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PURPOSE: Treatment-related adverse events associated with systemic anticancer therapy (SACT) can deter patients with sarcoma from completing treatment. With self-monitoring, patients may be better empowered to self-advocate for improved symptom management. We hypothesized that by incorporating journaling, a structured form of self-monitoring, care team communication, and symptom management would improve. We thus designed a prospective randomized trial exploring journaling as a therapeutic adjuvant for symptom management ( NCT03258892 ). METHODS: Participants with sarcoma initiating SACT were randomly assigned to receive either a symptom management journal at the start of SACT or after completing two cycles of SACT. Symptom journals were designed jointly by a cancer patient focus group and by education experts. Journals were reviewed with clinical staff at each visit. Participant responses were obtained through questionnaires. Patient call volume was obtained through the electronic health record. RESULTS: Of 64 participants consented for the trial, 53 were evaluable for analysis. Fifty-five percent of participants reported that the journal was at least moderately useful. These participants were more likely to report improved communication scores ( P = .027), symptom management ( P = .011), and quality of life (QOL) ( P = .019). Participants who received the journal early were less likely to report a decrease in QOL as compared with the late journal group ( P = .757 v P = .035). CONCLUSION: To our knowledge, this is the first prospective randomized trial evaluating the use of structured journaling as a low-cost means to improve treatment-related adverse event management and QOL in patients with sarcoma undergoing SACT. These promising results will need to be confirmed by additional studies.

Purpose For upper abdominal tumors, our institutional-standard motion reduction method is the expiration breath-hold (EBH) technique, using Active Breathing Coordinator (ABC). However, an individual patient's breath-hold (BH) reproducibility (RBH) may be improved in deep inspiration or inspiration breath-hold (DIBH or IBH). This trial compared the tumor position RBH, stability (SBH), and breath-hold time (TBH) of 3 BH methods, using ABC, to personalize the selection of technique, by using a preplanning screening assessment. Methods and Materials We invited patients planned for upper abdominal radiation therapy (kidney, pancreas, liver, or adrenal gland) to participate in this prospective trial. We conducted ABC education with the study participants, who then attempted EBH, DIBH, and IBH in randomized order. During 5 consecutive BH's for each method, we acquire kV fluoroscopy images of the diaphragm. We personalized the BH technique selection according to a decision matrix. We analyzed the EBH and the personalized technique cohort mean RBH and SBH. Results Between May 2019 and March 2020, we recruited 19 participants. Median age of participants was 68 years (range 32-81). Tumor sites included kidney (n = 1), adrenal gland (n = 5) and liver (n = 14). We excluded 1 participant due to poor BH compliance, leaving 270 images from 18 participants for analysis. Mean TBH was 22.1, 23.9, and 24.2 seconds for EBH, DIBH, and IBH respectively. Screening selected EBH for 44% (n = 8), IBH for 39% (n = 7), and DIBH for 17% (n = 3) of participants. The mean RBH was superior at 0.92 mm (0.79 mm SD) for the personalized technique, compared with EBH of 1.79 mm (1.49 mm SD) (P = .016). Preplanned subset analysis of participants whose personalized technique was not EBH showed improved mean RBH of 0.63 mm (0.29 mm SD) compared with their EBH RBH of 2.2 mm (1.7 mm SD) (P = .011). Conclusions In 56% of participants, DIBH or IBH demonstrated superior RBH compared with EBH. Personalised BH screening can inform selection of an ABC BH method which provides optimal RBH with improved TBH for an individual's planning and treatment course.

The incompetent bicuspid aortic valve (BAV) can be repaired using various techniques. This study presents a prospective comparison of external and subcommissural aortic annuloplasty.Fifty consecutive patients (38 males, age: 43.9 ± 15.8 years) with BAV insufficiency with or without aortic dilatation underwent valve repair in a single institution. They were prospectively allocated to one of two groups based on the aortic annulus stabilization technique: 25 patients were operated on using the subcommissural annuloplasty (SCA) and 25 using the external complete annuloplasty (EA). Transthoracic echocardiography was performed in all patients before the operation and 1 and 3 years after the operation. Moreover, mortality and morbidity at 7 years were evaluated.In prospective echocardiographic comparison, EA was associated with smaller diameter of the aortic annulus (24.1 ± 2.6 mm vs. 25.8±2.1 mm, p .05) and lower mean and peak transvalvular gradients (7 ± 4 mmHg vs. 13 ± 4 mmHg, p = .02 and 15.3 ± 9.7 mmHg vs. 20.7 ± 5.6 mmHg, p = .03, respectively). No patients died or required reoperation due to recurrent insufficiency at 6,81 (interquartile range-0,17) years after the operation. The Kaplan-Meier actuarial freedom from aortic regurgitation (AR) grade =2 or gradient20 mmHg at 35.1 ± 3.6 months years was 96% (24 out of 25) for patients who had external annuloplasty and amounted to 76% (19 out of 25) for those who had SCA, p = .05).External annuloplasty performed during repair of the BAV is associated with better hemodynamics at medium-term follow-up compared to SCA.

Background Pre-registration of a clinical trial before the first participant is recruited can help to prevent selective outcome reporting and salami-slicing that can distort the evidence base for an intervention and result in people being offered care or treatment that is not effective. Rates of clinical trial registration in nursing and midwifery are low. Aim To use a hypothetical example from midwifery practice to illustrate how selective outcome reporting and salami-slicing can distort the evidence base. Findings A trial of immersion in water during labour and birth is used to consider issues in outcome selection and how researchers may be drawn to switch primary outcomes or report different outcomes across multiple papers. Discussion In nursing and midwifery science, selective outcome and salami reporting are seemingly common. Prospective trial registration is intended to prevent these practices, enhancing the quality and integrity of the work. Conclusion Clinical trials are a robust form of primary research evidence and directly impact clinical practice. Researchers must ensure their trials are correctly registered and editors need to reconcile submitted papers and registration entries as part of the review process.

OBJECTIVE Previous research indicated that the International Committee of Medical Journal Editors guidelines of prospective trial registration with clearly identified primary and secondary outcome measures are only adhered to in 14.4% of studies published in the top five psychiatry journals between 1 January 2009 and 31 July 2013. This study examined if adherence has improved. METHODS The registration information, article information, primary outcome measures (POMs), participant numbers and funding source were extracted from studies published in the same five psychiatry journals between 1 January 2015 and 31 December 2019. Discrepancies between POMs in the articles and registry were tracked. RESULTS Of the 7268 publications, 268 studies required registration. Three (1.1%) were unregistered, 107 (39.9%) were retrospectively registered, and 158 (58.9%) were prospectively registered. Of the 158 prospectively registered studies, 16 (10.1%) had unclear POMs in the article or registration, 22 (13.9%) had discrepancies between registered and published POMs, and 33 (20.9%) had no POM discrepancies but had retrospectively updated POMs in the registry. Of the 22 studies with discrepancies, nine (40.9%) were determined to favour statistically significant results. Overall, 87 (32.5%) of the 268 studies were prospectively registered with no discrepancies between registered and published POMs and no changes to registered POMs or timeframes. CONCLUSION Although this rate of one third of published articles fully adhering to the guidelines is an improvement compared to previous research, further efforts still need to be made by both authors and journals to ensure full transparency in the reporting of studies in psychiatry.

