bims-minfam 2024-03-17 papers

Issue of 2024–03–17
six papers selected by
Ayesh Seneviratne, Western University

Front Aging. 2023 ;4 1327833

Premature aging in genetic diseases: what conclusions can be drawn for physiological aging.

Filip Milosic, Markus Hengstschläger, Selma Osmanagic-Myers.

According to current views the major hallmarks of physiological aging may be subdivided into three categories, primary causes of cellular damage (genomic instability, telomere attrition, loss of proteostasis, epigenetic alterations and compromised macroautophagy), antagonistic hallmarks that represent response to damage (deregulated nutrient sensing, cellular senescence, mitochondrial dysfunction) and integrative hallmarks that represent culprits of the phenotype (stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis). In contrast to physiological aging, premature aging diseases are driven by one or two distinct primary causes of aging, such as genomic instability in the case of Werner syndrome (WS), each displaying other hallmarks of aging to a variable extent. In this review we will focus on primary causes of well-investigated premature aging diseases Hutchinson-Gilford progeria syndrome (HGPS), WS, and Cockayne syndrome (CS) and for each provide an overview of reported aging hallmarks to elucidate resemblance to physiological aging on the mechanistic level and in the context of characteristic age-related diseases. Ubiquitous and tissue specific animal models of premature aging diseases will be discussed as useful tools to decipher fundamental aging-related mechanisms and develop intervention strategies to combat premature aging and age-related diseases.

Keywords: HGPS; aging; cockayne syndrome; premature aging; progeroid; senescence; werner syndrome

DOI: https://doi.org/10.3389/fragi.2023.1327833

Intensive Care Med. 2024 Mar 11.

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

Laveena Munshi, Guillaume Dumas, Bram Rochwerg, Farah Shoukat, Michael Detsky, Dean A Fergusson, Bruno L Ferreyro, Paul Heffernan, Margaret Herridge, Sheldon Magder, Mark Minden, Rakesh Patel, Salman Qureshi, Aaron Schimmer, Santhosh Thyagu, Han Ting Wang, Sangeeta Mehta.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described.
METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival.
RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival.
CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Keywords: Hematologic malignancy; Immunocompromised; Long-term outcomes

DOI: https://doi.org/10.1007/s00134-024-07349-z

Ann Med Surg (Lond). 2024 Mar;86(3): 1590-1600

Relation between frailty and adverse outcomes in elderly patients with gastric cancer: a scoping review.

Zheng-Ke-Ke Tan, Wen-Zhen Tang, Kui Jia, Dan-Ni Li, Li-Yan Qiu, Xin Chen, Li Yang.

Background: Playing an exemplary role, frailty have crucial effect on the preoperative evaluation of elderly patients. Previous studies have shown that frailty is associated with complications and mortality in patients with gastric cancer (GC). However, with the development of the concept of "patient-centered", the range of health-related outcomes is broad. The differences in relation between frailty and various adverse outcomes will be further explored.
Method: The PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature databases were searched for keywords, including frailty (such as frail) and gastric cancer (such as stomach neoplasms or stomach cancer or gastrectomy or gastric surgery). The search period is until August 2023. The included studies were observational or cohort studies with postoperative related adverse outcomes as primary or secondary outcome measures. Valid assessment tools were used. The Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was used to assess methodological quality in the included literature.
Result: Fifteen studies were included, including 4 cross-sectional studies, 8 retrospective cohort studies, and 3 prospective cohort studies. Among them, 6 studies were rated as "Good" and 9 studies were rated as "Fair," indicating that the quality of the literature was high. Then, 10 frailty assessment tools were summarized and classified into two broad categories in accordance with frailty models. Results of the included studies indicated that frailty in elderly patients with GC was associated with postoperative complications, mortality, hospital days, readmissions, quality of life, non-home discharge, and admission to the intensive care unit.
Conclusion: This scoping review concludes that high levels of preoperative frailty increase the risk of adverse outcomes in elderly patients with GC. Frailty will be widely used in the future clinical evaluation of elderly gastric cancer patients, precise risk stratification should be implemented for patients, and frailty management should be implemented well to reduce the occurrence of adverse treatment outcomes.

Keywords: adverse outcomes; elderly; frailty; gastric cancer

DOI: https://doi.org/10.1097/MS9.0000000000001817