Search

Weichao Li,1,2 YuYan Liu,2 Xunhu Gu1 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Anesthesiology, Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, QingYuan, Guangdong, People’s Republic of ChinaCorrespondence: Xunhu Gu, Doctor of Medicine (MD), Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email 540523118@qq.comBackground: Catecholamine vasopressors are commonly used for intra- or post-operative hypotension for cardiac surgery, which have a side effect of new-onset atrial fibrillation (AF) and myocardial ischemia. However, it is not entirely clear whether catecholamine vasopressors increase the risk of new-onset AF after noncardiac surgery.Aim: The aim of this study was to analyze the association between the use of catecholamine vasopressors and the risk of developing new-onset AF after noncardiac surgery.Methods: In this prospective trial, available data from eligible elderly individuals receiving noncardiac surgery at a single center from November 2022 to January 2024 were gathered. Propensity score matching (PSM) was used to balance patient baseline characteristics and to control for confounders. To determine the association between catecholamine vasopressors and the risk of new-onset AF, univariate and multivariate logistic regression analyses were performed.Results: A total of 6000 subjects were included in this study (mean [SD] age, 70.73 [6.37] years; 910 [50.9%] males). After PSM, the patients were stratified into catecholamine vasopressor (n = 357) and comparator groups (n = 1432). A total of 18/357 patients in the catecholamine vasopressor group developed AF, and 25/1432 patients in the comparator group developed AF (incidence rate, 5.0% vs 1.7%). Compared with the comparator group, the catecholamine vasopressor group had an increased risk of new-onset AF (aOR, 2.77; 95% CI, 1.28– 5.89). Some sensitivity analyses also revealed consistent findings of increased new-onset AF risk associated with catecholamine vasopressor treatment.Conclusion: The findings from this study suggest that catecholamine vasopressor treatment is associated with an increased risk of new-onset AF and may help physicians select a modest medication for patients while also assessing the risk of new-onset AF. Keywords: catecholamine vasopressors, new-onset atrial fibrillation, risk, prospective trial, noncardiac procedures

To determine whether targeted sampling (TS), which omits biopsy of triple- normal lymph nodes (LNs) on positron emission tomography, computed tomography, and endobronchial ultrasound (EBUS), is noninferior to systematic sampling (SS) of mediastinal LNs during EBUS for staging of patients with early-stage non–small cell lung cancer (NSCLC). Patients who are clinical nodal (cN)0-N1 with suspected NSCLC eligible for EBUS based on positron emission tomography/computed tomography were enrolled in this prospective, multicenter trial. During EBUS, all patients underwent TS and then crossed over to SS, whereby at least 3 mediastinal LN stations (4R, 4L, 7) were routinely sampled. Gold standard of comparison was pathologic results. Based on the previous feasibility trial, a noninferiority margin of 6% was established for difference in missed nodal metastasis (MNM) incidence between TS and SS. The McNemar test on paired proportions was used to determine MNM incidence for each sampling method. Analysis was per-protocol using a level of significance of P <.05. Between November 2020 and April 2022, 91 patients were enrolled at 6 high-volume Canadian tertiary care centers. A total of 256 LNs underwent TS and SS. Incidence of MNM was 0.78% in SS and 2.34% in TS, with an absolute difference of 1.56% (95% confidence interval, −0.003% to 4.1%; P =.13). This falls within the noninferiority margin. A total of 6/256 LNs from 4 patients who were not sampled by TS were found to be malignant when sampled by SS. In high-volume thoracic endosonography centers, TS is not inferior to SS in nodal staging of early-stage NSCLC. This results in change of clinical management for a minority of patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited. Aims: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients. Methods and Results: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent’s University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed. Interpretation: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an entity with a growing incidence but only a few pharmacological options. In Romania, the prevalence of MASLD has been increasing, while that of viral hepatitis has been decreasing. The purpose of this study is to compare two supplements for the treatment of MASLD. Methods: Between January 2020 and May 2022, 90 patients with MASLD were randomized to receive either silymarin 150 mg b.i.d (45 subjects) or essential phospholipids (EPLs) 825 mg b.i.d. (45 subjects) for six months. All study participants received recommendations for lifestyle and diet modifications. Assessment of the severity of steatosis and liver fibrosis was performed using FibroScan® with controlled attenuated parameter (CAP) at the beginning and end of treatment. Results: A total of 68 patients completed the trial. The two groups were statistically comparable in terms of clinical, biological and FibroScan® parameters. Aspartate transferase (AST) decreased from a median of 40 to 28 IU/L in the EPL arm (compared to 25→25.5 IU/L in the silymarin arm) (p-value=0.11) and alanine transaminase (ALT) decreased from 46 to 37.5 IU/L (compared to 31→30 IU/L) (p-value = 0.38). Plasma cholesterol levels also decreased significantly in the EPL group (218→189.5 mg/dL) compared to the silymarin arm (217→209 mg/dL) (p = 0.01). At the end of treatment, liver stiffness decreased by 0.7 KPa (6.9→6.2 KPa) in the EPL group but increased by 2.3 KPa (7.2→9.5 KPa) in the silymarin group (p = 0.1). The reduction in hepatic steatosis was comparable between the two groups: it decreased by 5% of the initial value. Conclusion: In our study, a six-month treatment with EPLs was superior to silymarin in MASLD patients because it succeeded in improving both laboratory parameters and liver fibrosis, as estimated by FibroScan®. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex-differentiation and their association with gender-specific factors are limited. Aims: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients. Methods and Results: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent's University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed. Interpretation: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. Findings This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. Conclusions The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr ).

(1) Background: An increasing amount of research has supported the role of radiomics for predicting pathological complete response (pCR) to neoadjuvant chemoradiation treatment (nCRT) in order to provide better management of locally advanced rectal cancer (LARC) patients. However, the lack of validation from prospective trials has hindered the clinical adoption of such studies. The purpose of this study is to validate a radiomics model for pCR assessment in a prospective trial to provide informative insight into radiomics validation. (2) Methods: This study involved a retrospective cohort of 147 consecutive patients for the development/validation of a radiomics model, and a prospective cohort of 77 patients from two institutions to test its generalization. The model was constructed using T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI to understand the associations with pCR. The consistency of physicians' evaluations and agreement on pathological complete response prediction were also evaluated, with and without the aid of the radiomics model. (3) Results: The radiomics model outperformed both physicians' visual assessments in the prospective test cohort, with an area under the curve (AUC) of 0.84 (95% confidence interval of 0.70–0.94). With the aid of the radiomics model, a junior physician could achieve comparable performance as a senior oncologist. (4) Conclusion: We have built and validated a radiomics model with pretreatment MRI for pCR prediction of LARC patients undergoing nCRT. [ABSTRACT FROM AUTHOR]

