Efficacy of Protein and Essential Amino Acid Supplementation in Lower Limb Surgeries: A Systematic Review and Meta-Analysis.

This study aimed to examine the efficacy and safety of protein and/or essential amino acid (EAA) supplementation in all lower limb surgeries using systematic reviews and meta-analysis of randomized controlled trials (RCTs). We included RCTs that assessed the efficacy of protein and/or EAA supplementation in lower limb surgeries. On June 2, 2023, we searched EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The primary outcomes were mobility, patient-reported outcomes (PRO), and acute kidney injury (AKI). The secondary outcomes were exercise capacity, muscle strength, muscle mass, and all adverse events. We performed meta-analyses using the random-effects model. We assessed the risk of bias using the Cochrane risk-of-bias tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We included 12 RCTs (622 patients). These studies included four on hip fracture surgery, three on total hip arthroplasty, and five on total knee arthroplasty. Protein and/or EAA supplementation may slightly improve PRO (standard mean difference 0.51, 95% confidence interval (CI): 0.22 to 0.80, low certainty of evidence). Nevertheless, it may not improve mobility (mean difference 0.07 m/s, 95% CI: -0.01 to 0.16, low certainty of evidence). No adverse events including AKI were reported. Muscle strength may have increased (standard mean difference 0.31, 95% CI: 0.02 to 0.61, very low certainty of evidence). However, exercise capacity (mean difference 5.43 m, 95% CI: -35.59 to 46.45, very low certainty of evidence) and muscle mass (standard mean difference -0.08, 95% CI: -0.49 to 0.33, very low certainty of evidence) were not improved. While protein and/or EAA supplementation in lower limb surgeries may improve PRO, it is unlikely to affect mobility. Despite this, the medical team and patients might still consider protein and/or EAA supplementation a useful option.

Long-Term Rehabilitation Therapy Is Effective for Physical Function in a Patient With Amyloid Light Chain Amyloidosis Complicated by Nephrotic Syndrome: A Case Report and Literature Review.

We report on the rehabilitation of a patient with amyloid light chain (AL) amyloidosis complicated by nephrotic syndrome. Various symptoms produced by AL amyloidosis, including nephrotic syndrome, complicate rehabilitation therapy. In this case report, long-term physical therapy was initiated prior to autologous peripheral blood stem cell transplantation owing to the risk of further decline in physical function due to decreased mobility and physical activity. Patients were instructed on how to perform home exercise therapy. Furthermore, compliance was monitored using a checklist and regular face-to-face feedback. There was no increase in skeletal muscle mass, but improvements in grip strength, lower extremity muscle strength, and phase angle were observed after 24 weeks of physical therapy. Despite the absence of partial remission (urinary protein level of 3.5 g/gCre or higher), nephrotic syndrome demonstrated a trend toward improvement. Since the effectiveness of physical therapy in such patients has not yet been fully established, this report suggests that long-term rehabilitation therapy for physical function in patients with nephrotic syndrome complicated by persistent proteinuria may be effective.

Prevalence of fracture progression in fragility fractures of the pelvis: Systematic review and meta-analysis.

BACKGROUND: Fragility fractures of the pelvis (FFP) are a growing problem in aging populations. Fracture progression (FP) occasionally occurs during FFP treatment; however, its prevalence remains unclear. This systematic review and meta-analysis aimed to assess the prevalence of FP among patients with FFP. METHODS: We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. All cohort studies that reported the prevalence of FP in patients with FFP were included. FP was defined as the appearance of additional pelvic fractures after the initial FFP. We searched the CENTRAL, MEDLINE, and EMBASE databases until April 2024. The pooled prevalence was generated using a random-effects model and presented as a 95 % confidence interval (CI) and prediction interval (PI). We assessed the risk of bias in each study using the Joanna Briggs Institute's Prevalence Critical Appraisal Tool. RESULTS: This review included eight studies (925 patients). The pooled prevalence of FP in patients with FFP was 11 % (95 % CI, 5-19 %; 95 % PI, 0-44 %). Subgroup analysis showed that the pooled prevalence of FP in patients with FFP (conservative treatment vs. surgery for initial FFP) was 16 % (95 % CI, 9-24 %) and 2 % (95 % CI, 0-11 %), respectively (test for subgroup difference, P = 0.03). Additional analysis showed that in patients with FP, the pooled prevalence of the fractured site (ipsilateral site, contralateral site, and both sites) was 66 %, 12 %, and 19 %, respectively. The pooled prevalence of fractured bone (pubis, ischium, ilium, and sacrum) was 25 %, 0 %, 15 %, and 68 %, respectively. The risk of bias in the patient sampling method and sufficient data analysis in all included studies was high. CONCLUSION: This review suggests that the prevalence of FP in patients with FFP is relatively high. Clinicians should recognize FP as a possible diagnosis in patients experiencing additional pain after FFP. However, further prospective studies with adequate patient sampling are required to confirm the true prevalence.

