The effects of exposure to microgravity and reconditioning of the lumbar multifidus and anterolateral abdominal muscles: implications for people with LBP

BACKGROUND CONTEXTOne of the primary changes in the neuromuscular system in response to microgravity is skeletal muscle atrophy, which occurs especially in muscles that maintain posture while being upright on Earth. Reduced size of paraspinal and abdominal muscles has been documented after spaceflight. Exercises are undertaken on the International Space Station (ISS) during and following space flight to remediate these effects. Understanding the adaptations which occur in trunk muscles in response to microgravity could inform the development of specific countermeasures, which may have applications for people with conditions on Earth such as low back pain (LBP).PURPOSEThe aim of this study was to examine the changes in muscle size and function of the lumbar multifidus (MF) and anterolateral abdominal muscles (1) in response to exposure to 6 months of microgravity on the ISS and (2) in response to a 15-day reconditioning program on Earth.DESIGNProspective longitudinal series.PATIENT SAMPLEData were collected from five astronauts who undertook seven long-duration missions on the ISS.OUTCOME MEASURESFor the MF muscle, measures included cross-sectional area (CSA) and linear measures to assess voluntary isometric contractions at vertebral levels L2 to L5. For the abdominal muscles, the thickness of the transversus abdominis (TrA), obliquus internus abdominis (IO) and obliquus externus abdominis (EO) muscles at rest and on contraction were measured.METHODSUltrasound imaging of trunk muscles was conducted at four timepoints (preflight, postflight, mid-reconditioning, and post reconditioning). Data were analyzed using multilevel linear models to estimate the change in muscle parameters of interest across three time periods.RESULTSBeta-coefficients (estimates of the expected change in the measure across the specified time period, adjusted for the baseline measurement) indicated that the CSA of the MF muscles decreased significantly at all lumbar vertebral levels (except L2) in response to exposure to microgravity (L3=12.6%; L4=6.1%, L5=10.3%; p<.001), and CSAs at L3-L5 vertebral levels increased in the reconditioning period (p<.001). The thickness of the TrA decreased by 34.1% (p<.017), IO decreased by 15.4% (p=.04), and the combination of anterolateral abdominal muscles decreased by 16.2% (p<.001) between pre- and postflight assessment and increased (TrA<0.008; combined p=.035) during the postreconditioning period. Results showed decreased contraction of the MF muscles at the L2 (from 12.8% to 3.4%; p=.007) and L3 (from 12.2% to 5%; p=.032) vertebral levels following exposure to microgravity which increased (L2, p=.046) after the postreconditioning period. Comparison with preflight measures indicated that there were no residual changes in muscle size and function after the postreconditioning period, apart from CSA of MF at L2, which remained 15.3% larger than preflight values (p<.001).CONCLUSIONSIn-flight exercise countermeasures mitigated, but did not completely prevent, changes in the size and function of the lumbar MF and anterolateral abdominal muscles. Many of the observed changes in size and control of the MF and abdominal muscles that occurred in response to prolonged exposure to microgravity paralleled those seen in people with LBP or exposed to prolonged bed rest on Earth. Daily individualized postflight reconditioning, which included both motor control training and weight-bearing exercises with an emphasis on retraining strength and endurance to re-establish normal postural alignment with respect to gravity, restored the decreased size and control of the MF (at the L3-L5 vertebral levels) and anterolateral abdominal muscles. Drawing parallels between changes which occur to the neuromuscular system in microgravity and which exercises best recover muscle size and function could help health professionals tailor improved interventions for terrestrial populations. Results suggested that the principles underpinning the exercises developed for astronauts following prolonged exposure to microgravity (emphasizing strength and endurance training to re-establish normal postural alignment and distribution of load with respect to gravity) can also be applied for people with chronic LBP, as the MF and anterolateral abdominal muscles were affected in similar ways in both populations. The results may also inform the development of new astronaut countermeasures targeting the MF and abdominal muscles.     

Endoscopic internal drainage for the management of leak,fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients

BackgroundEndoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases.ObjectivesTo evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG.SettingRetrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center.MethodsEID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)–guided deployment of DPS or lumen apposing metal stents.ResultsA total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818).ConclusionEarly EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.     

Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.     

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice

Quality of Life Research - Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance...     

Positive SARS-CoV-2 RT-qPCR of a nasal swab spot after 30 days of conservation on filter paper at room temperature

We tested the use of nasal swabs spotted onto filter paper (Whatman 3M) for the molecular diagnosis of SARS-CoV-2 infection. Spots of a positive nasal swab in conservation medium (B.1.177 strain, 21Ct) were still positive (duo E-gene/IP4) after 10, 20, and 30 days of conservation at room temperature, with Ct values of 28, 27, and 26, respectively. Direct spotting of the swab at bedside (omicron strain) still gave a positive result after 10 days in two RT-qPCR systems: 33.7 Ct using duo E-gene/IP4, and 34.8 using a specific Omicron system. Spotting of a dilution range of media spiked with the Delta (strain 2021/FR/0610, lineage B 1.617.2) and Omicron strains (strain UVE/SARS-CoV-2/2021/FR/1514) showed a threshold of 0.04 TCID₅₀ after 10 days of conservation. We show, for the first time, that this simple and low-cost conservation method can be used to store samples for RT-qPCR against SARS-CoV-2 for up to at least 1 month.     

