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.

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.

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.

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.

Risk factors for venous thromboembolism induced by prolonged bed rest during interstitial brachytherapy for gynecological cancer: a retrospective study.

BACKGROUND: Screening and management of venous thromboembolism (VTE) after surgery is important in preventing sublethal VTE. However, the risk factors for VTE during interstitial brachytherapy (ISBT) remain unknown, and appropriate screening and management strategies are yet to be established. Therefore, this study aimed to evaluate the risk factors for VTE resulting from requisite bed rest during ISBT for gynecologic cancers. METHODS: We retrospectively analyzed 47 patients. For patients without definitive preceding radiotherapy, whole pelvic irradiation (30-50 Gy) followed by ISBT of 12-30 Gy/2-5 fx/1-3 days was administered to CTV D90. For patients with preceding radiotherapy, 36-42 Gy/6-7 fx/3-4 days was delivered by ISBT alone. The supine position was required during ISBT. D-dimer (DD) was measured at initial presentation, 1 week before ISBT, pre-ISBT, on the day of, and the day following needle removal. Patients were divided into three groups according to the risk of VTE and were managed accordingly; Group 1: DD was not detected (negative) before ISBT, Group 2: VTE was not detected on venous ultrasound imaging, although DD was positive before ISBT, and Group 3: VTE was detected (positive) before ISBT. An intermittent pneumatic compression device was used during ISBT; for the patients without VTE before ISBT. Heparin or oral anticoagulants were administered to patients with VTE before ISBT. RESULTS: Overall, the median values of DD pre-ISBT, on the day of, and on the day following needle removal were 1.0 (0.4-5.8), 1.1 (0.5-88.9), and 1.5 (0.7-40.6) µg/mL, respectively. After ISBT, no patients had deep vein thrombosis (DVT) in groups 1 and 2. In group 3, 7 of 14 patients experienced worsening of VTE but remained asymptomatic. In univariate analysis, DVT diagnosed before ISBT, Caprini score ≥ 7, and difference in DD values between pre-ISBT and the day of or the day following needle removal ≥ 1 were associated with the incidence or worsening of VTE. CONCLUSION: DD should be measured before and after ISBT to detect the incidence or worsening of VTE in patients with DVT. The Caprini score may help in the prediction of VTE during or after ISBT.

Risk factors associated with deep venous thrombosis in patients with different bed-rest durations: A multi-institutional case-control study.

BACKGROUND: Deep vein thrombosis represents a threat to public health and a heavy economic burden to society, and often occurs as a complication or cause of death in bedridden patients. How to prevent deep vein thrombosis is a general concern in clinical practice. However, it remains uncertain whether the risk factors for deep vein thrombosis would be affected by different bed-rest durations. Solving this issue will be invaluable for the provision of more rational medical care to prevent deep vein thrombosis. OBJECTIVE: To explore whether risk factors for deep vein thrombosis are affected by bed-rest durations and to identify different risk factors in groups with different bed-rest durations. DESIGN: A retrospective multicenter case-control study. SETTINGS AND PARTICIPANTS: This multicenter study was conducted in wards with high rates of bed rest in 25 general hospitals in China. Participants were bedridden patients from these wards. METHODS: Bedridden patients were identified from the research database of bedridden patients' major immobility complications. These data were collected from prospective descriptive studies by a standardized web-based online case report form. Cases were defined as bedridden patients who suffered deep vein thrombosis during hospitalization (n=186). Each case was matched with three controls, bedridden patients who did not suffer deep vein thrombosis in the same center with the same bed-rest duration (n=558). Descriptive statistics, univariate analysis, and multivariate conditional logistic regression models were employed. RESULTS: Among 23,985 patients, the overall incidence of deep vein thrombosis during hospitalization was 1.0%. Multivariate analysis showed that for patients with bed-rest duration of 4 weeks or less, older age (odds ratio [OR] =1.027, 95% confidence interval [CI] 1.013-1.041) and being in a surgical department (OR=2.527, 95% CI 1.541-4.144) were significantly associated with increased risk of deep vein thrombosis. Female sex (OR=4.270, 95% CI 1.227-14.862), smoking (OR=10.860, 95% CI 2.130-55.370), and special treatment (OR=3.455, 95% CI 1.006-11.869) were independent factors predicting deep vein thrombosis for patients with bed-rest durations from 5 to 8 weeks. For those with bed-rest durations from 9 to 13 weeks, Charlson Comorbidity Index (OR=1.612, 95% CI 1.090-2.385) was the only independent risk factor for deep vein thrombosis. CONCLUSIONS: Risk factors for deep vein thrombosis varied among patients with different bed-rest durations. This finding is helpful for nurses to increase their awareness of prevention of deep vein thrombosis in patients with different bed-rest durations, and lays a more solid foundation for clinical decision making.