Ionizable Polymeric Micelles with Phenylalanine Moieties Enhance Intracellular Delivery of Self-Replicating RNA for Long-Lasting Protein Expression In Vivo.

mRNA-based therapeutics are revolutionizing the landscape of medical interventions. However, the short half-life of mRNA and transient protein expression often limits its therapeutic potential, demanding high treatment doses or repeated administrations. Self-replicating RNA (RepRNA)-based treatments could offer enhanced protein production and reduce the required dosage. Here, we developed polymeric micelles based on flexible poly(ethylene glycol)-poly(glycerol) (PEG-PG) block copolymers modified with phenylalanine (Phe) moieties via biodegradable ester bonds for the efficient delivery of RepRNA. These polymers successfully encapsulated RepRNA into sub-100 nm micelles assisted by the hydrophobicity of the Phe moieties and their ability to π-π stack with the bases in RepRNA. The micelles made from Phe-modified PEG-PG (PEG-PG(Phe)) effectively maintained the integrity of the loaded RepRNA in RNase-rich serum conditions. Once taken up by cells, the micelles triggered a pH-responsive membrane disruption, promoted by the strong protonation of the amino groups at endosomal pH, thereby delivering the RepRNA to the cytosol. The system induced strong protein expression in vitro and outperformed commercial transfecting reagents in vivo, where it resulted in enhanced and long-lasting protein expression.

Efficacy of neuromuscular electrical stimulation for thoracic and abdominal surgery: A systematic review and meta-analysis.

This systematic review and meta-analysis examined the efficacy of neuromuscular electrical stimulation (NMES) on lower limb muscle strength and health-related quality of life (HR-QOL) after thoracic and abdominal surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Excerpta Medica Database via Elsevier, Physiotherapy Evidence Database, Cumulative Index to Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform via their dedicated search portal, and ClinicalTrials.gov on November 2021 and updated in April 2023 to identify randomized controlled trials that examined the effects of NMES after thoracic and abdominal surgery. The primary outcomes were lower limb muscle strength, HR-QOL, and adverse events. We used the Cochrane Risk of Bias Tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence. A total of 18 randomized control trials involving 915 participants, including 10 on cardiovascular surgery, two on pulmonary surgery, five on digestive system surgery, and one on other surgery, were included. NMES slightly increased lower limb muscle strength and adverse events in cardiovascular surgery. Adverse events (hypotension, pain, and muscle discomfort) occurred in seven patients. HR-QOL was measured in two studies on cardiovascular surgery, but these were not pooled due to concept heterogeneity. Overall, NMES slightly increases lower limb muscle strength after cardiovascular surgery without serious adverse events. However, higher-quality randomized control trials in thoracic and abdominal surgeries are needed.

Safety and Feasibility of Fan Therapy for Dyspnea: A Scoping Review.

Fan therapy is a non-pharmacological approach useful in terminally ill patients that relieves dyspnea by directing a fan to blow air on one side of the patient's face. To date, there has been no systematic review of fan therapy for critically ill patients in the intensive care unit. This scoping review aimed to provide a comprehensive overview of fan therapy studies published to date, clarify the therapeutic intervention methods of fan therapy, evaluate its safety according to existing literature, and explore its potential use in critically ill patients. A scoping review was conducted using the Joanna Briggs Institute methodology. This scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension of the scoping reviews statement. All published studies conducted on patients who received fan therapy regardless of age, disease, setting, phase, country, or follow-up duration were included. The data sources included Medical Literature Analysis and Retrieval System Online, Embase, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Literature databases. Of the 685 studies obtained, 15 were included, comprising patients with terminal cancer and chronic lung diseases. The most common intervention was a single five-minute intervention for dyspnea at rest. The studies on patients receiving oxygen therapy did not report adverse events or worsening of blood pressure, pulse rate, respiratory rate, or SpO2 levels. However, there are no studies in the literature on the use of fan therapy for critically ill patients. Nevertheless, previous studies suggest that fan therapy is safe.

