Do Cementless Short Tapered Stems Reduce the Incidence of Thigh Pain After Hip Arthroplasty? Systematic Review and Meta-Analysis.

BACKGROUND: The purpose of this study was to determine whether short tapered stems reduce the rate of thigh pain through a systematic review and meta-analysis of comparative studies between short tapered stems and standard-length tapered stems. METHODS: We conducted a meta-analysis of comparative studies: 1) retrospective studies and 2) randomized controlled trials (RCTs), on 2 stem designs: short tapered stem versus standard-length tapered stem. Studies were selected by means of the following criteria: 1) study design: retrospective comparative studies, prospective comparative studies, RCTs; 2) study population: patients with total hip arthroplasty or hemiarthroplasty for hip disease or hip fracture; 3) intervention: short tapered stem and standard tapered stem; and 4) outcomes; thigh pain, other clinical results. RESULTS: Among the 250 articles that were identified at the initial search, 6 studies, 4 RCTs and 2 retrospective comparative studies, were included in this meta-analysis. In the analysis of retrospective studies, the short tapered stem reduced the risk of thigh pain compared to the standard tapered stem (risk ratio [RR] = 0.13; 95% confidence interval [CI], 0.02-0.09; Z = -2.07; P = 0.039). However, in the analysis of RCTs, the incidence of thigh pain was similar between the two stem designs (RR = 1.21; 95% CI, 0.76-1.93; Z = 0.82; P = 0.410). Overall meta-analysis including all studies showed that the short tapered stem did not reduce the incidence of thigh pain compared to the standard-length tapered stem (RR = 0.91; 95% CI, 0.59-1.40; Z = -0.44, P = 0.663). CONCLUSIONS: We did not find a significant difference in the incidence of thigh pain between short tapered stem and standard tapered stem in hip arthroplasty. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021231240.

Early Deconditioning of Human Skeletal Muscles and the Effects of a Thigh Cuff Countermeasure.

Muscle deconditioning is a major consequence of a wide range of conditions from spaceflight to a sedentary lifestyle, and occurs as a result of muscle inactivity, leading to a rapid decrease in muscle strength, mass, and oxidative capacity. The early changes that appear in the first days of inactivity must be studied to determine effective methods for the prevention of muscle deconditioning. To evaluate the mechanisms of muscle early changes and the vascular effect of a thigh cuff, a five-day dry immersion (DI) experiment was conducted by the French Space Agency at the MEDES Space Clinic (Rangueil, Toulouse). Eighteen healthy males were recruited and divided into a control group and a thigh cuff group, who wore a thigh cuff at 30 mmHg. All participants underwent five days of DI. Prior to and at the end of the DI, the lower limb maximal strength was measured and muscle biopsies were collected from the vastus lateralis muscle. Five days of DI resulted in muscle deconditioning in both groups. The maximal voluntary isometric contraction of knee extension decreased significantly. The muscle fiber cross-sectional area decreased significantly by 21.8%, and the protein balance seems to be impaired, as shown by the reduced activation of the mTOR pathway. Measurements of skinned muscle fibers supported these results and potential changes in oxidative capacity were highlighted by a decrease in PGC1-α levels. The use of the thigh cuff did not prevent muscle deconditioning or impact muscle function. These results suggest that the major effects of muscle deconditioning occur during the first few days of inactivity, and countermeasures against muscle deconditioning should target this time period. These results are also relevant for the understanding of muscle weakness induced by muscle diseases, aging, and patients in intensive care.

Detraining Effects on Muscle Quality in Older Men with Osteosarcopenia. Follow-Up of the Randomized Controlled Franconian Osteopenia and Sarcopenia Trial (FrOST).

