Efficacy of pembrolizumab and comprehensive CD274/PD-L1 profiles in patients previously treated with chemoradiation therapy as radical treatment in bladder cancer.

BACKGROUND: Chemoradiation therapy (CRT) has been increasingly reported as a possible alternative to total cystectomy (TC) for localized bladder cancer (BC). Pembrolizumab is the standard of care for platinum-refractory metastatic urothelial carcinoma, although it is unknown whether the efficacy of pembrolizumab in patients previously treated with curative CRT varies from the results of benchmark trials. METHODS: We retrospectively assessed whether the survival benefit of pembrolizumab differs between patients previously treated with TC or CRT as radical treatment. A total of 212 patient records were collected for a logistic regression propensity score model. An independent dataset with next-generation sequencing (n=289) and PD-L1 Combined Positive Score (CPS: n=266) was analyzed to assess whether CRT-recurrent tumor harbors distinct CD274/PD-L1 profiles. RESULTS: Propensity score matching was performed using putative clinical factors, from which 30 patients in each arm were identified as pair-matched groups. There was no significant difference in overall survival from the initiation of pembrolizumab (p=0.80) and objective response rate (p=0.59) between CRT and TC treatment groups. In the independent 289 BC cohort, 22 samples (7.6%) were collected as CRT-recurrent tumors. There was no significant difference in CD274 mRNA expression level between CRT-naïve and CRT-recurrent tumors. The compositions of CD274 isoforms were comparable among all isoforms detected from RNAseq between CRT-naïve (n=267) and CRT-recurrent (n=22) tumors. No actionable exonic mutation in CD274 was detected in CRT-recurrent tumors. PD-L1 CPS was positively correlated with CD274 mRNA expression level, and PD-L1 CPS was comparable between CRT-naïve and CRT-recurrent tumors. CONCLUSIONS: The efficacy of pembrolizumab for patients previously treated with CRT was similar to those treated with TC. The enhanced tumor regression by combining programmed cell death protein 1/PD-L1 inhibitor and CRT might be expected only in the concurrent administration.

The acute and prolonged effects of 20-s static stretching on muscle strength and shear elastic modulus.

INTRODUCTION: Static stretching (SS) is commonly performed as part of warm-up routine. However, only few previous studies have reported on the effects of short-duration SS, which is often used in the sports field. The purpose of this study was to investigate the acute and prolonged effects of 20-s SS on isokinetic contraction muscle strength, range of motion (ROM), and the shear elastic modulus. METHOD: Twenty male volunteers participated in this study. The ROM and both concentric and eccentric contraction muscle strengths were measured using a dynamometer. In addition, the shear elastic modulus of medial gastrocnemius muscle in dominant leg was measured by ultrasonic shear wave elastography. The participants visited the laboratory on four occasions each separated by >3 days. The first visit was a familiarization trial, and the subsequent three visits included the following experimental conditions in a random order. All measurements were performed prior to and immediately after SS or 5 min and 10 min after 20-s SS. RESULTS: The results of this study showed that the ROM was significantly increased SS intervention in all conditions compared with prior to SS intervention. In addition, ROM was significantly higher post SS and 5 min after SS than 10 min after SS. However, there were no significant interaction effects for isokinetic contraction muscle strength and the shear elastic modulus. CONCLUSION: In the sports field, from the point of performance, a 20-s SS intervention could be a useful technique before exercise because it increases ROM and does not decrease maximum torque.

Effect of Rest Duration Between Static Stretching on Passive Stiffness of Medial Gastrocnemius Muscle In Vivo.

