OBJECTIVE: To compare the effect of clear twin block (CTB) and traditional twin block (TTB) appliances on speech.
METHODS: In this randomized clinical trial, 18 skeletal Class II (Class II, division 1) growing patients were selected and randomly divided into CTB and TTB groups. Objective and semiobjective speech assessment tests were performed for vowel and consonant analyses at four time intervals: before (T0), immediately after (T1), 1 month after (T2), and 3 months after (T3) inserting the appliance. Data were analyzed using analysis of variance and independent t-test at the .05 significance level.
RESULTS: Intergroup comparisons showed that the CTB group had less speech distortion immediately after insertion of the appliance (P < .05) than the TTB group; however, the differences were not significant at other time intervals. Intragroup comparisons showed that the number of distortions decreased significantly from T1 to T3 in both groups (P < .05). In contrast to CTB, the T0-T3 comparison was significant in the TTB group.
CONCLUSIONS: Although both appliances had some effects on speech, CTB had less speech distortion immediately after insertion, which is a very crucial moment in patient compliance. Additionally, articulation structures adapted to CTB faster than to TTB.

OBJECTIVE: We report the use of IV dalbavancin in Canadian patients using data captured by the national CLEAR registry.
METHODS: The CLEAR registry uses the web-based data management program, REDCap™ (online survey https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=TPMWJX98HL) to facilitate clinicians entering details associated with their clinical experiences using IV dalbavancin.
RESULTS: Data were available for 40 patients. The most common infections treated were acute bacterial skin and skin structure infection (ABSSSI) (62.5% of patients), bone/joint infection (22.5%), bloodstream/vascular infection (7.5%) and endocarditis (5.0%). Dalbavancin was used as directed (75.0%) and empiric therapy (25.0%). MRSA was the most common identified pathogen (70.0%). Dalbavancin was used both in outpatient (e.g., emergency department) (65.0%), and inpatient treatment settings (e.g., hospital ward) (35.0%). Dalbavancin was used due to the convenience of a single dose treatment (77.5%) as well as to facilitate hospital discharge (7.5%). Dalbavancin was primarily used alone (90.0%), and most commonly using a single 1500 mg dose (77.5%). Microbiological success (pathogen eradicated or presumed eradicated) occurred in 88.2% of known cases, while clinical success (cure and/or improvement) occurred in 93.3% of known cases. No adverse events were reported.
CONCLUSIONS: In Canada, IV dalbavancin is used as both directed and empiric therapy to treat ABSSSI as well as off-label (bone/joint, bacteremia/vascular, endocarditis, device-related) infections. It is used in both outpatient and inpatient settings due primarily to its convenience as a single-dose treatment regimen and to facilitate early hospital discharge. Dalbavancin use is associated with high microbiological and clinical cure rates along with an excellent safety profile.

Metastasis of clear cell renal cell carcinoma (clear cell RCC) to the gynecologic tract is infrequent, and involvement of the uterus is extremely rare. A review of the literature identified a total of 12 reported examples with metastasis to the uterine serosa (1), endometrium (5), cervix (5) and only one with metastasis to the myometrium. This report represents the first case of tumor-to-tumor metastasis involving a clear cell RCC with metastasis to a uterine leiomyoma. The patient was a 50-year-old woman status post-radical nephrectomy for newly diagnosed unilateral clear cell RCC (stage pT3a) with negative margins, who subsequently underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for the incidental finding of multiple uterine masses measuring up to 14.5 cm suggestive of fibroid on pelvic ultrasound. The pathologic exam of the specimen was consistent with metastatic clear cell RCC (1.2 cm) to uterine leiomyoma, confirmed with keratin, vimentin, CD10, CA9, and PAX8 immunohistochemistry. The patient\'s postoperative course was uneventful, and no new lesions were identified at follow-up during the past 6 months.

Filter trocar designed to eliminate harmful smoke is also regarded as effective for improving surgical visualization. The aim of this study is to evaluate the efficacy of filter trocar in maintaining clear operative view. From 2019 to 2020, 100 patients underwent laparoscopic cholecystectomy and they were randomized to either the control or filter group. The primary end point was a laparoscopic operative view score (1, clear; 2, slightly blurry; 3, completely blurry) during gallbladder dissection from the liver bed when dissection was started (LV1), when dissection was half completed (LV2) and when dissection was completed (LV3). Between the control and filter groups, there were no significant differences in mean LV1 (1.44 vs. 1.40, p = 0.234) and LV3 (1.86 vs. 2.01, p = 0.880). There was no significant difference in the mean duration of suction after dissection (3.82 s vs. 3.67 s, p = 0.097) and the mean number of laparoscope removals from inside to outside the body to clean during gallbladder dissection from the liver bed (0.55 vs. 0.22, p = 0.963) or the mean amount of time required to dissect the gallbladder from the liver bed (221.58 s vs. 177.09 s, p = 0.253). The study demonstrated that filter trocar is not as effective as expected in the maintenance of clear operative view. Further study is needed to develop devices to improve clear surgical visualization.