Objective: Debridement, the removal of nonviable tissue, forms the foundation of wound care practice. Clinicians have a variety of debridement methods at their disposal: sharp, biologic, enzymatic, autolytic and mechanical. The choice of debridement technique depends on the patient care setting, ulcer type and the clinician's experience, training, comfort level and licensure. This prospective study evaluated a novel debridement instrument, EZ-Debride (MDM Ventures, US). Cutting flutes on the head of the tool permit uniform removal of dead tissue while lessening the risk of deeper injury. It may also minimise pain during the debridement procedure. Method: Subjects with hard-to-heal wounds, drawn from a single wound care centre, participated in this institutional review board-approved prospective clinical study. Pain was measured before, during and after debridement using a numerical scale. Assessment of bacterial burden using fluorescence imaging (MolecuLight, Canada) was performed before and after debridement. Results: Enrolment of 10 male and 12 female subjects, with a total of 28 wounds, was carried out over a two-month period by two investigators at a single institution. The average age of subjects was 64 years (range: 22–95 years). The average wound duration was 29 weeks (range: 6–142 weeks). Wound types included diabetic foot, venous leg and pressure ulcers, post-surgical and traumatic wounds. The average pain score at the time of enrolment was 3.9. Subjects reported an average increase in pain with debridement of 0.6 points (range: 0–8). Fluorescence imaging demonstrated a reduction in bacterial load in 69% of cases, with complete resolution in 19% of wounds. Haemostasis was achieved with direct pressure in all cases and the only adverse event was a wound infection that occurred four days after debridement. Conclusion: The results suggest that this novel debridement tool can safely remove nonviable tissue with minimal discomfort and reduce bacterial burden similar to results achieved by sharp debridement.

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

Purpose A post-operative cooling method in oral and maxillofacial surgery is the cooling with hilotherapy. The aim of this study was the post-operative comparison of cooling temperatures of 18°C and 22°C. The parameters of this trial were swelling and the post-operative pain levels. Methods This study included 156 patients, divided into two groups among whom a mono-one, bignathic osteotomy or genioplasty was indicated. The post-operative assessment of swelling was performed using a 3D optical scanner. This examination was repeated on post-operative days 1, 2, 3, 7, 14, 30, and 90. The examination on day 90 served as a reference value in respect of swelling and pain. Results Group 1 (18°C, 78 patients) showed an increase in post-operative swelling on the 1st post-OP day of 52.06 ± 35.41ml. The maximum was reached on the 2nd post-OP day with 75.82 ± 38.97ml. On the 30th post-OP day, residual swelling measured 11.60 ± 12.62ml. Group 2 (22 °C, 78 patients) showed an increase in postoperative swelling on the 1st post-OP day of 76.07 ± 63.15ml. The maximum was reached on the 2nd post-OP day with 106.97 ± 69.63 ml. On the 30th post-OP day, residual swelling measured 14.36 ± 32.26ml. The differences between the two groups and between different visits were statistically significant. Conclusion The study results indicate less residual swelling in group 1 on the 30th post-OP day, possible based on the lower cooling temperature. The post-operative pain exhibits a comparable level of pain intensity between the two groups. In overall terms, a subjectively more agreeable treatment was observed in group 1.

Introduction: Programming directional leads poses new challenges as the optimal strategy is yet to be established. We designed a randomized control study to establish an evidence-based programming algorithm for patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation with directional leads. Methods: Fourteen consecutive patients were randomized to programming with either early or delayed (i.e., starting with a “ring mode”) steered stimulation. Motor scores, number of programming visits, calls to the clinic, battery consumption, and stimulation adjustments required were recorded and compared between groups, using the Wilcoxon signed-ranks test, after 3 months of open-label programming. Results: Thirteen patients (25 electrodes) were included, of which 23 were steerable. Nine out of 14 electrodes allocated to delayed steered stimulation were changed to steered mode due to side effects during the course of the study. No patients (11 electrodes) initially allocated to early steered stimulation were converted to ring mode. The 2 study arms did not differ in any of the considered measures at 3 months. Conclusion: Programming with early or delayed steered stimulation is equally effective in the short term. However, delayed steering is less time consuming and is not always needed.

PURPOSE: This prospective trial’s objective was to determine feasibility and outcomes of an exercise-based intervention for rural overweight/obese female cancer survivors. MATERIALS AND METHODS: Survivors of endometrial, breast, or ovarian cancer enrolled in a 6-month program of increased aerobic activity (30 minutes daily walking) and strength-training exercises using exercise bands (THERABAND; Akron, OH) with personalized telephone motivational coaching. Baseline demographics, anthropomorphic measurements, quality of life (QOL), fitness, and readiness to adopt exercise changes were assessed; daily steps, band use, and follow-up measurements were assessed at 3 and 6 months. Study completion was modeled using logistic regression. RESULTS: The mean age of the 99 women was 59.9 years, the mean body mass index (BMI) was 35.9 kg/m2, 88.9% were white, and 41.4% reported current exercise. Fifty-five women (55.6%) completed the 6-month program, and 36 (36.4%) completed exercise interventions. Using logistic regression to model study completion, only baseline QOL scores (physical component summary) and mental component summary) remained significant predictors. The mean weight change was a gain (0.88 kg). Higher MCS baseline scores and prior regular exercise predicted continued exercise and increased step counts, whereas higher BMI and baseline sleep predicted decreased QOL. Top walking barriers were feeling unwell and weather; barriers to strength exercises were band dislike and pain. CONCLUSION: The most significant predictor of trial completion and improved exercise outcomes was a higher baseline mental QOL. Motivation, belief in the importance of exercise, and prescribed/monitored exercise regimens were not sufficient; supportive and cognitive behavioral therapy interventions for survivors are needed to sustain uptake.

