Exploring the Risk Factors for Deep Vein Thrombosis after Percutaneous Nephrolithotomy.

BACKGROUND: Deep vein thrombosis (DVT), a frequent complication following percutaneous nephrolithotomy (PCNL), may lead to severe conditions like pulmonary embolism. Current knowledge on postoperative DVT risk factors is, however, limited. The aim of our study was to investigate the risk of DVT after PCNL. METHODS: A retrospective study was conducted on patients who underwent PCNL from March 2020 to March 2023 at our institution. Patient demographics and clinical data, including, DVT-specific information, preoperative labs, and surgical details, was evaluated. RESULTS: One hundred patients were included. Thirty-two (20 males, 12 females, mean age 52.5 ± 7.4 years) developed lower limb DVT post-surgery, while the remaining 68 (48 males, 20 females, mean age 51.1 ± 5.5 years) had no DVT symptoms. Analysis revealed significant correlations between hyperlipidemia, operating time, postoperative bed rest duration, D-dimer level on the first day after surgery, Caprini risk assessment model (RAM) score, and DVT risk. D-dimer on the first day after percutaneous nephrolithotomy, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL. Sex, age, hypertension status, diabetes status and smoking and drinking habits were not significantly associated with DVT risk. CONCLUSIONS: D-dimer on the first day after PCNL, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL.

Prevención de la preeclampsia: desde la dieta hasta la aspirina: revisión de la literatura / Prevention of preeclampsia: from diet to aspirin: review of the literature

Introducción y objetivo: Explorar las estrategias de prevención de la preeclampsia que se han propuesto a lo largo de la historia. Método: Revisión narrativa de la literatura sobre la evidencia científica histórica disponible entre 2016 y 2023 acerca de la aspirina y otras estrategias de prevención de la preeclampsia, en bases de datos bibliográficas computarizadas de estudios publicados en revistas indexadas. Resultados: Varios estudios confirman la efectividad de la aspirina para prevenir la preeclampsia en población de alto riesgo, siendo un medicamento con bajo riesgo de complicaciones, con mayor evidencia de efectividad si se inicia antes de las 16 semanas de gestación y con un aparente efecto dependiente de la dosis. Intervenciones como la disminución del consumo de sal, el reposo en cama, la suplementación con ácidos grasos, antioxidantes, L-arginina, zinc o magnesio, y el uso de diuréticos o de inhibidores de la bomba de protones, no han mostrado su utilidad en la prevención de la preeclampsia. Conclusiones: La aspirina a dosis baja es un medicamento seguro en el embarazo y efectivo para prevenir la preeclampsia en población de alto riesgo. Es la estrategia de prevención más ampliamente estudiada a lo largo de la historia para la disfunción endotelial durante la gestación.

Introduction and objective: To explore the different prevention strategies for preeclampsia that have been proposed throughout the history. Method: A narrative review of the historical, scientific evidence available between 2016 and 2021 on aspirin and other preeclampsia prevention strategies in computerized bibliographic databases of studies published in indexed journals. Results: Several studies confirm the effectiveness of aspirin to prevent preterm preeclampsia in high-risk populations, considering this as a safe drug with low risk of complications, with greater evidence of effectiveness when started before 16 weeks of gestation and apparently with a dose-dependent effect. Interventions such as reducing salt intake, bed rest, supplementation with fatty acids, antioxidants, L-arginine, zinc, magnesium, the use of diuretics or proton pump inhibitors have not shown its usefulness in the prevention of high risk preeclampsia patients. Conclusions: Low-dose aspirin is a safe drug in pregnancy and is effective to prevent preeclampsia in high-risk populations. Is the most widely studied throughout history prevention strategy for endothelial dysfunction during pregnancy.

Effects of short-term multicomponent exercise intervention on muscle power in hospitalized older patients: A secondary analysis of a randomized clinical trial.