Efficacy of Pelvic Floor Muscle Training for Postoperative Patients With Rectal Cancer: A Systematic Review and Meta-Analysis.

This study aimed to assess the effectiveness of pelvic floor muscle training (PFMT) for fecal incontinence (FI) and health-related quality of life (HR-QOL) after colorectal cancer surgery. This systematic review (SR) and meta-analysis included randomized controlled trials (RCTs) that examined the effects of PFMT after colorectal cancer surgery, which were extracted from several databases in January 2023. The primary outcomes were FI (Wexner scores), HR-QOL, and adverse events. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence (CoE). A total of seven RCTs were included. Our SR results suggested that PFMT showed little to no difference in FI (mean difference 0.62 higher; 95% CI: -1.26 to 2.5, low CoE) and adverse events (risk ratio 5.78; 95% CI: 0.28-117.22, low CoE). Two adverse events occurred in the PFMT group (anastomotic stenosis, suboptimal use of laxatives) and were not observed in controls. HR-QOL was measured in two RCTs using 12-item Short Form Survey (SF-12) and fecal incontinence quality of life (FIQL). Two RCTs found no trend toward a positive impact on HR-QOL. Higher quality RCTs on colorectal cancer after surgery are required. Furthermore, extending the duration of the PFMT intervention may be necessary to ensure its success.

Case-control study of the correlation between the five times sit to stand and 6-min walk distance in patients with pancreatic cancer.

PURPOSE: Cases of pancreatic cancer are increasing, and the risk of developing this disease reportedly increases with age. In recent years, there has been an increasing number of reports on physical function in patients with pancreatic cancer. Methods such as the 6-min walk distance (6 MWD) should be established to evaluate physical function, as a decline in exercise capacity is an important index in these patients. Recently, the 6 MWD has also been used to evaluate physical function in patients with pancreatic cancer. In healthy older adults, a decrease in 6 MWD is reportedly associated with intrinsic capacity and health status. Such factors make assessing 6 MWD important. However, the measurement of 6 MWD requires a sizable measurement environment. The five times sit to stand (FTSTS) test is a simple method that can be performed using a chair. FTSTS is hypothesized to be a useful assessment scale in patients with pancreatic cancer because it is easy to estimate the decline in physical function in clinical practice if the decline in 6 MWD can be estimated by evaluating FTSTS. The study's purpose was to clarify this hypothesis and ascertain the cutoff required to determine the decrease in 6 MWD in clinical practice. METHODS: Sixty consecutive patients with preoperative pancreatic cancer who were assessed for physical function were studied. 6 MWD (< 400 m) was the objective variable, and binary logistic regression analysis was performed, with age, BMI, sex, FTSTS, and HGS as explanatory variables. Receiver-operating characteristic (ROC) curve analysis was performed for the explanatory variables, which were found to be significant based on logistic regression analysis. The area under the curve (AUC) was also calculated. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were evaluated. This study was approved by Hiroshima University Hospital's ethics committee (approval number: E808-1). RESULTS: Fifty-seven of the 60 patients were included in the analysis. Logistic regression analysis showed that FTSTS was a significant explanatory variable; ROC curve analysis showed an AUC of 0.872 and a cutoff value of 8.98 s. The sensitivity, specificity, PPV, and NPV were 82.4%, 80.0%, 63.6%, and 91.4%, respectively. CONCLUSIONS: A decrease in 6 MWD in preoperative pancreatic cancer patients can be identified by performing FTSTS.

ß-Carotene enhances the expression of inflammation-related genes and histone H3 K9 acetylation, K4 dimethylation, and K36 trimethylation around these genes in juvenile macrophage-like THP-1 cells.