OBJECTIVES/HYPOTHESIS Although vidian neurectomy (VN) is associated with decreased lacrimation, its impact on dry eye quality-of-life is not well-defined. Endoscopic endonasal transpterygoid approaches (EETA) may require vidian nerve sacrifice. STUDY DESIGN A prospective cohort trial. METHODS A prospective trial evaluating VN during EETA on lacrimation by phenol red thread testing and dry eye severity by the five-item Dry Eye Questionnaire (DEQ-5) was performed. Preservation of the contralateral vidian nerve allowed comparison between the eye subjected to VN and the control eye postoperatively. RESULTS Twenty-one subjects were enrolled with no preoperative difference in lacrimation between eyes (P = .617) and overall mild dry eye severity. Although the control eye had no difference in lacrimation pre- and postoperatively, decreased tearing was noted in the VN eye at 1 month (20.8 mm vs. 15.8 mm, P = .015) and at 3 months (23.2 mm vs. 15.8 mm, P = .0051) postoperatively. Overall, no difference was noted in the DEQ-5 score for dry eye severity between the pre- and postoperative measures. However, six patients were noted to have moderate to severe dry eye severity postoperatively and five of these six had decreased lacrimation (

Purpose We investigated in a single-center prospective trial (NCT03376386) the use of serial fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) to determine the boost dose and to guide boost segmentation in head and neck cancer. Methods and Materials Patients were eligible when treated with curative radiation therapy with or without systemic treatment for T2-4 squamous cell carcinoma of the hypopharynx, larynx, or oropharynx (20 patients in total). FDG-PET/CT scans were made at baseline and for redelineation and replanning at the end of weeks 2 and 4 of radiation therapy. The metabolically active part of the primary tumor received a 4 Gy boost on top of the 70 Gy baseline dose per partial metabolic response. The study would be considered feasible when ≥80% of adaptations were successful and no Common Terminology Criteria for Adverse Events grade ≥4 acute toxicity occurred. Results One patient received 70 Gy after complete metabolic response in week 2, and 12 patients received 78 Gy because of partial metabolic response at weeks 2 and 4. Seven patients received 74 Gy, either because of complete metabolic response at week 4 (n = 3) or a missed FDG-PET/CT (n = 4). The patients missed their FDG-PET/CT scans because they did not fast (n = 2) or at patients’ request (n = 2). In addition to the 4 missed FDG-PET/CT scans, 2 adaptive plans could not be finished successfully owing to logistical problems. In total, 85% of adaptations were completed correctly. No patient experienced grade ≥4 toxicity, and 40% had grade 3 dysphagia (tube feeding) during treatment. This decreased at 12 weeks posttreatment to 20%. Conclusions This prospective trial demonstrates the feasibility of serial FDG-PET/CT scans for dose escalation and patient selection.

Aim To evaluate the effect of the Valsalva maneuver on ease of the endometrial sampling procedure in cases where the cervix cannot be passed spontaneously. Methods A randomized prospective trial was conducted in 84 patients whose cervix could not pass spontaneously with pipelle, and they were randomized for the Valsalva maneuver or tenaculum groups. In 43 of a total of 84 patients, we requested Valsalva maneuver throughout the process to pass the cervical canal, and in 41 patients, we performed tenaculum to pass the cervix. Results Valsalva and tenaculum groups did not differ in success rates (P = 0.314). There was no difference between the two groups in the history of the disease, past surgery and education (P > 0.05). Conclusion In endometrial sampling procedure with pipelle, when the cervix cannot be passed spontaneously, the transition with the Valsalva maneuver should be tried before using the tenaculum. Thus, a more painful procedure can be avoided and patient satisfaction may increase.

Objectives Preoperative grading of pancreatic neuroendocrine tumors (PanNET) is challenging. The aim of this study was to prospectively evaluate the use of a 25-gauge needle with a core trap for diagnosis and grading of PanNET. Methods This multicenter prospective trial was registered with the University Hospital Medical Information Network (UMIN000021409). Consecutive patients with suspected PanNET between June 2016 and November 2017 were enrolled. All patients underwent endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a 25-gauge needle with a core trap. Samples obtained after the first needle pass were used for central pathological review. EUS-FNB was evaluated in terms of (i) technical success rate, (ii) adequacy for histological evaluation, (iii) complication rate during the procedure, and (iv) concordance between PanNET grading on EUS-FNB and that after analysis of the resected tumor. Results Fifty-two patients were enrolled. Of the 36/52 patients who underwent surgical resection, 31 were finally diagnosed with PanNET and were eligible for analysis. The technical success rate of EUS-FNB was 100%. The rate of adequacy for histological evaluation was 90.3%. There were no complications related to EUS-FNB. The concordance rate between PanNET grading on EUS-FNB and that after analysis of the resected tumor was 82.6% (95% confidence interval = 61.22–95.05, P = 0.579). Conclusions EUS-FNB using a 25-gauge needle with a core trap is feasible, providing histological samples are of sufficient quality for diagnosis and grading of PanNET.

Objective: To compare two commercially available ureteral access sheaths in their ability to access the renal collecting system and assess ureteral wall trauma using a prospective, randomized trial...

Historically, the presence of cardiac implantable electronic devices (CIEDs), including pacemakers and implantable cardioverter defibrillators (ICDs), was widely considered an absolute contraindication to magnetic resonance imaging (MRI). The recent development of CIEDs with MR Conditional labeling, as well as encouraging results from retrospective studies and a prospective trial on the safety of MRI performed in patients with CIEDs without MR Conditional labeling, have led to a reevaluation of this practice. The purpose of this report is to provide a concise summary of recent developments, including practical guidelines that an institution could adopt for radiologists who choose to image patients with CIEDs that do not have MR Conditional labeling. This report was written on behalf of and approved by the International Society for Magnetic Resonance in Medicine (ISMRM) Safety Committee. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 1.

ObjectiveThis trial compared the efficacy and safety of transarterial chemoembolisation (TACE) plus sorafenib with TACE alone using a newly established TACE-specific endpoint and pre-treatment of sorafenib before initial TACE.DesignPatients with unresectable hepatocellular carcinoma (HCC) were randomised to TACE plus sorafenib (n=80) or TACE alone (n=76). Patients in the combination group received sorafenib 400 mg once daily for 2–3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable (unTACEable) progression (TTUP), defined as untreatable tumour progression, transient deterioration to Child-Pugh C or appearance of vascular invasion/extrahepatic spread. Co-primary endpoints were progression-free survival (PFS), which is not a conventional one but defined as TTUP, or time to any cause of death plus overall survival (OS). Multiplicity was adjusted by gatekeeping hierarchical testing.ResultsMedian PFS was significantly longer in the TACE plus sorafenib than in the TACE alone group (25.2 vs 13.5 months; p=0.006). OS was not analysed because only 73.6% of OS events were reached. Median TTUP (26.7 vs 20.6 months; p=0.02) was also significantly longer in the TACE plus sorafenib group. OS at 1 year and 2 years in TACE plus sorafenib group and TACE alone group were 96.2% and 82.7% and 77.2% and 64.6%, respectively. There were no unexpected toxicities.ConclusionTACE plus sorafenib significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with those of previous TACE combination trials.Trial registration numberNCT01217034.

Background Shared decision making (SDM) preceding lung cancer screening is important for populations that are underrepresented in lung cancer screening trials. Current evidence-based guidelines; however, do not address personal risk and outcomes in underrepresented populations. This study compared two SDM decision aids (Option Grids and Shouldiscreen.com) for SDM efficacy, decision regret and knowledge. Methods We conducted a prospective trial of lung cancer screening patients (N = 237) randomized to SDM with Option Grids or Shouldiscreen.com. To evaluate the SDM process after lung cancer screening, patients answered two questionnaires: CollaboRATE and Decision Regret. Patients also completed a questionnaire to test their knowledge of lung cancer screening. Results Patients were predominantly African American (61.6%), though multiple races, varying education levels and equal genders were represented. Patients in both Option Grids and Shouldiscreen.com groups reported favorable SDM experiences (P = 0.60) and equivalent knowledge about lung cancer screening (P = 0.43). Patients using Shouldiscreen.com had less knowledge regarding the potential complications of subsequent testing (P = 0.02). Shouldiscreen.com patients had increased regret regarding their decision to pursue screening (P = 0.02). Conclusions Option Grids and Shouldiscreen.com both facilitated a meaningful SDM process. However, Option Grids patients experienced decreased decision regret and enhanced knowledge of the potential complications of screening.

