Improve Success Rates Research Articles

A single-centre experience of His bundle pacing without electrophysiological mapping system: implant success rate, safety, pacing characteristics and one-year follow up.

Despite the challenges related to His bundle pacing (HBP), recent data suggest an improved success rate with experience. As a non-university, non-electrophysiology specialised centre in Singapore, we report our experiences in HBP using pacing system analyser alone. Data of 28 consecutive patients who underwent HBP from August 2018 to February 2019 was retrospectively obtained. The clinical and technical outcomes of these patients were compared between two timeframes of three months each. Patients were followed up for 12 months. Immediate technical success was achieved in 21 (75.0%) patients (mean age 73.3 ± 10.7 years, 47.6% female). The mean left ventricular ejection fraction was 53.9% ± 12.1%. The indications for HBP were atrioventricular block (n = 13, 61.9%), sinus node dysfunction (n = 7, 33.3%) and upgrade from implantable cardioverter-defibrillator to His-cardiac resynchronisation therapy (n = 1, 4.8%). No significant difference was observed in baseline characteristics between Timeframe 1 and Timeframe 2. Improvements pertaining to mean fluoroscopy time were achieved between the two timeframes. There was one HBP-related complication of lead displacement during Timeframe 1. All patients with successful HBP achieved non-selective His bundle (NSHB) capture, whereas only eight patients had selective His bundle (SHB) capture. NSHB and SHB capture thresholds remained stable at the 12-month follow-up. Permanent HBP is feasible and safe, even without the use of an electrophysiology recording system. This was successfully achieved in 75% of patients, with no adverse clinical outcomes during the follow-up period.

A public-private collaboration model for clinical innovation.

Launched in May 2012 as part of the New Therapeutic Uses program, the National Center for Advancing Translational Sciences (NCATS)’ National Institutes of Health (NIH)‐Industry Partnerships initiative fostered collaboration between pharmaceutical companies and the biomedical research community to advance therapeutic development. Over the 10‐year life of the initiative, the industry partners included: AstraZeneca; AbbVie (formerly Abbott); Bristol‐Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; Janssen Pharmaceutical Research & Development, L.L.C.; Pfizer; Sanofi; and Mereo (out licensed assets). The initiative provided researchers at academic medical centers with a rare opportunity to propose clinical trials to test ideas for new therapeutic uses for a selection of clinic‐ready and often previously proprietary experimental pharmaceutical assets that were provided by industry partners. Here, we describe the process by which collaborations between pharmaceutical companies with viable experimental assets and academic researchers with ideas for new uses of those assets were established; and how NCATS/NIH funding supported not only phase I and II clinical trials as well as any nonclinical studies needed before testing in a new patient population, it also provided an opportunity for testing innovative outcome measures for proof‐of‐concept trials. Although the program did not demonstrate improved success rates for phase II clinical trials, this collaboration model leverages the strengths of each party and with a focus toward evaluating an innovative outcome measure, could be used to reduce patient burden and trial costs, and improve patient engagement.

A Two-Stage Bedside Intubation Method to Improve Success Rate of Post-pyloric Placement of Spiral Nasoenteric Tubes in Critically Ill Patients: A Multi-Center, Prospective Study.

