Dehydrogenative Coupling of Alkylamines with Primary Alcohols Forming α-Amino Ketones.

Acceptorless dehydrogenative coupling reactions between C-H bonds offer straightforward and atom-economical methods connecting readily available materials while liberating gaseous hydrogen as the sole byproduct. Despite the growing interest in such transformations, their realization still poses a significant challenge. Here we report a photoinduced dehydrogenative coupling reaction of alkylamines with primary alcohols. C-H bonds adjacent to nitrogen and oxygen are site-selectively cleaved, and a C-C bond is created between the carbon atoms in a cross-selective manner to produce α-amino ketones. Diverse polar functionalities such as esters, amides, and carboxylic acids survived, demonstrating the broad applicability of the present method.

Drug development for major chronic health conditions-aligning with growing public health needs: Proceedings from a multistakeholder think tank.

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022. Herein, we summarize the proceedings of this meeting, including an overview of the current state of drug development for chronic health conditions and key barriers that were identified. Six major action items were formulated to accelerate drug development for chronic diseases, with a focus on improving the efficiency of clinical trials and rapid implementation of evidence into clinical practice.

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry.

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

Body Weight as a Preferred Method for Normalizing the Computed Tomography-Derived Liver Volume in Dogs without Hepatic Disease.

The assessment of liver size is usually performed using radiography in dogs. However, due to wide variations in patients' sizes and body conformations, accurate diagnosis of hepatomegaly or microhepatia is difficult. Computed tomographic (CT) volumetry can quantitatively and accurately measure liver volume. However, a reliable method for the standardization or normalization of volume in dogs without hepatic disease using CT has not yet been established. The purpose of this study was to assess seven different anatomic measures for normalizing liver volume in dogs and determine the tentative range of liver volume in dogs without hepatic disease. We retrospectively searched medical records from 1 January 2017 through to 1 June 2020 and included dogs with abdominal computed tomography without hepatic disease. The liver volume, lengths of four vertebrae (T11, T12, L2, L3), diameter of the abdominal aorta, body weight, and body condition scores (BCSs) of the dogs were recorded. Forty-one client-owned dogs without evidence of hepatic disease were included. The CT-derived liver volume was 813.8 ± 326.5 cm3 (mean ± SD). Body weight was determined to be the most reliable single-variable method for normalizing liver volume, with a raw CT-derived liver-volume-to-body-weight ratio of 22.1 cm3/kg (95% CI: 12.9-31.3 cm3/kg) and regression prediction model of volume = 19 × BWkg + 97. However, a better normalizing factor would likely be provided by the fat-free mass if it can be accurately measured.

Ultrasonographic Renal Subcapsular Thickening in Cats with Primary and Metastatic Carcinoma.

Ultrasonographic subcapsular thickening caused by renal neoplasia other than lymphoma has been previously reported in cats; however, detailed information is lacking. This study aims to describe ultrasonographic findings in renal subcapsular thickening and renal parenchyma in cats diagnosed or presumed with primary and metastatic carcinoma in the kidney. Ultrasound reports were retrospectively searched from 3 veterinary hospitals and 6 cats with 9 affected kidneys were included. Renal lesions were confirmed either cytologically or histopathologically as primary renal carcinoma with metastasis in the contralateral kidney (in 1 case), or metastatic pulmonary carcinoma (in 3 cases). Two patients were cytologically diagnosed with pulmonary carcinoma with concurrent renal subcapsular thickening. Eight kidneys affected by metastatic carcinomas showed relatively thin, focal, and homogeneously hypoechoic subcapsular thickening while a single kidney affected by primary renal carcinoma showed markedly thick, circumferential, and heterogeneously mixed iso- to hypoechoic lesion. The renal parenchyma, especially when just beneath the subcapsular lesion, exhibited at least one abnormality in all affected kidneys, most characterized by hyperechoic renal cortex with concurrent hypoechoic striations. This is the first report describing metastatic carcinoma causing renal ultrasonographic subcapsular thickening in cats. Our results suggest that renal carcinoma should be included in differential diagnoses when ultrasonographic subcapsular thickening is present in cats.

Improved detection of air-filled lesions using computed tomography in dogs with recurrent spontaneous pneumothorax through reduction of pulmonary atelectasis via positive pressure ventilation.

Introduction: Spontaneous pneumothorax in dogs is predominantly caused by the rupture of air-filled lesions, such as bullae or blebs. The efficacy of Computed Tomography (CT) in detecting these lesions has been deemed limited due to its reportedly low sensitivity. This retrospective, cross-sectional study investigates the utility of CT in eight dogs diagnosed with recurrent pneumothorax, all of which had surgical confirmation of the cause of the pneumothorax. Materials and methods: Thoracic radiographs were obtained before and the day following the CT studies. Initially, a CT study was conducted without positive pressure ventilation (pre-PPV CT). Subsequent CT studies were performed post-evacuation of pneumothorax and with positive pressure ventilation of 15 cmH2O until lung atelectasis was resolved (post-PPV CT). The pre-PPV CT and post-PPV CT images were anonymized and reviewed by two board-certified radiologists. The presence and morphology of air-filled lesions were evaluated on all images. Surgical findings were recorded and compared to the CT findings. Results: Air-filled lesions were detected in 5 out of 8 dogs in the pre-PPV CT studies and in all 8 dogs in the post-PPV CT studies. The CT findings of air-filled lesions were consistent with surgical findings. None of the dogs showed increased severity of pneumothorax in radiographs taken the day following the CT studies. Discussions: The study concludes that the resolution of lung atelectasis by evacuation of pneumothorax and positive pressure ventilation during CT studies is feasible and enhances the detection of air-filled lesions in dogs with recurrent spontaneous pneumothorax. This could potentially aid in improving surgical planning.