Aim of the study Since over 80% of sudden cardiac arrests occur in the home, cardiopulmonary resuscitation (CPR) training for family members of high-risk cardiac patients represents a promising intervention. The use of mobile application-based (mApp) CPR training may facilitate this approach, but evidence regarding its efficacy is lacking. Methods We conducted a multicenter, pragmatic, cluster-randomized trial assessing CPR training for family members of cardiac patients. The interventions were mApp (video, no manikin) and VSI (video + manikin). CPR skills were evaluated 6-months post-training. We hypothesized that chest compression (CC) rate from training with an mApp would be no worse than 5 compressions per minute (CPM) lower compared to VSI. Results From 01/2016 to 01/2018, we enrolled 1325 eligible participants (mean age 51.6 years, 68.2% female and 59.4% white). CPR skills were evaluated 6-months post-training in 541 participants (275 VSI, 266 mApp). Mean rate was 84.6 CPM (95% CI: 80.4, 88.6) in VSI, compared to 82.7 CPM (95% CI: 76.2, 89.1) in the mApp, and mean depth was 42.1 mm (95% CI: 40.3, 43.8) in VSI, compared to 38.9 mm (95% CI: 36.2, 41.6) in the mApp. After adjustment, the mean difference in CC rate was −2.3 CPM (95% CI −9.4, 4.8, p = 0.25, non-inferiority) and CC depth was −3.2 mm (95% CI −5.9, 0.1, p = 0.056). Conclusion In this large prospective trial of CPR skill retention for family members of cardiac patients, mApp training was associated with lower CC quality. Future work is required to understand additional approaches to improve CPR skill retention. Clinical Trial Registration URL: ClinicalTrials.gov, Identifier: NCT02548793 .

To assess the outcome of a novel method of preventing facial pressure ulcers in spinal surgery and a review of literature. A prospective trial using a novel method of facial protection using paraffin tulle gras dressing to cover bony prominences during spinal surgical procedures was performed. Patients were reviewed at 24 hours and 6 weeks. A telephone survey was also conducted post discharge. Over an 8-month period, 12 patients (7F:5M, age 9-72 years) underwent spine surgery for tumour stabilisation (n = 7), deformity correction (n = 4), and degenerative presentation (n = 1) with mean operative time of 472 minutes (range 150-785 minutes) in prone position. All patients were managed by the same team using an agreed protocol. No pressure ulcers were noted in our study. One patient sustained minimal erythema, which resolved after 24 hours. All patients were satisfied with the care received. Facial pressure ulcers though much reduced are still common in spinal surgery. The common factors are the long duration of surgery, shear, friction, moisture, and intrinsic factors. Our strategy of an appropriate facial support and constant vigilance helped eliminate the incidence of iatrogenic facial ulcers in spinal surgery.

Anogenital skin care for the elderly remains an umbrella term concerning protective and non-interventional regimens, particularly for ordinary diaper users. Our recent investigation has demonstrated the preventive effect of daily anogenital washing with miconazole nitrate-containing soap to the development of diaper candidiasis. We extended this work to cover our hypothesis as to whether the miconazole soap has a therapeutic benefit in genital candidiasis. The study outline includes: (i) the enrollment of 21 bedridden inpatients (84 ± 9 years; eight men and 13 women) who were diagnosed clinically and mycologically with genital candidiasis, and who had never received topical and/or systemic antifungal agents; (ii) administration of anogenital washing with 0.75% miconazole-containing soap once daily for 4 weeks; and (iii) assessment of clinical symptoms and detection of Candida materials by culture and microscopic examination. As assessed by clinical symptom scoring for incontinence-associated dermatitis (IAD), the ratio of patients with severe to moderate symptoms dramatically decreased by 2 weeks and 10 of 21 patients became symptom-free at 4 weeks. The IAD clinical severity score was significantly decreased at 4 weeks. Compared with the baseline positivity, both microscopic and cultured Candida-positive rates were significantly decreased at 4 weeks after washing. All culture-detected fungi were Candida albicans. Severe adverse events did not occur in all participants. Individual medical and risk factors had no significant correlation with clinical severity and duration of candidiasis on variance analysis. In conclusion, topical washing with miconazole soap is a safe and reliable non-medical approach for soothing diaper-associated genital candidiasis in bedridden inpatients in whom it is difficult to perform prompt medical examination.

In critically ill brain-injured patients maintaining balanced fluid management is a crucial part of critical care. Many factors influence the relationship between fluid management, cerebral blood flow and cerebral oxygenation. Passive leg raising (PLR)-induced changes predict fluid responsiveness in the majority of non-neurological ICU patients. In patients with intracranial lesions, PLR testing has been hypothesized to increase intracranial pressure (ICP), although data are lacking. We wanted to investigate the feasibility of PLR with expected intracranial pressure increase, according to the higher cerebral blood volume. This should be self-limiting in patients with intact cerebral autoregulation.We prospectively included patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (aSAH) in this pilot trial. PLR was performed within 48 hours after the initial diagnosis and on days 5-8. All patients had ICP monitoring. Absence of intracranial hypertension (defined as ICP25 mm Hg) was considered a positive test result.Ten patients were recruited for this study. The cohort consisted of 6 male patients with TBI and 4 female patients with aSAH. Mean patient age was 55.6 years (range 35-76). Overall, 18 tests could be performed, of which only one had to be terminated due to temporarily elevated ICP. 9 out of 10 patients had no intracranial hypertension during the acute (mean ICP increase 8.45 mm Hg, range 4-16) or during the subacute phase (mean ICP increase 9.12 mm Hg, range 3-18).PLR is feasible in patients with intracranial pathology to assess fluid responsiveness and provide optimized patient volume management without increasing the risk of persistent intracranial hypertension.

