Predictive performance of PD-L1 tumor proportion score for nivolumab response evaluated using archived specimens in patients with non-small cell lung cancer experiencing a postoperative recurrence.

OBJECTIVES: Postoperative recurrence in patients with non-small-cell lung carcinoma (NSCLC) is a major issue for life expectancy. Programmed cell death ligand 1 (PD-L1) expression on tumor cells is important in the prognosis of NSCLC. However, the predictive ability of PD-L1 evaluated with archived surgical specimens for nivolumab treatment have remained unknown. This study was aimed to analyze the predictive ability of the PD-L1 tumor proportion score (TPS) for nivolumab response in patients with NSCLC experiencing a postoperative recurrence using archived surgical specimens. MATERIALS AND METHODS: This retrospective cohort study involved patients with advanced NSCLC (N = 78) treated with nivolumab between April 2016 and September 2018. They were categorized into postoperative recurrence (N = 24) and non-postoperative recurrence (N = 54) groups. The predictive ability of PD-L1 TPS for response to nivolumab treatment in these two groups was determined using receiver operating characteristic (ROC) analysis. Additionally, we evaluated the predictive ability of PD-L1 TPS using rebiopsy specimens collected from the recurrent lesions in six patients of the postoperative recurrence group. RESULTS: PD-L1 TPS exhibited lower predictive performance in the postoperative recurrent group (area under the curve [AUC] = 0.58) compared with that in the non-post operative recurrent group (AUC = 0.81). Furthermore, PD-L1 TPS was significantly increased in rebiopsy specimens. The predictive performance of PD-L1 TPS in these specimens was higher (AUC = 0.90) than that in the archived surgical specimens. CONCLUSION: The study revealed that archived surgical specimens are inadequate for assessing the predictive ability of PD-L1 for nivolumab response, while rebiopsy specimens are adequate.

Chest wall pseudotumor: a case of non-tuberculous mycobacterial infection.

BACKGROUND: Non-tuberculous mycobacterial (NTM) infections are increasing worldwide, making them an international public health problem. Surgical management is often indicated for localized infectious disease; however, most surgeons are unaware of the potential risks of transmission during surgery. CASE PRESENTATION: An 88-year-old Asian female was referred to our hospital for a tumor in the right lateral thoracic region. One month prior, she had a feeling of fullness and complained of localized pain and warmth in the right lateral thoracic wall. Pain and warmth gradually resolved without intervention; however, the fullness was getting worse. Computed tomography (CT) scan showed a mass of approximately 65 × 30 mm with an osteolytic change, involving the right 8th rib. Based on the rapid growth rate and CT findings, we strongly suspected a malignant chest wall tumor, and en bloc tumor resection with the 8th rib was performed. When the specimen was cut, a large amount of viscous pus was drained and its culture showed growth of Mycobacterium avium. Microscopically, the non-caseating epithelioid cell granuloma extended into the rib, infiltrating the bone cortex. On follow-up 1 month after discharge, there were no signs of infection or other adverse events associated with the surgery. CONCLUSIONS: Herein, we report about a patient with a mass diagnosed as an NTM abscess involving the rib cage, which was confused with a malignant tumor and eventually diagnosed following surgical excision. This report emphasizes the need to be aware of the possibility of NTM infection and take appropriate precautions if the patient has a rapidly growing mass in the chest wall.

Natural history and clinical characteristics of multiple pulmonary nodules with ground glass opacity.

BACKGROUND AND OBJECTIVE: Ground glass nodules (GGNs) are frequently encountered in the lungs. We report the natural history and characteristics of multiple GGNs, and propose a management plan for patients with multiple GGNs. METHODS: We retrospectively analysed patients with GGNs that met the following criteria: (i) GGN diameter of 3 cm or less, (ii) ground glass opacity proportion of 50% or more and (iii) observation without treatment for ≥6 months. We evaluated size changes in computed tomography images. Two end points, 'incidence of growth at 36 months' and 'time to growth' were analysed using logistic regression models and Cox proportional hazards model. RESULTS: Between April 2008 and December 2014, 187 patients fulfilled the inclusion criteria (78 (42%) had multiple lesions). Among the multiple-GGN patients, the median observation period was 45.5 months, 25 patients (32%) experienced GGN progression at 36 months and 4 patients (5.1%) after 36 months. Between the multiple and single GGNs, there were no significant differences in growth incidence at 36 months (P = 0.1), after 36 months (P = 0.6) or in time to growth (P = 0.3). Among patients with multiple GGNs who experienced one GGN growth, 41% of patients experienced residual GGN growth afterwards. CONCLUSION: Patients with multiple GGNs showed a tendency to growth within the first 36 months, and a significant proportion of patients experienced multiple GGN progression. We suggest that the optimal observation period for patients with multiple GGNs is 36 months, but careful observation is needed after a lesion begins to grow.