Abdominal radiographic features of anticoagulant rodenticide toxicity in 14 dogs and 2 cats.

Background: Anticoagulant rodenticide toxicity is commonly encountered in veterinary practice that can result in internal bleeding. We have observed dogs with retroperitoneal hemorrhage secondary to anticoagulant rodenticide toxicity. However, abdominal radiographic changes in dogs with rodenticide toxicity have not been studied and retroperitoneal hemorrhage secondary to rodenticide toxicity has rarely been reported. Aim: The objective is to describe abdominal radiographic features of anticoagulant rodenticide toxicity and concurrent thoracic radiographic changes in dogs and cats. Methods: Dogs and cats diagnosed with rodenticide toxicity and with available abdominal radiographs were included in this retrospective analysis. Board-certified radiologists reviewed the abdominal and thoracic radiographs. Evaluation of abdominal radiographic changes included assessment of peritoneal or retroperitoneal effusion, subcutaneous hemorrhage, and internal hemorrhage of abdominal organs. Results: Fourteen dogs and two cats with confirmed rodenticide toxicity were included in the study. In dogs, retroperitoneal effusion (28.6%) was the most commonly observed abdominal radiographic change, followed by peritoneal effusion (14.3%). Thoracic radiographic changes in dogs included pleural effusion (63.6%) and mediastinal widening (63.6%) as the most common findings, followed by pulmonary hemorrhage (36.4%) and tracheal narrowing (36.4%). Subcutaneous hemorrhage or edema (9.1%) was also noted. No abdominal radiographic changes consistent with hemorrhage secondary to rodenticide toxicity were noted in the two cats. Conclusion: Based on our findings, it is suggested that rodenticide toxicity may result in retroperitoneal effusion even in the absence of thoracic disease. Therefore, abdominal radiographs may be valuable when suspecting hemorrhage due to coagulopathy. However, abdominal radiographic changes associated with rodenticide toxicity are considered rare in cats.

A case of intestinal intussusception with unique hemorrhagic polyps due to AL amyloidosis and excessive anticoagulation.

Most adult intussusceptions are secondary to various pathological conditions that serve as a lead point. Because of their serious nature, intussusceptions often require emergency surgery. We report a surgical case of amyloidosis associated with intussusception, probably due to polypoid protrusions and bleeding tendencies. An 80-year-old man with abdominal pain was suspected of having jejunal intussusception on computed tomography. He had been prescribed warfarin for atrial fibrillation, and excessive anticoagulation was observed with a prolonged prothrombin time/international normalized ratio of 5.44 at presentation. After the excessive anticoagulation was resolved, emergency surgery was performed. The intussuscepted jejunum was resected, and a 7 cm long dark-red pedunculated polyp was identified as the lead point, which was accompanied by multiple small pedunculated polyps. Histopathological examination showed that these were all hemorrhagic polyps. Amyloid depositions were observed in the muscularis mucosae, submucosa, and the walls of the blood vessels. Immunohistochemical analysis revealed immunoglobulin light chain amyloidosis. This case is informative to discuss the clinical sequelae of gastrointestinal amyloid deposition.

Cystoscopic-guided laser ablation of intramural ectopic ureters in a female cat.

Case summary: An 8-month-old female spayed domestic shorthair cat was presented for chronic urinary incontinence (UI). Since being adopted 6 months earlier, the cat had a history of urine leakage during both activity and rest. Baseline blood work and urine culture showed no significant abnormalities and no evidence of a urinary tract infection. An abdominal CT with excretory urography followed by a focal urinary tract ultrasound revealed a suspected right intramural ectopic ureter (EU) and potential left EU. Cystoscopy confirmed bilateral intramural EUs. Cystoscopic-guided laser ablation (CLA) of both EUs was performed. The cat developed temporary urinary obstruction (UO) 36 h after the procedure, which was medically managed with prazosin and buprenorphine. Ultimately, the cat's urinary signs completely resolved with no UI recognized after the procedure and the cat has remained continent during 18 months of follow-up. Relevance and novel information: CLA of intramural EUs is routinely performed in dogs, but this technique has not been previously reported in cats with this condition. Although post-procedural urinary tract signs were initially present, the cat ultimately had an excellent outcome with resolution of UI after this procedure.

Bidirectional Patellar Luxation in Small- or Miniature-Breed Dogs in Japan; Patient Characteristics and Radiographic Measures Compared with Medial Patellar Luxation.

Bidirectional patellar luxation (BPL) is a relatively rare form of patellar luxation, with limited information reported regarding breed predisposition and etiology. The purpose of this study was to describe the patient characteristics and radiographic measures of proximodistal patellar position associated with BPL in dogs in Japan, compared with dogs with medial patellar luxation (MPL). A retrospective medical record search of surgically corrected MPL and BPL dogs was performed, and breed, age, sex, body weight, and presence of the patella alta in the extended-stifle position were recorded. The ratio of the patellar ligament length to patella length (PLL/PL) and the ratio of the distance between the proximal pole of the patella and the femoral condyle to patella length (A/PL) were measured on stifle radiographs. A total of 35 dogs with BPL and 95 dogs with MPL were included. The BPL was most commonly present in Toy Poodles (odds ratio compared to MPL dogs: 7.05) in the present study. There were no significant differences in age, sex, or body weight between the BPL and MPL groups. Patella alta in the extended-stifle position was more common in the BPL group (23.4%) than in the MPL group (0.8%). However, there were no significant differences in PLL/PL or A/PL between the BPL and MPL groups. The study highlights BPL in different dog breeds in Japan, and suggests that the occurrence of BPL may be related to stifle extension. However, more research is needed to fully understand the etiology of BPL.