Angiotensin 1-7 protects against ventilator-induced diaphragm dysfunction.

Mechanical ventilation (MV) is a life-saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator-induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin-angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1-7 (Ang1-7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1-7 protects the diaphragm against MV-induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1-7 shielded diaphragm fibers against MV-induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1-7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1-7 has the therapeutic potential to protect against VIDD by preventing MV-induced contractile dysfunction and atrophy of both slow and fast muscle fibers.

Characteristics of effective home-based resistance training in patients with noncommunicable chronic diseases: a systematic scoping review of randomised controlled trials.

Skeletal muscle atrophy, dysfunction, and weakness are consequences of noncommunicable diseases which result in exercise and functional limitations which contribute to poor quality of life and increased mortality. Home-based resistance training may promote skeletal muscle health. Electronic-based systematic searches were performed identifying randomised controlled trials utilising home-based resistance training in patients with noncommunicable diseases defined as cancer, cardiovascular disease, diabetes mellitus (type 1 and 2), chronic kidney disease (including dialysis), and chronic respiratory disease (asthma, chronic obstructive pulmonary disease, pulmonary hypertension). A comparator group was defined as one containing "non-exercise" or "usual care". Of the 239 studies identified (published between 1996 and 2020), 22 met the inclusion criteria. Sixteen studies contained an adjunct aerobic training component. Study designs and outcome measures showed large variation. Reporting of the principles of training applied within interventions was poor. Heterogeneity in study characteristics, and poor reporting of training characteristics, prevents formal recommendations for optimising home-based resistance training. However, home-based interventions are less resource-intensive than supervised programmes and appear to have the ability to improve or preserve pertinent outcomes such as strength, functional ability, and quality of life; potentially reducing the risk of mortality in patients with chronic disease.

Intraoperative Lumbar Muscle Motor Evoked Potential Monitoring With Transcortical Stimulation.

BACKGROUND: Stimulating electrodes for lower extremity motor-evoked potential (LE-MEP) monitoring with transcortical stimulation are usually placed on the medial side of motor cortex convexity, which is not lower extremity but lumbar motor area. Lumbar MEP may be elicited with lower stimulation intensity than LE-MEP through this location, and it is useful to monitor lower extremity motor function intraoperatively. METHODS: Intraoperative lumbar and LE-MEP monitoring with transcortical stimulation during surgery of 12 patients with lesions involving the motor cortex from January 2012 to February 2019 at Shinshu University Hospital were reviewed retrospectively. Stimulations were delivered by a train of 5 pulses of anodal constant current stimulation. Stimulating electrode position was determined by motor cortex mapping. Recording needle electrodes were placed on bilateral lumbar muscles and contralateral leg muscles. The threshold-level stimulation method was used for MEP monitoring. The thresholds, monitoring result, and postoperative motor function of lumbar and lower extremities were compared. RESULTS: The mean baseline thresholds were 19.9 ± 8.9 mA for lumbar MEP and 26.5 ± 11.5 mA for LE-MEP (P = 0.02). Patterns of intraoperative monitoring changes were the same between lumbar and LE-MEP monitoring. CONCLUSIONS: Lumbar MEP was stimulated with lower stimulation intensity than the LE-MEP with the same intraoperative pattern of waveform changes in 12 patients. Lumbar MEP monitoring may be useful for preserving the corticospinal tract of lower extremities intraoperatively.

MitoTEMPOL, a mitochondrial targeted antioxidant, prevents sepsis-induced diaphragm dysfunction.

