Themes, Rates, and Risk of Adverse Events of the Artificial Pancreas in the United States Using MAUDE.

Three manufacturers sell artificial pancreas systems in the United States for management of Type 1 Diabetes. Given the life-saving task required of an artificial pancreas there needs to be a high level of trust and safety in the devices. This evaluation sought to find the adjusted safety event reporting rate and themes along with device-associated risk in events reported utilizing the MAUDE database. We searched device names in the MAUDE database over the period from 2016 until August 2023 (the date of retrieval). Thematic analysis was performed using dual-reviewer examination with a 96% concurrence. Relative risk (RR) was calculated for injury, malfunction, and overall, for each manufacturer, as well as adjusted event rate per manufacturer. Most events reported related to defects in the manufacturing of the casing materials which resulted in non-delivery of therapy. Tandem Diabetes Care, Inc. had an adjusted event rate of 50 per 100,000 units and RR of 0.0225. Insulet had an adjusted event rate of 300 per 100,000 units and RR of 0.1684. Medtronic has an adjusted event rate of 2771.43 per 100,000 units and RR of 20.7857. The newer Medtronic devices show improvements in likely event rate. While the artificial pancreas is still in its infancy, these event rates are not at an acceptable level for a device which can precipitate death from malfunctions. Further exploration into safety events and much more research and development is needed for devices to reduce the event rates. Improved manufacturing practices, especially the casing materials, are highly recommended. The artificial pancreas holds promise for millions but must be improved before it becomes a true life-saving device that it has the potential to become.

Alternative Conduits for Lower Extremity Bypass.

While single-segment great saphenous vein (GSV) remains the gold-standard conduit for infrainguinal bypass, several alternative options are available for use when GSV is absent in patients with chronic limb threatening ischemia requiring infrainguinal revascularization including alternative autologous vein, prosthetic conduits, and cryopreserved vein grafts.

Association of JAK2V617F allele burden and clinical correlates in polycythemia vera: a systematic review and meta-analysis.

Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.

Factors Associated with Statin Discontinuation Following Metabolic and Bariatric Surgery: A Retrospective Analysis of 2012-2021 Electronic Medical Records Network Data.

BACKGROUND: Bariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, it is uncertain if discontinuation risks differ between those with and without ASCVD history. AIM: The study aims to analyze the rate and reasons for statin cessation post-bariatric surgery in the US using real-world data. METHODS: Using the TriNetX electronic medical records network from 2012 to 2021, the study involved patients aged 18 or older on statins at the time of bariatric surgery. They were categorized into primary and secondary prevention groups based on prior ASCVD. Statin discontinuation was defined as a 90-day gap post the last statin dosage. The Cox model assessed factors influencing statin cessation. RESULTS: Seven hundred and thirty-three statin users undergoing bariatric surgery were identified, with 564 (77%) in primary prevention. Six months post-surgery, 48% of primary prevention patients and 34.5% of secondary ones stopped statins. Primary prevention patients had a 30% higher likelihood of cessation compared to secondary prevention (hazard ratio, 1.30; 95% CI, 1.06-1.60) as shown by multivariable analysis. CONCLUSIONS: Post-bariatric surgery, primary prevention patients are more likely to discontinue statins than secondary prevention patients.

Statistical 3D morphology characterization of vaterite microspheres produced by engineered Escherichia coli.

Hollow vaterite microspheres are important materials for biomedical applications such as drug delivery and regenerative medicine owing to their biocompatibility, high specific surface area, and ability to encapsulate a large number of bioactive molecules and compounds. We demonstrated that hollow vaterite microspheres are produced by an Escherichia coli strain engineered with a urease gene cluster from the ureolytic bacteria Sporosarcina pasteurii in the presence of bovine serum albumin. We characterized the 3D nanoscale morphology of five biogenic hollow vaterite microspheres using 3D high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) tomography. Using automated high-throughput HAADF-STEM imaging across several sample tilt orientations, we show that the microspheres evolved from a smaller more ellipsoidal shape to a larger more spherical shape while the internal hollow core increased in size and remained relatively spherical, indicating that the microspheres produced by this engineered strain likely do not contain the bacteria. The statistical 3D morphology information demonstrates the potential for using biogenic calcium carbonate mineralization to produce hollow vaterite microspheres with controlled morphologies. STATEMENT OF SIGNIFICANCE: The nanoscale 3D structures of biomaterials determine their physical, chemical, and biological properties, however significant efforts are required to obtain a statistical understanding of the internal 3D morphology of materials without damaging the structures. In this study, we developed a non-destructive, automated technique that allows us to understand the nanoscale 3D morphology of many unique hollow vaterite microspheres beyond the spectroscopy methods that lack local information and microscopy methods that cannot interrogate the full 3D structure. The method allowed us to quantitatively correlate the external diameters and aspect ratios of vaterite microspheres with their hollow internal structures at the nanoscale. This work demonstrates the opportunity to use automated transmission electron microscopy to characterize nanoscale 3D morphologies of many biomaterials and validate the chemical and biological functionality of these materials.