BackgroundsProkinetic agents could improve the success rate of post-pyloric placement of self-propelled spiral nasoenteric tubes (NETs), and bedside blind technique might apply as a rescue therapy subsequent to spontaneous transpyloric migration failure. The objective of this study was to investigated the validity and safety of these two bedside intubation methods as a sequential procedure for post-pyloric placement of spiral NETs in critically ill patients.MethodsThe multicenter, prospective study was conducted in intensive care units of four tertiary hospitals (June 2020 to January 2021). Eligible patients received self-propelled spiral NET placements, promoted by prokinetic agents (Stage 1). An abdominal X-ray performed 24 h post-intubation confirmed the position of the tube tip. Patients with a failed transpyloric migration entered Stage 2, where beside blind intubation was conducted (reconfirmed by X-ray). The primary end point was the overall success rate of post-pyloric placement.ResultsThe overall success rate of post-pyloric placement of the spiral NET was 91.1% (73.4% in the third portion of the duodenum [D3] or beyond). The total adverse event rate was 21.0%, without any serious adverse events. In Stage 1, 55.6% of participants achieved transpyloric migration, of these, 44.4% migrated to D3 or beyond. The median time from decision to intubate to the initiation of enteral nutrition (EN) was 25 h. In Stage 2, 83.0% of patients had successful post-pyloric intubation (67.9% in D3 or beyond). The median time from decision to EN initiation after the two-stage process was 36 h.ConclusionsProkinetic agents-assisted self-propelled intubation and remedial bedside blind technique as a sequential procedure for post-pyloric placement of spiral NETs were effective and safe, and this two-stage process did not affect the implementation of early EN in critically ill patients.Trial RegistrationChinese Clinical Trial Registry, ChiCTR1900026381. Registered on 6 October 2019.

Endoscopic radial incision and cutting for benign stenosis of the lower gastrointestinal tract: An investigation of novel endoscopic treatment in multicenter trial.

The standard therapies for benign gastrointestinal stenosis are endoscopic balloon dilation or surgery; each have their advantages and disadvantages. In contrast, radial incision and cutting (RIC) is a novel approach for such stenosis. This study aimed to investigate the feasibility, safety, and effectiveness of RIC. We enrolled 20 patients with benign stenosis of the lower gastrointestinal tract developed by various causes and conducted RIC. We evaluated the re-intervention free rate 52weeks after RIC, technical success rate, adverse events, procedure time, and improvement of symptoms using a visual analog scale. We performed 20 sessions of first RIC for 20 lesions and seven sessions of additional RIC due to re-stenosis. The cumulative re-intervention-free survival rate 52weeks after the first RIC was 55.8%. The technical success rate of the first RIC was 100% (20/20) while that of the additional RIC was 85.7% (6/7). One case developed perforation during the additional RIC and urgent surgery was performed. The additional RIC tended to show worse results in adverse events and procedure time compared with the first RIC. The patients' symptoms including abdominal bloating and dyschezia were significantly improved. Although RIC demonstrated a higher technical success rate for lower gastrointestinal stricture and subsequent improvement of patient symptoms, several issues including preventing delayed bleeding, perforation, and the long-term prognosis should be solved and clarified in further investigations.

PO-708-06 FEASIBILITY OF RIGHT SIDED LEFT BUNDLE BRANCH AREA PACEMAKER INSERTION: A SINGLE CENTER PROSPECTIVE STUDY

Conduction system pacing with the left bundle branch area (LBBAP) is gaining traction as an alternative to traditional right ventricular (RV) pacing. Current implantation systems are designed for insertion through left axillary venous system, which is not always feasible. To evaluate the feasibility of right sided LBBAP lead implantations. Consecutive patients undergoing LBBAP implantation between Feb 2019 and July 2021 at Virginia Commonwealth University were analyzed. Laterality of site access and success rates were recorded. Baseline patient characteristics were tabulated. A total of 422 patients with LBBAP had procedural data available. 408 patients underwent left-sided device insertion with a success rate of 92% and 14 patients underwent right-sided insertion with a success rate of 79% (P=0.10, Table 1). Baseline demographics and indications for pacemaker implantation are listed in Table 1. Patients with right-sided implants were more likely to be referred for CRT (36% vs 9%, p=0.01) and had left bundle branch block (46% vs 14%, p=0.01) compared with left-sided implants. Procedural times were longer in right-sided implants compared with left-sided implants (113±27 vs 93±31 minutes, p=0.02). There was no difference in the mean LVAT and paced QRSd between right sided and left sided implants (Table 2). Lead parameters such as sensing, thresholds and impedances were comparable between the 2 groups. There was no difference in complications. LBBAP success rates may be influenced by the laterality of device insertion. Equipment designed specifically for right-sided implantation may improve success rates, but larger patient populations will be needed to confirm these results. Operator experience with right sided implants is also likely to affect success rates.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