ß-Carotene is converted into vitamin A in the body and can remove reactive oxygen species. However, it is still unclear whether ß-carotene alters the expression levels of inflammation-related genes in macrophages and how this is regulated. In the present study, we investigated whether the administration of ß-carotene under hyperglycemic conditions altered the expression level of inflammation-related genes and whether any observed differences were associated with changes in histone modifications in juvenile macrophage-like THP-1 cells. THP-1 cells (from a human monocytic leukemia cell line) were cultured in low glucose (5 mM), high glucose (25 mM), or high glucose (25 mM) + ß-carotene (5 µM) media for 1 day, and mRNA expression levels of genes related to oxidative stress and inflammation, and histone modifications were determined by mRNA microarray and qRT-PCR analyses, and chromatin immunoprecipitation assays, respectively. The expression of inflammation-related genes, such as IL31RA, CD38, and NCF1B, and inflammation-associated signaling pathway genes, such as ITGAL, PRAM1, and CSF3R, were upregulated by ß-carotene under high-glucose conditions. Under these conditions, histone H3 lysine 4 (K4) demethylation, H3K36 trimethylation, and H3K9 acetylation around the CD38, NCF1B, and ITGAL genes were higher in ß-carotene-treated cells than in untreated cells. Treatment of juvenile macrophage-like THP-1 cells with ß-carotene under these high glucose conditions induced the expression of inflammation-related genes, K9 acetylation, and K4 di- and K36 trimethylation of histone H3 around these genes.

Therapeutic effects of sleeve gastrectomy for non-alcoholic steatohepatitis estimated by paired liver biopsy in morbidly obese Japanese patients.

ABSTRACT: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG.

Changes in motor function and quality of life after surgery in patients with pancreatic cancer.

OBJECTIVE: To determine the changes in motor function and health-related quality of life after pancreatectomy and identify factors influencing postoperative physical functioning in health-related quality of life. METHODS: This single-centre, prospective, observational study measured 6-min walking distance, grip strength, knee extension strength and health-related quality of life variables in patients with pancreatic cancer, before and after surgery. Paired t- and Wilcoxon signed-rank tests were used to compare pre- and postoperative motor function and health-related quality-of-life variables. Factors associated with postoperative physical functioning scores of health-related quality of life were assessed using multiple regression analysis. RESULTS: Fifty-nine individuals were enrolled. Motor function values decreased significantly postoperatively, including 6-min walking distance (mean ± standard deviation: 402.5 ± 95.4 vs. 497.7 ± 80.4 m, p < 0.001), knee extensor strength (0.42 ± 0.10 vs. 0.47 ± 0.10 kgf/kg, p < 0.001) and grip strength (22.0 ± 8.9 vs. 24.5 ± 9.2 kg, p = 0.001). Multiple regression analysis showed significant association between 6-min walking distance change and postoperative physical functioning scores of health-related quality of life (p = 0.036). CONCLUSION: The results suggest that motor function decreases postoperatively, and a decrease in 6-min walking distance after surgery is associated with postoperative physical functioning in patients with pancreatic cancer.

Anaplastic Carcinoma Arising From Ovarian Mucinous Adenocarcinoma With Massive Cardiopulmonary Metastasis: An Autopsy Case Report.

BACKGROUND: The presence of anaplastic and sarcomatoid components in ovarian mucinous carcinoma is extremely rare. CASE: A 64-year-old woman underwent radical surgery for right ovarian cancer. Pathological examination showed mucinous adenocarcinoma with a focal mural nodule of anaplastic and sarcomatoid carcinoma (FIGO stage IIB). She underwent adjuvant chemotherapy but developed severe respiratory failure and died after 9 months. Autopsy showed that the bilateral pulmonary parenchyma was filled with a multinodular hemorrhagic mass, and the cardiac wall had a massive invasive lesion. Histopathological examination of the lung and myocardium revealed diffuse invasion of the anaplastic carcinoma component with infiltrating osteoclastic giant cells. CONCLUSION: This case is very rare, and the clinical management of anaplastic carcinoma arising in mucinous neoplasms remains challenging.

Natural killer cell activity in women with recurrent miscarriage: Etiology and pregnancy outcome.