We present a case of a 58-year-old male who presented following 4 months of progressively worsening right upper extremity pain. Initial pathology demonstrated pleomorphic chondroblasts with increased mitotic activity indicating an intermediate grade (Grade 2) clear cell chondrosarcoma of the proximal humerus. Following surgical resection, the primary lesion demonstrated aggressive behavior and early metastasis to the cervical and thoracic spine. The patient unfortunately expired 30 months after initial presentation. Although clear cell chondrosarcoma has been historically regarded as low grade, we present a unique example of an aggressive clinical course of clear cell chondrosarcoma.

UNASSIGNED: Corneal lenticules can be utilized as an additive material for stromal keratophakia. However, following extraction, they must be reimplanted almost immediately or cryopreserved in lenticule banks. Electron-beam (E-beam) irradiated corneas permit room-temperature storage for up to 2 years, enabling keratophakia to be performed on demand. This study aims to compare the performance of high nano Joule (nJ)-energy (VisuMax) and low nJ-energy (FEMTO LDV) femtosecond laser systems on the thickness consistency and surface quality and collagen morphology of lenticules produced from fresh and E-beamed corneas.
UNASSIGNED: A total of 24 lenticules with -6.00 dioptre power were cut in fresh human donor corneas and E-beamed corneas with VisuMax and FEMTO LDV. Before extraction, the thickness of the lenticules was measured with anterior segment-optical coherence tomography (AS-OCT). The incisional surface roughness of extracted lenticules was analyzed using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Multiphoton microscopy was then used to assess the surface collagen morphometry.
UNASSIGNED: The E-beamed lenticules that were cut using FEMTO LDV were significantly thicker than the fresh specimens as opposed to those created with VisuMax, which had a similar thickness as the fresh lenticules. On the vertex, they were ∼11% thicker than the fresh lenticules. The surface roughness (Rq) of E-beamed lenticules incised with FEMTO LDV did not differ significantly from the fresh lenticules. This contrasted with the VisuMax-fashioned lenticules, which showed notably smoother surfaces (∼36 and ∼20% lower Rq on anterior and posterior surfaces, respectively) on the E-beamed than the fresh lenticules. The FEMTO LDV induced less cumulative changes to the collagen morphology on the surfaces of both fresh and E-beamed lenticules than the VisuMax.
UNASSIGNED: It has been previously demonstrated that the low nJ-energy FEMTO LDV produced a smoother cutting surface compared to high nJ-energy VisuMax in fresh lenticules. Here, we showed that this effect was also seen in the E-beamed lenticules. In addition, lower laser energy conferred fewer changes to the lenticular surface collagen morphology. The smaller disparity in surface cutting quality and collagen disturbances on the E-beamed lenticules could be beneficial for the early visual recovery of patients who undergo stromal keratophakia.

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 European Society of Cardiology (ESC) congress.
The NATURE-PARADOX was a naturally randomized trial that used genetic data from the UK Biobank registry to create \"cumulative exposure to low-density lipoprotein-cholesterol (LDL-C)\" biomarker and evaluate its association with major CV events regardless of plasma LDL-C levels or age. Safety and efficacy data of inclisiran, a PCSK9-interfering mRNA (PCSK9i) administered subcutaneously twice annually, were presented. Data on two new PCSK9is were presented, recaticimab, an oral drug, and lerodalcibep, a subcutaneous drug with a slightly different architecture than currently available PSCK9is. A phase 1 trial on muvalaplin, an oral lipoprotein (a) inhibitor, was presented. An atherosclerotic CV disease (ASCVD) risk prediction algorithm for the Asian population using SCORE2 data was presented. Long-term follow-up of patients enrolled in the CLEAR outcomes trial showed sustained and more significant ASCVD risk reduction with bempedoic acid in high-risk patients. The late-breaking clinical science at the 2023 congress of the ESC extends the known safety and efficacy data of a PCSK9i with the introduction of new drugs in this class. Using cumulative exposure to LDL-C rather than a single value will help clinicians tailor the LDL-C reduction strategy to individual risk and is an important step towards personalized medicine.