BACKGROUND: Bed rest during hospitalization can negatively impact functional independence and clinical status of older individuals. Strategies focused on maintaining and improving muscle function may help reverse these losses. This study investigated the effects of a short-term multicomponent exercise intervention on maximal strength and muscle power in hospitalized older patients. METHODS: This secondary analysis of a randomized clinical trial was conducted in an acute care unit in a tertiary public hospital. Ninety (39 women) older patients (mean age 87.7 ± 4.8 years) undergoing acute-care hospitalization [median (IQR) duration 8 (1.75) and 8 (3) days for intervention and control groups, respectively]) were randomly assigned to an exercise intervention group (n = 44) or a control group (n = 46). The control group received standard care hospital including physical rehabilitation as needed. The multicomponent exercise intervention was performed for 3 consecutive days during the hospitalization, consisting of individualized power training, balance, and walking exercises. Outcomes assessed at baseline and discharge were maximal strength through 1 repetition maximum test (1RM) in the leg press and bench press exercises, and muscle power output at different loads (≤30% of 1RM and between 45% and 55% of 1RM) in the leg press exercise. Mean peak power during 10 repetitions was assessed at loads between 45% and 55% of 1RM. RESULTS: At discharge, intervention group increased 19.2 kg (Mean Δ% = 40.4%) in leg press 1RM [95% confidence interval (CI): 12.1, 26.2 kg; P < 0.001] and 2.9 kg (Mean Δ% = 19.7%) in bench press 1RM (95% CI: 0.6, 5.2 kg; P < 0.001). The intervention group also increased peak power by 18.8 W (Mean Δ% = 69.2%) (95% CI: 8.4, 29.1 W; P < 0.001) and mean propulsive power by 9.3 (Mean Δ% = 26.8%) W (95% CI: 2.5, 16.1 W; P = 0.002) at loads ≤30% of 1RM. The intervention group also increased peak power by 39.1 W (Mean Δ% = 60.0%) (95% CI: 19.2, 59.0 W; P < 0.001) and mean propulsive power by 22.9 W (Mean Δ% = 64.1%) (95% CI: 11.7, 34.1 W; P < 0.001) at loads between 45% and 55% of 1RM. Mean peak power during the 10 repetitions improved by 20.8 W (Mean Δ% = 36.4%) (95% CI: 3.0, 38.6 W; P = 0.011). No significant changes were observed in the control group for any endpoint. CONCLUSIONS: An individualized multicomponent exercise program including progressive power training performed over 3 days markedly improved muscle strength and power in acutely hospitalized older patients.

Early ambulation versus prolonged bed rest for incidental durotomies in spine procedures: a systematic review and meta-analysis.

Incidental durotomies are frequent complications of spine surgery associated with cerebrospinal fluid (CSF) leak-related symptoms. Management typically involves prolonged bed rest to reduce CSF pressure at the durotomy site. However, early ambulation may be a safer, effective alternative. PubMed, Web of Science, Embase, Cochrane, and Scopus were systematically searched for studies comparing early ambulation (bed rest ≤ 24 h) with prolonged bed rest (> 24 h) for patients with incidental durotomies in spine surgeries. The outcomes of interest were CSF leak, hypotensive headache, additional surgical repair, pseudomeningocele, and pulmonary complications. Systematic reviews and meta-analysis were performed following the Cochrane Handbook for Systematic Reviews of Interventions. We included a total of 704 patients from 6 studies. There was a significant reduction in the incidence of pulmonary complications (RR 0.23; 95% CI 0.08-0.67; p = 0.007) in the early mobilization group. The incidence of CSF leak (RR 1.34; 95% CI 0.83-2.14; p = 0.23), hypotensive headache (RR 0.72; 95% CI 0.27-1.90; p = 0.50), additional repair surgery (RR 1.29; 95% CI 0.76-2.2; p = 0.35), and pseudomeningocele (RR 1.29; 95% CI 0.20-8.48; p = 0.79) did not differ significantly. In patients with incidental durotomy following spinal surgery, early mobilization was associated with a lower incidence of pulmonary complications as compared with prolonged bed rest. There was no significant difference between groups in terms of CSF leak, need for additional repair, pseudomeningocele, and hypotensive headache.

Effects of antioxidant supplementation on bone mineral density, bone mineral content and bone structure in healthy men during 60 days of 6° head-down tilt bed rest: Results from a randomised controlled trial.