MP29-18 POST-OPERATIVE BLADDER PRESSURE MONITORING FOR SAME DAY CATHETER REMOVAL AFTER HOLEP

You have accessJournal of UrologyCME1 May 2022MP29-18 POST-OPERATIVE BLADDER PRESSURE MONITORING FOR SAME DAY CATHETER REMOVAL AFTER HOLEP Gopal Narang, Charlotte Pougnier, Lanyu Mi, Kevin Wymer, Mitchell Humphreys, and Scott Cheney Gopal NarangGopal Narang More articles by this author , Charlotte PougnierCharlotte Pougnier More articles by this author , Lanyu MiLanyu Mi More articles by this author , Kevin WymerKevin Wymer More articles by this author , Mitchell HumphreysMitchell Humphreys More articles by this author , and Scott CheneyScott Cheney More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002572.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Early catheter removal represents a potential opportunity to improve quality of life and limit treatment burden for patients undergoing BPH procedures. It has proven feasible in patients undergoing HoLEP but only under strict criteria. Furthermore, the influence of patient factors, such as post-operative bladder function, on early catheter removal has not been studied. To help address these limitations, we sought to determine if same day catheter removal was feasible in a generalizable population of HoLEP patients and if bladder pressure assessment could improve success rates. METHODS: From February 2021 to August 2021, we prospectively evaluated same day catheter removal for patients undergoing HoLEP. Patients were excluded if they had a history of atonic or hypocontractile bladder. All patients were anesthetized with general anesthesia and paralyzed. Criteria for proceeding with same day catheter removal included: an uncomplicated procedure, continuous bladder irrigation weaned within 120 minutes of arrival to PACU, minimal hematuria rated with a standardized scale and a bladder pressure over 30 cmH20 as measured using the VP TestTM device (SRS Medical). RESULTS: Over a 6-month period, 45 patients were enrolled in our study. The median age was 68 (IQR: 63.0-72.0) and prostate volume 79.1cc (IQR: 61.0-103.5). Criteria for catheter removal was met by 35 patients; 9 patients were unable to meet bladder pressure cutoffs and 1 was excluded for hematuria. Of those that attempted a trial of void, 29/35 passed for an effective pass rate of 83%. For those that failed trial of void, 100% had uncomplicated catheter replacement in PACU with a median catheter duration of 2 days (IQR: 1-3). Median maximum detrusor pressure for those that passed, failed, and did not attempt a trail of void were 55.0 cmH20 (IQR: 43.0-84.0), 46.0 cmH20 (IQR: 35.0-61.0) and 13.0 cmH20 (IQR: 8.0-23.0), respectively. CONCLUSIONS: In a population of patients who received general anesthesia and paralysis for HoLEP, same day catheter removal is feasible. There are differences in measured post-operative bladder pressure between those that passed and failed trial of void. Bladder pressure measurements in the post-operative setting may be a helpful adjunct for those considering same day catheter removal in HoLEP patients. Source of Funding: SRS medical supplied devices free of charge © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e476 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gopal Narang More articles by this author Charlotte Pougnier More articles by this author Lanyu Mi More articles by this author Kevin Wymer More articles by this author Mitchell Humphreys More articles by this author Scott Cheney More articles by this author Expand All Advertisement PDF DownloadLoading ...

Cumulus cell antioxidant system is modulated by patients' clinical characteristics and correlates with embryo development.