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 American College of Cardiology (ACC) conference.
The CLEAR outcomes randomized control trial (RCT) compared bempedoic acid to placebo in patients at high-risk of cardiovascular disease (CVD) or prevalent CVD and statin intolerance for CV outcomes. The YELLOW III was a single-arm study that evaluated the effect of Evolocumab on coronary plaque characteristics in patients with stable coronary artery disease (CAD). A cohort evaluated the association between a self-reported low-carbohydrate high-fat (ketogenic) diet and serum lipid levels as compared to a standard diet. The LOADSTAR trial compared CV outcomes with targeted low-density lipoprotein cholesterol (LDL-C) approach vs. high-intensity statin in patients with CAD. The PCDS statin cluster randomized trial compared the effectiveness of an electronic reminder to the clinician on a high-intensity statin use among patients with a history of ASCVD as compared to no reminder. A prospective cohort study compared the extent of coronary atherosclerosis among lifelong endurance athletes and healthy non-athletes. A causal artificial intelligence study combined polygenic risk scores with data from large CV prevention RCTs to guide systolic blood pressure and LDL-C reduction targets to reach average CV risk. The ACCESS trial evaluated the impact of eliminating copayment for low-income older adults in Canada with chronic CV diseases on composite CV outcomes. A pooled analysis of 3 large RCTs evaluated the association between residual inflammatory risk and CV outcomes, as compared to residual elevated cholesterol risk in patients receiving statin therapy. A Phase 2B RCT compared the efficacy of an oral PCSK9i, MK-0616, in reducing LDL-C as compared to a placebo. The late-breaking clinical science presented at the 2023 conference of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Data on the use of intravenous (IV) fosfomycin in Canada are limited. Using data captured by the Canadian LEadership on Antimicrobial Real-life usage (CLEAR) registry, we report the use of IV fosfomycin in Canadian patients.
The CLEAR registry uses the web-based data management program, REDCapTM (https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=F7JXNDFXEF) to facilitate clinicians\' entering of details associated with their clinical experiences using IV fosfomycin.
Data were available for 59 patients treated with IV fosfomycin. The most common infections treated were: bacteraemia or sepsis (25.4% of patients), complicated urinary tract infection (20.3%), ventilator-associated bacterial pneumonia (18.6%), and hospital-acquired pneumonia (13.6%). IV fosfomycin was used to treat Gram-negative (88.1%) and Gram-positive (10.2%) infections. The most common pathogens treated were carbapenem-resistant Enterobacterales (44.1%), multidrug-resistant Pseudomonas aeruginosa (18.6%), vancomycin-resistant Enterococcus faecium (5.1%), and methicillin-resistant Staphylococcus aureus (3.4%). IV fosfomycin was primarily used due to resistance to initially prescribed therapies (69.5%), frequently in combination with other agents (86.4%). Microbiological success (eradication/presumed eradication) occurred in 77.4% of patients, and clinical success (clinical cure/improvement) occurred in 62.5%. Overall, 15.3% of patients died because of their infection. Adverse effects were not documented in 73.1% of patients, and no patient discontinued therapy because of an adverse effect.
In Canada, IV fosfomycin is used primarily as directed therapy to treat a variety of severe infections caused by Gram-negative and Gram-positive bacteria. It is primarily used in patients infected with bacteria resistant to other agents and as part of combination therapy. Its use is associated with relatively high microbiological and clinical cure rates, and it has an excellent safety profile.

Metastatic renal cell carcinoma (mRCC) involving the central nervous system is currently an excluded subgroup of patients in the systemic treatment; for this reason, there is no solid data to support the efficacy of therapies in this subgroup. That is why it is important to describe real-life experiences in order to know if there is a special change in clinical behavior or treatment response in these kinds of patients. Patients and methods A retrospective review was performed to characterize mRCC patients diagnosed with brain metastases (BrM) during treatment at the National Institute of Cancerology of Bogota, Colombia. Descriptive statistics and time-to-event methods are used to evaluate the cohort. For the descriptive measures of quantitative variables, the mean with standard deviation was taken, and the minimum and maximum values were reported. In the case of qualitative variables, absolute and relative frequencies were used. The software used was R - Project v4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results A total of 16 patients were included with mRCC between January 2017 to August 2022 with a median 35.1-month follow-up, 4/16 (25%) were diagnosed with BrM at the time of screening and 12/16 (75%) during treatment. The International Metastatic RCC Database Consortium risk (IMDC) was favorable for 12.5%, intermediate for 43.7%, and poor for 25%, and not classified for 18.8%, BrM involvement was multifocal in 50% of the population and localized, brain-directed therapy was done in 43.7% of patients, predominantly palliative radiotherapy. Median overall survival (OS) for all the patients regardless of the time of metastatic presentation of the disease in the central nervous system was 53.5 months (0-70.3), and OS for cases with central nervous system involvement was 10.9 months. IMDC risk did not correlate with survival (log-rank, p=0.67). The OS for the subgroup of patients who debut with metastatic disease in the central nervous system is different from the group that developed metastasis in the progression of their disease (OS of 42 vs 3.6 months, respectively). Conclusions This is the largest descriptive study in Latin America and the second in the world from one institution that admits patients with metastasic renal cell carcinoma and central nervous system metastasis. In these kinds of patients with metastatic disease or progression to the central nervous system, there is a hypothesis that shows more aggressive clinical behavior. There is limited data on locoregional intervention to metastatic disease in the nervous system drastically, but trends show this could impact overall survival outcomes.