Looking beyond the eyeball test: A novel vitality index to predict recovery after esophagectomy

ObjectivesTo (1) measure 4 physiologic metrics before esophagectomy, (2) use these in an index to predict composite postoperative outcome after esophagectomy, and (3) compare predictive accuracy of this index to that of the Fried Frailty Index and Modified Frailty Index.MethodsGrip strength (kilograms), 30-second chair sit-stands (number), 6-minute walk distance (meters), and normalized psoas muscle area (cm²/m) were measured for 77 consenting patients from January 1, 2018, to April 1, 2019. Imbalanced random forest classification estimated probability of a composite postoperative outcome, which included mortality, respiratory complications, anastomotic leak, delirium, length of stay ≥14 days, discharge to nursing facility, and readmission. G-mean error was used to compare predictive accuracy among indexes.ResultsMedian grip strength was 38 kg (25th-75th percentiles, 31-44), number of sit-stands 11 (10-14), psoas muscle area to height ratio 6.9 cm²/m (6.0-8.2), and 6-minute walk distance 407 m (368-451). There was generally weak correlation between these metrics, with the highest between 30-second sit-stands and 6-minute walk distance (r = 0.57). Age, degree of patient-reported exhaustion, and the 4 objective metrics comprised the Esophageal Vitality Index, which had a lower G-mean error of 32% (31-33) than the Fried Frailty Index, 37% (37-38), and the Modified Frailty Index, 48% (47-48).ConclusionsThe Esophageal Vitality Index, an objective, simple assessment consisting of grip strength, 30-second chair sit-stands, 6-minute walk, and psoas muscle area to height ratio outperformed commonly used frailty indexes in predicting postesophagectomy mortality and morbidity. The index provides a robust picture of patients' fitness for surgery beyond the qualitative “eyeball” test.     

Cloning and expression of chicken erythrocyte transglutaminase.

We report the sequences of cDNAs encoding chicken erythrocyte transglutaminase (EC 2.3.2.13). The complete mRNA consists of 3345/3349 nucleotides and predicts a single open reading frame. Nine peptide sequences derived from partial digests of the isolated protein agreed with the corresponding translation of the open reading frame. Approximately 60% identities between the avian protein and three related mammalian enzymes were found. Chicken erythrocyte transglutaminase mRNA is most abundant in red blood cells and kidney, and it accumulates during erythroid cell differentiation.     

Inflammatory myofibroblastic tumours of the maxillary sinus: A brief clinical report and review of the literature

Although inflammatory myofibroblastic tumours (IMTs) have been accepted as a clonal neoplasm, their pathology is poorly understood due to variable presentation. There is no identifiable cause and they are usually observed as tumour growth combined with inflammation. In the current WHO classification, IMTs are designated as intermediate malignancies. In terms of biological potential, IMTs are classified under ‘rarely metastasizing’. IMTs are rare in the maxillary sinus but, when reported, can be locally aggressive or even destructive if they invade the orbit. The authors present a brief clinical report describing a five-year-old girl with a slow-growing mass in the right maxillary sinus extending into the lacrimal sac and its management.     

Tn, a carcinoma-associated antigen, reacts with anti-Tn of normal human sera

Tn antigen is the immediate precursor of the carcinoma (CA)-associated T antigen; both are masked in non-CA tissues. Tn antigen was detected by absorption of human anti-Tn antibody in 46 of 50 primary breast CAs and in all 6 metastases originating from Tn-positive primary CAs. Thirteen of 25 (52%) anaplastic CAs, but only 2 of 15 (13%) well differentiated CAs had more Tn than T; 1 anaplastic CA had neither antigen. Eighteen of 20 benign breast lesions had no Tn; the 2 positive lesions were premalignant. All 19 breast CAs, studied immunohistochemically, reacted strongly with human polyclonal anti-Tn; benign or normal glandular tissues had minimal or no reactivity. Among live cancer cell lines, the most malignant sublines had more Tn than T on their cell surfaces. Preliminary studies with rodent monoclonal anti-Tn and anti-T antibodies gave immunohistochemical reactivity patterns similar to those of the polyclonal antibodies, but the former were less sensitive in absorption tests. Tn is a CA marker that promises to be useful in tumor detection.     

Hypolipidemic Activity of o-(N-Phthalimido)acetophenone in Sprague Dawley Rats

o-(N-Phthalimido)acetophenone has proven to be an effective hypolipidemic agent in rats at 20 mg/kg/ day orally. The agent suppressed the activity of the rate-limiting enzyme of the liver involved in de novo synthesis of triglycerides. The synthetic rate-limiting enzyme for cholesterol esters was also inhibited by the drug in vivo. o-(N-Phthalimido)acetophenone lowered cholesterol in the liver and the aorta wall and generally caused an increase in phospholipids in body tissues. Serum lipoproteins were modulated by the drug with a decrease in cholesterol and triglycerides in the chylomicron, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) and an increase in high-density lipoprotein (HDL) cholesterol. The phospholipid content was increased in the chylomicron, VLDL, and LDL fractions. In hyperlipidemic rats, o-(N-phthalimido)acetophenone lowered elevated blood lipid levels at 20 mg/kg/day orally after 3 weeks of administration. The hypolipidemic rat after drug treatment had a lower LDL cholesterol and a higher HDL cholesterol content, which is therapeutically desirable to protect against cardiovascular disease.     

pH-sensitive polymers that enhance intracellular drug delivery in vivo.

Cytosolic delivery from endosomes is critical for those drugs that are susceptible to attack by lysosomal enzymes, such as DNA, RNA, oligonucleotides, proteins and peptides. Therefore, we have designed pH-sensitive, membrane-disruptive polymers to enhance the release of drugs from the acidic endosomal compartment to the cytoplasm. We have found that one polymer in particular, poly(propylacrylic acid) (PPAA), is very effective at membrane disruption at pHs below 6.5, based on hemolysis studies. PPAA also significantly enhances in vitro transfections of lipoplex formulations in cell culture, and does so in the presence of as much as 50% serum. In this study, we have extended our in vitro hemolysis and cell culture studies to an in vivo murine excisional wound healing model. A pilot study with a green fluorescent protein (GFP)-encoding plasmid indicated that injection of formulations containing PPAA into healing wounds resulted in increased GFP expression. Subsequently, by administering sense and antisense DNA for the angiogenesis inhibitor thrombospondin-2 (TSP2), we were able to alter the wound healing response in TSP2-null and wild type mice, respectively. Our findings showed that when PPAA was added to lipoplex formulations, expression of TSP2 was enhanced in TSP2-null mice compared to control formulations. These results show that PPAA can enhance in vivo transfections and that inhibition of TSP2 expression may lead to improved wound healing. These results suggest that PPAA can provide significant improvements in the in vivo efficacy of drugs such as DNA.