To study whether the cumulus cell antioxidant system varies accordingly to patients clinical characteristics' as age, infertility diagnosis, BMI, and stimulation protocol applied and if the antioxidant profile of cumulus cells could be used as a predictor of embryo development. A prospective study including 383 human cumulus samples provided by 191 female patients undergoing intracytoplasmic sperm injection during in vitro fertilization treatments from a local in vitro fertilization center and processed in university laboratories. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) enzyme activity levels and reduced glutathione (GSH) levels were measured in cumulus oophorus cells individually collected from each aspirated cumulus-oocyte complex, and the results of each sample were compared considering the oocytes outcome after ICSI and patients clinical characteristics. A total of 223 other human cumulus samples from previous studies were submitted to a gene expression meta-analysis. The antioxidant system changes dramatically depending on patients' age, infertility diagnosis, stimulation protocol applied, and oocyte quality. SOD activity in cumulus cells revealed to be predictive of top-quality blastocysts for young patients with male factor infertility (P < 0.05), while GST levels were shown to be extremely influenced by infertility cause (P < 0.0001) and stimulation protocol applied (P < 0.05), but nonetheless, it can be used as a complementary tool for top-quality blastocyst prediction in patients submitted to intracytoplasmic sperm injection technique (ICSI) by male factor infertility (P < 0.05). Through a simple and non-invasive analysis, the evaluation of redox enzymes in cumulus cells could be used to predict embryo development, in a personalized matter in specific patient groups, indicating top-quality oocytes and improving success rates in in vitro fertilization treatments. The trial was registered at UFRGS Research Ethics Committee and Plataforma Brasil under approval number 68081017.2.0000.5347 in June 6, 2019.

Mulch more so than compost improves soil health to reestablish vegetation in a semiarid rangeland

Up to half of the world's drylands have degraded, dysfunctional soils that lower success rates of restoration efforts to reestablish lost vegetation. Because soil amendments of organic matter have the potential to improve multiple ecosystem functions and overall soil health, we added a mulch of whole mesquite (Prosopis velutina) branches—both alone and in combination with 3 and 6 cm of compost—to a degraded semiarid rangeland. We then measured effects of these organic amendments on a suite of soil health indicators as well as plant cover and abundance. We found that surface applications of these amendments improved several indicators of soil health after two summer growing seasons. Soil temperature decreased and soil moisture increased in all treatments with organic amendments. However, during drier times of the year and in response to smaller rain events, mulch alone increased soil moisture more so than when combined with compost. As expected, total soil nitrogen was greatest with compost addition. Soil organic carbon, water‐stable aggregate size, and microbial abundance did not respond significantly to any treatment. Mesquite mulch increased native plant cover and abundance when applied without compost and increased plant cover when combined with 3 cm of compost, but it did not increase plant abundance or cover when combined with 6 cm of compost. Collectively, these results suggest that a thin layer of compost—but particularly woody branches used as mulch—can improve success rates of revegetation in dryland ecosystems by moderating the soil microclimate.

Differences or Disorders of sex development in Boys: impact on fertility

Differences or disorders of sex development (DSD) include various congenital conditions in which chromosomal, gonadal, or anatomical sex development is atypical. The incidence varies according to the category of DSD but the total incidence is high if hypospadias and undescended testes are included. Fertility prospects may be a concern for DSD patients and their parents. With the development of modern medical technologies and treatment opportunities, fertility diagnostics, information, and treatment have changed. Assisted reproductive technology has developed during the past decades and has become more available with an improving success rate. Intracytoplasmic sperm injection and testicular sperm retrieval, have further improved the possibilities for men with DSD to become biological parents. Some studies have determined the presence of germ cells in the gonads of patients with DSD suggesting that the potential for fertility may be higher than previously thought. However, fertility outcomes among individuals with DSD have not been fully investigated. Moreover, previous study showed that information on fertility problems and treatment possibilities given to patients with DSD needs to be improved. The use of registries to study fertility outcomes is essential for a better knowledge of fertility in patients with these rare conditions.

Fatalism, distrust, and breast cancer treatment refusal in Ghana.