The prognostic value of serum CA 19-9 for patients with advanced lung adenocarcinoma.

BACKGROUND: This study aimed to assess the prognostic accuracy of serum CA 19-9 in patients with advanced lung adenocarcinoma. METHODS: We retrospectively reviewed data of 246 patients who were diagnosed at our institute with advanced (stage IIIB or IV) lung adenocarcinoma between March 2006 and December 2012. We excluded patients who received no chemotherapy, or for whom we had no data on pre-treatment tumor markers. We also evaluated 116 consecutive resected specimens from patients with clinical stage I lung adenocarcinoma pathologically. RESULTS: The 76 (31 %) patients who were CA 19-9+ had shorter overall survival (OS) than CA 19-9- group (12.5 vs 26.2 months, P = 0.005). Cox's multivariate regression analysis identified Eastern Cooperative Oncology Group Performance Status 0 or 1 (P < 0.001), mutated epidermal growth factor receptor (EGFR) status (P < 0.001), stage IIIB (P < 0.001), CYFRA 21-1- (P < 0.001), CA 19-9- (P = 0.005) and use of platinum doublet therapy (P = 0.034) as independent predictors of longer OS. We stratified patients by CA 19-9 and CYFRA 21-1 as double positive (CA 19-9+/CYFRA 21-1+, n = 59), single positive (either CA19-9+ or CYFRA 21-1+, n = 113), or double negative (CA 19-9-/CYFRA 21-1-, n = 74). Their respective OS were 10.0, 23.3 and 31.8 months (P < 0.001). Pathological analysis also correlated CA 19-9 expression with malignant features such as vessel invasion, pleural invasion, cancer invasive factors and mucin production. CONCLUSIONS: CA 19-9 and CYFRA 21-1 are independent prognostic markers in patients with advanced lung adenocarcinoma. Combined use of CA 19-9 and CYFRA 21-1 provides further prognostic information in patients with advanced lung adenocarcinoma.

[Pulmonary Arterioplasty with Autologous Pericardial Patch for Lung Cancer].

Three patients underwent left upper lobectomy with arterioplasty of left pulmonary artery trunk for lung cancer. For pulmonary arterioplasty, wide wedge resection and patch plasty with autologous pericardium was performed. No in-hospital death or no postoperative complications due to arterioplasty was encountered. The mean follow-up period was 3.6 years and long-term patency of the reconstructed pulmonary artery was confirmed by computed tomography in all patients.

Asymptomatic traumatic diaphragmatic hernia discovered during an aortic valve replacement.

Asymptomatic traumatic diaphragmatic hernia, which presents in an adult, is an extremely rare entity. We discuss the management of a 63-year-old male with an asymptomatic traumatic diaphragmatic hernia discovered during aortic valve replacement.

Pneumocephalus resulting from traumatic pneumothorax and brachial plexus avulsion.

Background: Traumatic pneumocephalus is commonly encountered after basal skull fractures and rarely associated with blunt chest trauma. Here, we report a case of pneumocephalus caused by traumatic pneumothorax and brachial plexus avulsion. Case Presentation: A 20-year-old male was admitted to our hospital following a motorcycle accident with complete paralysis of the right upper limb. 2 days later, follow-up computed tomography revealed a slight right pneumothorax, pneumomediastinum around the neck, and intracranial air without skull fracture. Air migrates into the subarachnoid space through a dural tear caused by a brachial plexus avulsion. The pneumocephalus immediately improved after the insertion of a chest drain. Conclusion: Pneumothorax combined with brachial plexus avulsion could lead to pneumocephalus. Immediate chest drainage might be the best way to stop the migration of air; however, care should be taken to not worsen cerebrospinal fluid leakage.

Penetrating cardiac injury caused by multiple rib fractures following high-energy trauma: Usefulness of the exploratory video-assisted thoracoscopic surgery.

Background: Penetrating cardiac injuries are usually fatal and associated with poor survival rates. