Perioperative management of sarcopenia in patients undergoing major surgeries in Singapore: a modified delphi consensus.

BACKGROUND: Ageing population is a worldwide phenomenon with correspondingly higher proportion of older patients being treated in the hospital setting. Sarcopenia, which increases with age, has serious negative implications on health, hospitalization and overall postoperative recovery. There is no mutual consensus on perioperative management of sarcopenia in surgical patients in Singapore. The purpose of this study is to create greater clarity pertaining to the recognition of sarcopenia, the application of assessment criteria of sarcopenia and perioperative management of surgical patients in Singapore. METHODS: A modified Delphi consensus consisting of a panel of experts from Singapore forming a multidisciplinary team, including surgeons, geriatricians, anesthesiologists, physiotherapists and dieticians. Eight recommendations were proposed by the steering committee. Literature search from MEDLINE, Embase and Scopus for articles up till June 2023 were performed to support recommendation statements. The expert panel voted on agreement to recommendation statements and graded the level of evidence supporting each statement through surveys to achieve consensus, set at 85% a priori. RESULTS: The panelists underwent two rounds of anonymized, independent voting before reaching consensus for all eight statements. After the first round, seven statements reached consensus, including the corresponding grading for level of evidence. The statement which did not achieve consensus was revised with supporting literature and after the second round of survey, all eight statements and level of evidence reached consensus, completing the Delphi process. These eight statements covered themes to (1) encourage the identification of sarcopenia, (2) guide pre-operative and (3) post-operative management of sarcopenia. CONCLUSION: With the varying approaches in perioperative management, poor understanding of and identification of sarcopenia can result in suboptimal management of sarcopenia in surgical patients. Given the abundance of evidence linking beneficial impact on recovery and post-operative complications with prudent management of sarcopenia, it is imperative and urgent to achieve awareness and consensus.

Feasibility of Combining Functional Mobilisation with Resistance and Endurance Training for Mechanically Ventilated Patients in Intensive Care Unit Setting-A Pilot Study.

Background: Intensive-care-acquired weakness resulting in functional impairment is common in critical care survivors. This study aims to evaluate the feasibility of a combined early functional training with endurance and resistance training and its effect on the functional outcome. Methods: It is a pilot study performed in a 39-bed Medical and Surgical Intensive Care Unit (ICU). Patients who were premorbidly independent and were mechanically ventilated for ≥24 h were recruited to receive functional mobilisation (sit out of bed, ambulation), endurance (bed cycling), and resistance training (selected upper and lower limb muscle training using weights). The primary outcomes were feasibility of training, muscle strength, handgrip strength, quadricep strength, and Functional Status Score-Intensive Care Unit (FSS-ICU) collected at the first assessment in the ICU, at the ICU discharge, and at hospital discharge. Secondary outcomes were functional capacity (6-Minute Walk Distance) and quality of life measures, EQ-5D, at hospital discharge and at 3 months. Results: Out of the 11 patients, 6 (54.54%) patients achieved level 2 functional mobilisation, 2 (18.18%) patients achieved level 2 resistance training, and 1 (9.09%) patient achieved level 2 endurance training. There were no significant differences in the medical research council (MRC) score, quadricep strength, and handgrip strength between the first assessment in the ICU, at the ICU discharge, and at hospital discharge. However, there was a significant difference in FSS_ICU (p < 0.008) from the first assessment in the ICU up to hospital discharge. EQ-5D visual analogue scale also showed a change of 8.5% at 3-month follow-up. 6MWD showed significant difference (p < 0.043) at 3-month follow-up compared to that at hospital discharge. Conclusions: The study found low compliance to resistance and endurance training in patients with mechanical ventilation. However, functional mobilisation in terms of sit out of bed was possible in more than half of the recruited patients.

Regulation of Helicoverpa armigera ecdysone receptor by miR-14 and its potential link to baculovirus infection.

Baculoviruses are well known for their ability to suppress the host development by altering its physiological and morphological changes. During its pathogenesis, the virus targets the host immune system, steroid hormones or apoptotic genes to evade anti-viral responses. Recent evidence indicate that viruses may use their own or host-encoded microRNAs (miRNA) to achieve this. In this study, utilizing microarray analysis, we found that the miRNA profile of Helicoverpa armigera larvae alters upon H. armigera single nucleopolyhedrovirus (HaSNPV) infection. Northern blot analyses revealed down-regulation of four miRNAs including the well-conserved and abundantly expressed miR-14. It was established that miR-14 positively regulates the H. armigera ecdysone receptor (Ha-EcR). Consistent with decreased levels of miR-14 following HaSNPV infection, the transcript levels of its target gene Ha-EcR declined around 72h post-infection. In vivo and in vitro studies revealed that in the presence of the synthetic miR-14 mimic the transcript levels of Ha-EcR significantly increased. The miRNA-target interaction was further confirmed by a GFP reporter assay. Further, application of the miRNA mimic led to reduced replication of the virus. These results suggest that, by down-regulating miR-14, HaSNPV may reduce the Ha-EcR transcript levels providing another classic example of virus-mediated manipulation of host physiology.

An insect trypsin-like serine protease as a target of microRNA: utilization of microRNA mimics and inhibitors by oral feeding.

MicroRNAs (miRNAs) are non-coding small RNAs (18-25 nt) that play crucial roles in various biological processes, including development, as gene regulators. In this study, we identified a miRNA, har-miR-2002b, that is specifically expressed during larval stages of Helicoverpa armigera (cotton bollworm). For the first time, we explored the possibility of utilizing synthetic inhibitor and mimic of a miRNA by oral feeding and confirmed that the inhibitor and mimic can successfully inhibit/oversupply har-miR-2002b in H. armigera larvae. Bioassays by oral feeding indicated 70% reduction in fecundity and 40% larval mortality in the presence of har-miR-2002b mimic. In addition, a large proportion of those larvae that made it to the pupal stage were deformed and only few moths emerged from them. This implied an important role of har-miR-2002b in larval development and adult fecundity. A trypsin-like serine protease (Ha-TLP) was identified as a target of har-miR-2002b. In vivo and in vitro studies revealed that in the presence of the miRNA mimic Ha-TLP transcript/protein levels and enzyme activity were significantly reduced. In contrast, inhibition of har-miR-2002b led to significant up-regulation of Ha-TLP transcript levels. This is the first study which shows the potential of utilization of miRNA mimics and inhibitors in pest control by targeting specific insect genes.

RNA interference as a cellular defense mechanism against the DNA virus baculovirus.

In insects, the RNA interference (RNAi) pathway plays a major role in antiviral responses, as shown against many RNA viruses. The response includes the cleavage of double-stranded RNA genome or intermediates, produced during replication, into viral short interfering RNAs (v-siRNAs). Using deep sequencing, we found that a large number of small reads of ∼20 nucleotides from Helicoverpa armigera larvae infected with Helicoverpa armigera single nucleopolyhedrovirus (HaSNPV) were mapped to certain open reading frames in the viral genome (hot spots) that are mostly structural and auxiliary late genes. After excluding the possibility of these small RNAs being microRNAs, it was determined that Dicer-2, the main enzyme implicated in the RNAi response in insects, is involved in the generation of v-siRNAs. In Dicer-2- but not Dicer-1-silenced cells, higher transcript levels of the hot spot genes were detected, and as a consequence the virus replicated more efficiently. The results suggest that the viral transcripts are degraded by the RNAi response of the host. This may, however, be to the advantage of the virus by preventing overreplication of the virus, which may otherwise lead to the premature death of the host cells.