A Decade of Nipple-Sparing Mastectomy: Lessons Learned in 3035 Immediate Implant-Based Breast Reconstructions.

BACKGROUND: Nipple-sparing mastectomy is commonly performed for breast cancer treatment or prevention. The authors present one of the largest breast reconstruction series in the literature. METHODS: A single-institution retrospective review was conducted from 2007 to 2019. RESULTS: The authors' query identified 3035 implant-based breast reconstructions after nipple-sparing mastectomy, including 2043 direct-to-implant and 992 tissue expander-to-implant reconstructions. The overall major complication rate was 9.15%, and the nipple necrosis rate was 1.20%. Therapeutic mastectomy was associated with higher overall complications and explantations compared with prophylactic mastectomy ( P < 0.01). In comparisons of unilateral and bilateral procedures, bilateral mastectomy had an increased risk for complications (OR, 1.46; 95% CI, 0.997 to 2.145; P = 0.05). Tissue-expander reconstructions had higher rates of nipple necrosis (1.9% versus 0.88%; P = 0.015), infection (4.2% versus 2.8%; P = 0.04), and explantation (5.1% versus 3.5%; P = 0.04) compared with direct-to-implant reconstruction. When assessing plane of reconstruction, the authors found similar rates of complications between subpectoral dual-plane and prepectoral reconstruction. There was no difference in complications between reconstruction with acellular dermal matrix or mesh compared with total or partial muscle coverage without acellular dermal matrix/mesh (OR, 0.749; 95% CI, 0.404 to 1.391; P = 0.361). Multivariable regression analysis revealed preoperative radiotherapy (OR, 2.465; 95% CI, 1.579 to 3.848; P < 0.001), smoking (OR, 2.53; 95% CI, 1.581 to 4.054; P < 0.001), and a periareolar incision (OR, 3.657; 95% CI, 2.276 to 5.875; P < 0.001) to be the strongest predictors of complications and nipple necrosis ( P < 0.05). CONCLUSIONS: Nipple-sparing mastectomy and immediate breast reconstruction has a low rate of complications. In this series, radiation therapy, smoking, and incision choice predicted overall complications and nipple necrosis, whereas direct-to-implant reconstruction and acellular dermal matrix or mesh did not increase risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus.

Rapid-eye-movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

Metabolic and Bariatric Surgery Utilization Trends in the United States: Evidence From 2012 to 2021 National Electronic Medical Records Network.

Background: Bariatric surgery has evolved over the past 2 decades yet assessing trends of bariatric surgery utilization in the growing eligible population is lacking. Aim: This study aimed to update the trends in bariatric surgery utilization, changes in types of procedures performed, and the characteristics of patients who underwent bariatric surgery in the United States, using real-world data. Method: This retrospective descriptive observational study was conducted using the TriNetX, a federated electronic medical records network from 2012 to 2021, for adult patients 18 years old or older who had bariatric surgery. Descriptive statistical analysis was conducted to assess patients' demographics and characteristics. Annual secular trend analyses were conducted for the annual rate of bariatric surgery, and the specific procedural types and proportions of laparoscopic surgeries. Results: A steady increase in the number of procedures performed in the United States over the first 6 years of the study, a plateau for the following 2 years, and then a decline in 2020 and 2021 (during the coronavirus disease 2019 pandemic). The annual rate of bariatric surgery was lowest in 2012 at 59.2 and highest in 2018 at 79.6 surgeries per 100,000 adults. During the study period, 96.2% to 98.8% of procedures performed annually were conducted laparoscopically as opposed to the open technique. Beginning in 2012, the Roux-en-Y gastric bypass (RYGB) procedure fell to represent only 17.1% of cases in 2018, along with a sharp decline in the adjustable gastric band (AGB) procedure, replaced by a sharp increase in the sleeve gastrectomy (SG) procedure to represent over 74% of cases in 2018. Conclusions: Bariatric surgery utilization in the United States showed a moderate decline in the number of RYGB procedures, which was offset by a substantial increase in the number of SG procedures and a precipitous drop in the annual number of AGB procedures.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

Quantitative Geometric Modeling of Blood Cells from X-ray Histotomograms of Whole Zebrafish Larvae.