The present study aimed to determine the effect of detraining on muscle quality (MQ) in older men with osteosarcopenia. Forty-three community-dwelling older men (78 ± 4 years) were randomly allocated to a consistently supervised high-intensity resistance exercise training (HIRT) group (n = 21) or a control group (CG, n = 22). The HIRT scheduled a periodized single set protocol twice weekly. After the intervention, the men were subjected to six months of detraining. Muscle quality (MQ), defined as maximum isokinetic hip/leg extensor strength per unit of mid-thigh intra-fascia volume, was determined by magnetic resonance imaging (MRI) or per unit of thigh muscle mass assessed by dual-energy X-ray absorptiometry (DXA). Intention-to-treat analysis with multiple imputations was applied. We observed significant exercise effects for MQ (p = 0.001). During detraining, the HIRT group lost about one-third of the intervention-induced gain and displayed significantly (p = 0.001) higher MQ reductions compared to the CG. Nevertheless, after training and detraining, the overall intervention effect on MQ remained significant (p ≤ 0.004). In summary, six months of absence from HIRT induce a significant deleterious effect on MQ in older osteosarcopenic men. We conclude that intermitted training programs with training breaks of six months and longer should be replaced by largely continuous exercise programs, at least when addressing MQ parameters.

A 70-Year-Old Man With Conspicuous Thigh Pain and ST-Segment Elevations.

CASE PRESENTATION: A 70-year-old man presented to the ED with sudden onset of left thigh pain followed by transient chest discomfort. His history included cerebrovascular disease, hypertension, and cocaine and methamphetamine use. Physical examination revealed an uncomfortable male subject with a temperature of 37 °C, heart rate of 129 beats/min, BP of 130/65 mm Hg, and 98% oxygen saturation on room air. There was point tenderness in the left lateral thigh without erythema, swelling, or overlying skin changes. His cardiac examination revealed an irregular tachycardia at 129 beats/min and normal first and second heart sounds without murmurs, gallops, or rubs. The remainder of the examination was unremarkable.

Aberrant activity in an intact residual muscle is associated with phantom limb pain in above-knee amputees.

Many individuals who undergo limb amputation experience persistent phantom limb pain (PLP), but the underlying mechanisms of PLP are unknown. The traditional hypothesis was that PLP resulted from maladaptive plasticity in sensorimotor cortex that degrades the neural representation of the missing limb. However, a recent study of individuals with upper limb amputations has shown that PLP is correlated with aberrant electromyographic (EMG) activity in residual muscles, posited to reflect a retargeting of efferent projections from a preserved representation of a missing limb. Here, we assessed EMG activity in a residual thigh muscle (vastus lateralis, VL) in patients with transfemoral amputations during cyclical movements of a phantom foot. VL activity on the amputated side was compared to that recorded on patients' intact side while they moved both the phantom and intact feet synchronously. VL activity in the patient group was also compared to a sample of control participants with no amputation. We show that phantom foot movement is associated with greater VL activity in the amputated leg than that seen in the intact leg as well as that exhibited by controls. The magnitude of residual VL activity was also positively related to ratings of PLP. These results show that phantom limb movement is associated with aberrant activity in a residual muscle after lower-limb amputation and provide evidence of a positive relationship between this activity and phantom limb pain.NEW & NOTEWORTHY This study is the first to assess residual muscle activity during movement of a phantom limb in individuals with lower limb amputations. We find that phantom foot movement is associated with aberrant recruitment of a residual thigh muscle and that this aberrant activity is related to phantom limb pain.

Muscle activity of cutting manoeuvres and soccer inside passing suggests an increased groin injury risk during these movements.

Cutting manoeuvres and inside passing are thought to increase the risk of sustaining groin injuries. But both movements have received little research attention in this regard. The purpose of this study was to investigate the muscle activity of adductor longus and gracilis as well as hip and knee joint kinematics during [Formula: see text]-cutting and inside passing. Thirteen male soccer players were investigated with 3D-motion capturing and surface electromyography of adductor longus and gracilis while performing the two movements. Hip and knee joint kinematics were calculated with AnyBody Modelling System. Muscle activity of both muscles was significantly higher during the cutting manoeuvre compared to inside passing. Kinematics showed that the highest activity occurred during phases of fast muscle lengthening and eccentric contraction of the adductors which is known to increase the groin injury risk. Of both movements, cutting showed the higher activity and is therefore more likely to cause groin injuries. However, passing might also increase the risk for groin injuries as it is one of the most performed actions in soccer, and therefore most likely causes groin injuries through overuse. Practitioners need to be aware of these risks and should prepare players accordingly through strength and flexibility training.

Reduced Neural Excitability and Activation Contribute to Clinically Meaningful Weakness in Older Adults.