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment. [ABSTRACT FROM AUTHOR]

Abstract Background JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015. Methods Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. Results The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less). Conclusions The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

Dog owners are more physically active than non-dog owners, but evidence of a causal relationship between dog acquisition and increased physical activity is lacking. Such evidence could inform programs and policies that encourage responsible dog ownership. Randomized controlled trials are the 'gold standard' for determining causation, but they are prohibited in this area due to ethical concerns. In the BuddyStudy, we tested the feasibility of using dog fostering as a proxy for dog acquisition, which would allow ethical random assignment. In this single-arm trial, 11 participants fostered a rescue dog for six weeks. Physical activity and psychosocial data were collected at baseline, 6, and 12 weeks. At 6 weeks, mean change in steps/day was 1192.1 ± 2457.8. Mean changes on the Center for Epidemiologic Studies Depression Scale and the Perceived Stress Scale were -4.9 ± 8.7 and -0.8 ± 5.5, respectively. More than half of participants (55%) reported meeting someone new in their neighborhood because of their foster dog. Eight participants (73%) adopted their foster dog after the 6-week foster period; some maintained improvements in physical activity and well-being at 12 weeks. Given the demonstrated feasibility and preliminary findings of the BuddyStudy, a randomized trial of immediate versus delayed dog fostering is warranted.

Objective: Irreversible electroporation (IRE) is a nonthermal ablation technique for the treatment of malignant liver tumors. IRE has demonstrated efficacy and safety in the treatment of malignant liver tumors and its unique advantages in the treatment of nearby vascular lesions. This study aimed to compare the efficacy, safety, and intermediate-term outcomes of IRE and radiofrequency (RF) therapy in malignant liver tumors. Methods: Twenty-four patients with primary or secondary liver malignancies were included in this prospective, double-arm clinical trial. Patients were randomly divided into the IRE and RF groups. The primary outcome was the efficacy (local ablation control evaluation at 90 days). The secondary outcomes were safety (procedure-related complications at ​≤ ​90 days) and intermediate-term survival (at 24 months). Results: The ablation assessment at 90 days after surgery with mRECIST for IRE versus RF were 70%, 20%, 0%, and 10% versus 92.9%, 7.1%, 0%, and 0% (CR, PR, SD, and PD, respectively). The complication rates of IRE versus RF with Clavien-Dindo classification were 16.7%, 25%, 0%, 8.3%, and 8.3% versus 8.3%, 50%, 0%, 0%, and 0% (Grade I, II, III, IV, and V, respectively). The average overall survival (OS) was 17.55 months in the IRE group (95% CI 15.13-22.37) and 18.75 months in the RF group (95% CI 12.48-22.61). There was no statistical difference between the IRE and RF groups in terms of efficacy (p ​= ​0.48), safety(p ​= ​0.887), or 24-month OS (p ​= ​0.959). Conclusions: IRE ablation revealed similar efficacy and safety in a short-term follow-up, and similar OS in mid-term survival as RF ablation in treating malignant hepatic tumors.

Background: Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. Findings: This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. Conclusions: The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 (https://cris.nih.go.kr). [ABSTRACT FROM AUTHOR]

Introduction: Indications for reverse shoulder arthroplasties (rTSA) have increased since their development by Paul Grammont in 1985. Prosthesis design was enhanced over time, but the management of the tendon of the M. subscapularis (SSC-tendon) in primary rTSA is still a controversial subject with regard to perform a refixation or not. Methods: 50 patients were randomized in a refixation group (A) and a non-refixation-group (B) of the SSC-tendon in a double-blinded fashion. SSC-function was assessed at baseline before surgery, such as 3 and 12 months after surgery. Constant–Murley-Shoulder Score (CS), American Shoulder and Elbow Surgeons Score (ASES), strength, range of motion (ROM), and pain on numeric rating scale (NRS) were measured in all examinations. An ultrasound examination of the shoulder was performed for evaluation of subscapularis tendon integrity at 3 and 12 month follow-up visits. Pain was evaluated on NRS via phone 5 days after surgery. Surgery was performed by a single experienced senior surgeon in all patients. Results: Patients with a refixation of the SSC-tendon and primary rTSA had improved internal rotation [40° (20°–60°) vs. 32° (20°–45°); p = 0.03] at 12 months of follow-up. Additionally, the A-group had increased CS [74 (13–90) vs. 69.5 (40–79); p = 0.029] 1 year after surgery. Results were strengthened by subgroup analysis of successful refixation in ultrasound examination vs. no refixation. No differences were seen in ASES and NRS 1 year after rTSA. Conclusion: SSC-tendon repair in rTSA improves CS and internal rotation 12 months after surgery. [ABSTRACT FROM AUTHOR]

Guidelines for anticoagulation in patients with atrial fibrillation (AF) aim to decrease the risk of ischemic stroke. However, there is a gap in actual practice between patients who have an indication for anticoagulation and those who are actually prescribed anticoagulation. We sought to evaluate the efficacy of prior population-based interventions aimed at decreasing this AF anticoagulation gap. This study was prospectively registered in the International Prospective Register of Systematic Reviews database (CRD42021287875). A systematic literature review was conducted to obtain all prospective individually randomized and cluster randomized trials by searching 4 electronic databases: PubMed, Google Scholar, Web of Science, and Medline. After a review of 1474 studies, 20 trials were included in this systematic literature review. Forty-five percent were effective in decreasing the AF anticoagulation gap. Trial interventions that improved anticoagulation prescribing included 6 trials of electronic risk assessment or decision support, 1 trial of provider education, 2 trials of new protocol or pathway, and 2 trials of patient education. Six of 15 ambulatory trials, 2 of 4 inpatient trials, and 1 trial that spanned inpatient and outpatient settings improved anticoagulation prescribing rates. Interventions focused on patient education, provider education, and electronic risk assessment or decision support increased absolute appropriate anticoagulation prescribing by 8.3%, 4.9%, and 2.0%, respectively. Interventions aimed at improving anticoagulation prescribing patterns in AF can be effective, although there is heterogeneity in outcomes across intervention type. The most effective interventions appeared to target patient education, provider education, and electronic risk assessment or decision support. [ABSTRACT FROM AUTHOR]