CONTEXT: In clinical and sports settings, static stretching (SS) is usually performed to increase range of motion (ROM) and decrease passive muscle stiffness. Recently, the shear elastic modulus was measured by ultrasonic shear wave elastography as an index of muscle stiffness. Previous studies reported that the shear elastic modulus measured by ultrasound shear wave elastography decreased after SS, and the effects of SS on shear elastic modulus were likely affected by rest duration between sets of SS. OBJECTIVE: To investigate the acute effects of SS with different rest durations on ROM and shear elastic modulus of gastrocnemius and to clarify whether the rest duration between sets of SS decreases the shear elastic modulus. DESIGN: A randomized, repeated-measures experimental design. SETTING: University laboratory. PARTICIPANTS: Sixteen healthy males volunteered to participate in the study (age 21.3 [0.8] y; height 171.8 [5.1] cm; weight 63.1 [4.5] kg). MAIN OUTCOME MEASURES: Each participant underwent 3 different rest interval durations during SS (ie, long rest duration: 90 s; normal rest duration: 30 s; and short rest duration: 10 s). This SS technique was repeated 10 times, thus lasting a total of 300 seconds with different rest durations in each protocol. The dorsiflexion ROM and shear elastic modulus were measured before and after SS. RESULTS: Our results revealed that dorsiflexion ROM and shear elastic modulus were changed after 300-second SS; however, no effects of the rest duration between sets of SS were observed. CONCLUSIONS: In terms of decreasing the shear elastic modulus, clinicians and coaches should not focus on the rest duration when SS intervention is performed.

The effect of low-intensity resistance training after heat stress on muscle size and strength of triceps brachii: a randomized controlled trial.

BACKGROUND: The purpose of this study was to clarify whether there is a synergistic effect on muscular strength and hypertrophy when low-intensity resistance training is performed after heat stress. METHODS: Thirty healthy young male volunteers were randomly allocated to either the low-intensity resistance training with heat stress group or the control group. The control group performed low-intensity resistance training alone. In the low-intensity resistance training with heat stress group, a hot pack was applied to cover the muscle belly of the triceps brachii for 20 min before the training. The duration of the intervention was 6 weeks. In both groups, the training resistance was 30% of the one repetition maximum, applied in three sets with eight repetitions each and 60-s intervals. The one repetition maximum of elbow extension and muscle thickness of triceps brachii were measured before and after 6 weeks of low intensity resistance training. RESULTS: There was no significant change in the one-repetition maximum and muscle thickness in the control group, whereas there was a significant increase in the muscle strength and thickness in the low-intensity resistance training with heat stress group. CONCLUSION: The combination of heat stress and low-intensity resistance training was an effective method for increasing muscle strength and volume. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000036167; March 11, 2019).

Tone-Inhibiting Insoles Enhance the Reciprocal Inhibition of Ankle Plantarflexors of Subjects With Hemiparesis After Stroke: An Electromyographic Study.

BACKGROUND: Spasticity is a common sequela of upper motor neuron pathology, such as cerebrovascular diseases and cerebral palsy. Intervention for spasticity of the ankle plantarflexors in physical therapy may include tone-inhibiting casting and/or orthoses for the ankle and foot. However, the physiological mechanism of tone reduction by such orthoses remains unclarified. OBJECTIVE: To investigate the electrophysiologic effects of tone-inhibiting insoles in stroke subjects with hemiparesis by measuring changes in reciprocal Ia inhibition (RI) in the ankle plantarflexor. DESIGN: An interventional before-after study. SETTING: Acute stroke unit or ambulatory rehabilitation clinic of a university hospital in Japan. PARTICIPANTS: Ten subjects (47-84 years) with hemiparesis and 10 healthy male control subjects (31-59 years) were recruited. METHODS: RI of the spastic soleus in response to the electrical stimulation of the deep peroneal nerve was evaluated by stimulus-locked averaging of rectified electromyography (EMG) of the soleus while subjects were standing. MAIN OUTCOME MEASUREMENTS: The magnitude of RI, defined as the ratio of the lowest to the baseline amplitude of the rectified EMG at approximately 40 milliseconds after stimulation, was measured while subjects were standing with and without the tone-inhibiting insole on the hemiparesis side. RESULTS: Enhancement of EMG reduction with the tone-inhibiting insole was significant (P < .05) in the subjects with hemiparesis, whereas no significant changes were found in controls. CONCLUSION: Tone-inhibiting insoles enhanced RI of the soleus in subjects after stroke, which might enhance standing stability by reducing unfavorable ankle plantarflexion tone. LEVEL OF EVIDENCE: III.