Dietary countermeasures to mitigate detrimental spaceflight-induced effects on bone health would alleviate the requirements and the consequences imposed by other types of countermeasures for this risk. We hypothesised that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR), an analogue of spaceflight, would have a protective effect on bone mineral density (BMD), content (BMC) and bone structure parameters. An exploratory, randomised, controlled, single-blind intervention trial was conducted in a parallel design with 20 healthy male volunteers (age 34 ± 8 y, weight 74 ± 6 kg). The study included 14 days of baseline data collection (BDC) before bed rest, followed by 60 days of HDBR and a 14-day recovery period. Ten subjects in the antioxidant group received a supplement (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E and 80 µg/d selenium) daily. Ten subjects in the control group received no supplement. The diet was consistent with dietary reference intakes, individually tailored based on the subject's bodyweight and strictly controlled. We measured whole-body, lumbar spine and femur BMD and BMC, as well as BMD of the cortical and trabecular compartments of the distal radius and tibia, and cortical and trabecular thickness during BDC, HDBR and recovery. Data were analysed using linear mixed models. The supplementation of an antioxidant cocktail did not mitigate the deteriorating effects of HDBR on BMD, BMC and bone structure parameters. Our findings do not support a recommendation for antioxidant supplementation for astronauts.

The Role of Prolonged Bed Rest in Postoperative Cerebrospinal Fluid Leakage After Surgery of Intradural Pathology-A Retrospective Cohort Study.

BACKGROUND: Postoperative cerebrospinal fluid leakage (CSFL) is a feared complication after surgery on intradural pathologies and may cause postoperative complications and subsequently higher treatment costs. OBJECTIVE: To assess whether prolonged bed rest may lower the risk of CSFL. METHODS: We performed a retrospective cohort study including patients with intradural pathologies who underwent surgery at our department between 2013 and 2021. Cohorts included patients who completed 3 days of postoperative bed rest and patients who were mobilized earlier. The primary end point was the occurrence of clinically proven CSFL. RESULTS: Four hundred and thirty-three patients were included (female [51.7%], male [48.3%]) with a mean age of 48 years (SD ±20). Bed rest was ordered in 315 cases (72.7%). In 7 cases (N = 7/433, 1.6%), we identified a postoperative CSFL. Four of them (N = 4/118) did not preserve bed rest, showing no significant difference to the bed rest cohort (N = 3/315; P = .091). In univariate analysis, laminectomy (N = 4/61; odds ratio [OR] 8.632, 95% CI 1.883-39.573), expansion duraplasty (N = 6/70; OR 33.938, 95% CI 4.019-286.615), and recurrent surgery (N = 5/66; OR 14.959, 95% CI 2.838-78.838) were significant risk factors for developing CSFL. In multivariate analysis, expansion duraplasty was confirmed as independent risk factor (OR 33.937, 95% CI 4.018-286.615, P = .001). In addition, patients with CSFL had significant higher risk for meningitis (N = 3/7; 42.8%, P = .001). CONCLUSION: Prolonged bed rest did not protect patients from developing CSFL after surgery on intradural pathologies. Avoiding laminectomy, large voids, and minimal invasive approaches may play a role in preventing CSFL. Furthermore, special caution is indicated if expansion duraplasty was done.

Acetazolamide, Short Bed Rest, and Subfascial Off-Suction Drainage in Preventing Persistent Spinal Fluid Leaks from Incidental Dural Tears.

BACKGROUND: Postoperative cerebrospinal fluid (CSF) leak might occur after the repair of dural tears. Acetazolamide lowers intradural pressure by decreasing CSF production. The aim of this study was to investigate the incidence of persistent CSF leak from incidental dural tears after using acetazolamide, short bed rest, and subfascial off-suction drainage. METHODS: The medical records at the Ain Shams University hospital were examined retrospectively for this descriptive single-arm cohort study. Adult patients who underwent lumbar degenerative spine surgery from January 2011 through January 2021 were enrolled. The included patients experienced a CSF leak and were administered acetazolamide 1.5 g/d from postoperative day (POD) 1 to POD 7. Subfascial drainage was kept for a maximum of 5 days without suction. RESULTS: Seventy-four patients met the inclusion criteria of the study. Fifty-nine patients (79.7%) had recurrent lumbar surgery. The average age of the patients was 55.7 years. In all patients, the quantity of fluid in the drain decreased on a daily basis. The subfascial drain was kept for 5 days in 26 patients (35.1%). There was no wound infection, collection, or persistent CSF leakage in any of the patients over the 6-month follow-up period. CONCLUSIONS: In this study, acetazolamide was well tolerated by the patients and, in addition to short bed rest (72 hours) and off-suction subfascial drainage, did not result in persistent CSF leakage in any patient. A prospective placebo-controlled study is beneficial to confirm the efficacy of acetazolamide in preventing CSF leakage.

Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading-dependent changes linked to muscle atrophy.