Following recent advancements in science and technology, cancer treatment options have increased remarkably alongside improved survival rates. Yet, some individuals diagnosed with breast cancer refuse treatment. This study aimed to explore how breast cancer patients' personal beliefs and ideas influence their decision to refuse medical treatment. Thirteen participant interviews were selected from a larger cohort for a secondary analysis using the grounded theory approach. The decision to forgo medical treatment was influenced mainly by personal beliefs, which were framed as: 1. Triangle of religion, superstition, and ignorance, 2. Ghanaian traditional belief system, 3. My destiny, 4. Frail patient-staff relationships, 5. Futile appointments, and 6. Endless journey. Together, these fit into two overall themes-fatalism and poor communication patterns between healthcare providers and patients. Personal beliefs and managerial gaps within the health system mainly influence the growing trend of refusal of medical treatment among breast cancer patients in Ghana. These findings highlight the need for breast cancer education, professional counselling, and psychological support services.

Effect of side guide marks of ultrasound transducer on the success rate of ultrasound transducer-guided radial artery puncture: A randomized trial.

Compared with blind technique, ultrasound (US) transducer-guided technique for radial artery puncture can improve the success rate. However, difficulty in handling US transducer-guided technology is a key limitation to its wider use. The aim of the study was to explore the effect of guide marks on the side of US transducer on the success rate of US transducer-guided radial artery puncture. In this parallel-group trial, 127 patients undergoing elective liver cancer resection and splenectomy under general anesthesia were randomly allocated to the traditional group or the Intervention group. The traditional group used the conventional US transducer-guided radial artery puncture technology, while the Intervention group used the US transducer-guided radial artery puncture technology with the guide marks on the side of the US transducer probe. The primary observation index was success rate of radial artery cannulation at the first attempt; the secondary observation indices were failure rate of cannulation, location time, and total time for successful cannulation. The successful rate of cannulation in the Intervention group (59 out of 63, 93.6%) was greater than that in the traditional group (50 out of 64, 78.1%, p = 0.01). The posterior wall puncture rate in the Intervention group was lower than that in the traditional group (11.1% vs 32.8%, p = 0.005). The location time in the Intervention group was longer than that in the traditional group (20.1 ± 3.8 vs 16.6 ± 4.0 s, p < .001), while the total cannulation time was significantly shorter (20.7 ± 4.3 vs 32.4 ± 7.4 s, p < 0.001). Using guide marks on the side of US transducer can help improve success rate of US transducer-guided radial artery puncture at the first attempt and reduce the risk of puncture-related complications.

Hemoglobinopathies and preimplantation diagnostics.

Hemoglobinopathies constitute some of the most common inherited disorders worldwide. Manifestations are very severe, patient management is difficult and treatment is not easily accessible. Preimplantation genetic testing for monogenic disorders (PGT-M) is a valuable reproductive option for hemoglobinopathy carrier-couples as it precludes the initiation of an affected pregnancy. PGT-M is performed on embryos generated by assisted reproductive technologies and only those found to be free of the monogenic disorder are transferred to the uterus. PGT-M has been applied for 30 years now and β-thalassemia is one of the most common indications. PGT may also be applied for human leukocyte antigen typing to identify embryos that are unaffected and also compatible with an affected sibling in need of hemopoietic stem cell transplantation. PGT-M protocols have evolved from PCR amplification-based, where a small number ofloci were analysed, to whole genome amplification-based, the latter increasing diagnostic accuracy, enabling the development of more generic strategies and facilitating multiple diagnoses in one embryo. Currently, numerous PGT-M cycles are performed for the simultaneous diagnosis of hemoglobinopathies and screening for chromosomal abnormalities in the embryo in an attempt to further improve success rates and increase deliveries of unaffected babies.

Practical consideration for successful sequential tumor biopsies in first-in-human trials

