report the long-term tumor control outcomes of DaRT for the treatment of locally advanced and recurrent squamous cancers (SCC) of the skin and head and neck. <h3>Materials/Methods</h3> This retrospective study evaluated the outcomes of patients with histologically-confirmed SCC of the skin and head and neck who either previously failed or were medically unfit for definitive therapy. For this study, 28 lesions in 23 patients were eligible and treated per protocol. Treatment was delivered via a percutaneous interstitial technique with placement of the radioactive DaRT to encompass the tumor volume with margin. Tumor control was assessed using serial radiographic imaging or clinical assessments. The median follow-up time was 28 months following treatment. <h3>Results</h3> Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 79%); 6 lesions (6/28, 21%) manifested a partial response. Among the 22 lesions with a CR, 9 (41%) developed a subsequent local relapse at the site of DaRT implantation at a median time of 6.2 months (range: 2.8-35.4 months). The 2-year local progression-free survival (PFS) probability at the implanted site was 50% (95% Confidence Interval, CI: 28-68%) for complete responders. The 2-year overall survival rates post-DaRT implantation was 65% (95% CI: 42%-81%) among all patients and was 77% (95% CI: 50%-91%) among complete responders. <h3>Conclusion</h3> Despite prior therapy among these recurrent, locally advanced tumors, Ra-224 DaRT treatment was well tolerated and associated with excellent 2-year tumor control outcomes. A pivotal US trial for marketing approval is already underway.

Effects of oocyte vitrification on gene expression in the liver and kidney tissues of adult offspring.

Oocyte vitrification is an important assisted reproductive technology (ART) that preserves the fertility of unmarried patients with malignant tumors, and promotes the development of the oocyte donation program. In recent years, the effects of ART, including the vitrification of oocytes and embryos on the health of offspring, have attracted much attention; however, it is difficult to conduct long-term follow-up and biochemical evaluation in humans. In this study, we detected the effect of oocyte vitrification on gene expression in the organs of adult mice offspring by RNA sequencing for the first time. Our results showed that only a small amount of gene expression was significantly affected. Seven genes (Tpm3, Hspe1-rs1, Ntrk2, Cyp4a31, Asic5, Cyp4a14, Retsat) were abnormally expressed in the liver, and ten genes (Lbp, Hspe1-rs1, Prxl2b, Pfn3, Gm9008, Bglap3, Col8a1, Hmgcr, Ero1lb, Ifi44l) were abnormal in the kidney. Several genes were related to metabolism and disease occurrence in the liver or kidney. Besides, we paid special attention to the expression of known imprinted genes and DNA methylation-related genes in adult organs, which are susceptible to oocyte cryopreservation in the preimplantation stage. As a result, some of these transcripts were detected in adult organs, but they were not affected by oocyte vitrification. In conclusion, we first report that oocyte vitrification did not significantly change the global gene expression in offspring organs; nonetheless, it can still influence the transcription of a few functional genes. The potential adverse effects caused by oocyte vitrification need attention and further study.

Long-term surgical outcomes of nerve-sparing discoid and segmental resection for deep endometriosis.

The aim of this study was to investigate long-term outcomes in terms of pain, quality of life (QoL), and gastrointestinal symptoms in women following colorectal surgery for deep endometriosis. In this historical cohort, women who underwent surgical treatment for deep endometriosis by either nerve-sparing full-thickness discoid resection (DR) or colorectal segmental resection (SR) between March 2011 and August 2016 were re-evaluated through telephone interviews about their long-term pain symptoms, subjective overall QoL as rated using a score from 0 (worst) to 10 (optimal), and gastrointestinal outcomes reflected by lower anterior resection syndrome (LARS) following a first postsurgical evaluation (visit 1) published previously and a long-term follow-up evaluation (visit 2). The median long-term follow-up time was 35.4 months at visit 1 and 86 months at visit 2. Of 134 patients, 77 were eligible for final analysis and 57 were lost to follow-up. Compared with presurgical values, QoL scores were significantly increased at both postsurgical evaluation visits in both the SR cohort (scores of 3, 8.5, and 10 at the presurgical visit, visit 1, and visit 2, respectively; p < 0.001) and the DR cohort (scores of 3, 9, and 10, respectively; p < 0.001). Pain scores for dysmenorrhea (SR group scores of 8, 2, and 2, respectively; p < 0.001; DR group scores of 9, 2, and 1, respectively; p < 0.001), dyspareunia (SR group scores of 4, 0, and 0, respectively; p < 0.001; DR group scores of 5, 0, and 1, respectively; p=0.003), and dyschezia (SR group scores of 8, 2, and 2, respectively; p < 0.001; DR group scores of 9, 2, and 1, respectively; p < 0.001) significantly decreased after surgery and remained stable in both cohorts over the follow-up period. Minor and major LARS, reflecting gastrointestinal function, was observed in 6.5% and 8.1% of the SR group and in 13.3% and 6.7% of the DR group, respectively, at visit 1 and in 3.2% and 3.2% of the SR group and 0% and 0% of the DR group, respectively, at visit 2, without significant differences between the SR and DR groups. Colorectal surgery for deep endometriosis, either by DR or SR, provides stable and long-term pain relief with low rates of permanent gastrointestinal function impairment.