Background/Aim: Upcoming radiotherapy may cause distress and sleep disorders (SDO). This prospective interventional trial investigated SDO during a course of radiotherapy for breast cancer. Patients and Methods: Fifty patients were eligible. The primary endpoint was improvement of SDO after 15 fractions. Additional endpoints included SDO after 5 fractions and at the end of radiotherapy (EOT). Additional characteristics were analysed including use of smartphones/tablets, age, body mass index, performance score, comorbidity score, surgery, distress score, and emotional/ physical/practical problems. Results: After 15 fractions, 38% of patients reported improvement of SDO (p

BACKGROUND: Patients with dyskinetic cerebral palsy are often severely impaired with limited treatment options. The effects of deep brain stimulation (DBS) are less pronounced than those in inherited dystonia but can be associated with favorable quality of life outcomes even in patients without changes in dystonia severity. OBJECTIVE: The aim is to assess DBS effects in pediatric patients with pharmacorefractory dyskinetic cerebral palsy with focus on quality of life. METHODS: The method used is a prospective, single-arm, multicenter study. The primary endpoint is improvement in quality of life (CPCHILD [Caregiver Priorities & Child Health Index of Life with Disabilities]) from baseline to 12 months under therapeutic stimulation. The main key secondary outcomes are changes in Burke-Fahn-Marsden Dystonia Rating Scale, Dyskinesia Impairment Scale, Gross Motor Function Measure-66, Canadian Occupational Performance Measure (COPM), and Short-Form (SF)-36. After 12 months, patients were randomly assigned to a blinded crossover to receive active or sham stimulation for 24 hours each. Severity of dystonia and chorea were blindly rated. Safety was assessed throughout. The trial was registered at ClinicalTrials.gov, number NCT02097693. RESULTS: Sixteen patients (age: 13.4 ± 2.9 years) were recruited by seven clinical sites. Primary outcome at 12-month follow-up is as follows: mean CPCHILD increased by 4.2 ± 10.4 points (95% CI [confidence interval] -1.3 to 9.7; P = 0.125); among secondary outcomes: improvement in COPM performance measure of 1.1 ± 1.5 points (95% CI 0.2 to 1.9; P = 0.02) and in the SF-36 physical health component by 5.1 ± 6.2 points (95% CI 0.7 to 9.6; P = 0.028). Otherwise, there are no significant changes. CONCLUSION: Evidence to recommend DBS as routine treatment to improve quality of life in pediatric patients with dyskinetic cerebral palsy is not yet sufficient. Extended follow-up in larger cohorts will determine the impact of DBS further to guide treatment decisions in these often severely disabled patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. ispartof: MOVEMENT DISORDERS vol:37 issue:4 pages:799-811 ispartof: location:United States status: published

Background The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy. Methods/Principal findings We validated CystiAgent against results from the Ring Strategy Trial (RST)–a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively. Conclusions/Significance The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment., Author summary Neurocysticercosis, caused by the ingestion of Taenia solium eggs, is a major cause of human epilepsy around the world. A wide spectrum of tools to fight T. solium is are now available and include antiparasitic treatment for pigs and humans, porcine vaccines, and sanitation improvements; however, the ideal combination of interventions applied to populations to maximize effectiveness and feasibility is not known. Transmission models are one tool that can be used to compare and evaluate different intervention strategies, but no currently available T. solium models have been tested for accuracy. In this research, we validated our model (“CystiAgent”) by comparing simulations of the model to the results of a large-scale trial testing a variety of T. solium control interventions. The model was calibrated using observed epidemiological data from these villages and evaluated for its ability to reproduce the effect of T. solium control interventions. The validation showed that the model was able to reproduce the baseline levels of disease, but generally overestimated the effect that each intervention would have on transmission. These results will allow us to identify limitations of the current model to improve future versions, and represent a step forward in the creation of a tool to design and evaluate future programs to control and eliminate T. solium.

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.

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.

Context Scarce data exist regarding the relevance of stimulatory (TSAb) and blocking (TBAb) thyrotropin receptor antibodies in the management of Graves disease (GD). Objective To evaluate the clinical utility and predictive value of TSAb/TBAb. Design Prospective 2-year trial. Setting Academic tertiary referral center. Patients One hundred consecutive, untreated, hyperthyroid GD patients. Methods TSAb was reported as percentage of specimen-to-reference ratio (SRR) (cutoff SRR < 140%). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine thyrotropin (TSH, thyroid stimulating hormone) alone (cutoff > 40% inhibition). Main Outcome Measures Response versus nonresponse to a 24-week methimazole (MMI) treatment defined as biochemical euthyroidism versus persistent hyperthyroidism at week 24 and/or relapse at weeks 36, 48, and 96. Results Forty-four patients responded to MMI, of whom 43% had Graves orbitopathy (GO), while 56 were nonresponders (66% with GO; P < 0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibitory immunoglobulins (TBII) differentiated between thyroidal GD-only versus GD + GO (P < 0.001). Furthermore, at baseline, responders demonstrated marked differences in diluted TSAb titers compared with nonresponders (P < 0.001). During treatment, serum TSAb levels decreased markedly in responders (P < 0.001) but increased in nonresponders (P < 0.01). In contrast, TBII strongly decreased in nonresponders (P = 0.002). All nonresponders and/or those who relapsed during 72-week follow-up period were TSAb-positive at week 24. A shift from TSAb to TBAb was noted in 8 patients during treatment and/or follow-up and led to remission. Conclusions Serum TSAb levels mirror severity of GD. Their increase during MMI treatment is a marker for ongoing disease activity. TSAb dilution analysis had additional predictive value.

Three-dimensional (3-D) high-definition (HD) stereovision and two-dimensional (2-D) ultra-high-resolution (4K) monitors have recently become available for laparoscopic surgery. The aim of this study was to compare laparoscopic performance between inexperienced participants using 3-D/HD and 2-D/4K monitors and those using conventional 2-D/HD monitors.The study enrolled 66 participants with no previous surgical experience or medical training. They were randomly divided into three equal groups, each using a different type of monitor (2-D/HD, 2-D/4K, or 3-D/HD), to perform three phantom tasks using a laparoscopic simulator: Task 1, touching markers on a non-flat surface; Task 2, bimanual peg transfer; and Task 3, passing a straight rod through a loop. Each task was performed three times. The performance scores (operative time, path length of the forceps, and technical errors) were compared for each monitor type and by age group ( 30 vs. 30 years).For all three tasks, scores using the 3-D monitor were significantly better than those using either 2-D monitor, with no difference between the 2-D/4K and 2-D/HD monitors. Using the 2-D monitors, the performance of Task 3 by the participants 30 years was worse than that by the younger participants; however, there was no difference between the age groups when using the 3-D monitor.Participants with no prior experience using a 3-D monitor showed better laparoscopic performance than those using 2-D monitors, even with 4K resolution. This improvement was more marked in older participants, suggesting a greater loss of depth perception in a 2-D environment.

BackgroundThe addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone.MethodsThe primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions.ResultsA total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reachedp ConclusionsFrom this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results.Trial registrationThe study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).

To evaluate the efficacy and safety of the Triple-P procedure as a conservative method in women with morbidly adherent placenta (MAP).A prospective trial conducted on 20 women performing elective cesarean sections (CS) at 37 weeks for anterior placenta previa accreta or increta. All women were young aged with low parity and previous CS deliveries. Triple-P procedure involved delivery of the fetus through a uterine incision placed above the upper border of the placenta, bilateral uterine arteries ligation immediately after delivery of the fetus followed by placental nonseparation and myometrial excision with reconstruction of the uterine wall in a T-shaped manner. The study outcome measures included duration of surgery, amount of intra and postoperative blood loss, Percentage of hemoglobin (Hb %) reduction, the need to perform hysterectomy and postoperative complications.Mean duration of surgery was 58 ± 1.8 min, mean intraoperative blood loss was 1.3 ± 0.3 l, mean postoperative blood loss was 180 ± 94 ml and mean Hb % reduction was 1.5 ± 0.1 g/dl. Only one case necessitated hysterectomy for severe bleeding.Triple-P procedure is a novel effective weapon that can replace hysterectomy in suitable women with MAP, especially in young patients with low parity.