Clinical studies indicate that sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. Currently there is no drug to treat this form of diaphragm weakness. Sepsis-induced muscle dysfunction is thought to be triggered by excessive mitochondrial free radical generation; we therefore hypothesized that therapies that target mitochondrial free radical production may prevent sepsis-induced diaphragm weakness. The present study determined whether MitoTEMPOL, a mitochondrially targeted free radical scavenger, could reduce sepsis-induced diaphragm dysfunction. Using an animal model of sepsis, we compared four groups of mice: 1) sham-operated controls, 2) animals with sepsis induced by cecal ligation puncture (CLP), 3) sham controls given MitoTEMPOL (10 mg·kg-1·day-1 ip), and 4) CLP animals given MitoTEMPOL. At 48 h after surgery, we measured diaphragm force generation, mitochondrial function, proteolytic enzyme activities, and myosin heavy chain (MHC) content. We also examined the effects of delayed administration of MitoTEMPOL (by 6 h) on CLP-induced diaphragm weakness. The effects of MitoTEMPOL on cytokine-mediated alterations on muscle cell superoxide generation and cell size in vitro were also assessed. Sepsis markedly reduced diaphragm force generation. Both immediate and delayed MitoTEMPOL administration prevented sepsis-induced diaphragm weakness. MitoTEMPOL reversed sepsis-mediated reductions in mitochondrial function, activation of proteolytic pathways, and decreases in MHC content. Cytokines increased muscle cell superoxide generation and decreased cell size, effects that were ablated by MitoTEMPOL. MitoTEMPOL and other compounds that target mitochondrial free radical generation may be useful therapies for sepsis-induced diaphragm weakness.

The Use of Recombinant Human Growth Hormone to Protect Against Muscle Weakness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pilot, Randomized Placebo-Controlled Trial.

BACKGROUND: Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps muscle weakness that limits their successful return to play and are also at an increased risk of developing knee osteoarthritis (OA). Human growth hormone (HGH) has been shown to prevent muscle atrophy and weakness in various models of disuse and disease but has not been evaluated in patients undergoing ACLR. HYPOTHESIS: Compared with placebo treatment, a 6-week perioperative treatment course of HGH would protect against muscle atrophy and weakness in patients undergoing ACLR. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 19 male patients (aged 18-35 years) scheduled to undergo ACLR were randomly assigned to the placebo (n = 9) or HGH (n = 10) group. Patients began placebo or HGH treatment twice daily 1 week before surgery and continued through 5 weeks after surgery. Knee muscle strength and volume, patient-reported outcome scores, and circulating biomarkers were measured at several time points through 6 months after surgery. Mixed-effects models were used to evaluate differences between treatment groups and time points, and as this was a pilot study, significance was set at P < .10. The Cohen d was calculated to determine the effect size. RESULTS: HGH was well-tolerated, and no differences in adverse events between the groups were observed. The HGH group had a 2.1-fold increase in circulating insulin-like growth factor 1 over the course of the treatment period (P < .05; d = 2.93). The primary outcome measure was knee extension strength, and HGH treatment increased normalized peak isokinetic knee extension torque by 29% compared with the placebo group (P = .05; d = 0.80). Matrix metalloproteinase-3 (MMP3), which was used as an indirect biomarker of cartilage degradation, was 36% lower in the HGH group (P = .05; d = -1.34). HGH did not appear to be associated with changes in muscle volume or patient-reported outcome scores. CONCLUSION: HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR. On the basis of this pilot study, further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients undergoing ACLR are warranted. REGISTRATION: NCT02420353 ( ClinicalTrials.gov identifier).

Modification of Neuromuscular Junction Protein Expression by Exercise and Doxorubicin.

PURPOSE: Doxorubicin (DOX) is a highly effective antitumor agent widely used in cancer treatment. However, it is well established that DOX induces muscular atrophy and impairs force production. Although no therapeutic interventions exist to combat DOX-induced muscle weakness, endurance exercise training has been shown to reduce skeletal muscle damage caused by DOX administration. Numerous studies have attempted to identify molecular mechanisms responsible for exercise-induced protection against DOX myotoxicity. Nevertheless, the mechanisms by which endurance exercise protects against DOX-induced muscle weakness remain elusive. In this regard, impairments to the neuromuscular junction (NMJ) are associated with muscle wasting, and studies indicate that physical exercise can rescue NMJ fragmentation. Therefore, we tested the hypothesis that exercise protects against DOX-induced myopathy by preventing detrimental changes to key proteins responsible for maintenance of the NMJ. METHODS: Female Sprague-Dawley rats were assigned to sedentary or exercise-trained groups. Exercise training consisted of a 5-d treadmill habituation period followed by 10 d of running (60 min·d, 30 m·min, 0% grade). After the last training bout, exercise-trained and sedentary animals were paired with either placebo (saline) or DOX (20 mg·kg i.p.) treatment. Two days after drug treatment, the soleus muscle was excised for subsequent analyses. RESULTS: Our results indicate that endurance exercise training prevents soleus muscle atrophy and contractile dysfunction in DOX-treated animals. These adaptations were associated with the increased expression of the following neurotrophic factors: brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, nerve growth factor, and neurotrophin-3. In addition, exercise enhanced the expression of receptor-associated protein of the synapse and the acetylcholine receptor (AChR) subunits AChRß, AChRδ, and AChRγ in DOX-treated animals. CONCLUSION: Therefore, upregulating neurotrophic factor and NMJ protein expression may be an effective strategy to prevent DOX-induced skeletal muscle dysfunction.