The effect of short-term exercise prehabilitation on skeletal muscle protein synthesis and atrophy during bed rest in older men.

BACKGROUND: Poor recovery from periods of disuse accelerates age-related muscle loss, predisposing individuals to the development of secondary adverse health outcomes. Exercise prior to disuse (prehabilitation) may prevent muscle deterioration during subsequent unloading. The present study aimed to investigate the effect of short-term resistance exercise training (RET) prehabilitation on muscle morphology and regulatory mechanisms during 5 days of bed rest in older men. METHODS: Ten healthy older men aged 65-80 years underwent four bouts of high-volume unilateral leg RET over 7 days prior to 5 days of inpatient bed rest. Physical activity and step-count were monitored over the course of RET prehabilitation and bed rest, whilst dietary intake was recorded throughout. Prior to and following bed rest, quadriceps cross-sectional area (CSA), and hormone/lipid profiles were determined. Serial muscle biopsies and dual-stable isotope tracers were used to determine integrated myofibrillar protein synthesis (iMyoPS) over RET prehabilitation and bed rest phases, and acute postabsorptive and postprandial myofibrillar protein synthesis (aMyoPS) rates at the end of bed rest. RESULTS: During bed rest, daily step-count and light and moderate physical activity time decreased, whilst sedentary time increased when compared with habitual levels (P < 0.001 for all). Dietary protein and fibre intake during bed rest were lower than habitual values (P < 0.01 for both). iMyoPS rates were significantly greater in the exercised leg (EX) compared with the non-exercised control leg (CTL) over prehabilitation (1.76 ± 0.37%/day vs. 1.36 ± 0.18%/day, respectively; P = 0.007). iMyoPS rates decreased similarly in EX and CTL during bed rest (CTL, 1.07 ± 0.22%/day; EX, 1.30 ± 0.38%/day; P = 0.037 and 0.002, respectively). Postprandial aMyoPS rates increased above postabsorptive values in EX only (P = 0.018), with no difference in delta postprandial aMyoPS stimulation between legs. Quadriceps CSA at 40%, 60%, and 80% of muscle length decreased significantly in EX and CTL over bed rest (0.69%, 3.5%, and 2.8%, respectively; P < 0.01 for all), with no differences between legs. No differences in fibre-type CSA were observed between legs or with bed rest. Plasma insulin and serum lipids did not change with bed rest. CONCLUSIONS: Short-term resistance exercise prehabilitation augmented iMyoPS rates in older men but did not offset the relative decline in iMyoPS and muscle mass during bed rest.

Clinical warning signs of life-threatening hematochezia in neurosurgical patients with long-term bed rest: Three cases report.

