New Findings
What is the central question of this study?
Maximal sniff nasal inspiratory and reverse sniff nasal expiratory pressures are measured as inspiratory and expiratory muscle strength, ...respectively. Is the genioglossus muscle activated during short maximal inspiratory and expiratory efforts through the nose?
What is the main finding and its importance?
Genioglossus muscle activity occurred with inspiratory muscle activity during a maximal sniff and with expiratory muscle activity during a maximal reverse sniff. These results indicate that genioglossus muscle activity is closely related to the generation of maximal sniff nasal inspiratory and reverse sniff nasal expiratory pressures.
Maximal sniff nasal inspiratory pressure (SNIPmax) is widely used to assess inspiratory muscle strength. The sniff nasal inspiratory pressure (SNIP) is lower in patients with neuromuscular disease with bulbar involvement compared with those without, possibly owing to impaired upper airway muscle function. However, the degree to which the genioglossus (GG) muscle, one of the upper airway muscles, is activated during inspiratory and expiratory efforts through the nose remains unclear. Therefore, we examined GG activity during short and sharp inspiratory and expiratory efforts through the nose, i.e. sniff and reverse sniff manoeuvres. In eight normal young subjects, we inserted fine wire electrodes into the GG muscle, parasternal intercostal and scalene (inspiratory) muscles and transversus abdominis (expiratory) muscle. We assessed EMG activity of each muscle and measured SNIP and reverse sniff nasal expiratory pressure (RSNEP) during sniffs and reverse sniffs from low to high intensities in the sitting position. The highest SNIP and RSNEP were analysed as SNIPmax and maximal RSNEP (RSNEPmax), respectively. In each subject, GG EMG activity increased linearly with increasing SNIP and RSNEP. The SNIPmax and RSNEPmax were −85.1 ± 15.9 and 83.2 ± 24.2 cmH2O, respectively. Genioglossus EMG activity varied with EMG activity of the parasternal intercostal and scalene muscles during generation of SNIPmax and with EMG activity of the transversus abdominis muscle during RSNEPmax. Genioglossus EMG activity during generation of SNIPmax was higher than during RSNEPmax (62.9 ± 31.1% EMG of SNIPmax, P = 0.012). These results suggested that GG activity was closely related to the generation of both SNIPmax and RSNEPmax.
Pulmonary function and patient complaints appear to improve up to 12 months after lobectomy but long-term prospective studies based on clinical data are scarce. Improvement in pulmonary function may ...depend on the area and extent of the resection and the time from the operation. This prospective study aimed to determine pulmonary function changes according to the resected lobe.
This prospective study included 59 patients requiring single lobectomy. Total volume and low-attenuation volume (LAV) for each lobe and the entire lungs were calculated based on helical computed tomography images. Vital capacity (VC), forced expiratory volume in one second (FEV
), percent FEV
(%FEV
), percent lung diffusion capacity for carbon monoxide (%DL
), %DL
divided by the alveolar volume (%DL
/V
), modified Medical Research Council (mMRC) grades, and COPD Assessment Test (CAT) scores were compared at 3, 6, and 12 months after surgery.
VC was higher at 12 months than at 3 months after right upper lobectomy (RUL) or right lower lobectomy (RLL). FEV
and %FEV
were higher at 12 months than at 6 months after left lower lobectomy (LLL). %DL
was higher at 12 months than at 3 months after RUL or left upper lobectomy (LUL). DL
/V
, mMRC grades, and CAT scores did not change significantly in the period from 3 to 12 months after any lobectomy procedure. Compared to the predicted postoperative values, the observed values of VC for RUL, RLL, and LUL; FEV
for RLL; %FEV
for RLL and LUL; %DL
for LUL; and %DL
/V
for all lobectomy procedures were higher at 12 months.
Improvements in pulmonary function and symptoms varied according to the resected lobe. Some of the observed pulmonary function values were higher than the predicted postoperative values. Pulmonary function changes may be related to the location, volume, and extent of emphysematous changes.
We conducted a Phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor. The aim was to determine the maximum tolerated dose (MTD) of ...amrubicin combined with a fixed dose of CPT-11 as well as the dose-limiting toxicities (DLT) of this combination in patients with advanced non-small cell lung cancer.