Objective: To explore the difference in effectiveness between a dynamic rehabilitation protocol and a traditional static rehabilitation protocol after the treatment of acute Achilles tendon rupture with channel assisted minimally invasive repair (CAMIR) technique through a prospective comparative trial, aiming to provide a reference for clinically selecting a feasible treatment regimen., Methods: Patients with acute Achilles tendon rupture admitted between June 2021 and June 2022 were included in the study, with 60 patients meeting the selection criteria. They were randomly divided into a dynamic rehabilitation group ( n =30) and a static rehabilitation group ( n =30) using a computer-generated random number method. There was no significant difference in baseline data such as gender, age, body mass index, smoking history, injured side, cause of injury, and disease duration between the two groups ( P >0.05). After Achilles tendon anastomosis by using CAMIR technique, the dynamic rehabilitation group implemented early partial weight-bearing training with the assistance of an Achilles heel boot and controlled ankle joint exercises for 6 weeks, while the static rehabilitation group maintained a non-weight-bearing status during this period. Complications in both groups were recorded. At 3 and 6 months after operation, the Achilles tendon total rupture score (ATRS) was used to evaluate the degree of functional limitation of the Achilles tendon in the affected limb, and the 12-Item Short Form Health Survey (SF-12 scale) was used to assess the patients' quality of life, including physical component summary (PCS) and mental component summary (MCS) scores., Results: No sural nerve injury occurred during operation in both groups. All patients were followed up 12-18 months (mean, 14 months). The dynamic rehabilitation group had significantly higher ATRS scores at 3 and 6 months after operation compared to the static rehabilitation group ( P <0.05). At 3 months after operation, the dynamic rehabilitation group had significantly lower PCS, MCS, and SF-12 total scores compared to the static rehabilitation group ( P <0.05). At 6 months, all quality of life scores in the two groups were similar ( P >0.05). Two cases (6.6%) in the dynamic rehabilitation group and 5 cases (16.7%) in the static rehabilitation group developed complications, with no significant difference in incidence of complications ( P >0.05)., Conclusion: For acute Achilles tendon rupture, the dynamic rehabilitation protocol after Achilles tendon anastomosis by using CAMIR technique can improve early functional recovery and maintains comparable safety and effectiveness compared to static rehabilitation.

Background: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015.Methods: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities.Results: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less).Conclusions: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the safety and efficacy of a novel therapeutic strategy, a microneedle fractional radiofrequency system, for hand rejuvenation. Material and Method: Sixteen subjects were enrolled in a self‐controlled evaluator‐blind prospective trial. All subjects received three microneedle fractional radiofrequency treatments at 4 weeks intervals. Hand volume was evaluated through subjective (Hand Volume Rating Scale) and quantitative measurements. Patients were also assessed on the Global Aesthetic Improvement Scale using digital photographs. Patients were followed up at 1, 3, and 6 months after the last radiofrequency treatment. Results: Statistically significant improvements on the Global Aesthetic Improvement Scale and Hand Rating Volume Scale were noted (p < 0.05). Compared with the control side, the treated hand showed a 44% improvement in dorsal skin surface roughness (p < 0.05). Quantitative measurements of hand volume showed a trend toward increased volume for the treated hand, but the difference was not statistically significant. Conclusion: We conclude that microneedle fractional radiofrequency is a safe therapeutic option for hand rejuvenation. [ABSTRACT FROM AUTHOR]

BackgroundBipolar disorder is a serious and common psychiatric disorder characterized by manic and depressive mood switches and a relapsing and remitting course. The cornerstone of clinical management is stabilization and prophylaxis using mood-stabilizing medications to reduce both manic and depressive symptoms. Lithium remains the gold standard of treatment with the strongest data for both efficacy and suicide prevention. However, many patients do not respond to this medication, and clinically there is a great need for tools to aid the clinician in selecting the correct treatment. Large genome wide association studies (GWAS) investigating retrospectively the effect of lithium response are in the pipeline; however, few large prospective studies on genetic predictors to of lithium response have yet been conducted. The purpose of this project is to identify genes that are associated with lithium response in a large prospective cohort of bipolar patients and to better understand the mechanism of action of lithium and the variation in the genome that influences clinical response.Methods/designThis study is an 11-site prospective non-randomized open trial of lithium designed to ascertain a cohort of 700 subjects with bipolar I disorder who experience protocol-defined relapse prevention as a result of treatment with lithium monotherapy. All patients will be diagnosed using the Diagnostic Interview for Genetic Studies (DIGS) and will then enter a 2-year follow-up period on lithium monotherapy if and when they exhibit a score of 1 (normal, not ill), 2 (minimally ill) or 3 (mildly ill) on the Clinical Global Impressions of Severity Scale for Bipolar Disorder (CGI-S-BP Overall Bipolar Illness) for 4 of the 5 preceding weeks. Lithium will be titrated as clinically appropriate, not to exceed serum levels of 1.2 mEq/L. The sample will be evaluated longitudinally using a wide range of clinical scales, cognitive assessments and laboratory tests. On relapse, patients will be discontinued or crossed-over to treatment with valproic acid (VPA) or treatment as usual (TAU). Relapse is defined as a DSM-IV manic, major depressive or mixed episode or if the treating physician decides a change in medication is clinically necessary. The sample will be genotyped for GWAS. The outcome for lithium response will be analyzed as a time to event, where the event is defined as clinical relapse, using a Cox Proportional Hazards model. Positive single nucleotide polymorphisms (SNPs) from past genetic retrospective studies of lithium response, the Consortium on Lithium Genetics (ConLiGen), will be tested in this prospective study sample; a meta-analysis of these samples will then be performed. Finally, neurons will be derived from pluripotent stem cells from lithium responders and non-responders and tested in vivo for response to lithium by gene expression studies. SNPs in genes identified in these cellular studies will also be tested for association to response.DiscussionLithium is an extraordinarily important therapeutic drug in the clinical management of patients suffering from bipolar disorder. However, a significant proportion of patients, 30-40 %, fail to respond, and there is currently no method to identify the good lithium responders before initiation of treatment. Converging evidence suggests that genetic factors play a strong role in the variation of response to lithium, but only a few genes have been tested and the samples have largely been retrospective or quite small. The current study will collect an entirely unique sample of 700 patients with bipolar disorder to be stabilized on lithium monotherapy and followed for up to 2 years. This study will produce useful information to improve the understanding of the mechanism of action of lithium and will add to the development of a method to predict individual response to lithium, thereby accelerating recovery and reducing suffering and cost.Trial registrationClinicalTrials.gov Identifier: NCT01272531 Registered: January 6, 2011.