1p36 deletion syndrome: Review and mapping with further characterization of the phenotype,a new cohort of 86 patients

Chromosome 1p36 deletion syndrome (1p36DS) is one of the most common terminal deletion syndromes (incidence between 1/5000 and 1/10,000 live births in the American population), due to a heterozygous deletion of part of the short arm of chromosome 1. The 1p36DS is characterized by typical craniofacial features, developmental delay/intellectual disability, hypotonia, epilepsy, cardiomyopathy/congenital heart defect, brain abnormalities, hearing loss, eyes/vision problem, and short stature. The aim of our study was to (1) evaluate the incidence of the 1p36DS in the French population compared to 22q11.2 deletion syndrome and trisomy 21; (2) review the postnatal phenotype related to microarray data, compared to previously publish prenatal data. Thanks to a collaboration with the ACLF (Association des Cytogénéticiens de Langue Française), we have collected data of 86 patients constituting, to the best of our knowledge, the second-largest cohort of 1p36DS patients in the literature. We estimated an average of at least 10 cases per year in France. 1p36DS seems to be much less frequent than 22q11.2 deletion syndrome and trisomy 21. Patients presented mainly dysmorphism, microcephaly, developmental delay/intellectual disability, hypotonia, epilepsy, brain malformations, behavioral disorders, cardiomyopathy, or cardiovascular malformations and, pre and/or postnatal growth retardation. Cardiac abnormalities, brain malformations, and epilepsy were more frequent in distal deletions, whereas microcephaly was more common in proximal deletions. Mapping and genotype–phenotype correlation allowed us to identify four critical regions responsible for intellectual disability. This study highlights some phenotypic variability, according to the deletion position, and helps to refine the phenotype of 1p36DS, allowing improved management and follow-up of patients.     

Respiratory effects of tracheal gas insufflation in spontaneously breathing COPD patients

Objective To evaluate the effect of tracheal gas insufflation (TGI) in spontaneously breathing, intubated patients with chronic obstructive pulmonary disease (COPD) undergoing weaning from the mechanical ventilation.Design A prospective study in humans.Setting Polyvalent intensive care unit (14-bed ICU) in a 700-bed general university hospital.Patients Twelve patients with chronic obstructive pulmonary disease (COPD) who required intubation and mechanical ventilation were studied. All patients met standard criteria for weaning from mechanical ventilation. Seven patients (group 1) had been transorally intubated during episodes of acute respiratory failure. Five patients, all men (group 2), had previously undergone tracheostomy and had a transtracheal tube in place.Interventions Intratracheal, humidified, O₂-mixture insufflation (TGI) was given via a catheter placed in distal or proximal position. Gas delivered through the intratracheal catheter was blended to match the fractional of inspired gas through the endotracheal tube. Continuous flows of 3 and 6 l/min in randomized order were used in each catheter position. Prior to data collection at each stage, an equilibration period of at least 30 min was observed, and thereafter blood gases were analyzed every 5 min. A new steady state was assumed to have been established when values of bothP _aCO₂ and CO₂ changed by less than 5% between adjacent measurements. The last values of blood gases were taken as representative. The new steady state was confirmed within 35–50 min. Baseline measurements with zero were made at the beginning and end of the experiment.Results This study shows that V_T, MV,P _aCO₂, and V_D/V_T are reduced in a flow-dependent manner when gas is delivered through an oral-tracheal tube (group 1). The distal catheter position was more effective than the proximal one. In contrast, when gas was delivered through tracheostomy (group 2), TGI was ineffective in the proximal position and less effective than in group 1 in distal position.Conclusion Under the experimental conditions, tracheal gas insufflation decreased dead space, increased alveolar ventilation and possibly reduced work of breathing. From the preliminary data reported here, we believe that TGI may help patients experiencing difficulty during weaning.     

Use of Drug Kinetics in Dermis to Predict in VivoBlood Concentration After Topical Application

Purpose. To use the drug kinetics in dermis to predict the in vivo blood concentration after topical administration. Methods. A two-step pharmacokinetic model was established. The first step was to calculate the drug input rate or flux from the skin to the systemic circulation using the drug kinetic parameters in dermis. These parameters include (a) distance over which the drug concentration declines by 50%, (b) drug concentration at the epidermal-dermal junction, and (c) minimal plateauing drug concentration in the muscle layer. These parameters were experimentally determined from the drug concentration-tissue depth profiles in the dermis, after the application of a topical dose of ddI (200 mg/kg) to rats. The second step was to use the drug input rate together with the systemic disposition pharmacokinetics of ddI in rats to predict the plasma concentration-time profiles. The model-predicted plasma concentration-time profiles were compared with the observed profiles, to determine the validity of the proposed pharmacokinetic model. Results. The observed steady state concentration (C_ss) in individual animals (n = 6) deviated from the predicted values by 3 to 55% with 3 of 6 rats showing a <15% deviation. The mean observed C_ss of all animals deviated from the mean predicted values by less than 15%. Conclusions. The close agreement between the observed and the model-predicted drug concentrations indicates that the systemic drug input can be calculated from the drug kinetics in the dermis.     

Chromatographic approach to study beta-cyclodextrin as a promoter of the penetration of bifonazole into keratinic tissue

A high-performance liquid chromatographic method for the determination of bifonazole in dimethyl sulfoxide solvent was developed to study its penetration into sheephoof. The analytical method was linear over the concentration range studied, i.e., from 0.1 mg/ml to 1 mg/ml. The relative standard deviation was less than 2%. The data obtained showed that complex forming with beta-cyclodextrin greatly improved the penetration of bifonazole.