Combined Application of Electrically Stimulated Antagonist Muscle Contraction and Volitional Muscle Contraction Prevents Muscle Strength Weakness and Promotes Physical Function Recovery After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Osteoarthritis of the knee (KOA) is the most common cause of disability in both the United States and in Japan. The Hybrid training system (HTS) has been developed as a resistance exercise method combining electrical stimulation with voluntary exercise. The purpose of the present study is to compare the effects of a conventional rehabilitation program with or without HTS on knee muscle strength and physical function after Total knee arthroplasty (TKA). METHODS: We conducted a 12-week randomized controlled trial, using standard rehabilitation (the control group, n = 27) or standard rehabilitation plus HTS (the HTS group, n= 26), in 53 female patients after TKA. The HTS group underwent HTS three times per week for twelve weeks after TKA. Muscle strength, thigh circumference, physical functional testing, QOL and knee pain were assessed before surgery, 6 and 12 weeks after TKA. RESULTS: There was a significant decrease in quadriceps strength and thigh circumference on the operative side in the control group, but not in the HTS group at 6 weeks. Hamstring strength on the operative side in the HTS group significantly increased and thigh circumference was bigger than in the control group at 12 weeks. Physical function improved at 6 weeks in the HTS group, but not in the control group. Knee pain significantly improved in both groups at 6 weeks. CONCLUSIONS: HTS was effective in preventing quadriceps weakness and in improving physical function and QOL after TKA.

Repetitive vascular occlusion stimulus (RVOS) versus standard care to prevent muscle wasting in critically ill patients (ROSProx):a study protocol for a pilot randomised controlled trial.

BACKGROUND: Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients. METHODS: This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge. DISCUSSION: If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN44340629. Registered on 26 October 2017.

Small-hairpin RNA and pharmacological targeting of neutral sphingomyelinase prevent diaphragm weakness in rats with heart failure and reduced ejection fraction.

Heart failure with reduced ejection fraction (HFREF) increases neutral sphingomyelinase (NSMase) activity and mitochondrial reactive oxygen species (ROS) emission and causes diaphragm weakness. We tested whether a systemic pharmacological NSMase inhibitor or short-hairpin RNA (shRNA) targeting NSMase isoform 3 (NSMase3) would prevent diaphragm abnormalities induced by HFREF caused by myocardial infarction. In the pharmacological intervention, we used intraperitoneal injection of GW4869 or vehicle. In the genetic intervention, we injected adeno-associated virus serotype 9 (AAV9) containing shRNA targeting NSMase3 or a scrambled sequence directly into the diaphragm. We also studied acid sphingomyelinase-knockout mice. GW4869 prevented the increase in diaphragm ceramide content, weakness, and tachypnea caused by HFREF. For example, maximal specific forces (in N/cm2) were vehicle [sham 31 ± 2 and HFREF 26 ± 2 ( P < 0.05)] and GW4869 (sham 31 ± 2 and HFREF 31 ± 1). Respiratory rates were (in breaths/min) vehicle [sham 61 ± 3 and HFREF 84 ± 11 ( P < 0.05)] and GW4869 (sham 66 ± 2 and HFREF 72 ± 2). AAV9-NSMase3 shRNA prevented heightening of diaphragm mitochondrial ROS and weakness [in N/cm2, AAV9-scrambled shRNA: sham 31 ± 2 and HFREF 27 ± 2 ( P < 0.05); AAV9-NSMase3 shRNA: sham 30 ± 1 and HFREF 30 ± 1] but displayed tachypnea. Both wild-type and ASMase-knockout mice with HFREF displayed diaphragm weakness. Our study suggests that activation of NSMase3 causes diaphragm weakness in HFREF, presumably through accumulation of ceramide and elevation in mitochondrial ROS. Our data also reveal a novel inhibitory effect of GW4869 on tachypnea in HFREF likely mediated by changes in neural control of breathing.