BACKGROUND: Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. METHODS: We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10 days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. RESULTS: Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P = 0.02) and decreased to 0.6-fold the initial abundance after 2 days of recovery at normal daily activity (R + 2, 2.7E9, P = 3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P = 1.5E-4) at BR10 and remained as low at R + 2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P = 0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. CONCLUSIONS: Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10 days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.

Bed rest after incidental durotomy in lumbar surgery: a redundant measure in case of watertight dural repair.

BACKGROUND: Cerebrospinal fluid (CFS) leaks are a well-known complication in spinal surgery, caused mostly by incidental durotomy (ID). Management of ID is a matter of ongoing debate. Different treatment strategies have been described ranging from no specific treatment to intraoperative suture or even complex reconstructive procedures. The role of bedrest has also been controversially discussed. The aim of this study was thus to evaluate a potential benefit of postoperative bedrest after ID. METHODS: ID management following lumbar spine surgery at a high-volume center between 01/2014 and 12/2017 was retrospectively assessed. Several risk factors such as type of surgery, size of dural lesion, intraoperatively chosen strategy, postoperative management (e.g., bedrest) and surgery-related complications were analyzed. Failure of the chosen strategy was defined as symptomatic CSF leakage, requiring revision surgery. RESULTS: Sufficient data was available for 135 patients with intraoperatively detected incidental durotomy. Eighty-seven patients with intraoperatively detected ID (64.4%) were additionally managed with bedrest, whereas 48 patients (35.6%) were immediately mobilized after surgery. Sixteen patients overall needed to be revised. However, patients treated with additional bedrest did not show a significant reduction of CSF fistula rate (P=0.27). The degree of laceration (>5mm) negatively affected the outcome (P=0.027). The hospital stay was significantly prolonged in patients, who were subjected to additional bedrest (P=0.001). CONCLUSIONS: Postoperative CSF leakage represents a serious postoperative complication of lumbar surgery. Intraoperative dural repair plays a crucial role to avoid further neurological morbidity. Postoperative bedrest might be spared in case of watertight dural closure.

Capillary rarefaction during bed rest is proportionally less than fibre atrophy and loss of oxidative capacity.

BACKGROUND: Muscle disuse from bed rest or spaceflight results in losses in muscle mass, strength and oxidative capacity. Capillary rarefaction may contribute to muscle atrophy and the reduction in oxidative capacity during bed rest. Artificial gravity may attenuate the negative effects of long-term space missions or bed rest. The aim of the present study was to assess (1) the effects of bed rest on muscle fibre size, fibre type composition, capillarization and oxidative capacity in the vastus lateralis and soleus muscles after 6 and 55 days of bed rest and (2) the effectiveness of artificial gravity in mitigating bed-rest-induced detriments to these parameters. METHODS: Nineteen participants were assigned to a control group (control, n = 6) or an intervention group undergoing 30 min of centrifugation (n = 13). All underwent 55 days of head-down tilt bed rest. Vastus lateralis and soleus biopsies were taken at baseline and after 6 and 55 days of bed rest. Fibre type composition, fibre cross-sectional area, capillarization indices and oxidative capacity were determined. RESULTS: After just 6 days of bed rest, fibre atrophy (-23.2 ± 12.4%, P < 0.001) and reductions in capillary-to-fibre ratio (C:F; 1.97 ± 0.57 vs. 1.56 ± 0.41, P < 0.001) were proportional in both muscles as reflected by a maintained capillary density. Fibre atrophy proceeded at a much slower rate between 6 and 55 days of bed rest (-11.6 ± 12.1% of 6 days, P = 0.032) and was accompanied by a 19.1% reduction in succinate dehydrogenase stain optical density (P < 0.001), without any further significant decrements in C:F (1.56 ± 0.41 vs. 1.49 ± 0.37, P = 0.459). Consequently, after 55 days of bed rest, the capillary supply-oxidative capacity ratio of a fibre had increased by 41.9% (P < 0.001), indicating a capillarization in relative excess of oxidative capacity. Even though the heterogeneity of capillary spacing (LogR SD) was increased after 55 days by 12.7% (P = 0.004), tissue oxygenation at maximal oxygen consumption of the fibres was improved after 55 days bed rest. Daily centrifugation failed to blunt the bed-rest-induced reductions in fibre size and oxidative capacity and capillary rarefaction. CONCLUSIONS: The relationship between fibre size and oxidative capacity with the capillary supply of a fibre is uncoupled during prolonged bed rest as reflected by a rapid loss of muscle mass and capillaries, followed at later stages by a more than proportional loss of mitochondria without further capillary loss. The resulting excessive capillary supply of the muscle after prolonged bed rest is advantageous for the delivery of substrates needed for subsequent muscle recovery.