Cardiovascular functions and arterial stiffness after JUUL use.

INTRODUCTIONThe rapid growth in the e-cigarette market after the launch of JUUL e-cigarettes led to much discussion on the potential benefits and risks of pods, JUUL devices, and conventional e-cigarettes compared with combustible cigarettes. Independent data are required to assess the effects of these products on cardiovascular surrogate parameters and cardiovascular risk.METHODSWe conducted a single-center three-arm study comparing combustible cigarettes with JUUL e-cigarettes with the old and new technology. We recruited 32 participants who were active smokers (n=15) or vapers (n=17) and performed a total of 39 measurements before and 5, 15, and 30 minutes, after participants smoked a combustible cigarette or vaped a JUUL e-cigarette with the new or old technology. Measurements included peripheral and central blood pressures and parameters of arterial stiffness, including pulse wave velocity and augmentation index.RESULTSPeripheral systolic blood pressure, central blood pressure, and peripheral pulse rate increased significantly in all three groups (each p<0.05). Heart rate (HR) changes lasted significantly longer than blood pressure changes. The augmentation index and pulse wave velocity increased in all three groups, and a multivariate analysis of variance showed that the increases were independent of systolic blood pressure, sex, age, device, and HR.CONCLUSIONSChanges in blood pressure and arterial stiffness are similar after cigarette smoking and JUUL use. These changes may be associated with an increased cardiovascular risk compared with no product use. However, a long-term follow-up evaluation of JUUL use and a head-to-head comparison with conventional e-cigarettes are still needed.

The Pivotal Role of Quality Technical Structures for Clinical Trials Oversight in the Achievement of Long-Term Capacity Strengthening Outcomes.

BackgroundDevelopment of safe and efficacious medicines in many sub-Sahara African countries remains hampered due to fragmented health research infrastructure and ineffective regulatory oversight. To boost the latter in the area of Clinical Trials (CT) Oversight (CTO), many international programs and Regional Centers for Regulatory Excellence (RCORE) initiatives offer various trainings to help strengthen human resource capacity. Here, we aimed at evaluating the training outcomes (at home-institution level) of sponsored fellows for one of such capacity strengthening interventions; a measure that is less often reported and thus remains poorly understood.MethodThe Global Health Protection Programme's VaccTrain project sponsored nine regulatory staff from eight National Medicines Regulatory Authorities (NMRAs) in sub-Saharan Africa for the RCORE CT Training Fellowship by FDA Ghana in a particular year. Using a systematized evaluation framework based on the theory of change, we assessed the individual- and NMRA-level achievement of pre-defined training outcomes. For this purpose, data was collected at pre-training and at short- and long-term evaluation time-points using a survey instrument.ResultsAt pre-training, our data revealed existence of differential expectations and orientations among the training participants, thus providing an early indication of potential distinctive patterns in achievement of desired training outcomes. In a short-term post-training follow-up evaluation, a two-group clustering of fellows based on the achievement of training outcomes where only one group (representing 44%) reported achievement of CTO-related outcomes was observed. At this time-point, achievement of training outcomes was associated with the vibrancy of CT activity and existence of a comprehensive technical structure for CTO. In a further long-term follow-up evaluation, our data revealed a successful achievement of CTO-related individual- and/or institutional-level outcomes in all but one fellow. Here again, availability of a robust technical structure for CTO (and perhaps fellow affiliation/selection)–but not CT vibrancy–showed a trend of temporal association with achievement of training outcomes.ConclusionGiven the pivotal role operational structures of international standards at home institutions play in translating training-acquired knowledge into measurable CTO-related outcomes, we encourage that capacity strengthening projects aimed at achieving health-related targets of Sustainable Development Goals adopt an approach built on this foundation.