Background Narrowband UVB phototherapy (NB‐UVB) is a mainstay in the treatment of numerous inflammatory dermatoses. Whereas, a wealth of studies has shown that NB‐UVB treatment increases 25‐hydroxyvitamin D3 (25(OH)D) levels, only sparse and controversial data exist on its effect on serum folate and cobalamin. Objectives To determine whether exposure to NB‐UVB alters serum folate or cobalamin levels. Methods A single‐centre, prospective, open observational study on 101 patients subjected to NB‐UVB phototherapy between late fall and early spring. Serum folate, 25(OH)D and cobalamin levels were measured after 0, 12, 24 and 36 NB‐UVB exposures. Results After 12 NB‐UVB exposures a significant decrease of mean serum folate (−1.0 nmol/L; P = 0.03) and cobalamin (−14.5 pmol/L, P = 0.03) levels was observed whereas serum levels of 25(OH)D showed a significant increase (35.4 nmol/L, P

In this prospective trial, we investigate the effectiveness of maternal Body Roundness Index in predicting the spread of spinal anaesthesia and vasopressor requirement in parturients receiving spinal anaesthesia during the elective caesarean section. We prospectively enrolled 175 parturients. Spinal anaesthesia performed with 10 mg 0.5% hyperbaric bupivacaine at the L3-L4 intervertebral space and the optimal cut-off points of the BRI evaluated as 6.59 by receiver operating characteristic analysis calculating area under the curve. Parturients were divided into two groups with BRI6.59 and BRI ≥6.59 for analyses. Multivariate logistic regression analysis was used to test for a relationship between variables and maximum sensory block level and vasopressor requirement. BRI was found as an independent risk factor associated with maximum sensory block level (OR = 1.378, 95% CI: 1.125-1.687

PURPOSE To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial. PATIENTS AND METHODS Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort. The predictive performance of the model was quantified by assessing its discriminatory and calibration abilities. RESULTS Prospective validation of predictive and prognostic models for localized RCC showed a substantial decrease in each of the predictive abilities of the model compared with their original and externally validated discriminatory estimates. Among the models, the SSIGN score performed best (0.688; 95% CI, 0.686 to 0.689), and the UISS model performed worst (0.556; 95% CI, 0.555 to 0.557). Compared with the 2002 TNM staging system (C-index, 0.60), most models only marginally outperformed standard staging. Importantly, all models, including TNM, demonstrated statistically significant variability in their predictive ability over time and were most useful within the first 2 years after diagnosis. CONCLUSION In RCC, as in many other solid malignancies, clinicians rely on retrospective prediction tools to guide patient care and clinical trial selection and largely overestimate their predictive abilities. We used prospective collected adjuvant trial data to validate existing RCC prediction models and demonstrate a sharp decrease in the predictive ability of all models compared with their previous retrospective validations. Accordingly, we recommend prospective validation of any predictive model before implementing it into clinical practice and clinical trial design.

Background/aimsSurvival after diagnosis of metastasis from uveal melanoma is poor. Identifying individuals at high risk for metastasis and developing adjuvant therapy to prevent clinically apparent metastasis could improve survival. We conducted an adjuvant trial of sequential, low-dose dacarbazine (DTIC) and interferon-alpha-2b (IFN-α−2b) in patients with cytogenetic high-risk uveal melanoma.MethodsPatients diagnosed with iris, ciliary body or choroidal melanoma with high-risk tumour cytogenetics (monosomy 3) were offered adjuvant treatment with low-dose DTIC and IFN-α−2b following primary therapy. Eligible but not enrolled patients were observed for comparison. DTIC was administered at 850 mg/m2 intravenously on days 1 and 28. IFN-α−2b was administered at 3 million units three times a week subcutaneously for 24 weeks beginning at week 9. Hepatic imaging was performed prior to adjuvant therapy and then at least every 6 months. Survival data were collected for 5 years after enrolment.Results33 patients (22%) were enrolled (treatment group), 29 (19%) were eligible but did not enrol (observation group) and 88 (59%) were not eligible. The 5-year metastasis-free survival (MFS) was 64%±9% for treated and 33%±10% for observed patients (p=0.05). The 5-year overall survival (OS) rate was 66%±9% for treated and 37%±10% for observed patients (p=0.02).ConclusionsWhen adjusted for differences in age, tumour size and initial treatment, survival between treated and observed patients was no longer significant (p=0.56 MFS and p=0.92 OS). Differences in baseline tumour characteristics between treated and observed patients can influence interpretation of results.Trial registration numberNCT01100528.

Introduction We conducted this study to show the safety and efficacy of a new implantable cardiac monitor (ICM), the BioMonitor 2 (Biotronik SE & Co. KG; Berlin, Germany), and to describe the arrhythmia detection performance. Methods The BioMonitor 2 has an extended sensing vector and is implanted close to the heart. It can transmit up to six subcutaneous electrocardiogram strips by Home Monitoring each day. We enrolled 92 patients with a standard device indication for an ICM in a single‐arm, multicenter prospective trial. Patients were followed for 3 months, and 48‐h Holter recordings were used to evaluate the arrhythmia detection performance. Results One patient withdrew consent and in one patient, the implantation failed. Two study device‐related serious adverse events were reported, satisfying the primary safety hypothesis. Implantations took 7.4 ± 4.4 min from skin cut to suture. At 1 week, the R‐wave amplitude was 0.75 ± 0.53 mV. In the 82 patients with completed Holter recordings, all patients with arrhythmias were correctly identified. False positive detections of arrhythmia were mostly irregular rhythms wrongly detected as atrial fibrillation (episode‐based positive predictive value 72.5%). Daily Home Monitoring transmission was 94.9% successful. Conclusion Safety and efficacy of the new device has been demonstrated. The detected R‐wave amplitudes are large, leading to a low level of inappropriate detections due to over‐ or undersensing.