Iron metabolism regulation in females and males exposed to simulated microgravity: results from the randomized trial Artificial Gravity Bed Rest-European Space Agency (AGBRESA).

BACKGROUND: Iron metabolism imbalance could contribute to physical deconditioning experienced by astronauts due to its essential role in energy metabolism, cellular respiration, and oxygen transport. OBJECTIVES: In this clinical exploratory study, we wanted to determine whether artificial gravity (AG) training modulated iron metabolism, RBC indices, and body lean mass in healthy male and female participants exposed to head-down tilt (HDT) bed rest, the reference ground-based model of microgravity. METHODS: We recruited 8 healthy female and 16 healthy male participants who were all exposed to HDT bed rest for 60 d. In addition, they were assigned to 3 experimental groups (n = 8/each): controls, continuous AG training in a short-arm centrifuge (1 × 30 min/d), and intermittent AG training (6 × 5 min/d). RESULTS: The iron metabolism responses to simulated microgravity of the AG training groups did not differ significantly from the responses of controls. Independently from AG, we found that both serum iron concentrations (+31.3%, P = 0.027) and transferrin saturation levels (+28.4%, P = 0.009) increased in males after 6 d of HDT bed rest, as well as serum hepcidin concentrations (+36.9%, P = 0.005). The increase of transferrin saturation levels persisted after 57 d of HDT bed rest (+13.5%, P = 0.026), suggesting that long-term exposure to microgravity sustainably increases serum iron availability in males, and consequently the risk of iron excess or misdistribution. In females, 6 and 57 d of HDT bed rest did not significantly change serum iron, transferrin saturation, or hepcidin levels. CONCLUSIONS: The data from this exploratory study suggest that 1) AG training does not influence the iron metabolism responses to microgravity; and 2) iron metabolism parameters, especially iron availability for cells, are significantly increased in males, but not in females, exposed to long-term simulated microgravity. Because of the small sample size of females, we nevertheless must be cautious before concluding that iron metabolism could differently respond to microgravity in females. This trial was registered at https://www.drks.de as DRKS00015677.

Therapeutic Effects of Conservative Treatment with 2-Week Bed Rest for Osteoporotic Vertebral Fractures: A Prospective Cohort Study.

UPDATE: This article was updated on October 19, 2022, because of previous errors, which were discovered after the preliminary version of the article was posted online. On page 1787, in the legend for Figure 2, the sentence that had read "The vertebral collapse rate (in %) was defined as 1 - (A/P) × 100, and vertebral instability (in %) was defined as the difference in vertebral collapse rate between the loaded and non-loaded images." now reads "The vertebral collapse rate (in %) was defined as (1 - [A/P]) × 100, and vertebral instability (in %) was defined as the difference in vertebral collapse rate between the loaded and non-loaded images." On page 1788, in the section entitled "Data Collection," the sentence that had read "The vertebral collapse rate (in %) was defined as 1 - (anterior vertebral wall height/posterior vertebral wall height) × 100, and vertebral instability (in %) was defined as the difference in vertebral collapse rate between the loaded and non-loaded images 9 ." now reads "The vertebral collapse rate (in %) was defined as (1 - [anterior vertebral wall height/posterior vertebral wall height]) × 100, and vertebral instability (in %) was defined as the difference in vertebral collapse rate between the loaded and non-loaded images 9 ." Finally, on page 1791, in Table IV, the footnote for the "Primary outcome" row that had read "N = 113 in the rest group and 99 in the no-rest group." now reads "N = 116 in the rest group and 108 in the no-rest group."