Quantitative Assessment of Muscle Strength Following "Slow" Surgical Lengthening of the Medial Hamstring Muscles in Children With Cerebral Palsy.

BACKGROUND: Classic teaching for surgical lengthening of muscle contractures in children with cerebral palsy (CP) has emphasized complete correction of the deformity acutely, with immobilization of the targeted muscles in the fully corrected position. Clinical experience has led to the impression that the muscles are invariably weakened by this approach. We have developed an alternative technique for correction of contractures called slow surgical lengthening (SSL). The goal of the study was to determine the physical examination, kinematic, and muscle strength outcomes following SSL of the medial hamstring muscles in children with CP. METHODS: The study group included 41 children with CP who underwent SSL of the medial hamstring muscles as part of a comprehensive single-event multilevel surgery, who had preoperative and 1-year postoperative evaluations in our Motion Analysis Center, which included quantitative assessment of isometric and isokinetic muscle strength. RESULTS: All subjects were Gross Motor Function Classification System I and II. Mean age at the time of surgery was 10.8 years. The mean popliteal angle improved by 16.2 degrees (P<0.001) following SSL of the medial hamstrings. Sagittal plane kinematics following SSL of the medial hamstrings showed improvement of knee extension at initial contact of 10.2 degrees (P<0.001), decrease of peak knee flexion in mid-swing of 3.6 degrees (P=0.014), improved minimum knee flexion in stance of 4.9 degrees (P=0.002), and no significant change in mean anterior pelvic tilt (P=0.123). Mean peak isometric knee flexion torque remained unchanged from preoperative to postoperative studies (P=0.154), whereas mean peak isokinetic knee flexion torque significantly increased by 0.076 Nm/kg (P=0.014) following medial hamstring SSL. DISCUSSION: SSL was developed based upon clinical experience and improved understanding of the pathophysiology of skeletal muscle in children with CP. The SSL technique allows the tendinous tissue to separate spontaneously at the time of recession, but does not force further acute lengthening by intraoperative manipulation, thereby minimizing the damage to the underlying muscle. It is broadly believed that muscle weakness is inevitable following surgical lengthening. The current study shows that the SSL technique does not cause weakness. LEVEL OF EVIDENCE: Level IV-therapeutic.

Blood Flow-Restricted Training for Lower Extremity Muscle Weakness due to Knee Pathology: A Systematic Review.

CONTEXT:: Blood flow-restricted training (BFRT) has been suggested to treat lower extremity muscle weakness. The efficacy of BFRT for muscle problems related to knee pathology is unclear. OBJECTIVE:: To determine whether BFRT (1) improves muscle strength and cross-sectional area (CSA) for chronic knee-related lower extremity atrophy and (2) prevents muscle atrophy after knee surgery. DATA SOURCES:: A systematic review of the literature from 1974 to 2017 was conducted using the PubMed and Cochrane databases. STUDY SELECTION:: Controlled trials that used BFRT to treat chronic knee-related lower extremity muscle atrophy or to prevent muscle atrophy after knee surgery that measured the effects on quadriceps or hamstrings muscle strength or CSA were included. STUDY DESIGN:: Systematic review. LEVEL OF EVIDENCE:: Level 2. DATA EXTRACTION:: Data were extracted as available from 9 studies (8 level 1, 1 level 2). Assessment of study quality was rated using the Physiotherapy Evidence Database or Methodological Index for Non-Randomized Studies instruments. RESULTS:: BFRT was used after anterior cruciate ligament reconstruction and routine knee arthroscopy and in patients with knee osteoarthritis or patellofemoral pain. There were a total of 165 patients and 170 controls. Vascular occlusion and exercise protocols varied; all studies except 1 incorporated exercises during occlusion, most of which focused on the quadriceps. Six of 7 studies that measured quadriceps strength reported statistically significant improvements after training. Few benefits in quadriceps CSA were reported. Hamstrings strength was only measured in 2 studies. There were no complications related to training. CONCLUSION:: Published limited data show BFRT to be safe and potentially effective in improving quadriceps muscle strength in patients with weakness and atrophy related to knee pathology. The use of short-duration vascular occlusion and light-load resistance exercises appears safe after knee surgery or in arthritic knees. This treatment option requires further investigation to refine protocols related to cuff pressure and exercise dosage and duration.