Tissue phenotyping is foundational to understanding and assessing the cellular aspects of disease in organismal context and an important adjunct to molecular studies in the dissection of gene function, chemical effects, and disease. As a first step toward computational tissue phenotyping, we explore the potential of cellular phenotyping from 3-Dimensional (3D), 0.74 µm isotropic voxel resolution, whole zebrafish larval images derived from X-ray histotomography, a form of micro-CT customized for histopathology. As proof of principle towards computational tissue phenotyping of cells, we created a semi-automated mechanism for the segmentation of blood cells in the vascular spaces of zebrafish larvae, followed by modeling and extraction of quantitative geometric parameters. Manually segmented cells were used to train a random forest classifier for blood cells, enabling the use of a generalized cellular segmentation algorithm for the accurate segmentation of blood cells. These models were used to create an automated data segmentation and analysis pipeline to guide the steps in a 3D workflow including blood cell region prediction, cell boundary extraction, and statistical characterization of 3D geometric and cytological features. We were able to distinguish blood cells at two stages in development (4- and 5-days-post-fertilization) and wild-type vs. polA2 huli hutu ( hht ) mutants. The application of geometric modeling across cell types to and across organisms and sample types may comprise a valuable foundation for computational phenotyping that is more open, informative, rapid, objective, and reproducible.

Real-world patient characteristics and treatment patterns of polycythemia vera in Taiwan between 2016 and 2017: a nationwide cross-sectional study.

Background: Polycythemia vera (PV) patients often experience constitutional symptoms and are at risk of thromboembolism as well as disease progression to myelofibrosis or acute myeloid leukemia. Not only is PV often overlooked but treatment options are also limited, however. Objectives: To explore the patient characteristics and treatment pattern of PV patients in Taiwan, and compare with other countries reported in the literature. Design: This is a nationwide cross-sectional study. Methods: The National Health Insurance Research Database in Taiwan, which covers 99% of the population, was utilized. Patients were identified during the cross-sectional period between 2016 and 2017, and their retrospective data were retrieved from 2001 to 2017. Results: A total of 2647 PV patients were identified between 1 January 2016 and 31 December 2017. This study described the demographic information of these patients, including number of patients by risk stratification and by sex, age at diagnosis, age at cross-sectional period, rate of bone marrow aspiration/biopsy at diagnosis, comorbidities, number of postdiagnosis thrombosis, number of disease progression, and death. The mortality rate of PV patients (4.1%) over 60 of age was higher than the general population of the same age group (2.8%). This study also compared the different treatment patterns between sexes and risk groups. Hydroxyurea was deferred to an older age, but conversely was prescribed at higher dose to younger patients. Alarmingly, a high proportion of patients did not receive phlebotomy or hydroxyurea for at least 2 years. Furthermore, discrepancies in prevalence, age at diagnosis, sex ratio, incidence of thrombosis and mortality were also found when compared with data reported in other countries. Conclusion: The clinical landscape of PV in Taiwan between 2016 and 2017 was examined. Distinctive patterns of phlebotomy and hydroxyurea were identified. Overall, these findings highlight the importance of understanding the patient characteristics and treatment patterns of PV in different regions to better inform clinical practice and improve patient outcomes.

Application of Pharmacogenomics Testing in a Community-based Facility.

This study was designed to examine the use of pharmacogenomics (PGx) testing in a community-based facility, the adoption of the PGx recommendations by providers, and assess challenges and opportunities for pharmacists in using PGx testing in a real-world setting. This was a retrospective study involving chart reviews of 137 patients with mood disorders who underwent PGx testing between September 2017 and December 2017. Eighty-seven patients who met inclusion and exclusion criteria were analyzed to evaluate the impact of PGx testing on psychotropic medication treatment and to evaluate the PGx test process. PGx test results were used by providers to guide their therapeutic modifications based on the gene-drug interactions identified. Patient medication use increased from 125 to 190 (P < .001) prescriptions. Patient medication belonging to no gene-drug interaction significantly increased from 46.4% to 87.4% (P < .001), medications belonging to moderate and significant gene-drug interaction decreased from 32.8% to 7.9% (P < .001) and 11.2% to 2.1% (P = .012), respectively. 88.5% of patients' psychotropic medication treatment after PGx testing was consistent with the PGx test report recommendations. The PGx test lengths of time analysis indicated that patient follow-up exceeded the standard time set by guidelines at multiple steps in the test process. There are multiple opportunities for pharmacists to become involved in the PGx testing process to improve patient care.

