Longitudinal impact of screening colonoscopy on greenhouse gas emissions.

BACKGROUND AND AIM: Colonoscopy is the gold-standard screening test for colorectal cancer. However, it has come under scrutiny for its carbon footprint and contribution to greenhouse gas (GHG) emissions compared to other medical procedures. Notwithstanding, screening colonoscopies may have a positive effect on GHG emissions that is unknown. This study estimated the carbon emissions prevented by screening colonoscopies in the U.S. METHODS: Using the reported number of screening colonoscopies performed annually in the U.S. and the absolute risk reduction (ARR) reported in the NorDICC trial, we calculated the expected minimum number of cancer treatment and surveillance visits prevented through screening based on the cancer stage. The average carbon emission averted per mile traveled was computed using the Environmental Protection Agency's (EPA) GHG equivalencies calculator. The final estimate of carbon emissions averted over a decade by screening colonoscopies performed in one year was determined. RESULT: 6.3 million screening colonoscopies performed in one year prevent 1,134,000 colorectal cancers over a ten-year period. Of these, 38∙3% (434,254) are localized, 38∙8% (440,281) are regional, and 22∙9% (259,465) are metastatic disease. The minimum number of post-diagnosis visits prevented is 11 for stage I, ≥ 21 for stage II, ≥25 for stage III, and ≥ 20 for stage IV disease, comprised of diagnostic, surgical evaluation, chemotherapy, and surveillance visits. The total number of visits prevented by screening is 2,388,397 for stage I, 5,254,421 for stage II, 13,120,369 for stage III, and 9,210,972 for stage IV disease. Approximately 395 million miles of travel and 158,263 metric tons of CO2, equivalent to 177 million pounds of coal burned, 19 billion smartphones charged, or 18 million gallons of gasoline consumed, were saved over ten years through screening. CONCLUSION: Colorectal cancer screening decreases cancer-related GHG emissions and minimizes the environmental impact of cancer treatment.

Dysregulation of cardiac mitochondrial aldehyde dehydrogenase 2: Studies in dogs with chronic heart failure.

Mitochondrial (MITO) dysfunction occurs in the failing heart and contributes to worsening of heart failure (HF). Reduced aldehyde dehydrogenase 2 (ALDH2) in left ventricular (LV) myocardium of diabetic hearts has been implicated in MITO dysfunction through accumulation of toxic aldehydes including and elevated levels of 4-hydroxy-2-nonenal (4HNE). This study examined whether dysregulation of MITO ALDH2 (mALDH2) occurs in mitochondria of the failing LV and is associated with increased levels of 4HNE. LV tissue from 7 HF and 7 normal (NL) dogs was obtained. Protein quantification of total mitochondrial ALDH2 (t-mALDH2), phosphorylated mALDH2 (p-mALDH2), total MITO protein kinase c epsilon (t-mPKCε), phosphorylated mPKCε (p-mPKCε) was performed by Western blotting, and total mALDH2 enzymatic activity was measured. Protein adducts of 4HNE-MITO and 4HNE-mALDH2 were also measured in MITO fraction by Western Blotting. Protein level of t-mALDH2 was decreased in HF compared with NL dogs (0.63 ± 0.07 vs 1.17 ± 0.08, p < 0.05) as did mALDH2 enzymatic activity (51.39 ± 3 vs. 107.66 ± 4 nmol NADH/min/mg, p < 0.05). Phosphorylated-mALDH2 and p-mPKCε were unchanged. 4HNE-MITO proteins adduct levels increased in HF compared with NL (2.45 ± 0.08 vs 1.30 ± 0.03 du, p < 0.05) as did adduct levels of 4HNE-mALDH2 (1.60 ± 0.20 vs 0.39 ± 0.08, p < 0.05). In isolated failing cardiomyocytes (CM) exposure to 4HNE decreased mALDH2 activity, increased ROS and 4HNE-ALDH2 adducts, and worsened MITO function. Stimulation of mALDH2 activity with ALDA-1 in isolated HF CMs compared to NL CMs improved ADP-stimulated respiration and maximal ATP synthesis to a greater extant (+47 % and +89 %, respectively). Down-regulation of mALDH2 protein levels and activity occurs in HF and contributes to MITO dysfunction and is likely caused by accumulation of 4HNE-mALDH2 adduct. Increasing mALDH2 activity (via ALDA-1) improved MITO function in failing CMs.