Objective We sought to examine the feasibility of a home practice curriculum of vascular anastomosis in cardiovascular surgery using a low-fidelity simulation platform and to examine its effectiveness in skill acquisition in senior surgical trainees. Design We organized a multicenter prospective randomized study of senior residents and fellows, who were oriented to a low-fidelity cardiac simulator and an 8-week curriculum of independent practice of aortic and coronary anastomosis. “Treatment” trainees received a simulator and the curriculum. Control trainees received only their usual operative experience. The groups then crossed over; all were studied for 16 weeks in total. Video skill assessments were captured at 0, 8, and 16 weeks and were scored by one blinded investigator using the Joint Council on Thoracic Surgery Education Assessment tool. A post-hoc survey was distributed to invited participants following study completion. Setting University of Minnesota Department of Surgery, Mayo Clinic Department of Cardiovascular Surgery, and the University of Texas Health Science Center at Houston. Participants used the simulator in offices, call rooms, and their homes. Participants Program participation in the study was solicited through the Thoracic Education Cooperative Group. Four institutions expressed interest and a total of 29 trainees were invited to the study and randomized. Of these, 12 (38%) completed the curriculum and submitted the requisite 3 sets of videos (6 treatment, 6 control). All were senior residents and fellows in general and cardiothoracic surgery. Results No significant differences were detected in assessment scores before and after the curriculum nor before or after the control period in the overall or postgraduate year-stratified populations. Participant case numbers during the study did not have a significant effect on assessment scores. Randomized participants reported strong interest in deliberate practice of technical skills but identified competing clinical and personal obligations and significant barriers to simulation. Conclusions Considerable variability in performance existed among participants who completed the study, but overall, the curriculum alone was insufficient to improve simulator Joint Council on Thoracic Surgery Education scores compared to those not undergoing the curriculum. Among senior residents and fellows, provision of a practice curriculum and simulator for repeated practice is feasible but clinical and personal responsibilities were barriers to repetitive practice.

Purpose/Objectives: We aimed to assess the predictive value of a lung cancer gene panel for the development of brain metastases. Materials/Methods: Between 2011 and 2015, 102 patients with lung cancer were prospectively enrolled in a clinical trial in which a diagnostic fine-needle aspirate was obtained. Gene expression was conducted on all samples that rendered a diagnosis of non-small cell lung cancer (NSCLC). Subsequent retrospective analysis of brain metastases-related outcomes was performed by reviewing patient electronic medical records. A competing risk multivariable regression was performed to estimate the adjusted hazard ratio for the development of brain metastases and non-brain metastases from NSCLC. Results: A total of 49 of 102 patients had died by the last follow-up. Median time of follow-up was 13 months (range 0.23–67 months). A total of 17 patients developed brain metastases. Median survival time after diagnosis of brain metastases was 3.58 months (95% confidence interval (CI) 2.17, not available). A total of 30 patients developed metastases without any evidence of brain metastases until the time of death or last follow-up. Competing risk analysis identified three genes that were downregulated differentially in the patients with brain metastases versus non-brain metastatic disease: CD37 (0.017), cystatin A (0.022), and IL-23A (0.027). Other factors associated with brain metastases include: stage T ( P ⩽ 8.3e-6) and stage N ( P= 6.8e-4). Conclusions: We have identified three genes, CD37, cystatin A, and IL-23A, for which downregulation of gene expression was associated with a greater propensity for developing brain metastases. Validation of these biomarkers could have implications on surveillance patterns in patients with brain metastases from NSCLC.

I would like to congratulate Dr Schmeler and colleagues on completing an important, well-designed, and well-monitored study evaluating the feasibility and oncologic outcomes of conization alone or simple hysterectomy (conservative surgery for fertility preservation) in stage IA2-IB1 cervical cancers

INTRODUCTION Some free flaps develop postoperative vessel thrombosis, which influences the flap survival rate. Early discovery and identification of vascular crisis are critical to the success rate of flap salvage. The primary aims of this study were to determine the features of postoperative blood supply changes in fibular flaps with normal and abnormal blood flow, using near-infrared spectroscopy (NIRS), to monitor oxygenation and blood flow, and to characterize the probable risk factors for vascular crisis. METHODS Sixty-three consecutive patients undergoing reconstruction of unilateral mandibular defects with free fibular flaps at the Peking University School of Stomatology were included. Patients were divided into 2 groups, A (n = 38) and B (n = 25); fibular flaps in group A underwent continuous NIRS monitoring from immediately postoperatively until 7 days postoperatively (approximately 150 hours), whereas fibular flaps and opposite mandibles in group B underwent intermittent monitoring: once every 4 hours during the first 24 hours postoperatively and once every 12 hours from 24 to 168 hours postoperatively. RESULTS Six fibular flaps developed vascular thromboses: 4 were venous thromboses and 2 were arterial thromboses; 5 were rescued after exploration. Of 6 regional oxygen saturation (rSO2) values in the continuous monitoring group, 4 showed no significant differences at any time point compared with the intermittent monitoring group (P > 0.05). The rSO2 of the fibular flap was significantly different from that in the opposite mandible in the first 36 hours postoperatively (P < 0.05). This difference decreased over time. During the initial period of venous thrombosis, rSO2, deoxyhemoglobin, and oxygenated hemoglobin all rose slightly, then showed simultaneous rapid reduction. However, the magnitude of reduction was smaller for deoxyhemoglobin than for oxygenated hemoglobin. CONCLUSIONS Near-infrared spectroscopy can be used for noninvasive and reliable assessment of oxygenation and blood flow in free flaps through continuous, real-time monitoring. It is also portable, inexpensive, and simple to operate. In addition, the detection depth of NIRS is up to 2.0 cm, so it can be used to monitor buried flaps with depths

Purpose: This study aimed to study the impact of continuous positive airway pressure (CPAP) on chest anatomy and tumor motion in patients receiving radiation therapy.Methods and Materials: Patients with primary or secondary lung tumors, left-sided breast cancer, or liver metastases referred for radiation therapy were trained to breathe with a CPAP device using a face mask to a maximal pressure of 15 cm H2O. Three- and 4-dimensional computed tomography simulation was performed twice for each patient: once with free breathing (FB) and again using CPAP. Volumetric and dosimetric parameters of treatment plans were compared.Results: Forty-nine patients were enrolled, of whom 6 withdrew consent before simulation and 3 withdrew because of discomfort. Thus, a total of 40 patients were analyzed. Twenty-seven patients (67.5%) were treated with CPAP based on confirmation of the volumetric or dosimetric benefit of CPAP. Mean lung volume increased by 37% (P