BACKGROUND: Weakness is a risk factor for physical limitations and death in older adults (OAs). We sought to determine whether OAs with clinically meaningful leg extensor weakness exhibit differences in voluntary inactivation (VIA) and measures of corticospinal excitability when compared to young adults (YAs) and OAs without clinically meaningful weakness. We also sought to estimate the relative contribution of indices of neural excitability and thigh lean mass in explaining the between-subject variability in OAs leg extensor strength. METHODS: In 66 OAs (75.1 ± 7.0 years) and 20 YAs (22.0 ± 1.9 years), we quantified leg extensor strength, thigh lean mass, VIA, and motor evoked potential (MEP) amplitude and silent period (SP) duration. OAs were classified into weakness groups based on previously established strength/body weight (BW) cut points (Weak, Modestly Weak, or Not Weak). RESULTS: The OAs had 63% less strength/BW when compared to YAs. Weak OAs exhibited higher levels of leg extensor VIA than Not Weak OAs (14.2 ± 7.5% vs 6.1 ± 7.5%). Weak OAs exhibited 24% longer SPs compared to Not Weak OAs, although this difference was insignificant (p = .06). The Weak OAs MEPs were half the amplitude of the Not Weak OAs. Regression analysis indicated that MEP amplitude, SP duration, and thigh lean mass explained ~62% of the variance in strength, with the neural excitability variables explaining ~33% of the variance and thigh lean mass explaining ~29%. CONCLUSION: These findings suggest that neurotherapeutic interventions targeting excitability could be a viable approach to increase muscle strength in order to reduce the risk of physical impairments in late life.

Single stage reconstruction of a neglected open book pelvic injury with bladder herniation into the upper thigh: a case-report.

When open-book injuries are neglected and result into a pelvic malunion or nonunion, long-term problems, such as chronic pain, gait abnormalities, sitting discomfort, neurological symptoms and urogenital symptoms can occur. In this case report, we describe the repair of a neglected pelvic disruption with the dislocation of the urinary bladder in a one-stage procedure. The clinical image with which the patient presented could be split into unique sub-problems, for which separate solutions needed to be chosen: large symphysis diastasis, instability and pain in both SI joints, malunion of the superior and inferior pubic rami fractures; and urinary bladder herniation into the upper thigh. In a single-stage procedure, the pelvic ring was reconstructed and the bladder reduced. The patient was thereafter continent for urine and could walk independently. A complex clinical problem was divided into its sub-problems, for which specific solutions were found.

Low knee-related quality of life and persistent physical asymmetries in participants up to 10 years post-ACL reconstruction - A cross-sectional study.

OBJECTIVE: To compare self-report and functional outcomes between participants with anterior cruciate ligament reconstruction (ACLR) with age and activity matched controls. DESIGN: Cross-sectional study. SETTING: University laboratory-based study. PARTICIPANTS: Twenty-five participants (30.8 ± 9.7 years; 13 women), two to ten years post anterior cruciate ligament reconstruction; 24 controls (31.0 ± 10 years, 13 women). MAIN OUTCOME MEASURES: Knee Osteoarthritis and Injury Outcome Score (KOOS), Tegner, Marx Activity and Fear of Re-injury scales, and SF-12; isokinetic quadriceps and hamstring peak torque and single-leg hop distance. RESULTS: There were no between-groups differences for the Tegner and the Marx Activity Scales. The ACLR group had lower KOOS dimensions (p < 0.001), SF-12 Physical Component Scores (p = 0.008), and higher Fear of Reinjury Scores (<0.001) than the controls. No significant differences were found for physical performance measures between the ACLR and the control groups. Significant between-side differences for the ACLR group were evident for concentric quadriceps (p < 0.001) and concentric hamstring peak torque (p = 0.002), and hop distance (p < 0.001). CONCLUSION: Knee-specific symptoms and function, activity and quality of life were lower, and fear of re-injury was higher for participants with ACLR than controls. Side-to-side thigh muscle strength and hop distance deficits were evident for the ACLR group.

Coordination Pattern of the Thigh, Pelvic, and Lumbar Movements during the Gait of Patients with Hip Osteoarthritis.