RATIONALE: Patients with long term bed rest in intensive care unit after neurosurgery could experience splanchnic hypoperfusion. These patients have several other medical conditions that exacerbate splanchnic hypoperfusion during treatment and the splanchnic hypoperfusion could result in "stress-induced intestinal necrosis", which could cause massive hematochezia. We report here the experience of life-threatening hematochezia in 3 patients who underwent brain surgery in our institution. PATIENTS CONCERNS: One female patient (72-year-old) and 2 male patients (58- and 35-year-old) were admitted to our institution because of traumatic intracerebral hemorrhage, subarachnoid hemorrhage due to a ruptured anterior communicating artery, and subarachnoid hemorrhage with unknown cause respectively. All patients underwent emergency brain surgery for diagnosis and treatment. After surgery, they all experienced long-term bed rest in intensive care unit. Hematochezia occurred on postoperative day 15, 17, and 49, respectively. DIAGNOSES: All of the patients were assessed by abdomen/pelvis computed tomography and underwent a colonoscopy. INTERVENTIONS: The female patient underwent embolization through pelvic arteriography and epinephrine injection through colonoscopy, but a total colectomy and ileostomy was performed due to refractory hematochezia. 58-year-old male patient had a laparoscopic ileostomy for the bowel rest. The other patient underwent nil per os and conservative treatment for 2 weeks. OUTCOMES: The female patient was discharged without further treatment plan, 58-year-old male patient survived after laparoscopic ileostomy, while the other patient survived after 2 weeks of nil per os. LESSON: Abdominal symptoms, such as hematochezia, should be actively managed in neurosurgical patients who are undergoing long-term bed rest in an intensive care unit under physiologically stressful medical conditions.

Simulated microgravity disturbs iron metabolism and distribution in humans: Lessons from dry immersion, an innovative ground-based human model.

The objective of the present study was to determine the effects of dry immersion, an innovative ground-based human model of simulated microgravity and extreme physical inactivity, on iron homeostasis and distribution. Twenty young healthy men were recruited and submitted to 5 days of dry immersion (DI). Fasting blood samples and MRI were performed before and after DI exposure to assess iron status, as well as hematological responses. DI increased spleen iron concentrations (SIC), whereas hepatic iron store (HIC) was not affected. Spleen iron sequestration could be due to the concomitant increase in serum hepcidin levels (P < .001). Increased serum unconjugated bilirubin, as well as the rise of serum myoglobin levels support that DI may promote hemolysis and myolysis. These phenomena could contribute to the concomitant increase of serum iron and transferrin saturation levels (P < .001). As HIC remained unchanged, increased serum hepcidin levels could be due both to higher transferrin saturation level, and to low-grade pro-inflammatory as suggested by the significant rise of serum ferritin and haptoglobin levels after DI (P = .003 and P = .003, respectively). These observations highlight the need for better assessment of iron metabolism in bedridden patients, and an optimization of the diet currently proposed to astronauts.

Locomotion replacement exercise cannot counteract cartilage biomarker response to 5 days of immobilization in healthy adults.

Biomarkers of cartilage metabolism are sensitive to changes in the biological and mechanical environment and can indicate early changes in cartilage homeostasis. The purpose of this study was to determine if a daily locomotion replacement program can serve as a countermeasure for changes in cartilage biomarker serum concentration caused by immobilization. Ten healthy male subjects (mean ± 1 standard deviation; age: 29.4 ± 5.9 years; body mass: 77.7 ± 4.1 kg) participated in the crossover 5-day bed rest study with three interventions: control (CON), standing (STA), and locomotion replacement training (LRT). Serum samples were taken before, during, and after bed rest. Biomarker concentrations were measured using commercial enzyme-linked immunosorbent assays. Cartilage oligomeric matrix protein (COMP) levels after 24 hours of bed rest decreased independently of the intervention (-16.8% to -9.8%) and continued to decrease until 72 hours of bed rest (minimum, -23.2% to -20.6%). LRT and STA did not affect COMP during bed rests (P = .056) but there was a strong tendency for a slower decrease with LRT (-9.4%) and STA (-11.7%) compared with CON (-16.8%). MMP-3 levels decreased within the first 24 hours of bed rest (CON: -22.3%; STA: -14.7%; LRT: -17%) without intervention effect. Both COMP and MMP-3 levels recovered to baseline levels during the 6-day recovery period. MMP-1, MMP-9, and TNF-α levels were not affected by immobilization or intervention. COMP and MMP-3 are mechano-sensitive cartilage biomarkers affected by immobilization, and simple interventions such as standing upright or LRT during bed rest cannot prevent these changes. Clinical significance: simple locomotion interventions cannot prevent cartilage biomarker change during bed rest.