In first-in-human (FIH) trials, sequential tumor biopsies, i.e., two consecutive tumor biopsies, the first performed at baseline (pretreatment) and the second during the early treatment period (on-treatment), provide proof of concept in investigational new drugs. We evaluated the success of sequential tumor biopsies in FIH trials, and explored approaches for improved success rates. We retrospectively reviewed the sequential tumor biopsies required in 17 of 52 FIH trials conducted from 2015 to 2020. One hundred and thirty-eight patients were identified. Success of either pretreatment or on-treatment biopsy alone, and of sequential tumor biopsies, was defined as the acquisition of viable tumor cells and as obtaining tumor cells from both biopsy specimens, respectively. The success rates of pretreatment and on-treatment biopsy were 98.6% and 94.2%, respectively, and of sequential tumor biopsies was 70.3%. Adverse events associated with the pretreatment biopsies (33.3% positive; 72.0% negative) and timing of the first imaging assessment (before on-treatment biopsy = 40.0%; after on-treatment biopsy = 82.7%) correlated with successful sequential tumor biopsies. The reasons for unsuccessful sequential tumor biopsies could be categorized into two groups: 1) patient refusal of the on-treatment biopsy (most frequently due to early disease progression); and 2) absence of tumor cells in the pretreatment or on-treatment biopsy specimen. We propose an approach to achieving greater success in sequential tumor biopsies in FIH trials; the first imaging assessment during the study should be scheduled after on-treatment biopsy. (Registration number UMIN000042487, Date of registration November 18, 2020).

Utility of a cloud-based lesion data collection software to record, monitor, and analyze an ablation strategy.

Catheter radiofrequency (RF) ablation–based pulmonary vein isolation is the predominant approach to ablation of atrial fibrillation (AF). Attempts to improve success rates have included real-time monitoring of factors related to lesion formation, such as contact force (CF), power, impedance changes, lesion duration, and calculated indices such as ablation index (AI) (SURPOINT, Biosense Webster, Diamond Bar, CA). Data created from each lesion typically are lost because of logistical challenges related to storage, retrieval, and analysis.

Role of Artificial Intelligence with Regards to Improving Success Rate in Human In Vitro Fertilization with Emphasis on the Blastocyst Characteristics with Respect to Improving Implantation, Avoiding Aneuploidy for Optimization of Live Birth Rates

Artificial Intelligence (AI) is an expanding field to optimize results in medicine with special emphasis in radiology with optimization of images. Similarly in reproductive medicine it has taken over in the last few years. Ideally embryo assessment as well as selection decides the ultimate fate of the in vitro fertilization (IVF) event. The objective is to pick the best out of the large cohort of the oocytes that managed to get fertilized. Maximum of which would work out to be nonviable secondary to aberrant generation or chromosomal aberrations. It has usually been recognized that despite embryo selection depending on the compounded results of morphology, morph kinetics characteristics, time lapse microscopic (TLM) photography, or embryo biopsy with Preimplantation genetic testing for aneuploidy (PGT-A), implantation rates in the human has not been easy to anticipate. Hence in our efforts to escalate embryo assessment as well as selection along with escalation of live birth rate (LBR) would need innovative methods. Currently AI-dependent techniques have come out having standardized, objective along with great effectiveness in embryo assessment. Thus a systematic review was carried out utilizing the search engine PubMed, Google scholar; web of science; embase; Cochrane review library from 2000 to 2020 till date. The MeSH terms utilized were AI; ART; IVF; ICSI; PGT; TLM; BL(blastocyst) morph kinetics; morphology; annotation studies; sperm parameters; ploidy evaluation by AI; utilization of images static vs video for generation of standards; embryo grading; infertility evaluation. We found a total of 316 articles out of which we selected 56 articles for this review. No meta-analysis was carried out. Further AI can be utilized for other aspects of IVF like gonadotropin stimulation individualization protocols as well as assessment of Reproductive potential. Moreover AI possesses capacity to evaluate Big Data. Moreover our main objective would be the application of AI tools for evaluation of embryological, genetic as well as clinical data to give patients specific treatment

Immunomodulatory Properties of Immune Checkpoint Inhibitors-More than Boosting T-Cell Responses?