Can postoperative deltoid weakness after cervical laminoplasty be prevented by using intraoperative neurophysiological monitoring?

Laminoplasty, frequently performed in patients with cervical myelopathy, is safe and provides relatively good results. However, motor palsy of the upper extremities, which occurs after decompression surgery for cervical myelopathy, often reduces muscle strength of the deltoid muscle, mainly in the C5 myotome. The aim of this study was to investigate prospectively whether postoperative deltoid weakness (DW) can be predicted by performing intraoperative neurophysiological monitoring (IONM) during cervical laminoplasty and to clarify whether it is possible to prevent palsy using IONM. We evaluated the 278 consecutive patients (175 males and 103 females) who underwent French-door cervical laminoplasty for cervical myelopathy under IONM between November 2008 and December 2016 at our hospital. IONM was performed using muscle evoked potential after electrical stimulation to the brain [Br(E)-MsEP] from the deltoid muscle. Seven patients (2.5%) developed DW after surgery (2 with acute and 5 with delayed onset). In all patients, deltoid muscle strength recovered to ≥ 4 on manual muscle testing 3-6 months after surgery. Persistent IONM alerts occurred in 2 patients with acute-onset DW. To predict the acute onset of DW, Br(E)-MsEP alerts in the deltoid muscle had both a sensitivity and specificity of 100%. The PPV of persistent Br(E)-MsEP alerts had both a sensitivity and specificity of 100% for acute-onset DW. There was no change in Br(E)-MsEP in patients with delayed-onset palsy. The incidence of deltoid palsy was relatively low. Persistent Br(E)-MsEP alerts of the deltoid muscle had a 100% sensitivity and specificity for predicting a postoperative acute deficit. IONM was unable to predict delayed-onset DW. In only 1 patient were we able to prevent postoperative DW by performing a foraminotomy.

The Speech Arm Vision Eyes (SAVE) scale predicts large vessel occlusion stroke as well as more complicated scales.

INTRODUCTION: The Speech Arm Vision Eyes (SAVE) scale, a 4-item clinical scale emphasizing binary scoring and avoidance of nuanced examination distinctions, predicts LVOs with similar characteristics as more complex scales. METHODS: Receiver operating characteristic analyses of the prospective STOPStroke study assessed the ability of the SAVE scale and other published scales to predict LVO. We identified scale thresholds with positive likelihood ratios with 95% confidence intervals of ≥5.0 or negative likelihood ratios with 95% confidence intervals of ≤0.5. RESULTS: 735patients were studied. LVO prevalence was 33%. Area under the curve was 0.79 for SAVE, 0.82 for FAST-ED, 0.80 for mNIHSS and NIHSS, and lower for all other scales. SAVE=4, EMSA=6, mNIHSS≥10, NIHSS≥16, and RACE≥8 had positive likelihood ratios with 95% confidence intervals ≥5.0. SAVE≥2, CPSS≥2, C-STAT≥1, EMSA≥4, FAST-ED≥3, G-FAST≥3, mNIHSS≥6, NIHSS≥9, PASS≥1, RACE≥2, VAN=1, and 3I-SS≥1 had negative likelihood ratios with 95% confidence intervals ≤0.5. CONCLUSIONS: SAVE=4 performed similarly to more complex scales at predicting LVO. Other simplified scales did not have thresholds with positive likelihood ratios with 95% confidence intervals ≥5.0. Validation is need in a prehospital cohort of patients with suspected stroke.