Optimal Reference Electrode Positioning for Electroneurography at the Orbicularis Oculi: A Case Report and Short Review.

Electroneurography is one of the most useful tests for evaluating facial nerve function. Because many patients with peripheral facial palsy complain of difficulty with eye closure, recording compound muscle action potentials (CMAPs) of the orbicularis oculi (OC) is important. However, electromyographers often encounter OC CMAPs that have an initial positivity. In the present study, facial motor potentials of a healthy subject were recorded using an electrode on the acromion and electrical activities over the facial muscles were evaluated.The contralateral OC electrode was the most inactive. A CMAP recorded using two electrodes on the ipsilateral OC showed an initial positivity. It is assumed that the onset discrepancy between electrical activities of the two electrodes on the OC results in an initial positivity. Thus, the authors recommend that electromyographers avoid using a reference electrode on the ipsilateral OC for recording its CMAP. The bilateral OC montage could be useful for recording OC CMAPs.

Can we accurately measure the onset latency to the first dorsal interosseous?

We present two cases with and without a latency difference of the compound muscle action potential (CMAP) from the abductor digiti minimi (ADM) and the first dorsal interosseous (FDI). In each case, onset latencies of FDI CMAPs using the contralateral small finger as E2 were shorter than those of belly-tendon CMAPs from the ADM and FDI. We conclude that onset of the belly-tendon FDI CMAP does not necessarily indicate initial activation of the FDI.

The influence of the reference electrode on the compound muscle action potential of the flexor digiti minimi brevis.

OBJECTIVE: When recording compound muscle action potentials, the active electrode is traditionally placed over the muscle and the reference over the corresponding tendon (belly-tendon recording). This placement assumes that the reference electrode is electrically inactive. We report on the influence of reference electrode placement on the compound muscle action potential recorded from the flexor digiti minimi brevis. DESIGN: We recorded compound muscle action potentials from the flexor digiti minimi brevis using belly electrodes, tendon electrodes, and an electrode on the contralateral medial malleolus from 11 healthy subjects. We measured compound muscle action potential amplitudes and onset latencies. RESULTS: Compound muscle action potentials recorded using electrodes on a tendon and the contralateral medial malleolus had higher amplitudes and shorter onset latencies than the compound muscle action potentials recorded with the belly-tendon montage. CONCLUSIONS: When recording compound muscle action potentials from flexor digiti minimi brevis, the influences of the tendon "reference" electrode on latency and amplitude are large. Electrodiagnositicians should consider the influences of the reference electrode when assessing the lateral plantar nerve. This study may also inform us about the influence of proximally innervated muscles on the compound muscle action potential recorded in the limbs.

Does display sensitivity influence motor latency determination?

It is known that display sensitivity can affect onset latency measurement of compound muscle action potentials (CMAPs). We compared two display sensitivities with respect to intrarater and interrater reliability and measured to what degree display sensitivity influences the motor latency. We asked seven raters to mark the onset points of median CMAPs from 24 patients printed with display sensitivities of 5 mV/division and 0.5 mV/division on paper. The onset latencies were measured, and intraclass correlation coefficients (ICCs) were calculated. Most of the raters had excellent intrarater repeatability within a single sensitivity display setting. In contrast, the intrarater reliability using two different sensitivity settings was poor. ICCs calculated for interrater reliability were 0.93 at 0.5 mV/division and 0.91 at 5 mV/division. On average, the latencies measured at 5 mV/division were about 0.3 ms longer. We conclude that reliability of latency measurement is excellent at either sensitivity; however, it is important to use a consistent sensitivity in order to avoid making measuring errors.

What is the origin of the premotor potential recorded from the second lumbrical?

When recording with a palm electrode, a premotor potential (PMP) precedes the compound muscle action potential that is evoked from the second lumbrical muscle following median nerve stimulation. The origin of this PMP has been uncertain. We demonstrate that median sensory nerve action potentials (SNAPs) can be recorded orthodromically with the palm electrode and conclude that the origin of the PMP is a median SNAP arising from antidromically activated digital sensory branches.