Although imaging findings that predict resistance to conservative treatment in patients with osteoporotic vertebral fracture (OVF) have recently been reported, no conservative treatment method has been standardized. In this study, the effects of initial bed rest on the outcomes of patients with OVF and in patients with and without poor prognostic findings on magnetic resonance imaging (MRI) were compared. This prospective cohort study at 2 facilities involved consecutive patients aged ≥65 years with OVF who began treatment within 2 weeks after their injury and were observed for 6 months. Patients at one hospital rested for 2 weeks (116 patients; mean age, 80.4 years), whereas those at the other hospital were not instructed to rest (108 patients; mean age, 81.5 years). Patients were further divided according to the presence or absence of poor prognostic MRI findings. The primary end point was the rate of transition to surgery; secondary end points included bone union rate, vertebral collapse progression, local kyphosis progression, and changes in activities of daily living (ADL). Forty-five patients in the rest group (including 3 who required surgery) and 37 patients in the no-rest group (including 9 who required surgery) had poor prognostic MRI findings. Although the difference in the rate of transition to surgery between the rest and no-rest groups did not reach significance among all patients (p = 0.06), the transition rate in the rest group was significantly lower (p = 0.02) in the patients with poor prognostic MRI findings. Both the bone union rate and changes in ADL were not significantly different between the rest and no-rest groups. The mean vertebral collapse progression was 6.4% in the rest group and 20.9% in the no-rest group (p < 0.001), and the mean local kyphosis progression was 2.4° in the rest group and 8.8° in the no-rest group (p < 0.001). Although bed rest is not recommended for all patients, hospitalized bed rest for 2 weeks reduced the number of patients with OVF who require surgery among patients with poor prognostic MRI findings. Bed rest also reduced progression of vertebral collapse and kyphosis, regardless of the MRI findings. Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Effects of Omega-3 and Antioxidant Cocktail Supplement on Prolonged Bed Rest: Results from Serum Proteome and Sphingolipids Analysis.

Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such as polyphenols, vitamins and essential fatty acids, can influence some metabolic features associated with physical inactivity and decrease the reactive oxidative and nitrosative stress (RONS). The aim of this study was to detect circulating molecules correlated with BR in serum of healthy male subjects enrolled in a 60-day BR protocol to evaluate a nutritional intervention with an antioxidant cocktail as a disuse countermeasure (Toulouse COCKTAIL study). The serum proteome, sphingolipidome and nitrosoproteome were analyzed adopting different mass spectrometry-based approaches. Results in placebo-treated BR subjects indicated a marked decrease of proteins associated with high-density lipoproteins (HDL) involved in lipemic homeostasis not found in the cocktail-treated BR group. Moreover, long-chain ceramides decreased while sphingomyelin increased in the BR cocktail-treated group. In placebo, the ratio of S-nitrosylated/total protein increased for apolipoprotein D and several proteins were over-nitrosylated. In cocktail-treated BR subjects, the majority of protein showed a pattern of under-nitrosylation, except for ceruloplasmin and hemopexin, which were over-nitrosylated. Collectively, data indicate a positive effect of the cocktail in preserving lipemic and RONS homeostasis in extended disuse conditions.

Physical therapy protocols to attenuate skeletal muscle atrophy in critically ill patients: narrative review / Protocolos de terapia física para atenuar la atrofia del músculo esquelético en pacientes críticos: revisión narrativa

SUMMARY: To describe the physical therapy protocols used in critically ill patients to attenuate skeletal muscle atrophy. We conducted a search in PubMed and Embase from inception to November 2020. Observational or experimental studies published in English or Spanish that evaluated the effect of physical therapy protocols on the attenuation of skeletal muscle atrophy in critically ill patients through muscle strength or mass measurement were considered eligible. Studies were only included if they reported a detailed description of the dosing of the interventions. Seventeen studies met the eligibility criteria. We included randomised clinical trials (n = 16) and observational studies (n = 1). The total population of the included studies was 872 critically ill patients. The studies aimed to evaluate the reliability, safety or effectiveness of neuromuscular electrical stimulation (n = 10) protocols, early mobilisation (n = 3), ergometer training (n = 2), transfers in tilt table (n = 1), and blood flow restriction (n = 1). Physical therapy protocols are part of the critically ill patient's integral management. Strategies such as passive mobilisation, in-bed and out-of-bed transfers, gait training, ergometer training, and neuromuscular electrical stimulation substantially impact critically ill patients' prognoses and quality of life after hospital discharge.