Background: The coronavirus SARS-CoV-2 is highly contagious. Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2. The FDA authorized emergency use of HCQ against COVID-19. HCQ may have dose-related cardiotoxicity. This clinical trial received ethical approval on May 15, 2020, operationalized in June to evaluate a low prophylaxis dose of HCQ (200mg BID) in household contacts of COVID-19-positive patients without physical contact between investigators and participants. It represents the first report of the FDA approved 6-lead EKGs with a smartphone KardiaMobile® 6L application. Methods: To reach a sample size of 170, household members were contacted by telephone, emailed consent forms with electronic signature capability, and randomized 2:1 to HCQ or observation for 10 days with follow-up of 14 days. Home saliva PCR tests recorded COVID status on days 1 and 14. Symptoms and 6-lead EKGs were obtained daily. Results: Fifty-one participants were randomized with 42 evaluable at day 14. Remote monitoring of 407 EKGs revealed no QTc prolongation or other ECG changes in either group. At time of consent, no participants were symptomatic or COVID+. On days 1 and 14, COVID tests were positive in 4 and 2 in the HCQ group and 4 and 0 in the observation group. No tests converted to positive. There were no deaths or hospitalizations. Conclusions: A clinical trial without personal contact, rapidly initiated and operationalized to exclude cardiac toxicity using daily remote 6-lead EKG monitoring, is feasible. Of 407 EKGs from 42 participants, there was no evidence of cardiac toxicity. Clinical trial registration: Clinicaltrials.gov: NCT04652648 registration date: December 3, 2020 [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the effects of electromagnetic waves generated by a commercial medical electromagnetic instrument (trade name, TDP, the Chinese phonetic abbreviation of “Te-ding Dian-ci-bo Pu”) as an adjuvant to improve the rate of increase of milk feeds per day by premature infants with necrotizing enterocolitis (NEC).MethodsThis study was a prospective randomized clinical trial. A total of 103 premature infants were diagnosed with NEC II, but there was no need for surgery. The infants were randomly divided into the TDP intervention group and the control group by a randomized method using SPSS 24.0. The patients in the TDP intervention group were treated with TDP irradiation and routine interventions; those in the control group were treated with routine interventions. The rate of increase of milk feeds per day, the time to achieve total gastrointestinal nutrition, the velocity of weight gain, and the complication incidence rate were recorded and compared.ResultsThe rate of increase of milk feeds per day in the TDP intervention group was significantly greater than that in the control group [14.51 (11.58~22.11) ml/kg/d vs. 10.15 (6.15~15.87) ml/kg/d, P = 0.002]. Compared to the control group, the time to achieve total gastrointestinal nutrition (21.45 ± 1.87 d vs. 36.43 ± 2.585 d, P = 0.000) and the velocity of weight gain (19.65 ± 15.27% vs. 13.68 ± 7.15%, P = 0.013) in the TDP intervention group were substantially better than those in the control group. The complication incidence rate was not significantly different between the two groups (P > 0.05).ConclusionTreatment with TDP-generated electromagnetic waves improved the volume of milk consumed per day in premature infants with NEC II and were conducive to improving their clinical outcomes.

Optimal therapeutic strategy in low advanced papillary thyroid carcinoma (PTC) is still a matter of debate. The management differs depending on the country.A prospective non-randomized study was performed to evaluate whether less extensive surgery could be a safe, acceptable, and sufficient therapeutic option in PTC cT1N0M0 patients. The present paper summarizes the results of over a 5-year follow-upMaterialOur prospective group (PG) treated between 2011 and 2015 consisted of 139 patients with cT1aN0M0 PTC who underwent lobectomy (LT) as initial surgical treatment (PGcT1aN0M0 group) and 102 cT1bN0M0 patients in whom total thyroidectomy (TT) with unilateral central neck dissection (CND) was performed (PGcT1bN0M0). PG was compared with the retrospective group (RG) of patients who underwent TT with bilateral CND between 2004 and 2006: 103 cT1aN0M0 patients (RGcT1aN0M0) and 91cT1bN0M0 (RGcT1bN0M0). The risks of reoperation, cancer relapse and postoperative complications were analyzed.ResultsOnly 12 cT1aN0M0 patients (7.6%) withdrew from the trial and underwent TT with bilateral CND. Over 90% of patients accepted less extensive surgery. In 4 cT1aN0M0 cases, TT with CND was performed due to lymph node metastases found intraoperatively. The initial clinical stage according to the TNM/AJCC 7th edition was confirmed histologically in 77% of cases in PGT1aN0M0 and in 72% in PGT1bN0M0, respectively. 24 PGcT1aN0M0 patients were reoperated on. In this group, cancer lesions in the postoperative histological specimens were found in 8 cases (32%). Five-year disease-free survival (DFS) was excellent. However, no statistically significant differences were found between PG and RG groups (99.3% in PGcT1aN0M0 and 99.0%, in RGcT1aN0M0; p = 0.41 and 98%, in PGcT1bN0M0 and 94.4% in RGcT1bN0M0; p=0.19). No significant differences were observed in the incidence of early paresis of the recurrent laryngeal nerves between PG and RG. However, as predicted, LT completely eliminated the risk of postoperative hypoparathyroidism.SummaryThe results of the prospective clinical trial confirm that less extensive surgery in adequately selected low-advanced PTC patients is both safe and sufficient.

Optimal therapeutic strategy in low advanced papillary thyroid carcinoma (PTC) is still a matter of debate. The management differs depending on the country. A prospective non-randomized study was performed to evaluate whether less extensive surgery could be a safe, acceptable, and sufficient therapeutic option in PTC cT1N0M0 patients. The present paper summarizes the results of over a 5-year follow-up Material: Our prospective group (PG) treated between 2011 and 2015 consisted of 139 patients with cT1aN0M0 PTC who underwent lobectomy (LT) as initial surgical treatment (PGcT1aN0M0 group) and 102 cT1bN0M0 patients in whom total thyroidectomy (TT) with unilateral central neck dissection (CND) was performed (PGcT1bN0M0). PG was compared with the retrospective group (RG) of patients who underwent TT with bilateral CND between 2004 and 2006: 103 cT1aN0M0 patients (RGcT1aN0M0) and 91cT1bN0M0 (RGcT1bN0M0). The risks of reoperation, cancer relapse and postoperative complications were analyzed. Results: Only 12 cT1aN0M0 patients (7.6%) withdrew from the trial and underwent TT with bilateral CND. Over 90% of patients accepted less extensive surgery. In 4 cT1aN0M0 cases, TT with CND was performed due to lymph node metastases found intraoperatively. The initial clinical stage according to the TNM/AJCC 7th edition was confirmed histologically in 77% of cases in PGT1aN0M0 and in 72% in PGT1bN0M0, respectively. 24 PGcT1aN0M0 patients were reoperated on. In this group, cancer lesions in the postoperative histological specimens were found in 8 cases (32%). Five-year disease-free survival (DFS) was excellent. However, no statistically significant differences were found between PG and RG groups (99.3% in PGcT1aN0M0 and 99.0%, in RGcT1aN0M0; p = 0.41 and 98%, in PGcT1bN0M0 and 94.4% in RGcT1bN0M0; p=0.19). No significant differences were observed in the incidence of early paresis of the recurrent laryngeal nerves between PG and RG. However, as predicted, LT completely eliminated the risk of postoperative hypoparathyroidism. Summary: The results of the prospective clinical trial confirm that less extensive surgery in adequately selected low-advanced PTC patients is both safe and sufficient. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in China with a reported prevalence of 8.2% people aged ≥40 years. It is recommended that Chinese physicians follow Global Initiative for Chronic Obstructive Lung Disease (GOLD) and national guidelines, yet many patients with COPD in China remain undiagnosed. Furthermore, missed diagnoses and a lack of standardized diagnosis and treatment remain significant problems. The situation is further complicated by a lack of large-scale, long-term, prospective studies of real-world outcomes, including exacerbation rates, disease severity, efficacy of treatment, and compliance of COPD patients in China. Methods/design The REALizing and improving management of stable COPD in China (REAL) study is a 52-week multi-center, prospective, observational trial. REAL aims to recruit approximately 5000 outpatients aged ≥40 years with a clinical diagnosis of COPD per GOLD 2016. Outpatients will be consecutively recruited from approximately 50 tertiary and secondary hospitals randomly selected across six geographic regions to provide a representative population. Patients will receive conventional medical care as determined by their treating physicians. The primary objective is to evaluate COPD patient outcomes including lung function, health status, exacerbations, hospitalization rate, and dyspnea following 1 year of current clinical practice. Secondary objectives are to assess disease severity, treatment patterns, adherence to medication, and associated risk factors. Data will be collected at two study visits, at patients’ usual care visits, and by telephone interview every 3 months. Discussion Knowledge of COPD among physicians in China is poor. The REAL study will provide reliable information on COPD management, outcomes, and risk factors that may help improve the standard of care in China. Patient recruitment began on 30 June 2017 and the estimated primary completion date is 30 July 2019. Trial registration ClinicalTrials.gov identifier: NCT03131362. Registered on 20 March 2017.

