Liposomal delivery of methylphosphonate antisense oligodeoxynucleotides in chronic myelogenous leukemia [see comments]

Chronic myelogenous leukemia (CML) is a hematologic malignancy characterized by the presence of the Philadelphia (Ph) chromosome. Bcr- abl, the fusion gene associated with the Ph chromosome, expresses a p210bcr-abl protein that promotes a selective expansion of mature myeloid progenitor cells. Methylphosphonate (MP) oligodeoxynucleotides complementary to specific regions of the bcr-abl mRNA were incorporated in liposomes. We studied the effects of liposomal MP (L-MP) on the growth inhibition of CML-like cell lines. L-MP targeted to the breakpoint junctions of the bcr-abl mRNA inhibited the growth of CML cells. Fifty percent inhibition was achieved at approximately 1 mumol/L of L-MP oligonucleotide concentrations. The inhibitory effect was selective because growth inhibition was observed only with CML but not with control cell lines. Moreover, CML cell growth inhibition was dependent on the sequence of the MP oligodeoxynucleotides incorporated in the liposomes. The growth inhibition of CML cells by L-MP resulted from selective inhibition of the expression of the p210bcr-abl protein.     

Rationing Limited Healthcare Resources in the COVID-19 Era and Beyond: Ethical Considerations Regarding Older Adults

Coronavirus disease 2019 (COVID-19) continues to impact older adults disproportionately with respect to serious consequences ranging from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these issues have focused attention on how these resources are ultimately allocated and used. Some strategies, for example, misguidedly use age as an arbitrary criterion that disfavors older adults in resource allocation decisions. This is a companion article to the American Geriatrics Society (AGS) position statement, “Resource Allocation Strategies and Age-Related Considerations in the COVID-19 Era and Beyond.” It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations that should be considered when developing strategies for allocation of scarce resources during an emergency involving older adults. This review presents the legal and ethical background for the position statement and discusses these issues that informed the development of the AGS positions: (1) age as a determining factor, (2) age as a tiebreaker, (3) criteria with a differential impact on older adults, (4) individual choices and advance directives, (5) racial/ethnic disparities and resource allocation, and (6) scoring systems and their impact on older adults. It also considers the role of advance directives as expressions of individual preferences in pandemics. J Am Geriatr Soc 68:1143–1149, 2020.     

Missing canines: a novel aetiology

Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of 1 year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub‐Saharan East Africa.     

Transjugular intrahepatic portosystemic shunt vs. small-diameter prosthetic H-graft portacaval shunt: Extended follow-up of an expanded randomized prospective trial

We report herein the results of extended follow-up of an expanded randomized clinical trial comparing transjugular intrahepatic portosystemic shunt (TIPS) to 8 mm prosthetic H-graft portacaval shunt as definitive treatment for variceal bleeding due to portal hypertension. Beginning in 1993, through this trial, both shunts were undertaken as definitive therapy, never as a “bridge to transplantation.” All patients had bleeding esophageal/gastric varices and failed or could not undergo sclerotherapy/banding. Patients were excluded from randomization if the portal vein was occluded or if survival was hopeless. Failure of shunting was defined as inability to shunt, irreversible shunt occlusion, major variceal rehemorrhage, hepatic transplantation, or death. Median follow-up after each shunt was 4 years; minimum follow-up was 1 year. Patients undergoing placement of either shunt were very similar in terms of age, sex, cause of cirrhosis, Child’s class, and circumstances of shunting. Both shunts provided partial portal decompression, although the portal vein-inferior vena cava pressure gradient was lower after H-graft portacaval shunt (P<0.01). TIPS could not be placed in two patients. Shunt stenosis/occlusion was more frequent after TIPS. After TIPS, 42 patients failed (64%), whereas after H-graft portacaval shunt 23 failed (35%) (P <0.01). Major variceal rehemorrhage, hepatic transplantation, and late death were significantly more frequent after TIPS (P <0.01). Both TIPS and H-graft portacaval shunt achieve partial portal decompression. TIPS requires more interventions and leads to more major rehemorrhage, irreversible occlusion, transplantation, and death. Despite vigilance in monitoring shunt patency, TIPS provides less optimal outcomes than H-graft portacaval shunt for patients with portal hypertension and variceal bleeding. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000.     

Ageing appearance in China: biophysical profile of facial skin and its relationship to perceived age

Background Perceived age is important to women and is a primary driver for topical product use and facial cosmetic surgery. Changes in facial features and biophysical skin parameters with chronological age and their associations with perceived age have not been described in Asian populations. Objective To investigate the relationship between biophysical properties of the skin, visual features of skin ageing and perceived facial age in Chinese women. Methods Facial photographs were collected of 250 Chinese women, aged 25–70 years in Shanghai, China. The perceived facial age was determined and related to the chronological age for each participant and to a range of visual assessments of skin appearance and objective biophysical measurements of the skin. The profile of changes in these parameters with age was investigated together with the differences in those parameters for women judged to look younger than their chronological age and those judged to look older than their chronological age. Results Large discrepancies in perceived age (up to 29 years) were found in women of the same chronological age. Each objective skin measure and visual assessment parameter had a stronger correlation with perceived age than with chronological age. The strongest relationships to perceived age were for wrinkles and hyperpigmentation. Skin colour, hydration and trans‐epidermal water loss (TEWL) had weaker associations with perceived age. Women judged to look older than their chronological age had significantly higher scores than those judged to look younger for coarse wrinkles and hyperpigmentation across all age groups. The appearance differences between these groups were evident in composite facial images of the same average chronological age. Conclusions We have identified the skin attributes which differ with perceived age in Chinese women. Perceived age is a better measure of the biological age of facial skin than is chronological age in this population.