Diagnóstico e intervención médica en la debilidad muscular adquirida / Diagnóstico e intervenção médica na fraqueza muscular adquirida / Diagnosis and medical intervention in acquired muscle weakness

Introducción: la debilidad adquirida del paciente en la Unidad de Terapia Intensiva es un problema que le provoca deficiencias en su estado físico y funcional. Objetivo: sistematizar contenidos esenciales relacionados con la debilidad adquirida del paciente en la Unidad de Terapia Intensiva. Método: en el Hospital General Docente Dr. Agostinho Neto, entre enero y septiembre de 2019 se hizo una revisión narrativa sobre el tema a través de una búsqueda en bases de datos electrónicas (Biblioteca Virtual en Salud, LILACS, PubMed, SciELO, RedALyC, Scopus). Se localizaron 135 documentos y se eligieron 25 relevantes para el objetivo de la revisión. La información se estructuró en los siguientes aspectos sobre la debilidad adquirida del paciente en la Unidad de Terapia Intensiva: definición, antecedentes históricos, epidemiología, fisiopatología, diagnóstico e intervención médica. Resultados: se identificaron controversias sobre los criterios diagnósticos precisos, el protocolo de actuación para su prevención y rehabilitación y la carencia de un instrumento para estratificar el riesgo de esta complicación. Conclusiones: se sistematizaron las bases para la preparación de los profesionales en el diagnóstico, la prevención de la debilidad adquirida del paciente en la Unidad de Terapia Intensiva y su rehabilitación(AU)

Introduction: the patient's acquired weakness in the Intensive Care Unit is a problem that causes deficiencies in his physical and functional state. Objective: systematize essential contents related to the patient's acquired weakness in the Intensive Care Unit. Method: in the General Teaching Hospital "Dr. Agostinho Neto", between January and September 2019, a narrative review of the subject was made through a search in electronic databases (Virtual Health Library, LILACS, PubMed, SciELO, RedALyC, Scopus). 135 documents were located and 25 relevant for the purpose of the review were chosen. The information was structured in the following aspects about the patient's acquired weakness in the Intensive Care Unit: definition, historical background, epidemiology, pathophysiology, diagnosis and medical intervention. Results: controversies were identified about the precise diagnostic criteria, the protocol of action for its prevention and rehabilitation and the lack of an instrument to stratify the risk of this complication. Conclusions: the bases for the preparation of the professionals in the diagnosis, the prevention of the acquired weakness of the patient in the Intensive Care Unit and its rehabilitation were systematized(AU)

Introdução: a fragilidade adquirida pelo paciente na Unidade de Terapia Intensiva é um problema que causa deficiências no seu estado físico e funcional. Objetivo: sistematizar conteúdos essenciais relacionados à fraqueza adquirida do paciente na Unidade de Terapia Intensiva. Método: no Hospital Geral de Ensino "Dr. Agostinho Neto", entre janeiro e setembro de 2019, foi realizada uma revisão narrativa do assunto através de uma busca em bases de dados eletrônicas (Biblioteca Virtual em Saúde, LILACS, PubMed, SciELO, RedALyC, Scopus). Foram localizados 135 documentos e escolhidos 25 relevantes para a finalidade da revisão. As informações foram estruturadas nos seguintes aspectos sobre a fragilidade adquirida pelo paciente na Unidade de Terapia Intensiva: definição, histórico, epidemiologia, fisiopatologia, diagnóstico e intervenção médica. Resultados: foram identificadas controvérsias sobre os critérios diagnósticos precisos, o protocolo de ação para sua prevenção e reabilitação e a falta de um instrumento para estratificar o risco dessa complicação. Conclusões: foram sistematizadas as bases para o preparo dos profissionais no diagnóstico, a prevenção da fragilidade adquirida do paciente na Unidade de Terapia Intensiva e sua reabilitação(AU)

Pancreatic Cancer-Induced Cachexia and Relevant Mouse Models.

Pancreatic cancer is the third leading cause of cancer death in the United States, with projections that it will become the second leading cause by the year 2030. It carries a dismal prognosis with a 5-year overall survival rate of less than 9% and is associated with numerous comorbidities, the most notable being cachexia. Defined as the loss of muscle mass not reversible by conventional nutritional support, cachexia is seen in over 85% of pancreatic cancer patients and contributes significantly to mortality, where nearly 30% of pancreatic cancer deaths are due to cachexia rather than tumor burden. Therefore, there is an urgent need to identify the mechanisms behind the development of muscle wasting in pancreatic cancer patients and design novel therapeutics targeting cachexia. This review highlights the current understanding surrounding the mechanisms underpinning the development of cachexia in pancreatic cancer, as well as the current mouse models of pancreatic cancer-induced muscle wasting described in the literature.

Complications and Prevention Strategies of Oblique Lateral Interbody Fusion Technique.