This study aimed to evaluate whether natural killer (NK) cell activity was associated with the etiology of recurrent miscarriage (RM), and to evaluate the predictive value of NK cell activity for outcomes of following pregnancies in women with RM. Peripheral NK cell activity was measured in 160 non-pregnant women with a history of two or more miscarriages. This activity was compared according to the etiology of RM and to pregnancy outcomes in women who became pregnant. NK cell activity in women with unexplained RM was significantly higher than that in those with known etiologies of RM. NK cell activity in women whose next pregnancies ended in miscarriage of fetuses with a normal chromosome karyotype (MN) was higher than that in those with live births (p<0.05). Women with NK cell activity ≥33% had a higher risk for MN (relative risk 3.4, 95% confidence interval 1.3-8.7). An increase in peripheral NK cell activity was associated with MN. This increase might be involved in the pathophysiology underlying RM.

An extremely rare case of tubo-ovarian abscesses involving corynebacterium striatum as causative agent.

BACKGROUND: We present an extremely rare case of tubo-ovarian abscesses involving Corynebacterium striatum (C. striatum) as causative agent in a 53-year-old woman. CASE PRESENTATION: The patient presented with stomach pain, chills, and nausea. Her medical history included poorly controlled psoriasis vulgaris and diabetes. Laboratory and imaging findings led to diagnosis of septic shock due to tubo-ovarian abscesses. She was treated with antibiotic therapy and surgery to remove the left adnexa. Various cultures detected Prevotella spp. and C. striatum. We concluded that C. striatum from skin contaminated by psoriasis vulgaris had caused the tubo-ovarian abscesses by way of ascending infection. CONCLUSIONS: This may be the first known case of tubo-ovarian abscesses due to C. striatum. In patients whose skin has been weakened by psoriasis vulgaris or other infections, Corynebacterium should be considered as causative microorganisms, and antibiotic therapy including vancomycin should be administered.

The Effect of Secoisolariciresinol on 3T3-L1 Adipocytes and the Relationship between Molecular Structure and Activity.

As we have reported, flaxseed lignan, (+)-secoisolariciresinol (SECO), (-)-SECO, and meso-SECO were stereoselectively synthesized and their biological functions were evaluated. In the present study, we focused on the effects of SECOs on the regulation of 3T3-L1 adipocytes, and identified the structure-activity relationships. Optically active SECO and meso-SECO were tested for their effects on lipid metabolism in 3T3-L1 adipocytes. (-)-SECO accelerated adiponectin production of 3T3-L1 adipocytes. On the other hand, (+)- and meso-SECO suppressed the production of adiponectin. In addition, triglyceride (TG) accumulation in 3T3-L1 adipocytes was significantly suppressed by all three SECOs tested here, as was 17beta-estradiol, when the SECOs were added to the medium during induction of 3T3-L1 preadipocytes to adipocytes. Especially, (-)-SECO strongly reduced TG accumulation. It is well-known that SECO has estrogen-like activity. Hence the estrogen-like activity of each SECO compound was assessed. Only (-)-SECO had estrogen-like activity.

First stereoselective synthesis of meso-secoisolariciresinol and comparison of its biological activity with (+) and (-)-secoisolariciresinol.

The first stereoselective synthesis of meso-secoisolariciresinol is reported. A comparison of the cytotoxic and immunosuppressive activity between meso-secoisolariciresinol and optically active secoisolariciresinols was similarly performed for the first time. Both enantiomers of secoisolariciresinol accelerated IgM production, although meso-secoisolariciresinol did not affect IgM production. Only meso-secoisolariciresinol showed cytotoxic activity.

Effect of benzylic oxygen on the cytotoxic activity for colon 26 cell line of phenolic lignans.

The cytotoxic activity for colon 26 cell line of matairesinol, oxidized matairesinol, 9,9'-epoxylignan and oxidized 9,9'-epoxylignan were examined. (-)-Matairesinol (Mat 1) showed greatest cytotoxic activity (LC(50)=9 microg/ml) of the lactone-type lignans. 7,7'-Oxomatairesinol having same steric configuration as that of (-)-matairesinol showed greater activity (LC(50)=25 microg/ml) than hydroxy or mono-oxomatairesinol. The activities of 9,9'-epoxylignan and 7,7'-oxo-9,9'-epoxylignan having same steric configurations as (-)-matairesinol were weaker than that of corresponding matairesinols. Different activity levels were observed between enantiomers.