Assessing recovery after cold challenge and thumb involvement can help to rule out systemic sclerosis in patients presenting with Raynaud?s phenomenon

Objective: Our aim was to study whether recovery from a Raynaud?s attack and involvement of the thumb are differentiators for systemic sclerosis (SSc) in patients with Raynaud?s phenomenon (RP). Method: A stepwise cooling and recovery procedure was performed, provoking an RP attack, in patients with primary Raynaud?s phenomenon (PRP, n =?68) and SSc (n?=?18). During the procedure, the perfusion of all five fingers during cooling and recovery was assessed by photoelectric plethysmography. Results: In SSc patients, perfusion after 10?min in one or more fingers was more frequently not restored than in PRP patients (p?=?0.001), with a negative predictive value of 98%. The thumb was more frequently involved in SSc patients (p?=?0.036), with a negative predictive value of 95%. Positive predictive values were low. Conclusions: In patients with RP, when there is restoration of perfusion in all fingers after 10?min or when the thumb is spared, the presence of an underlying SSc is very unlikely. Although these results need to be validated in a clinical setting in a larger prospective study, these signs can help physicians to select additional testing for SSc in RP patients

Prediction of response to biological treatment with monoclonal antibodies in severe asthma

In recent years, major developments have occurred in severe asthma management. Different asthma phenotypes and subgroups have been identified and new treatment options have become available. A total of five monoclonal antibodies are currently approved in severe asthma treatment: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. These drugs have been shown to reduce exacerbations and to have an oral corticosteroid-sparing effect in many severe asthma patients. However, biological treatment is not successful in all patients and should be discontinued in non-responsive patients. Treating the right patient with the right biologic, and therefore biologic response prediction, has become a major point of interest in severe asthma management. A variety of response outcomes is utilized in the different clinical trials, as well as a huge range of potential predicting factors. Also, regarding the timing of the response evaluation, there are considerable differences between studies. This review summarizes the results from studies on predicting responses and responders to biological treatment in severe asthma, taking into account clinical, functional and inflammatory parameters assessed prior to the start of treatment as well as following a few months of therapy. In addition, future perspectives are discussed, highlighting the need for more research to improve patient identification and treatment responses in the field of biological treatment in severe asthma

Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy:One-year follow-up

Objective: Follow-up of patients with treatment-resistant Raynaud's phenomenon (RP) one-year after single-port thoracoscopic sympathicotomy (SPTS). Methods: Eight patients (six males, two females, median age of 45 years) with treatment-resistant RP underwent left-sided SPTS at the third rib (R3), unilaterally. Questionnaires were taken, and number and duration of RP attacks were reported over a 2-week period. Perfusion was assessed with a cooling and recovery procedure at baseline and one year after SPTS. Furthermore, laser speckle contrast analysis, pulse wave velocity, heart rate variability and nailfold capillary microscopy were performed. Results: One year after SPTS the duration of the attacks of was reduced with 1.9 h in the left hand versus 0.3 h in the right hand. Furthermore, three aspects of the questionnaire showed a significant improvement (role limitations due to physical health (p = 0.017), pain (p = 0.027) and physical functioning (p = 0.025)). The total area under the curve of the total cooling and recovery procedure of the left hand was larger one year after surgery (101 (75–140) at baseline versus 118 (95–190) one year post-operatively, p = 0.012), implying a better perfusion in the fingers. This was mainly due to the improvement during the recovery phase (21 (1–41) at baseline versus 38 (24–43) one year post-operatively, p = 0.028). Conclusion: One year after unilateral R3 SPTS the benefit with regard to the majority of outcome variables persisted, though some effects seem to attenuate. Long-term effects and long-term follow-up results will be investigated in an on-going study. Clinical trial registration number: NCT02680509

Engineering Crystal Packing in RNA-Protein Complexes II: A Historical Perspective from the Structural Studies of the Spliceosome

Cryo-electron microscopy has greatly advanced our understanding of how the spliceosome cycles through different conformational states to conduct the chemical reactions that remove introns from pre-mRNA transcripts. The Cryo-EM structures were built upon decades of crystallographic studies of various spliceosomal RNA-protein complexes. In this review we give an overview of the crystal structures solved in the Nagai group, utilizing many of the strategies to design crystal packing as described in the accompanying paper

Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy:a novel minimally invasive endoscopic technique