Simple SummaryTumor immune evasion is mediated in large part by the inhibition of anti-tumor T cell responses. Both the induction of tumor antigen-specific T cells and the activation state of T effector cells may be attenuated by surface receptors, which upon binding to counter receptors on immunoregulatory cell types and tumor cells, induce inhibitory T cell signaling. Immune checkpoint inhibitors (ICI) are antibodies that block interaction of these receptor pairs and thereby prevent T cell inhibition. Only a small percentage of tumor patients are responsive to treatment with ICI, which on the one hand raises the issue of possible reasons for failure, and on the other hand has spurred the development of additional ICI targeting other T cell inhibitory receptors. Our review aims to summarize knowledge on the functional role of these (inhibitory) receptors by additional types of leukocytes, and consequences of receptor blockade by ICI as a potential cause for unwanted side effects limiting the success of therapy. Deeper knowledge in this regard is a prerequisite for the development of more refined combination therapies.The approval of immune checkpoint inhibitors (ICI) that serve to enhance effector T-cell anti-tumor responses has strongly improved success rates in the treatment of metastatic melanoma and other tumor types. The currently approved ICI constitute monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein (CTLA)-4 and anti-programmed cell death (PD)-1. By this, the T-cell-inhibitory CTLA-4/CD80/86 and PD-1/PD-1L/2L signaling axes are inhibited. This leads to sustained effector T-cell activity and circumvents the immune evasion of tumor cells, which frequently upregulate PD-L1 expression and modulate immune checkpoint molecule expression on leukocytes. As a result, profound clinical responses are observed in 40–60% of metastatic melanoma patients. Despite the pivotal role of T effector cells for triggering anti-tumor immunity, mounting evidence indicates that ICI efficacy may also be attributable to other cell types than T effector cells. In particular, emerging research has shown that ICI also impacts innate immune cells, such as myeloid cells, natural killer cells and innate lymphoid cells, which may amplify tumoricidal functions beyond triggering T effector cells, and thus improves clinical efficacy. Effects of ICI on non-T cells may additionally explain, in part, the character and extent of adverse effects associated with treatment. Deeper knowledge of these effects is required to further develop ICI treatment in terms of responsiveness of patients to treatment, to overcome resistance to ICI and to alleviate adverse effects. In this review we give an overview into the currently known immunomodulatory effects of ICI treatment in immune cell types other than the T cell compartment.

Trajectory-Based Skill Learning for Overhead Construction Robots Using Generalized Cylinders with Orientation

Overhead work involving the construction and maintenance of civil infrastructure (e.g., tunnels, overpasses, and buildings) is strenuous and fatigue-inducing for human workers and is particularly well-suited for co-robotization. Such work is typically quasi-repetitive, and on-site robots must adapt to unexpected workface conditions. Methods such as learning from demonstration can leverage human experts’ demonstration to let robots directly learn new skills to perform tasks. This paper proposes a generalized cylinders with orientation approach to teach robots how to perform quasi-repetitive overhead construction tasks from human demonstration. The demonstration trajectories are first used to construct a generalized cylinder and generate the robot trajectory. To ensure that the construction component (e.g., tunnel lining segment, building ceiling tile) being installed can satisfy the geometric constraints of the workspace, orientation constraints need to be determined, and the robot must follow such constraints. A trajectory adaptation and human-in-the-loop refinement approach are developed to refine the robot trajectory. The proposed method was evaluated in a robot simulator with variable workspace. The results showed that the proposed approach achieves an improved success rate (82.0%) compared to that demonstrated in previous work (71.3%) and enables overhead construction robots to readily adapt to new worksite conditions.

Airtraq® versus GlideScope® for tracheal intubation in adults: a systematic review and meta-analysis with trial sequential analysis.