A Phase I Study of Acapatamab, a Half-life Extended, PSMA-Targeting Bispecific T-cell Engager for Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Safety and efficacy of acapatamab, a prostate-specific membrane antigen (PSMA) x CD3 bispecific T-cell engager were evaluated in a first-in-human study in metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Patients with mCRPC refractory to androgen receptor pathway inhibitor therapy and taxane-based chemotherapy received target acapatamab doses ranging from 0.003 to 0.9 mg in dose exploration (seven dose levels) and 0.3 mg (recommended phase II dose) in dose expansion intravenously every 2 weeks. Safety (primary objective), pharmacokinetics, and antitumor activity (secondary objectives) were assessed. RESULTS: In all, 133 patients (dose exploration, n = 77; dose expansion, n = 56) received acapatamab. Cytokine release syndrome (CRS) was the most common treatment-emergent adverse event seen in 97.4% and 98.2% of patients in dose exploration and dose expansion, respectively; grade ≥ 3 was seen in 23.4% and 16.1%, respectively. Most CRS events were seen in treatment cycle 1; incidence and severity decreased at/beyond cycle 2. In dose expansion, confirmed prostate-specific antigen (PSA) responses (PSA50) were seen in 30.4% of patients and radiographic partial responses in 7.4% (Response Evaluation Criteria in Solid Tumors 1.1). Median PSA progression-free survival (PFS) was 3.3 months [95% confidence interval (CI): 3.0-4.9], radiographic PFS per Prostate Cancer Clinical Trials Working Group 3 was 3.7 months (95% CI: 2.0-5.4). Acapatamab induced T-cell activation and increased cytokine production several-fold within 24 hours of initiation. Treatment-emergent antidrug antibodies were detected in 55% and impacted serum exposures in 36% of patients in dose expansion. CONCLUSIONS: Acapatamab was safe and tolerated and had a manageable CRS profile. Preliminary signs of efficacy with limited durable antitumor activity were observed. Acapatamab demonstrated pharmacokinetic and pharmacodynamic activity.

Optimization of biometry for best refractive outcome in cataract surgery.

High-precision biometry and accurate intraocular lens (IOL) power calculation have become essential components of cataract surgery. In clinical practice, IOL power calculation involves measuring parameters such as corneal power and axial length and then applying a power calculation formula. The importance of posterior corneal curvature in determining the true power of the cornea is increasingly being recognized, and newer investigative modalities that can estimate both the anterior and posterior corneal power are becoming the standard of care. Optical biometry, especially using swept-source biometers, with an accuracy of 0.01-0.02 mm, has become the state-of-the-art method in biometry. With the evolution of IOL formulas, the ultimate goal of achieving a given target refraction has also moved closer to accuracy. However, despite these technological efforts to standardize and calibrate methods of IOL power calculation, achieving a mean absolute error of zero for every patient undergoing cataract surgery may not be possible. This is due to inherent consistent bias and systematic errors in the measurement devices, IOL formulas, and the individual bias of the surgeon. Optimization and personalization of lens constants allow for the incorporation of these systematic errors as well as individual bias, thereby further improving IOL power prediction accuracy. Our review provides a comprehensive overview of parameters for accurate biometry, along with considerations to enhance IOL power prediction accuracy through optimization and personalization. We conducted a detailed search in PubMed and Google Scholar by using a combination of MeSH terms and specific keywords such as "ocular biometry," "IOL power calculations," "prediction accuracy of refractive outcome in cataract surgery," "effective lens position," "intraocular lens calculation formulas," and "optimization of A-constants" to find relevant literature. We identified and analyzed 121 relevant articles, and their findings were included.