Head and Neck Radiation Therapy Patterns of Practice Variability Identified as a Challenge to Real-World Big Data: Results From the Learning from Analysis of Multicentre Big Data Aggregation (LAMBDA) Consortium.

Purpose: Outside of randomized clinical trials, it is difficult to develop clinically relevant evidence-based recommendations for radiation therapy (RT) practice guidelines owing to lack of comprehensive real-world data. To address this knowledge gap, we formed the Learning from Analysis of Multicenter Big Data Aggregation consortium to cooperatively implement RT data standardization, develop software solutions for data analysis, and recommend clinical practice change based on real-world data analyzed. The first phase of this "Big Data" study aimed at characterizing variability in clinical practice patterns of dosimetric data for organs at risk (OARs) that would undermine subsequent use of large-scale, electronically aggregated data to characterize associations with outcomes. Evidence from this study was used as the basis for practical recommendations to improve data quality. Methods and Materials: Dosimetric details of patients with head and neck cancer treated with radiation therapy between 2014 and 2019 were analyzed. Institutional patterns of practice were characterized, including structure nomenclature, volumes, and frequency of contouring. Dose volume histogram (DVH) distributions were characterized and compared with institutional constraints and literature values. Results: Plans for 4664 patients treated to a mean plan dose of 64.4 ± 13.2 Gy in 32 ± 4 fractions were aggregated. Before implementation of TG-263 guidelines in each institution, there was variability in OAR nomenclature across institutions and structures. With evidence from this study, we identified a targeted and practical set of recommendations aimed at improving the quality of real-world data. Conclusions: Quantifying similarities and differences among institutions for OAR structures and DVH metrics is the launching point for next steps to investigate potential relationships between DVH parameters and patient outcomes.

Combining prostate health index and multiparametric magnetic resonance imaging may better predict extraprostatic extension after radical prostatectomy.

BACKGROUND: In patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), preoperative prediction of extraprostatic extension (EPE) can facilitate patient selection for nerve-sparing procedures. Since both multiparametric magnetic resonance imaging (mpMRI) and prostate health index (PHI) have shown promise for the diagnosis and prognostication of PCa, we investigated whether a combination of mpMRI and PHI evaluations can improve the prediction of EPE after RP. METHODS: Patients diagnosed with PCa and treated with RP were prospectively enrolled between February 2017 and July 2019. Preoperative blood samples were analyzed for PHI (defined as [p2PSA/fPSA] × âˆštPSA), and mpMRI examinations were performed and interpreted by a single experienced uroradiologist retrospectively. The area under the receiver operating characteristic curve (ROC) was used to determine the performance of mpMRI, PHI, and their combination in predicting EPE after RP. RESULTS: A total of 163 patients were included for analysis. The pathological T stage was T3a or more in 59.5%. Overall staging accuracy of mpMRI for EPE was 72.4% (sensitivity and specificity: 73.2% and 71.2%, respectively). The area under the ROC of the combination of mpMRI and PHI in predicting EPE (0.785) was higher than those of mpMRI alone (0.717; p = 0.0007) and PHI alone (0.722; p = 0.0236). mpMRI showed false-negative non-EPE results in 26 patients (16%), and a PHI threshold of >40 could avoid undiagnosed EPE before RP in 21 of these 26 patients. CONCLUSION: The combination of PHI and mpMRI may better predict the EPE preoperatively, facilitating preoperative counseling and tailoring the need for nerve-sparing RP.

Is Robotic Superior to Laparoscopic Approach for Radical Nephroureterectomy with Bladder Cuff Excision in Treating Upper Urinary Tract Urothelial Carcinoma?

Background: Laparoscopic nephroureterectomy (LNU) has become popular in treating upper urinary tract urothelial carcinoma (UTUC) and an emerging trend was observed in robotic approaches. Therefore, we compared robot-assisted radical nephroureterectomy (RANU) and LNU for the treatment of UTUC. Materials and Methods: This observational and retrospective case-series study included UTUC patients who underwent LNU or RANU. A pure laparoscopic approach was adopted in the LNU treatment group, and bladder cuff excision (BCE) was performed mostly with the open approach. Either the da Vinci Si or Xi surgical system was used for RANU. Extravesical BCE was performed, and bladder defects were closed intracorporeally. Perioperative and oncologic outcomes were compared between the LNU and RANU groups. Results: A total of 231 patients who underwent RANU (n = 87) or LNU (n = 144) were included. No significant differences were noted between the groups in terms of demographics, tumor characteristics, operative time, catheter time, or complications. Compared with LNU, RANU had a lower intraoperative blood loss (30 vs. 150 mL, p < 0.001) and shorter postoperative hospital stay (8 vs. 9 days, p = 0.009). The 5-year overall survival, cancer-specific survival, and bladder recurrence-free survival were comparable between the groups. Conclusion: Compared with LNU, RANU had similar perioperative and oncologic outcomes but was superior in terms of intraoperative blood loss and postoperative length of hospital stay. However, considering the potential biases owing to the heterogeneity of our cases, the interpretation of the results must be very cautious.