OBJECTIVE: To assess the minimally invasive single-port thoracoscopic sympathicotomy feasibility and efficacy in patients with treatment-resistant RP. METHODS: Single-port thoracoscopic sympathicotomy was performed unilaterally on the left side in eight patients with RP (six males, two females, with a median age of 45.2 years). Five patients had primary and three had secondary RP. Perfusion effects in the hands were assessed at baseline and after 1 month by using a cooling and recovery procedure, and by using laser speckle contrast analysis. Number and duration of RP attacks were reported over a 2-week period. RESULTS: Patient satisfaction was 100% after surgery. After surgery, a unilateral improvement in perfusion was observed in the left hand compared with the right hand, with cooling and recovery (P = 0.008) and with laser speckle contrast analysis (P = 0.023). In addition, the number and duration of the attacks in the left hand decreased compared with the right hand (both P = 0.028). No serious adverse events occurred in a follow-up period of at least 10 months. CONCLUSION: Single-port thoracoscopic sympathicotomy is feasible and can be effective in improving hand perfusion in patients with RP. However, long-term efficacy needs to be established. CLINICAL TRIAL REGISTRATION NUMBER: NCT02680509

Postoperative urinary retention:Risk factors, bladder filling rate and time to catheterization: an observational study as part of a randomized controlled trial

Background: Knowledge of risk factors for postoperative urinary retention may guide appropriate and timely urinary catheterization. We aimed to determine independent risk factors for postoperative urinary catheterization in general surgical patients. In addition, we calculated bladder filling rate and assessed the time to spontaneous voiding or catheterization. We used the patients previously determined individual maximum bladder capacity as threshold for urinary catheterization.Methods: Risk factors for urinary catheterization were prospectively determined in 936 general surgical patients. Patients were at least 18 years of age and operated under general or spinal anesthesia without the need for an indwelling urinary catheter. Patients measured their maximum bladder capacity preoperatively at home, by voiding in a calibrated bowl after a strong urge that could no longer be ignored. Postoperatively, bladder volumes were assessed hourly with ultrasound. When patients reached their maximum bladder capacity and were unable to void, they were catheterized by the nursing staff. Bladder filling rate and time to catheterization were determined.Results: Spinal anesthesia was the main independent modifiable risk factor for urinary catheterization (hyperbaric bupivacaine, relative risk 8.1, articaine RR 3.1). Unmodifiable risk factors were a maximum bladder capacity &lt;500 mL (RR 6.7), duration of surgery &gt;= 60 min (RR 5.5), first scanned bladder volume at the Post Anesthesia Care Unit &gt;= 250mL (RR 2.1), and age &gt;= 60 years (RR 2.0). Urine production varied from 100 to 200 mL/h. Catheterization or spontaneous voiding took place approximately 4 h postoperatively.Conclusion: Spinal anesthesia, longer surgery time, and older age are the main risk factors for urinary retention catheterization. Awareness of these risk factors, regularly bladder volume scanning (at least every 3 h) and using the individual maximum bladder capacity as volume threshold for urinary catheterization may avoid unnecessary urinary catheterization and will prevent bladder overdistention with the attendant risk of lower urinary tract injury.</p

Assessment of Contraceptive Counseling and Contraceptive Use in Women After Bariatric Surgery

BACKGROUND: Reproductive-aged women are, according to American and European guidelines, recommended to avoid pregnancy for 12-24 months after bariatric surgery. Oral contraceptives may have suboptimal efficacy after malabsorptive bariatric procedures. AIM: The aim of this study was to assess contraceptive use pre- and postoperatively in women who underwent bariatric surgery in two obesity clinics in The Netherlands. Also, the recall of contraceptive and pregnancy counseling was investigated. METHODS: A validated questionnaire was performed among women aged 18-45 years who underwent bariatric surgery from October 2017 through August 2018. RESULTS: In total, 230 women were eligible for final analysis. Postoperatively, 60% used safe contraception, 16.1% unsafe contraception, and 23.9% no contraception. In this study, 43.7% of women using a potential unsafe contraceptive method preoperatively switched to a safe method of contraception postoperatively (p < 0.0001). Only 62.6% of women confirmed to have received contraceptive counseling, mainly preoperatively. The odds ratio for receiving contraceptive counseling and using safe contraceptive methods compared with not receiving contraceptive counseling was 2.20 (95% CI, 1.27-3.79; p = 0.005). Eighty-three percent confirmed that they have received counseling regarding delaying a pregnancy, and 52.6% were familiar with the recommendation to avoid a pregnancy for 24 months postoperatively. CONCLUSIONS: In our study, 60% of women are using safe contraception postoperatively. Contraceptive counseling is suboptimal as 62.6% recall receiving counseling. Those who confirmed receiving counseling were more likely to use safe contraception after bariatric surgery. More counseling and monitoring in the postoperative and in the outpatient setting is recommended