BACKGROUND: Shoulder injections for conditions such as adhesive capsulitis are commonly performed and can be administered through image-based or landmark-based injection approaches. Ultrasound-guided injections are widely used and accurate because ultrasound allows real-time visualization of the needle and injected contrast. Landmark-based injections would be advantageous, if they were accurate, because they would save the time and expense associated with ultrasound. However, few prospective studies have compared well-described landmark-based shoulder injection techniques without ultrasound. QUESTION/PURPOSE: Using anatomic landmarks, and without using ultrasound, is the accuracy of glenohumeral injection for adhesive capsulitis greater via the posterior approach or via a new anterior approach? METHODS: Between 2018 and 2020, we treated 108 patients potentially eligible for adhesive capsulitis treatment. These patients had clinical symptoms of aggravating shoulder pain with a duration of less than 4 months and passively impaired, painful glenohumeral ROM. Due to the exclusion of patients with other shoulder conditions (full-thickness rotator cuff ruptures and posttraumatic stiffness), 95 patients received an injection in this sequential, prospective, comparative study. Between 2018 and 2019, 41 patients (17 males and 24 females; mean age 52 ± 5 years; mean BMI 24 ± 3 kg/m(2)) were injected through the posterior approach, with the acromion as the anatomical landmark, during the first part of the study period. After that, between 2019 and 2020, 54 patients (20 males and 34 females; mean age 54 ± 4 years; mean BMI 23 ± 3 kg/m(2)) received an injection through a new anterior approach, with the acromioclavicular joint as the anatomic landmark, during the second part of the study period. Injections via both approaches were administered by two experienced shoulder specialists (both with more than 10 years of experience). Both specialists had experience with the posterior approach before this study, and neither had previous training with the new anterior approach. Injections contained a corticosteroid, local anaesthetic, and contrast medium. Radiographs were taken within 20 minutes after the injection, and a radiologist blinded to the technique determined accuracy. Accurate injections were defined as having contrast fluid limited to the glenohumeral joint, while inaccurate injections displayed leakage of contrast fluid into the soft tissue or subacromial space. All of the enrolled patients were analyzed. RESULTS: In the group with the posterior approach, the accuracy was 78% (32 of 41) in contrast to 94% (51 of 54, odds ratio 0.21 [95% CI 0.05 to 0.83]; p = 0.03) in patients with the new anterior approach. CONCLUSION: The new anterior approach without the use of ultrasound was more accurate than the posterior approach. In fact, it was nearly as accurate as previously published ultrasound-guided approaches. We recommend using the new anterior approach for intraarticular glenohumeral injections instead of ultrasound-guided injections because it will save time and costs associated with ultrasound. Still, the clinical effects (anxiety, pain, functional outcome, and adverse events) of the new anterior approach should be compared with ultrasound-guided injections in a randomized study. LEVEL OF EVIDENCE: Level II, therapeutic study.

Background Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response. Methods The PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse. Results A total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness. Conclusions In this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy. publishedVersion

Aims: Recently a limited sampling strategy (LSS) for determination of metformin' pharmacokinetics was developed. The LSS utilizes the plasma concentration of metformin 3 and 10 hours after oral intake of a single dose to estimate the area under the concentration–time curve up to 24 hours (AUC 0–24h). The main purpose of this study was to support the feasibility of this strategy in a large prospective trial. Methods: Volunteers orally ingested two 500-mg tablets of metformin hydrochloride. A blood sample was drawn three and ten hours after the ingestion. Urine was collected for 0–10 and 10–24 hours and urine volumes recorded. The AUC 0–24h was calculated using the equation AUC 0–24h = 4.779 * C 3 + 13.174 * C 10. Additionally, all participants were genotyped for the single-nucleotide polymorphism A270S in OCT2, g.-66 T > C in MATE1, R61C, G465R, G401S and the deletion M420del in OCT1. Results: In total, 212 healthy volunteers participated. The median (25th - 75th interquartile range) AUC 0 − 24h, CL renal, C 3 and C 10, were 10 600 (8470–12 500) ng* hr* mL −1, 29 (24–34) L* hour −1, 1460 (1180–1770) and 260 (200–330) ng* mL −1, respectively, which is in agreement with our previous results. GFR i was correlated with metformin AUC and CL renal (P 0 − 24h. We were unable to reproduce our previous finding of a gene–gene interaction (OCT2 and MATE1) effect on CL renal in this cohort. Conclusion: This study further supports the use of the 2-point LSS algorithm in large pharmacokinetic trials.

Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates.Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology.A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility.Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.

ContextFollowing total thyroidectomy and radioactive iodine (RAI) ablation, serum thyroglobulin levels should be undetectable to assure that patients are excellent responders and at very low risk of recurrence.ObjectiveTo assess the utility of stimulated (sTg) and non-stimulated (nsTg) thyroglobulin levels in prediction of patients outcomes with differentiated thyroid cancer (DTC) following total thyroidectomy and RAI ablation.MethodA prospective observational study conducted at a University Hospital in Saudi Arabia. Patients diagnosed with differentiated thyroid cancer and were post total thyroidectomy and RAI ablation. Thyroglobulin levels (nsTg and sTg) were estimated 3–6 months post-RAI. Patients with nsTg ResultsOf 196 patients, nsTg levels were 1 occurred in 26 (35%) of patients with nsTg 0.1–2.0 ng/ml, 11 (15%) had structural incomplete response. None of the patients with sTg levels ConclusionSuppressed thyroglobulin (nsTg < 0.1 ng/ml) indicates a very low risk of recurrence that does not require stimulation. Stimulated thyroglobulin is beneficial with nsTg 0.1–2 ng/ml for re-classifying patients and estimating their risk for incomplete responses over a 7 years follow-up period.

Objective: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. Methods: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula procedure rates. Results: The proportions of patients with fistula use for hemodialysis was similar between groups, 70% vonapanitase and 65% placebo, ( p = 0.33). The Kaplan–Meier estimates of 12-month secondary patency were 78% (95% confidence interval [CI], 73–82) for vonapanitase and 76% (95% CI, 70–82) for placebo ( p = 0.93). The proportions with unassisted fistula use for hemodialysis were 46% vonapanitase and 37% placebo ( p = 0.054). The Kaplan–Meier estimates of 12-month primary unassisted patency were 50% (95% CI, 44–55) for vonapanitase and 43% (95% CI, 35–50) for placebo ( p = 0.18). There were no differences in the proportion of patients with fistula maturation or in fistula procedure rates. Adverse events were similar between groups. Vonapanitase was not immunogenic. Conclusions: Vonapanitase treatment did not achieve clinical or statistical significance to meaningfully improve radiocephalic fistula surgical outcomes. Outcome in the placebo group were better than in historical controls. Vonapanitase was well-tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov: NCT02414841 ( https://clinicaltrials.gov/ct2/show/NCT02414841 )

To compare FDG-PET/unenhanced MRI and FDG-PET/diagnostic CT in detecting infiltration in patients with newly diagnosed Hodgkin lymphoma (HL). The endpoint was equivalence between PET/MRI and PET/CT in correctly defining the revised Ann Arbor staging system. Seventy consecutive patients with classical-HL were prospectively investigated for nodal and extra-nodal involvement during pretreatment staging with same-day PET/CT and PET/MRI. Findings indicative of malignancy with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, positive-biopsy and/or response to treatment were evidenced as lymphoma. Sixty of the 70 (86%) patients were evaluable having completed the staging program. Disease staging based on either PET/MRI or PET/CT was correct for 54 of the 60 patients (90% vs. 90%), with difference between proportions of 0.0 (95% CI, −9 to 9%; P=0.034 for the equivalence test). As compared with reference standard, invasion of lymph nodes was identified with PET/MRI in 100% and with PET/CT in 100%, of the spleen with PET/MRI in 66% and PET/CT in 55%, of the lung with PET/MRI in 60% and PET/CT in 100%, of the liver with PET/MRI in 67% and PET/CT in 100%, and of the bone with PET/MRI in 100% and PET/CT in 50%. The only statistically significant difference between PET/MRI and PET/CT was observed in bony infiltration detection rates. For PET/CT, iodinate contrast medium infusions’ average was 86 mL, and exposure to ionizing radiation was estimated to be 4-fold higher than PET/MRI. PET/MRI is a promising safe new alternative in the care of patients with HL. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04537-5.