The Asia-Pacific AMS800 artificial urinary sphincter consensus statement.

This Asia-Pacific (AP) AMS 800™ artificial urinary sphincter (AUS) consensus statement aims to provide a set of practical recommendations to assist surgeons with the AMS 800 device surgery. The AP consensus committee consisted of key opinion leaders with extensive experience with AMS 800 surgery across several AP countries. The panel reviewed and discussed relevant findings with emphasis on locoregional and specific clinical challenges relevant to the AP region. Recommendations were made in key areas namely (1) patient selection and informed consent process; (2) preoperative assessment; (3) dealing with co-existing urological disorders; (4) surgical principles and intraoperative troubleshooting; (5) postoperative care; (6) special populations; and (7) cost analysis and comparative review. The AMS 800 device should be offered to males with moderate to severe stress urinary incontinence (SUI). Full informed consent should be undertaken, and emphasis is placed on surgical contraindications and high-risk candidates. The presence of a surgical mentor or referral to experts is recommended in complex AUS candidates. Preoperative cystoscopy with or without multichannel urodynamic study is necessary and patients with pre-existing urological disorders should be treated adequately and clinically stable before surgery. Adherence to strict patient selection and safe surgical principles are critical to ensure excellent clinical outcomes and minimize complications. Given that InhibiZone-coated device is not available in many AP countries, the use of prophylactic antibiotics pre-and post-operatively are recommended. The AMS 800 device should be prepared according to the manufacturer's guidelines and remains a cost-effective treatment for male SUI. The AMS 800 device remains the surgical benchmark for male SUI but is associated with certain mechanical limitations and a unique set of complications.

Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides.

Sulfoximines are emerging moieties for medicinal and biological chemistry, due in part to their efficacy in selective inhibition of amide-forming enzymes such as γ-glutamylcysteine synthetase. While small-molecule sulfoximines such as methionine sulfoximine (MSO) and its derivatives are well studied, structures with methionine sulfoximine residues within complex polypeptides have been generally inaccessible. This paper describes a straightforward means of late-stage one-step oxidation of methionine residues within polypeptides to afford NH-sulfoximines. We also present chemoselective subsequent elaboration, most notably by copper(ii)-mediated N-H cross-coupling at methionine sulfoximine residues with arylboronic acid reagents. This development serves as a strategy to incorporate diverse sulfoximine structures within natural polypeptides, and also identifies the methionine sulfoximine residue as a new site for bioorthogonal, chemoselective bioconjugation.

The comparison of different BCG strains in the intravesical treatment of non-muscle invasive urothelial carcinoma of urinary bladder-A real-world practice.

BACKGROUND: Bacillus Calmette-Guérin (BCG) has been well recognized as the first-line intravesical therapy for high-risk non-muscle-invasive bladder cancer (NMIBC). Oncotice, the Tice strain of BCG, serves as a viable alternative to the Connaught strain owing to the worldwide shortage of the latter. We retrospectively compared these two strains in terms of efficacy and adverse effects (AE) in patients who underwent at least one maintenance course after induction. METHODS: In this single-institution, retrospective study, patients diagnosed with NMIBC who were administered either Connaught or Tice intravesical therapy were enrolled. Recurrence was defined as the reappearance of urothelial carcinoma. Progression was defined as stage/grade advance, metastasis, or cancer-related death. The primary outcomes were recurrence-free survival (RFS) and progression-free survival (PFS), and the secondary outcome was AE. RESULTS: A total of 76 and 84 patients receiving Tice and Connaught, respectively were enrolled. The median follow-up periods for the Tice and Connaught groups were 32.0 months (range, 7-69 months) and 81.5 months (range, 9-154 months), respectively. Kaplan-Meier method showed no intergroup difference with regard to 3-year RFS and PFS. On Cox multivariate regression analysis, Tice was a significant predictor for inferior PFS (HR = 5.30; 95% CI, 1.11-25.29; p = 0.036). The AE incidence was 38.3% in the Connaught group and 25.0% in the Tice group (p = 0.079). CONCLUSION: Tice and Connaught were comparable in terms of RFS, PFS, and AE for patients with NMIBC accepting BCG induction and at least one maintenance course in our real-world practice. However, Tice was a predictor of inferior PFS on multivariate analysis.