• Combined ion-beam radiotherapy for osteosarcoma is a novel local therapeutic approach • Despite unfavorable size/localization toxicity was moderate/local control promising • FDG PET might serve as a surrogate for grading histopathologic regression in future. To investigate the role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma; final analysis of a one-armed, single center phase I/II trial. Between August 2011 until September 2018, 20 patients with primary (N = 18), metastatic (N = 3), or recurrent (N = 2) inoperable pelvic (70%) or craniofacial (30%) osteosarcoma were treated with protons up to 54 Gy (RBE) and a carbon ion boost of 18 Gy (RBE) and followed until May 2019. A Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before CIBRT in search for a prognostic factor. The primary endpoint was toxicity. Secondary endpoints included treatment response, global, local and distant progression free survival (PFS, LPFS and DPFS) and overall (OS), among others. The median age was 20; all patients finished treatment per protocol. LPFS, DPFS, PFS and OS were 73%, 74%, 60% and 75% after one year and 55%, 65% 65.3%, 45% and 68% after two years, respectively. The median clinical target volume (CTV) was 1042 cc and 415 cc for the primary and boost plan, respectively. Craniofacial localization, lower uptake of FDG in PET/CT and boost plan CTV ≤ median were associated with improved overall survival (p = 0.039, p = 0.016 and p = 0.0043, respectively). No acute toxicities > grade III were observed. We observed one case of secondary acute myeloid leukemia (AML) seven months after CIBRT for recurrent disease and one case of hearing loss. CIBRT shows a favorable toxicity profile and promising results particularly for patients with inoperable craniofacial osteosarcoma. [ABSTRACT FROM AUTHOR]

Clofarabine has been shown to effectively induce remission in children with refractory leukemia. We conducted a prospective trial (clinicval.trials.gov NCT01025778) to explore the use of clofarabine-based chemotherapy as a bridge-to-transplant approach. Children with refractory acute leukemia were enrolled to receive two induction courses of clofarabine, etoposide, and cyclophosphamide (CloEC). Responding patients were scheduled for T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). The primary objective was to improve survival by achieving sufficient disease control to enable stem cell transplantation. Secondary objectives were to evaluate safety and toxicity. Seven children with active disease entered the study. Two children responded to induction courses and underwent transplantation. Five children did not respond to induction: one died in progression after the first course; two received off-protocol chemotherapy and were transplanted; and two succumbed to progressive leukemia. All transplanted children engrafted and no acute skin graft-versus-host disease > grade I was observed. One child is alive and well 7.5 years after the first CloEC course. One child developed fulminant adenovirus hepatitis and died in continuous complete remission 7 months after start of induction. Two children relapsed and died 6.5 and 7.5 months after enrollment. Infection was the most common toxicity. CloEC can induce responses in some patients with refractory acute leukemia but is highly immunosuppressive, resulting in substantial risk of life-threatening infections. In our study, haploidentical HSCT was feasible with sustained engraftment. No clinically significant organ toxicity was observed. Also, repeating CloEC probably does not increase the chance of achieving remission. [ABSTRACT FROM AUTHOR]

Among patients with brain metastases, hippocampal avoidance whole brain radiation (HA-WBRT) preserves neurocognitive function relative to conventional WBRT but the feasibility of hippocampal sparing in patients with metastases in/near the hippocampus is unknown. We identified the incidence of hippocampal/perihippocampal metastases and evaluated the feasibility of HA-WBRT in such patients. Dosimetric data from 34 patients randomized to HA-WBRT (30 Gy/10 fractions) in a phase III trial (NCT03075072) comparing HA-WBRT to stereotactic radiation in patients with 5 to 20 brain metastases were analyzed. Patients with metastases in/near the hippocampi received HA-WBRT with prioritization of tumor coverage over hippocampal avoidance. Target coverage and hippocampal sparing metrics were compared between patients with targets in/near the hippocampus versus not. In total, 9 of 34 (26%) patients had targets in the hippocampus and an additional 5 of 34 (15%) patients had targets in the hippocampal avoidance zone (HAZ, hippocampus plus 5 mm expansion) but outside the hippocampus. Patients with targets within the hippocampus and those with targets in the HAZ but outside the hippocampus were spared 34% and 73% of the ipsilateral mean biologically equivalent prescription dose, respectively. Of the latter cohort, 88% and 25% met conventional hippocampal sparing metrics of Dmin ≤ 9 Gy and Dmax ≤ 16 Gy, respectively. Among 11 patients with unilateral hippocampal/perihippocampal involvement, the uninvolved/contralateral hippocampus was limited to Dmin ≤ 9 Gy and Dmax ≤ 17 Gy in all cases. In this study, a substantial percentage of patients with 5 to 20 brain metastases harbored metastases in/near the hippocampus. In such cases, minimizing hippocampal dose while providing tumor coverage was feasible and may translate to neurocognitive protection. [ABSTRACT FROM AUTHOR]

The article offers information associated with breast cancer-related lymphedema (BCRL) which affects more than one in five women treated for breast cancer. Topics discussed include treatment of BCRL with an impairment-based model wherein patients were diagnosed and treated for BCRL, objective measurements like patient symptomatology and clinical evaluation from BRCL diagnosis, and role of screening and early intervention in cancer treatment.