Skeletal Muscle Energetics and Mitochondrial Function Are Impaired Following 10 Days of Bed Rest in Older Adults.

BACKGROUND: Older adults exposed to periods of inactivity during hospitalization, illness, or injury lose muscle mass and strength. This, in turn, predisposes poor recovery of physical function upon reambulation and represents a significant health risk for older adults. Bed rest (BR) results in altered skeletal muscle fuel metabolism and loss of oxidative capacity that have recently been linked to the muscle atrophy program. Our primary objective was to explore the effects of BR on mitochondrial energetics in muscle from older adults. A secondary objective was to examine the effect of ß-hydroxy-ß-methylbuturate (HMB) supplementation on mitochondrial energetics. METHODS: We studied 20 older adults before and after a 10-day BR intervention, who consumed a complete oral nutritional supplement (ONS) with HMB (3.0 g/d HMB, n = 11) or without HMB (CON, n = 9). Percutaneous biopsies of the vastus lateralis were obtained to determine mitochondrial respiration and H2O2 emission in permeabilized muscle fibers along with markers of content. RNA sequencing and lipidomics analyses were also conducted. RESULTS: We found a significant up-regulation of collagen synthesis and down-regulation of ribosome, oxidative metabolism and mitochondrial gene transcripts following BR in the CON group. Alterations to these gene transcripts were significantly blunted in the HMB group. Mitochondrial respiration and markers of content were both reduced and H2O2 emission was elevated in both groups following BR. CONCLUSIONS: In summary, 10 days of BR in older adults causes a significant deterioration in mitochondrial energetics, while transcriptomic profiling revealed that some of these negative effects may be attenuated by an ONS containing HMB.

Abdominal visceral adipose tissue is associated with unsuspected pulmonary embolism on routine CT scans in patients with gastrointestinal cancer.

OBJECTIVE: Unsuspected pulmonary embolism (UPE) has been increasingly diagnosed as an incidental finding on CT scans for routine staging in cancer patients. Previous studies suggest that obesity is an independent risk factor for venous thromboembolism in patients with malignant tumors. In this study, we aimed to investigate the association between abdominal adipose tissue, especially visceral adipose tissue (VAT) and the occurrence of UPE in hospitalized patients with gastrointestinal cancer. METHODS: Routine contrast-enhanced chest and abdominal CT scans of 1974 patients were retrospectively assessed for the presence of UPE, of which 58 patients were identified with UPE and 108 non-UPE patients were selected as the non-UPE control group based on several matching criteria. Abdominal adipose tissue was measured by volumes of VAT and subcutaneous adipose tissue (SAT) at the navel level. RESULTS: VAT, SAT, indwelling venous catheters, surgery, chemotherapy, and bed rest or immobilization were associated with the occurrence of UPE. Higher VAT volumes were associated with increased risk of UPE (odds ratio: 1.96; 95% confidence interval: 1.25, 3.06; p = 0.003) adjusting body mass index (BMI), bed rest or immobilization, surgery, chemotherapy and smoking, while SAT was not associated with UPE adjusting the same confounders (p = 0.117). No statistical association was found between BMI and UPE (p = 0.102). CONCLUSION: Higher VAT rather than SAT is associated with an increased risk of unsuspected pulmonary embolism on routine CT scans in hospitalized gastrointestinal cancer patients. ADVANCES IN KNOWLEDGE: Our findings indicate that VAT is a stronger risk factor for unsuspected pulmonary embolism than BMI and SAT in hospitalized patients with gastrointestinal cancer.