RESUMEN: Describir los protocolos de terapia física usados en pacientes críticos para atenuar la atrofia muscular esquelética. Realizamos una búsqueda en PubMed y Embase desde el inicio hasta noviembre de 2020. Se consideraron los estudios observacionales o experimentales publicados en inglés o español que evaluaron el efecto de los protocolos de terapia física en la atenuación de la atrofia del músculo esquelético en pacientes críticos a través de la medición de la fuerza o la masa muscular. Los estudios solo se incluyeron si informaron una descripción detallada de la dosificación de las intervenciones. Diecisiete estudios cumplieron los criterios de elegibilidad. Se incluyeron ensayos clínicos aleatorizados (n = 16) y estudios observacionales (n = 1). La población total de los estudios incluidos fue de 872 pacientes en estado crítico. Los estudios tuvieron como objetivo evaluar la confiabilidad, seguridad o efectividad de los protocolos de estimulación eléctrica neuromuscular (n = 10), movilización temprana (n = 3), entrenamiento con ergómetro (n = 2), transferencias en mesa basculante (n = 1) y restricción del flujo sanguíneo (n = 1). Los protocolos de terapia física forman parte del manejo integral del paciente crítico. Es- trategias como la movilización pasiva, los traslados dentro y fuera de la cama, el entrenamiento de la marcha, el entrenamiento con ergómetro y la estimulación eléctrica neuromuscular tienen un impacto sustancial en el pronóstico y la calidad de vida de los pacientes críticos después del alta hospitalaria.

B-Cell Homeostasis Is Maintained During Two Months of Head-Down Tilt Bed Rest With or Without Antioxidant Supplementation.

Alterations of the immune system could seriously impair the ability to combat infections during future long-duration space missions. However, little is known about the effects of spaceflight on the B-cell compartment. Given the limited access to astronaut samples, we addressed this question using blood samples collected from 20 healthy male volunteers subjected to long-duration bed rest, an Earth-based analog of spaceflight. Hematopoietic progenitors, white blood cells, total lymphocytes and B-cells, four B-cell subsets, immunoglobulin isotypes, six cytokines involved in inflammation, cortisone and cortisol were quantified at five time points. Tibia microarchitecture was also studied. Moreover, we investigated the efficiency of antioxidant supplementation with a cocktail including polyphenols, omega 3, vitamin E and selenium. Our results show that circulating hematopoietic progenitors, white blood cells, total lymphocytes and B-cells, and B-cell subsets were not affected by bed rest. Cytokine quantification suggested a lower systemic inflammatory status, supported by an increase in serum cortisone, during bed rest. These data confirm the in vivo hormonal dysregulation of immunity observed in astronauts and show that bed rest does not alter B-cell homeostasis. This lack of an impact of long-term bed rest on B-cell homeostasis can, at least partially, be explained by limited bone remodeling. None of the evaluated parameters were affected by the administration of the antioxidant supplement. The non-effectiveness of the supplement may be because the diet provided to the non-supplemented and supplemented volunteers already contained sufficient antioxidants. Given the limitations of this model, further studies will be required to determine whether B-cell homeostasis is affected, especially during future deep-space exploration missions that will be of unprecedented durations.

RNA sequencing on muscle biopsy from a 5-week bed rest study reveals the effect of exercise and potential interactions with dorsal root ganglion neurons.

Sedentary lifestyle, chronic disease, or microgravity can cause muscle deconditioning that then has an impact on other physiological systems. An example is the nervous system, which is adversely affected by decreased physical activity resulting in increased incidence of neurological problems such as chronic pain. We sought to better understand how this might occur by conducting RNA sequencing experiments on muscle biopsies from human volunteers in a 5-week bed-rest study with an exercise intervention arm. We also used a computational method for examining ligand-receptor interactions between muscle and human dorsal root ganglion (DRG) neurons, the latter of which play a key role in nociception and are generators of signals responsible for chronic pain. We identified 1352 differentially expressed genes (DEGs) in bed rest subjects without an exercise intervention but only 132 DEGs in subjects with the intervention. Among 591 upregulated muscle genes in the no intervention arm, 26 of these were ligands that have receptors that are expressed by human DRG neurons. We detected a specific splice variant of one of these ligands, placental growth factor (PGF), in deconditioned muscle that binds to neuropilin 1, a receptor that is highly expressed in DRG neurons and known to promote neuropathic pain. We conclude that exercise intervention protects muscle from deconditioning transcriptomic changes, and prevents changes in the expression of ligands that might sensitize DRG neurons, or act on other cell types throughout the body. Our work creates a set of actionable hypotheses to better understand how deconditioned muscle may influence the function of sensory neurons that innervate the entire body.

The Role of Nutrition and Forest-Bathing in the Physical Rehabilitation of Physically Inactive Patients: From the Molecular Aspects to New Nature-Inspired Techniques.