OBJECTIVE: To analyze the early complications and causes of oblique lateral interbody fusion, and put forward preventive measures. METHODS: There were 235 patients (79 males and 156 females) analyzed in our study from October 2014 to May 2017. The average age was 61.9 ± 0.21 years (from 32 to 83 years). Ninety-one cases were treated with oblique lateral interbody fusion (OLIF) alone (OLIF alone group) and 144 with OLIF combined with posterior pedicle screw fixation through the intermuscular space approach (OLIF combined group). In addition, 137/144 cases in the combined group were primarily treated by posterior pedicle screw fixation, while the treatments were postponed in 7 cases. There were 190 cases of single fusion segments, 11 of 2 segments, 21 of 3 segments, and 13 of 4 segments. Intraoperative and postoperative complications were observed. RESULTS: Average follow-up time was 15.6 ± 7.5 months (ranged from 6 to 36 months). Five cases were lost to follow-up (2 cases from the OLIF alone group and 3 cases from the OLIF combined group). There were 7 cases of vascular injury, 22 cases of endplate damage, 2 cases of vertebral body fracture, 11 cases of nerve injury, 18 cases of cage sedimentation or cage transverse shifting, 3 cases of iliac crest pain, 1 case of right psoas major hematoma, 2 cases of incomplete ileus, 1 case of acute heart failure, 1 case of cerebral infarction, 3 case of left lower abdominal pain, 9 cases of transient psoas weakness, 3 cases of transient quadriceps weakness, and 8 cases of reoperation. The complication incidence was 32.34%. Thirty-three cases occurred in the OLIF alone group, with a rate of 36.26%, and 43 cases in the group of OLIF combined posterior pedicle screw fixation, with a rate of 29.86%. Fifty-seven cases occurred in single-segment fusion, with a rate of 30.0% (57/190), 4 cases occurred in two-segment fusion, with a rate of 36.36% (4/11), 9 cases occurred in three-segment fusion, with a rate of 42.86% (9/21), and 6 cases occurred in four-segment fusion, with a rate of 46.15% (6/13). CONCLUSION: In summary, OLIF is a relatively safe and very effective technique for minimally invasive lumbar fusion. Nonetheless, it should be noted that OLIF carries the risk of complications, especially in the early stage of development.

Diaphragm Muscle Weakness Following Acute Sustained Hypoxic Stress in the Mouse Is Prevented by Pretreatment with N-Acetyl Cysteine.

Oxygen deficit (hypoxia) is a major feature of cardiorespiratory diseases characterized by diaphragm dysfunction, yet the putative role of hypoxic stress as a driver of diaphragm dysfunction is understudied. We explored the cellular and functional consequences of sustained hypoxic stress in a mouse model. Adult male mice were exposed to 8 hours of normoxia, or hypoxia (FiO2 = 0.10) with or without antioxidant pretreatment (N-acetyl cysteine, 200 mg/kg i.p.). Ventilation and metabolism were measured. Diaphragm muscle contractile function, myofibre size and distribution, gene expression, protein signalling cascades, and oxidative stress (TBARS) were determined. Hypoxia caused pronounced diaphragm muscle weakness, unrelated to increased respiratory muscle work. Hypoxia increased diaphragm HIF-1α protein content and activated MAPK, mTOR, Akt, and FoxO3a signalling pathways, largely favouring protein synthesis. Hypoxia increased diaphragm lipid peroxidation, indicative of oxidative stress. FoxO3 and MuRF-1 gene expression were increased. Diaphragm 20S proteasome activity and muscle fibre size and distribution were unaffected by acute hypoxia. Pretreatment with N-acetyl cysteine substantially enhanced cell survival signalling, prevented hypoxia-induced diaphragm oxidative stress, and prevented hypoxia-induced diaphragm dysfunction. Hypoxia is a potent driver of diaphragm weakness, causing myofibre dysfunction without attendant atrophy. N-acetyl cysteine protects the hypoxic diaphragm and may have application as a potential adjunctive therapy.

Inspiratory muscle weakness, diaphragm immobility and diaphragm atrophy after neck dissection.