Purpose: The German Classification of Diverticular Disease was introduced a few years ago. The aim of this study was to determine whether Classification of Diverticular Disease enables an exact stratification of different types of diverticular disease in terms of course and treatment. Methods: This was a prospective, bicentric observational trial. Patients aged ≥ 18 years with diverticular disease were prospectively included. The primary endpoint was the rate of recurrence within 2 year follow-up. Secondary outcome measures were Gastrointestinal Quality of Life Index, Quality of life measured by SF-36, frequency of gastrointestinal complaints, and postoperative complications. Results: A total of 172 patients were included. After conservative management, 40% of patients required surgery for recurrence in type 1b vs. 80% in type 2a/b (p = 0.04). Sixty percent of patients with type 2a (micro-abscess) were in need of surgery for recurrence vs. 100% of patients with type 2b (macro-abscess) (p = 0.11). Patients with type 2a reached 123 ± 15 points in the Gastrointestinal Quality of Life Index compared with 111 ± 14 in type 2b (p = 0.05) and higher scores in the "Mental Component Summary" scale of SF-36 (52 ± 10 vs. 43 ± 13; p = 0.04). Patients with recurrent diverticulitis without complications (type 3b) had less often painful constipation (30% vs. 73%; p = 0.006) when they were operated compared with conservative treatment. Conclusion: Differentiation into type 2a and 2b based on abscess size seems reasonable as patients with type 2b required surgery while patients with type 2a may be treated conservatively. Sigmoid colectomy in patients with type 3b seems to have gastrointestinal complaints during long-term follow-up. Trial registration: https://www.drks.de ID: DRKS00005576 [ABSTRACT FROM AUTHOR]

• We conducted a prospective trial of haploidentical hematopoietic stem cell transplantation for nonmalignant diseases. • Post-transplantation cyclophosphamide and low-dose antithymocyte globulin were used as graft-versus-host disease (GVHD) prophylaxis. • All 6 patients achieved engraftment, and none developed severe GVHD. • All patients had sustained full donor chimerism without chronic GVHD. Allogeneic hematopoietic stem cell transplantation (HSCT) is performed as a curative treatment for children with nonmalignant diseases, such as bone marrow failure syndromes and primary immunodeficiencies. Because graft-versus-host-disease (GVHD) is a major factor affecting survival probability and quality of life after HSCT, the availability of HLA-matched donors restricts the application of HSCT. Recently, HSCT with post-transplantation cyclophosphamide (PTCy) has emerged as a potent method to prevent GVHD after HSCT from HLA-haploidentical donors, and some studies have suggested the safety of PTCy-HSCT for nonmalignant diseases. We conducted a prospective clinical trial aiming to help confirm the safety of HSCT and further reduction of GVHD using a combination of PTCy and low-dose antithymocyte globulin (ATG) from HLA-mismatched related donors for children with nonmalignant diseases. Six patients underwent HSCT and achieved engraftment at a median of 14.5 days, and no patient developed severe acute GVHD. All patients had sustained donor chimerism without developing chronic GVHD at the last follow-up. In conclusion, HSCT with PTCy and low-dose ATG from an HLA-mismatched related donor were feasible to control GVHD for nonmalignant diseases in the children involved in our study. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. [ABSTRACT FROM AUTHOR]

ObjectiveThe goal was to determine the impact of a community-wide educational intervention on parental misconceptions likely contributing to pediatric antibiotic overprescribing.MethodsWe conducted a cluster-randomized trial of a 3-year, community-wide, educational intervention directed at parents of children < 6 years of age in 16 Massachusetts communities to improve parental antibiotic knowledge and attitudes and to decrease unnecessary prescribing. Parents in 8 intervention communities were mailed educational newsletters and exposed to educational materials during visits to local pediatric providers, pharmacies, and child care centers. We compared responses from mailed surveys in 2000 (before the intervention) and 2003 (after the intervention) for parents in intervention and control communities. Analyses were performed on the individual level, clustered according to community.ResultsThere were 1106 (46%) and 2071 (40%) respondents to the 2000 and 2003 surveys, respectively. Between 2000 and 2003, the proportion of parents who answered > or = 7 of 10 knowledge questions correctly increased significantly in both intervention (from 52% to 64%) and control (from 54% to 61%) communities. We did not detect a significant intervention impact on knowledge regarding appropriate antibiotic use in the population overall. In a subanalysis, we did observe a significant intervention effect among parents of Medicaid-insured children, who began with lower baseline knowledge scores.ConclusionsAlthough knowledge regarding appropriate use of antibiotics is improving without additional targeted intervention among more socially advantaged populations, parents of Medicaid-insured children may benefit from educational interventions to promote judicious antibiotic use. These findings may have implications for other health education campaigns.