In recent years, various types of indirect laryngoscopes have been developed. Nevertheless, no conclusions have been drawn about which type of indirect laryngoscope is most effective for tracheal intubation. We performed a systematic review and meta-analysis to determine whether the Airtraq® or the GlideScope® is more effective for tracheal intubation. We extracted studies of adult prospective randomized trials comparing tracheal intubation between the Airtraq and GlideScope. An electronic database was used to extract the studies included in our meta-analysis. We extracted the following data from the identified studies: success rate, glottic visualization, and intubation time. Data from each trial were combined via a random-effects model for calculation of pooled relative risk (RR) or weighted mean difference (WMD) with a 95% confidence interval (CI). We also performed trial sequential analysis. We included eight trials comprising 571 patients for review. Compared with the GlideScope, Airtraq did not improve success rate, glottic visualization, or intubation time in tracheal intubation (success rate: RR, 0.98; 95% CI, 0.91 to 1.05; P = 0.58; I2 = 65%; glottic visualization: RR, 1.07; 95% CI, 0.88 to 1.29; P = 0.69; I2 = 64%; and intubation time: WMD, 1.4 seconds ; 95% CI, -6.2 to 9.1; P = 0.72; I2 = 96%). The quality of evidence was graded as "very low." Trial sequential analysis showed that total sample size did not reach the required information size for all parameters. In this meta-analysis, use of the Airtraq indirect laryngoscope did not result in improved success rate, glottic visualization, or intubation time in tracheal intubation compared with the GlideScope. Trial sequential analysis suggests that further studies are necessary to confirm these findings.

Electrochemically driven cross-electrophile coupling of alkyl halides.

Recent research in medicinal chemistry has suggested that there is a correlation between an increase in the fraction of sp3 carbons-those bonded to four other atoms-in drug candidates and their improved success rate in clinical trials1. As such, the development of robust and selective methods for the construction of carbon(sp3)-carbon(sp3) bonds remains a critical problem in modern organic chemistry2. Owing to the broad availability of alkyl halides, their direct cross-coupling-commonly known as cross-electrophile coupling-provides a promising route towards this objective3-5. Such transformations circumvent the preparation of carbon nucleophiles used in traditional cross-coupling reactions, as well as stability and functional-group-tolerance issues that are usually associated with these reagents. However, achieving high selectivity in carbon(sp3)-carbon(sp3) cross-electrophile coupling remains a largely unmet challenge. Here we use electrochemistry to achieve the differential activation of alkyl halides by exploiting their disparate electronic and steric properties. Specifically, the selective cathodic reduction of a more substituted alkyl halide gives rise to a carbanion, which undergoes preferential coupling with a less substituted alkyl halide via bimolecular nucleophilic substitution to forge a new carbon-carbon bond. This protocol enables efficient cross-electrophile coupling of a variety of functionalized and unactivated alkyl electrophiles in the absence of a transition metal catalyst,and shows improved chemoselectivity compared with existing methods.

Prehospital Simple Thoracostomy Does Not Improve Patient Outcomes Compared to Needle Thoracostomy in Severely Injured Trauma Patients.

ATLS suggests simple thoracostomy (ST) after failure of needle thoracostomy (NT) in thoracic trauma. Some EMS agencies have adopted ST into their practice. We sought to describe our experience implementing ST in the prehospital setting, hypothesizing that prehospital ST would reduce failure rates and improve outcomes compared to NT. This was a retrospective review of adult trauma patients who received prehospital ST or NT from 2017 to 2020. There were 48 patients with 64 procedures included. 83.7% were male and 65.8% injured by penetrating mechanism and of median (IQR) age of 31 (25-46)years. 28 (43.8%) procedures were NT and 36 (56.3%) were ST. Rates of improved patient response (P = .15), noted return of blood/air (P = .19), and return of spontaneous circulation (P = .62) did not differ. On-scene times were higher for ST (16.8 vs 11.5minutes; P < .02). Overall mortality did not differ between ST and NT (68.2% vs 46.4%, respectively; P = .125). For patients that survived beyond the ED, procedure-related complication rates were 2 of 21 patients (9.5%) in ST and 1 of 12 (8.3%) in NT. In penetrating trauma, simple thoracostomy had longer on-scene time and total prehospital time. ST did not improve success rates of ROSC and was associated with prolonged prehospital times, especially in penetrating trauma patients. Given the benefit of "scoop and run" in urban penetrating trauma, consideration should be given to direct transport in lieu of ST. Use of ST in blunt trauma should be evaluated prospectively.