There are limited reports on segment movement and their coordination pattern during gait in patients with hip osteoarthritis. To avoid the excessive stress toward the hip and relevant joints, it is important to investigate the coordination pattern between these segment movements, focusing on the time series data. This study aimed to quantify the coordination pattern of lumbar, pelvic, and thigh movements during gait in patients with hip osteoarthritis and in a control group. An inertial measurement unit was used to measure the lumbar, pelvic, and thigh angular velocities during gait of 11 patients with hip osteoarthritis and 11 controls. The vector coding technique was applied, and the coupling angle and the appearance rate of coordination pattern in each direction were calculated and compared with the control group. Compared with the control group, with respect to the lumbar/pelvic segment movements, the patients with hip osteoarthritis spent more rates in anti-phase and lower rates in in-phase lateral tilt movement. With respect to the pelvic/thigh segment movements, the patients with hip osteoarthritis spent more rates within the proximal- and in-phases for lateral tilt movement. Furthermore, patients with osteoarthritis spent lower rates in the distal-phase for anterior/posterior tilt and rotational movement. Patients with hip osteoarthritis could not move their pelvic and thigh segments separately, which indicates the stiffness of the hip joint. The rotational movement and lateral tilt movements, especially, were limited, which is known as Duchenne limp. To maintain the gait ability, it seems important to pay attention to these directional movements.

Relationships between Thigh and Waist Circumference, Hemoglobin Glycation Index, and Carotid Plaque in Patients with Type 2 Diabetes.

BACKGROUND: This study investigated the relationships of thigh and waist circumference with the hemoglobin glycation index (HGI) and carotid atherosclerosis in patients with type 2 diabetes. METHODS: This observational study included 3,075 Korean patients with type 2 diabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. HGI was defined as the measured hemoglobin A1c (HbA1c) level minus the predicted HbA1c level, which was calculated using the linear relationship between HbA1c and fasting plasma glucose levels. Carotid atherosclerosis was defined as a clearly isolated focal plaque or focal wall thickening >50% of the surrounding intima-media thickness. RESULTS: The frequency of a positive HGI decreased with increasing thigh circumference in men and increased with increasing waist circumference in women after adjusting for potential confounding variables. Thigh and waist circumference had a combined augmentative effect on the likelihood of positive HGI, which was dramatically higher in patients in higher waist-to-thigh ratio quartiles (adjusted odds ratios for the highest compared to the lowest quartile: 1.595 in men and 1.570 in women). Additionally, the larger the thigh circumference, the lower the risk of carotid atherosclerosis, although in women, this relationship lacked significance after adjustment for potential confounders. CONCLUSION: HGI was associated with thigh circumference in men and waist circumference in women. In addition, the combination of low thigh circumference and high waist circumference was strongly associated with a higher HGI in Korean patients with type 2 diabetes. In particular, thigh circumference was associated with carotid atherosclerosis in men. However, further longitudinal studies are warranted.

The Impact of Malnutrition on Acute Muscle Wasting in Frail Older Hospitalized Patients.

Very little is known about the effect of malnutrition on short-term changes of body composition, particularly muscle, among older hospitalized patients. We sought to investigate the association of malnutrition as assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria with changes of thigh muscle mass and muscle strength among older patients during hospitalization. Forty-one patients (age range 66-97 years, 73% female) participated in this prospective longitudinal observational study. Nutritional status was evaluated using the GLIM criteria on admission and at discharge. Functional status and mid-thigh magnetic resonance imaging (MRI) measurements of cross-sectional area (CSA) were conducted on admission and before discharge. In all, 17% were malnourished and 83% had no malnutrition. Mean mid-thigh muscle CSA declined by 7.0 cm2 (-9%) in malnourished patients during hospitalization (p = 0.008) and remained unchanged among non-malnourished patients (-1%, p = 0.390). Mean mid-thigh CSA of subcutaneous and intermuscular fat did not change significantly during hospitalization in both groups. Malnourished subjects lost 10% of handgrip strength (-1.8 kg) and 12% of knee extension strength (-1.5 kg) during hospitalization. However, the magnitude of both changes did not differ between groups. In a stepwise multiple regression analysis, malnutrition and changes in body weight during hospitalization were the major independent risk factors for the reduction of muscle CSA. Malnutrition according to the GLIM criteria was significantly and independently associated with acute muscle wasting in frail older patients during 2-week hospitalization.

Thigh Adipocyte Size is Inversely Related to Energy Intake and Respiratory Quotient in Healthy Women.