Background: In 2016 we published a phase II study exploring safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) delivered with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams techniques in prostate cancer (PC) patients. We present herein the updated results on late toxicity and long-term survival., Methods: Patients enrolled in the study had a biopsy-confirmed localized PC and the features of a low- or intermediate-risk disease (National Comprehensive Network Criteria). The radiotherapy (RT) schedule consisted of 35 Gy delivered in five fractions every other day. Toxicities were registered according to the common toxicity adverse events v4.0. Biochemical recurrence was defined as an increase of prostate specific antigen after nadir, confirmed at least once. Local recurrence (LR) and distant metastases were detected either with Choline- or PSMA-PET/CT scans. Kaplan-Meier curves for Biochemical Recurrence-Free Survival (BFS), Local Control (LC), Distant Metastasis Free Survival (DMFS) and Cancer Specific Survival, were calculated by using MedCalc., Results: Ninety patients were submitted to SBRT between February 2012 and March 2015. Fifty-eight patients (64.5%) had a Gleason Score of 6, while 32 (35.5%) had a Gleason Score of 7. A late grade 1 Genito-Urinary toxicity was observed in 54.5% of patients while a grade 2 in 3.3%. A late Gastro-intestinal grade 1 toxicity was reported in 18.9% of patients, while a grade 2 in 2.2%. Erectile dysfunction was reported by 13% of patients No heavier toxicities were observed. At a median follow-up of 102 months, 5- and 8-year BFS were 93.0% and 84.4% respectively, 5- and 8-year LC were 95.2% and 87.0% respectively, 5- and 8-year DMFS were 95.3% and 88.4%, respectively., Conclusions: This long-term update confirms that SBRT is a valid therapeutic strategy for low-intermediate risk PC. RT with VMAT and FFF warrants optimal results in terms of toxicity and disease control., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in China with a reported prevalence of 8.2% people aged ≥40 years. It is recommended that Chinese physicians follow Global Initiative for Chronic Obstructive Lung Disease (GOLD) and national guidelines, yet many patients with COPD in China remain undiagnosed. Furthermore, missed diagnoses and a lack of standardized diagnosis and treatment remain significant problems. The situation is further complicated by a lack of large-scale, long-term, prospective studies of real-world outcomes, including exacerbation rates, disease severity, efficacy of treatment, and compliance of COPD patients in China.Methods/design: The REALizing and improving management of stable COPD in China (REAL) study is a 52-week multi-center, prospective, observational trial. REAL aims to recruit approximately 5000 outpatients aged ≥40 years with a clinical diagnosis of COPD per GOLD 2016. Outpatients will be consecutively recruited from approximately 50 tertiary and secondary hospitals randomly selected across six geographic regions to provide a representative population. Patients will receive conventional medical care as determined by their treating physicians. The primary objective is to evaluate COPD patient outcomes including lung function, health status, exacerbations, hospitalization rate, and dyspnea following 1 year of current clinical practice. Secondary objectives are to assess disease severity, treatment patterns, adherence to medication, and associated risk factors. Data will be collected at two study visits, at patients' usual care visits, and by telephone interview every 3 months.Discussion: Knowledge of COPD among physicians in China is poor. The REAL study will provide reliable information on COPD management, outcomes, and risk factors that may help improve the standard of care in China. Patient recruitment began on 30 June 2017 and the estimated primary completion date is 30 July 2019.Trial Registration: ClinicalTrials.gov identifier: NCT03131362. Registered on 20 March 2017. [ABSTRACT FROM AUTHOR]

Introduction: Transurethral resection of the prostate (TURP) by resection loop or vaporization button is becoming a standard of care due to its better safety profile (less bleeding and less incidence of TUR syndrome). However, there are published data showing bipolar vaporization may be associated with increased late complications. In this study, we compared results of bipolar TURP using the resection loop versus vaporization button for treatment of benign prostatic hyperplasia (BPH) to determine the relative safety profile. Patients and methods: Between January 2013 and March 2014, 89 patients with BPH were randomized to surgical intervention either by Olympus (Gyrus) Bipolar loop TURP or Olympus (Gyrus) Bipolar button vaporization. Inclusion criteria were; BPH with Q-max < 10 ml/s, IPSS > 18 and prostate volume > 40 g. All patients were evaluated preoperatively and at 1, 3 and 9 months. Evaluation included IPSS, uroflowmetry, prostate volume by ultrasound. Clavien complications and operative time were recorded. Statistical analysis was done using Statistical Package of Social Science (SPSS) version 17 software. Results: 44 patients were included in bipolar TURP and 45 patients in vaporization arm. Preoperative mean prostate volume (59 g versus 58 g, p = 0.52) and mean IPSS (19 versus 20, p = 0.38) were equivalent in both groups. Vaporization was associated with a significant increase in operative time (mean of 81 ± 15 min range 40–110 versus 55 ± 10 min range 30–70 min, p < 0.001), less blood loss (0.8% versus 2.0% drop in hemoglobin, p < 0.001) but increased postoperative urinary frequency (80% versus 50%, p < 0.001), hematuria with clots up to 4 weeks post surgery (20% versus 2%, p < 0.001) and postoperative urethral stricture (11% versus 0%, p < 0.001). Both techniques improved urine flow with Q-max (17 ml/s versus 18 ml/s p = 0.22). Prostate volume (32 g versus 31 g, p = 0.31) and IPSS (6 versus 5, p = 0.22), were comparable in both treatment arms. Conclusions: Bipolar vaporization of the prostate, despite being a technically robust, speedy and with less intraoperative bleeding, appears to be associated with increased postoperative irritative symptoms, increased late-onset postoperative bleeding and high urethral stricture rates. [ABSTRACT FROM AUTHOR]

Introduction: Kyphoplasty is an established method of treating osteoporotic vertebral body compression fractures. In recent years, several techniques to enhance the efficiency and outcomes of this surgery have been developed and implemented in clinical practice. In the present study, we assess the impact of two new access instruments on overall operation time and the administered dose area product in comparison with the standard access instrument used in our clinical practice. The two newer comparator devices have been designed with the intention of streamlining intraoperative workflow by omitting several procedural steps.Materials and Methods: This was a single-center prospective randomized trial investigating three distinct access instruments compatible with the Joline Allevo balloon catheter system. Specifically, two newer access devices marketed as being able to enhance surgical workflow (Joline RapidIntro Vertebra Access Device with a trocar tip and Joline SpeedTrack Vertebra Introducer Device with a short, tapered tip) were compared with the older, established Joline Vertebra Access Device from the same firm. Consecutive eligible and consenting patients scheduled to undergo kyphoplasty for osteoporotic vertebral compression fracture refractory to conservative, medical treatment during the period May 2012-August 2015 were randomized to receive surgery using one of the three devices. Besides the use of the trial instruments, all other preoperative, intraoperative and postoperative care was delivered according to standard practice.Results: 91 kyphoplasties were performed on 65 unique patients during the study period. The median operation time across the three groups was 29 min (IQR 22.5-35.5) with a median irradiation time of 2.3 min (IQR 1.2-3.4). The median patient age was 74 years (IQR 66-80). The groups did not significantly differ in terms of age (p = 0.878), sex (p = 0.37), T score (p = 0.718), BMI (p = 0.285) or the applied volume of cement (p = 0.792). There was no significant difference between the treatment groups with respect to surgical duration (p = 0.157) or dose area product (p = 0.913).Conclusions: Although use of the two newer-generation access instruments were designed to involve fewer unique steps per operation, their use was not associated with reduction in surgical duration, irradiation time or dose area product administered compared with the older, established vertebral access device. Care should be taken to evaluate the impact of new instruments on key surgery-related parameters such as surgical duration and radiation exposure and claims made about new instruments should be assessed a structured fashion. [ABSTRACT FROM AUTHOR]