Physical rehabilitation plays a fundamental role in the management of individuals with disabilities associated with age-related muscle loss or affected by catastrophic conditions such as trauma, surgery, cancer or other severe pathologies. These events have in common an extended period of physical inactivity. Patients who undergo prolonged bed rest often present with a number of complications; for example, muscle loss that can exacerbate existing conditions determined by sarcopenia, which in turn greatly limits physical functions. The main scope of this work is to summarize certain key strategies for the physiotherapeutic management of physically inactive patients, regardless of the reason behind their prolonged bed rest, with a particular focus on physical rehabilitation, nutrition and forest-bathing. The importance of correct nutrition in counter-acting the loss of muscle mass and consequent function is explored alongside a description of the main nutrients that are needed for muscle regeneration. From a biomolecular perspective, some specific molecular mechanisms associated with physical rehabilitation are also reported not only in the context of physical therapy, but also within nature-inspired techniques, such as forest-bathing as well as body self-healing. Combining a targeted physiotherapeutic approach with an appropriate diet as well as nature-based therapy could thus help with the recovery of bed ridden patients.

Five-Day Bed Rest Reduces Postoperative Intracerebral Hemorrhage After Direct Bypass for Moyamoya Disease.

OBJECTIVE: Postoperative intracerebral hemorrhage (ICH) after direct bypass surgery for Moyamoya disease could contribute to neurologic deterioration. The aim of this study was to evaluate the effectiveness of 5-day bed rest in reducing the occurrence of postoperative ICH. METHODS: This study included 122 consecutive hemispheres in 87 Japanese adult MMD patients, composed of 80 control hemispheres from historical data and 42 hemispheres after 5-day bed rest. They all underwent direct bypass surgery. The incidence of postoperative ICH and neurologic deterioration assessed via the modified Rankin Scale were investigated and statistically analyzed. RESULTS: Postoperative ICH was observed in 9 out of the 80 (11.3%) control patients, but not in the 42 patients with 5-day bed rest. The incidence of postoperative ICH and neurologic deterioration via the modified Rankin Scale were significantly different between the 2 groups (P = 0.0268 and 0.0078, respectively). Univariate logistic analysis revealed that 5-day bed rest significantly reduced the incidence of postoperative ICH (P = 0.0048). CONCLUSIONS: Five-day bed rest after direct bypass surgery dramatically can reduce the incidence of postoperative ICH and neurologic deterioration after direct bypass surgery.

Older adults are not more susceptible to acute muscle atrophy after immobilisation compared to younger adults: a systematic review.

PURPOSE: To identify if older adults are more susceptible to acute muscle atrophy compared to younger adults. METHODS: All studies whose design involved a period of enforced immobilisation and a comparison between an older (> 40) and a younger cohort (< 40) were included. Outcome of interest was change in muscle mass, measured by radiological techniques or histological analysis of fibre size. Medline, Embase and Cochrane databases were systematically searched and records screened by two independent reviewers. Studies selected for inclusion were critically appraised and individually assessed for risk of bias. GRADE framework guided the assessment of quality of studies. RESULTS: Eight articles were included (193 participants). 14 (7.3%) were female and 102 (52.8%) were in older groups. Mean age for older adults was 66.3 years and for younger adults 23.3 years. Immobilisation periods spanned 4-14 days as simulated by bed rest, limb brace or limb cast. Studies measured muscle mass by DXA, CT, MRI or fibre cross-sectional area, or a combination of each. Muscles studied included quadriceps, adductor pollicis, vastus lateralis or combined lean leg mass. Of the radiological measures, three studies (74 participants) reported greater atrophy in the older group, three studies (76 participants) reported greater atrophy in the younger group. Reduction in muscle mass varied in older adults between 0.19 and 0.76% per day, and for younger adults between 0.06 and 0.70% per day. Due to substantial heterogeneity, a meta-analysis was not performed. Five studies reported fibre size. Change in fibre size varied considerably between each study, with no convincing overall trend for either older or younger groups. CONCLUSION: The current literature suggests that there is no difference in the rate of muscle atrophy after immobilisation in older people compared to younger people, and therefore that older people are not more susceptible to atrophy in the acute setting. However, the findings are inconsistent and provide statistically significant but opposing results. There is a lack of high-quality research available on the topic, and there is a paucity of literature regarding atrophy rates in women.