OBJECTIVE: The relationship between adipocyte size and ad libitum energy intake has not been previously examined. This study hypothesized an inverse relationship between adipocyte size and daily energy intake (DEI). METHODS: Seventy healthy adults (39 men and 31 women; BMI 30.0 [SD 6.3]) underwent dual-energy x-ray absorptiometry and subcutaneous fat biopsies from the abdomen and thigh. Osmium-fixed adipocytes were sized with a Coulter counter. Volunteers self-selected food from a vending machine paradigm as the only source of energy intake over 3 days as inpatients. Volunteers also had 24-hour respiratory quotient (RQ) measured in a whole-room indirect calorimeter. RESULTS: In women, the large cell peak diameter of the thigh depot was greater than that of the abdominal depot (Δ = +15.8 µm; P < 0.0001). In women, thigh peak diameter was inversely associated with DEI (ß = -264.7 kcal/d per 10-µm difference; P = 0.03) after adjusting for demographics and body composition. The thigh peak diameter in women was associated with 24-hour RQ (r = -0.47, P = 0.04) after adjusting for demographics, body composition, and 24-hour energy balance. These associations did not extend to men or the abdominal depot. CONCLUSIONS: In women, thigh adipocyte size was associated with reduced DEI and 24-hour RQ, indicating a special role for thigh fat in women. This depot-specific sexual dimorphism indicates common regulation of energy intake and adipocyte size in the thigh region of women.

Funicular pain: a case report of intermittent claudication induced by cervical cord compression.

BACKGROUND: Neurogenic origin intermittent claudication is typically caused by lumbar spinal canal stenosis. However, there are few reports of intermittent claudication caused by cervical spinal cord compression. CASE PRESENTATION: We present the case of a 75-year-old woman who presented with intermittent claudication. She had a history of lumbar spinal fusion surgery, but there was no sign of lumbar spinal stenosis. She also reported bilateral thigh pain on cervical extension. Electromyogram (EMG), posture-induced test, myelogram, and post-myelogram dynamic computed tomography (CT) were performed. Myelography and post-myelogram dynamic CT in the cervical extension position showed narrowing of the subarachnoid space; the patient reported pain in the front of the both thigh during the procedure. We performed an electromyogram (EMG), which implied neurogenic changes below the C5 level. Based on these results, we diagnosed cervical spinal cord compression and underwent laminoplasty at C4-6 including dome-like laminectomy, which significantly relieved the thigh pain and enabled her to walk for 40 minutes. CONCLUSIONS: In this case, funicular pain presented as leg pain, but was resolved by the decompression of the cervical spinal cord. Funicular pain has various characteristics without any upper extreme symptom. This often leads to errors in diagnosis and treatment. We avoid the misdiagnosis by evaluating post-myelogram dynamic CT compared between flexion and extension. In cases of intermittent claudication, clinicians should keep in mind that cervical cord compression could be a potential cause.

Compartment syndrome of the non-injured limb.

Compartment syndrome is a common limb-threatening entity in trauma. However, the occurrence of the same in the non-injured limb is rare. It seems to be multifactorial in origin, with abnormal positioning being the most common cause. We present such a case of well-leg compartment syndrome which was treated by an urgent fasciotomy. We emphasise on the fact that the diagnosis of compartment syndrome is clinical and the management remains the same irrespective of whether the limb has sustained an injury or not.

Sharp lower back pain • left-side paraspinal tenderness • anterior thigh sensory loss • Dx?

► Acute-onset, sharp nonradiating lower back pain ► Left-side paraspinal tenderness ► Anterior thigh sensory loss.

The prevalence of myofascial trigger points in hip and thigh areas in anterior knee pain patients.

BACKGROUND: Anterior knee pain (AKP) is a widespread problem among young athletes and soldiers. There are many theories on the etiology of AKP but there is little reference to myofascial trigger points (MTrPs) as a possible contributor. AIM: To evaluate the association between AKP and prevalence of active and latent MTrPs in the hip and thigh muscles in soldiers. METHODS: A cross-sectional study was conducted in the Beer-Sheva military outpatient physical therapy clinic. Subjects were 42 men and 23 women referred for physical therapy, 33 with a diagnosis of AKP (cases) and 32 with upper limb complaints (without AKP, controls). All subjects underwent physical evaluation by an examiner blinded to their identity and medical condition. The following muscles were assessed bilaterally for active or latent MTrPs: rectus femoris (proximal), vastus medialis (middle and distal), vastus lateralis (middle and distal) and gluteus medius (anterior, posterior and distal). RESULTS: In six out of eight areas, the cases had a higher prevalence of total active and latent MTrPs than the controls. When summarizing MTrPs by muscle, cases had significantly more MTrPs than controls in each muscle. The largest difference was found in vastus medialis and vastus lateralis; nearly half of the cases had MTrPs in these muscles. CONCLUSIONS: Subjects with AKP have a greater prevalence of MTrPs in their hip and thigh muscles than controls, indicating an association between MTrPs and AKP. Further research is necessary to determine whether MTrPs are the cause or the consequence of AKP.