Eleven patients with stage IIIB or IV disease were treated at 3-week intervals with amrubicin (5-min intravenous injection on days 1-3) plus 60 mg/m2 of CPT-11 (90-min intravenous infusion on days 1 and 8). The starting dose of amrubicin was 25 mg/m2, and it was escalated in 5 mg/m2 increments until the maximum tolerated dose was reached.
The 30 mg/m2 of amrubicin dose was one dose level above the MTD, since three of the five patients experienced DLT during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the DLT, while thrombocytopenia was only a moderate problem. Amrubicin did not affect the pharmacokinetics of CPT-11, SN-38 or SN-38 glucuronide. Except for one patient, the biliary index on day-1 correlated well with the percentage decrease of neutrophils in a sigmoid Emax model. There were five partial responses among 11 patients for an overall response rate of 45%.
The combination of amrubicin and CPT-11 seems to be active against non-small cell lung cancer with acceptable toxicity. The recommended dose for Phase II studies is 60 mg/m2 of CPT-11 (days 1 and 8) and 25 mg/m2 of amrubicin (days 1-3) administered every 21 days.
The clinical utility of intermittently scanned continuous glucose monitoring (isCGM) in patients with coronavirus disease 2019 (COVID-19) is unclear. Hence, we investigated the accuracy of isCGM in ...COVID-19 patients during dexamethasone therapy. We evaluated the accuracy of the FreeStyle Libre via smartphone isCGM device compared to point-of-care (POC) fingerstick glucose level monitoring in 16 patients with COVID-19 (10 with and 6 without diabetes, 13 men; HbA1c 6.9 ± 1.0%). Overall, isCGM correlated well with POC measurements (46.2% and 53.8% within areas A and B of the Parkes error grid, respectively). The overall mean absolute relative difference (MARD) for isCGM compared to POC measurements was 19.4%. The MARDs were 19.8% and 19.7% for POC blood glucose measurements ranging from 70 to 180 mg/dL and >180 mg/dL, respectively. When divided according to the presence and absence of diabetes, both groups of paired glucose measurements showed a good correlation (56.3% and 43.7%, and 27.1% and 72.9% within the A and B areas in patients with and without diabetes, respectively), but the MARD was not significant but higher in patients without diabetes (16.5% and 24.2% in patients with and without diabetes). In conclusion, although isCGM may not be as accurate as traditional blood glucose monitoring, it has good reliability in COVID-19 patients with and without diabetes during dexamethasone therapy.
Gefitinib is a synthetic, oral anilinoquinazoline specifically designed to inhibit the epidermal growth factor receptor tyrosine kinase, and is the first targeted drug to demonstrate reproducible ...activity in non-small cell lung cancer patients who do not respond to platinum-based chemotherapy. In this report, we present two cases of an interaction between gefitinib and warfarin which has not been reported previously. Because of the potentially serious consequences of this interaction, close monitoring of the International Normalized Ratio and warfarin dosage adjustment are recommended for patients receiving warfarin together with gefitinib.
When extra-diaphragmatic muscles are activated progressively under approximately isometric conditions, we expect a corresponding increase in respiratory muscle output. Therefore, we examined relative ...recruitment shown as the latency to onset of EMG activity, and the relationship between mouth pressure and electromyogram activity of the neck accessory and transversus abdominis (TRANS) muscles during respiratory maneuvers against occlusion. Fine wire electrodes were inserted into the scalene (SCLN), sternocleidomastoid (STERNO), trapezius (TRAPZ) and TRANS in six awake, healthy subjects. Mouth pressure, raw and moving average EMG signals were recorded during gradual production of expiratory or inspiratory mouth pressure to maximum (MP
max) at FRC in the standing posture. Group mean linear regression lines of EMG activity versus mouth pressure were strongly significant for SCLN and TRANS, less for STERNO, and least for TRAPZ. The SCLN and STERNO showed EMG activities with low, and TRAPZ showed EMG activity only with high, mouth pressure. At 90% MP
max, TRAPZ was much less active compared with TRANS, SCLN, or STERNO. These results suggest that over a wide range of respiratory effort there is a significant difference in the relationship between mouth pressure and EMG activity in the accessory muscles, with differential recruitment of individual respiratory muscles.