BACKGROUND: Inspiratory strength after a neck dissection has not been evaluated, and diaphragm function has not been adequately evaluated. OBJECTIVE: Evaluate diaphragm mobility and inspiratory strength after neck dissection. METHODS: Prospective data collection of a consecutive series of adult patients submitted to neck dissection for head and neck cancer treatment, in a tertiary referral cancer center, from January to September 2014, with 30 days of follow-up. A total of 43 were studied (recruited 56; excluded 13). MAIN OUTCOME MEASURES: Determine diaphragm mobility and inspiratory muscle strength after neck dissection, using diaphragm ultrasound and by measuring maximal inspiratory pressure (MIP) and sniff nasal inspiratory pressure (SNIP). RESULTS: Thirty patients underwent unilateral neck dissection, and thirteen patients underwent bilateral neck dissection. Diaphragm immobility occurred in 8.9% of diaphragms at risk. For the entire cohort, inspiratory strength decreased immediately after the dissection but returned to preoperative values after 1 month. Except for those with diaphragm immobility, diaphragm mobility remained unchanged after the dissection. One month after the dissection, the diaphragm thickness decreased, indicating diaphragm atrophy. CONCLUSIONS: Immediately after a neck dissection, just a few patients showed diaphragmatic immobility, and there was a transient decrease in inspiratory strength in all individuals. Such findings can increase the risk of postoperative complications in patients with previous lung disease.

The final word on nutritional screening and assessment in older persons.

PURPOSE OF REVIEW: To provide an updated perspective of how nutritional screening and assessment in older persons should be performed and reasonably implemented in the near future. RECENT FINDINGS: Although nutritional screening and assessment should be fast and easy procedures, there is increasing evidence that more time should be dedicated to them. This is probably an answer to the claim to a medicine being more preventive than curative. Increasing interest is currently given to healthy aging and nutritional status is more likely to be addressed for its implications on functional status and disability. Important prognostic conditions, such as frailty, sarcopenia, and cachexia, which are closely linked to the nutritional domain, are at the top of the agenda. Therefore, body composition is a key issue and functional status is suggested as primary endpoint of nutrition trials. In this scenario, there is also a rationale for systematic assessment of inflammation, protein intake, and vitamin D status as potential contributing factors to reduced muscle mass and function. SUMMARY: A 'second-generation' multidimensional nutritional screening and assessment including the evaluation of body composition, frailty, sarcopenia, and cachexia could be hypothesized. Nutritional assessment should be also completed by the systematic evaluation of inflammation, protein intake, and vitamin D status.

Transcranial Motor Evoked Potential Alarm Criteria to Predict Foot Drop Injury During Lumbosacral Surgery.

STUDY DESIGN: A retrospective cohort analysis. OBJECTIVE: This study aims to investigate whether waveform alterations in transcranial motor evoked potentials (TCMEPs) can reliably predict postoperative foot drop. SUMMARY OF BACKGROUND DATA: Nerve injury leading to foot drop is a potential complication of lumbosacral surgery. Very limited data exist on the use of intraoperative TCMEPs to identify iatrogenic foot drop. METHODS: We retrospectively reviewed neuromonitoring data from 130 consecutive spine surgeries with instrumentation involving L4-S1. TCMEP waveform analysis included amplitude (A), area under the curve (AUC), latency (L), and duration (D). Patient outcomes were correlated with neuromonitoring results. Intraoperative alert criteria were established on the basis of observed intraoperative changes. RESULTS: Three patients developed severe foot drop with a muscle weakness functional grade ranging from 0/5 to 3/5. Two patients developed a mild foot drop with functional grade 4/5. Twenty-three patients had preoperative weakness in an L5 distribution. One-hundred two patients who had neither preoperative nor postoperative neurological complications served as a control group. Amplitude significantly decreased in patients with a severe postoperative deficit (P = 0.005) as did AUC and duration (P < 0.05). Intraoperative alert criteria defined as a >65% decrease in AUC resulted in a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%, 91.4%, 12%, and 100%, respectively. When defining an alert criteria as a >50% decrease in amplitude, sensitivity, specificity, PPV, and NPV were 100%, 87.9%, 8.8%, and 100%, respectively. CONCLUSION: Reduction of TCMEP waveform associated with postoperative severe foot drop can be detected during lumbar surgery. Other waveform parameters such as AUC may predict foot drop better than the amplitude. Additional examinations in larger samples of foot drops are needed to validate these alert threshold findings. LEVEL OF EVIDENCE: 4.