Gluteus medius dysfunction in females with chronic ankle instability is consistent at different walking speeds.

BACKGROUND: Patients with chronic ankle instability often present with altered gait mechanics compared to ankle sprain copers. There is increasing evidence to suggest proximal neuromuscular alterations contribute to the injury etiology, however little is known about how these changes manifest during gait. The purpose of this study was to investigate ipsilateral gluteus maximus and medius functional activity ratios throughout treadmill walking at three speeds (preferred, 120% preferred, and 1.35 m per second) in chronic ankle instability patients compared to copers. METHODS: 28 females (14 chronic ankle instability, 14 copers) walked at the three gait speeds in randomized order. Ground reaction forces and 10-s gluteal ultrasound clips were simultaneously recorded. Clips were reduced using ground reaction forces to extract 55 measurement frames. Normalized gluteal thickness measures were used to determine functional activity ratios. 2 × 3 analyses of variance were run to assess group and speed effects on gluteal outcomes throughout walking using statistical parametric mapping. Post-hoc t-tests, mean differences, and Cohen's d effect sizes were assessed for significant findings (P ≤ .05). FINDINGS: The chronic ankle instability group had significantly decreased gluteus medius activity throughout the entire gait cycle when compared to the coper group, independent of gait speed (P < .001, mean differences: 0.10-0.18; d: 1.00-3.17). There were no significant group or speed main effects, nor an interaction for gluteus maximus activity. INTERPRETATION: Gluteal dysfunction throughout walking was identified in chronic ankle instability. The coper group remained within healthy reference muscle activity ranges, suggesting that proximal muscle activation alterations are associated chronic ankle impairments.

Changes in skin-physiology after local heat application using two different methods in individuals with complete paraplegia: a feasibility and safety trial.

STUDY DESIGN: Interventional feasibility study. OBJECTIVES: To evaluate safety and effects of local heat preconditioning on skin physiology using water-filtered infrared-A radiation (wIRA) or warm water therapy (wWT) in individuals with spinal cord injury (SCI). SETTING: Acute and rehabilitation center, specialized in SCI. METHODS: A convenience sample of 15 individuals (3 women, 12 men) with complete paraplegia from thoracic levels ranging between T2 and T12 received local heat applications either with wIRA or wWT on the thigh (paralyzed area) and on the upper arm (non-paralyzed area). Local heat was applied during three 30-min cycles, each separated by 30 min rest; thus, the treatment lasted for 180 min. Temperature, blood perfusion, and skin redness were measured at baseline, before and after heat application and 24 h after the last application. RESULTS: Heat applications with wIRA and wWT were well-tolerated. No burns or any other side effects were detected. Skin temperature (p ≤ 0.008) and blood perfusion (p ≤ 0.013) significantly increased after heat application. Local skin temperature (arm p = 0.004/leg p < 0.001) and blood perfusion (arm p = 0.011/leg p = 0.001) after the first and the second application cycle, respectively, were significantly higher during heat application with wIRA than with wWT. However, skin redness did not change significantly (p = 0.1). No significant differences were observed between the paralyzed and non-paralyzed areas for all parameters immediately, as well as 24 h after the treatment. CONCLUSIONS: Although both heating methods have been confirmed as safe treatments in this study, further investigations with regard to their efficacy in the context of preconditioning are warranted. SPONSORSHIP: The use of the instruments Hydrosun® 750 Irradiator (Hydrosun Medizintechnik, Germany) and Hilotherm-Calido 6 (Hilotherm GmbH, Germany) was sponsored by the Dr. med. h. c. Erwin Braun Foundation and by Hilotherm GmbH, respectively.