Gefitinib treatment has come to be recognized as the standard therapy for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. However, ...resistance to gefitinib has been observed in certain subpopulations of these patients. The purpose of this study was to evaluate the impact of smoking status on the efficacy of gefitinib in patients with NSCLC harboring EGFR mutations.
The records of NSCLC patients harboring EGFR mutations who were treated with gefitinib at Kitasato University Hospital were retrospectively reviewed, and the treatment outcomes were evaluated.
In 153 patients with NSCLC harboring EGFR mutations, the overall response rate and progression-free survival (PFS) were 66.7% and 9.0 months, respectively. PFS differed significantly among the current smokers and never-smokers/former light smokers (10.7 vs. 5.4 months, p=0.0002), and the response rate was significantly higher in the never-smokers/former light smokers than in the current smokers (72.3 vs. 55.8%, p=0.04). Multivariate analysis identified smoking status as an independent predictor of PFS.
The clinical data obtained in this study provide a valuable rationale for considering smoking status as a predictor of the efficacy of gefitinib in patients with NSCLC harboring activating EGFR mutations.
Action of the uppermost medial internal intercostal muscles-the parasternals-during rapid eye movement (REM) is uncertain; no direct recordings exist of shortening of these muscles during sleep. ...Historically, motor inhibition of skeletal muscles during REM sleep is thought to cause global loss of chest wall muscle function, REM "atonia," with preservation of only diaphragm function. However, recent evidence during wakefulness shows parasternals as distinctive obligatory inspiratory muscles. Therefore we hypothesized that attenuation of chest wall function during sleep may spare the parasternals along with the diaphragm, as essential muscles of inspiration during REM. We studied seven canines, comparing costal and crural diaphragm and parasternal intercostal muscle function during wakefulness and non-REM (NREM) and REM sleep, during normal spontaneous sleep, continuously recording ventilation and simultaneous muscle electromyogram (EMG) and length from sonomicrometry microtransducers. Ventilation during sleep declined significantly from wakefulness. From wakefulness to NREM and REM, costal and crural tidal EMG increased, while parasternal tidal EMG was preserved unchanged. Costal and crural shortening per breath during NREM and REM did not change significantly from wakefulness. Concurrently, parasternal shortening decreased equally in both NREM and REM despite preservation of the parasternal EMG. We conclude that diaphragm and parasternals are not inhibited, and both remain active together as essential inspiratory muscles, during REM sleep. The lesser contraction of parasternal intercostals compared with diaphragm may be attributed to net changes in mechanics affecting the chest wall during sleep.
Patients with plaster-cast immobilization of the lower limb have an estimated venous thromboembolism rate of 2.5 % without prophylaxis, which includes many fatal cases. However, there is no practical ...physical prophylaxis for deep-vein thrombosis (DVT) in these patients. The aim of this study was to examine the effects of intermittent pneumatic compression on the thigh alone (IPC to the thigh) on peak blood velocity (PBV) in the legs and to consider the possibility that IPC of the thigh could be used as physical prophylaxis for DVT in patients with plaster-cast immobilization of the lower leg. Nine healthy male volunteers and eighteen elderly males were recruited. We immobilized each subject’s right lower leg and ankle with a plaster splint, and applied the ActiveCare+S.F.T.
®
(Medical Compression Systems, Inc.) device to each subject’s right thigh. The PBV in the superficial femoral vein (PBVFV) and the popliteal vein (PBVPV) were measured using duplex Doppler ultrasonography. IPC to the thigh resulted in a 2.3-fold increase in PBVFV and a 3.0-fold increase in PBVPV compared with resting at supine in the elderly group. Although IPC to the thigh also increased PBVFV and PBVPV significantly in the sitting position, the change ratios of PBV in the supine and sitting positions were equal (2.6-fold increase in PBVFV and 2.9-fold increase in PBVPV). IPC to the thigh in supine and sitting positions significantly increased PBVFV and PBVPV, and could be a useful prophylaxis for DVT in patients with plaster-cast immobilization of the lower leg.
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