Background: In this prospective nonrandomized multicenter trial, we analyze the incidence of early and late complications after parotidectomy in correlation to the extent of dissection. Methods: A total of 148 patients underwent a parotidectomy for a benign lesion in the superficial lobe. The number of intraoperatively dissected main facial nerve branches was photo‐documented and defined the extent of tissue dissection. Early postoperative complications including sialocele were evaluated until 4 weeks after surgery. Late complications as facial nerve palsy, Frey's syndrome (FS) and the outcome of the scar and substance loss were furthermore assessed after 6 and 12 months. Results: Early complications occurred in 22 patients (14%) and did not depend on the extent of facial nerve dissection (all P > .05). However, patients with higher number of intraoperatively dissected facial nerve branches showed significantly higher palsy scores on the first postoperative day (P = .026). FS occurred with incidence of 69% and correlated significantly to the extent of dissection (P = .003). Appearance of the scar and substance loss improved significantly during the follow‐up (P < .001 and P < ,005, respectively) without significant correlation to the extent of dissection (P > .05 for both variables after 12 months). Conclusions: Less extensive tissue dissection resulted in better postoperative facial nerve function on the first postoperative day and in lower incidence of FS after 12 months. However, incidence of early complications did not depend on the extent of surgery. The study was registered in the German Clinical Trials Register prior to conducting the research. DRKS‐ID: DRKS00008967, URL:http://apps.who.int/trialsearch/. [ABSTRACT FROM AUTHOR]

Aim. To determine the immunoglobulin variable heavy chain (IgVH) genes and their somatic mutations and to compare these data with the clinical and laboratory parameters of patients and the outcomes of the disease. Subjects and methods. The investigation enrolled 24 patients (9 men and 15 women whose age was 32 to 77 years (median age, 60 years) with splenic marginal zone B-cell lymphoma (SMZBCL). The latter was diagnosed on the basis of histological and immunohistochemical examinations of a bone marrow trephine biopsy specimen, immunophenotyping of peripheral lymphoid cells or bone marrow aspirates. Results. The mutational status of the IgVH genes was analyzed in all the 24 patients. It was found that the tumor cells contained mutated IgVH genes (the VH1-family genes participated in most cases) in 15 (62.5%) patients with SMZBCL and unmutated ones in 9 (37.5%). There was a tendency towards more common tumor progression in patients with unmutated IgVH genes than in those with mutated ones. Conclusion. The presence of SMZBCL cases with both mutated and unmutated IgVH genes and the higher frequency of the VH1-2 gene are likely to indicate the molecular heterogeneity of the origin of this lymphoma.

Abstract Objectives Our objective was to determine the safety and efficacy of acute normovolemic hemodilution (ANH) to reduce the requirement for allogenic red blood cell (RBC) transfusions in patients undergoing primary cytoreduction for advanced ovarian cancer. Methods Patients undergoing primary cytoreduction for advanced ovarian cancer were enrolled in a prospective trial assessing ANH at time of surgery. Intraoperative blood withdrawal was performed to a target hemoglobin of 8.0 g/dL. A standardized transfusion protocol first using autologous then allogenic blood was applied intraoperatively and throughout hospitalization according to institutional guidelines. The primary endpoint was to determine the overall rate of allogenic RBC transfusions in the intra- and postoperative periods. A predetermined allogenic RBC transfusion rate <35% was deemed a meaningful reduction from a 50% transfusion rate in historical controls. Results Forty-one patients consented to participate. Median blood withdrawn during ANH was 1650 mL (range, 700–3000). Cytoreductive outcomes were as follows: 0 mm, 30 (73%); 1–10 mm, 8 (20%); and >10 mm, 3 (7%) residual disease. Estimated blood loss was 1000 mL (range, 150–2700). Fourteen patients (34%) received allogenic RBC transfusions intra- or postoperatively, meeting the primary endpoint. No patients were transfused outside protocol guidelines. The rate of ≥grade 3 complications (20%) and anastomotic leaks (7%) were similar to historical controls and met predefined safety thresholds. Conclusions For patients with advanced ovarian cancer undergoing primary cytoreductive surgery, ANH appears to reduce allogenic RBC transfusion rates versus historical controls without increasing perioperative complications. Further evaluation of the technique is warranted. Highlights • Acute normovolemic hemodilution (ANH) reduces RBC transfusion rates during ovarian cancer surgery vs. historical controls. • ANH can be performed safely for patients undergoing cytoreductive surgery for ovarian cancer. • ANH appears to be a promising strategy to reduce RBC transfusion rates during cytoreductive surgery for ovarian cancer. [ABSTRACT FROM AUTHOR]

Although azacitidine is the first‐line drug for higher‐risk myelodysplastic syndrome (MDS) patients, its efficacy for lower‐risk MDS remains unestablished. Therefore, we conducted a prospective study to examine the efficacy and safety of a 5‐day regimen of azacitidine (AZA‐5) for lower‐risk MDS. The primary endpoint was hematological improvement (HI) after 4 courses of therapy. A total of 51 patients with lower‐risk MDS based on the French‐American‐British (FAB) classification (44 patients with refractory anemia [RA] and 7 patients with refractory anemia with ringed sideroblasts [RARS]) were enrolled from 6 centers in Japan. The median age was 75 years (range: 51‐88). These patients received AZA‐5 (75 mg/m2; once daily for 5 sequential days). The median number of AZA‐5 courses was 8 (range: 1‐57), and 45 patients (88.2%) received more than 4 courses. HI and transfusion independency were seen in 24 patients (47.1%) and 11 patients (39.2%), respectively. A total of 11 patients (21.6%) achieved complete remission or marrow remission. WT1 mRNA levels were not significantly correlated with therapy response. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 26 (51.0%) and 11 (21.5%) patients, respectively. Nonhematological grade 3 or 4 adverse events were observed in 9 patients (17.6%). Together, these results indicate that AZA‐5 is feasible and effective for lower‐risk MDS patients as well as for higher‐risk MDS patients. [ABSTRACT FROM AUTHOR]

Dog owners are more physically active than non-dog owners, but evidence of a causal relationship between dog acquisition and increased physical activity is lacking. Such evidence could inform programs and policies that encourage responsible dog ownership. Randomized controlled trials are the ‘gold standard’ for determining causation, but they are prohibited in this area due to ethical concerns. In the BuddyStudy, we tested the feasibility of using dog fostering as a proxy for dog acquisition, which would allow ethical random assignment. In this single-arm trial, 11 participants fostered a rescue dog for six weeks. Physical activity and psychosocial data were collected at baseline, 6, and 12 weeks. At 6 weeks, mean change in steps/day was 1192.1 ± 2457.8. Mean changes on the Center for Epidemiologic Studies Depression Scale and the Perceived Stress Scale were −4.9 ± 8.7 and −0.8 ± 5.5, respectively. More than half of participants (55%) reported meeting someone new in their neighborhood because of their foster dog. Eight participants (73%) adopted their foster dog after the 6-week foster period; some maintained improvements in physical activity and well-being at 12 weeks. Given the demonstrated feasibility and preliminary findings of the BuddyStudy, a randomized trial of immediate versus delayed dog fostering is warranted.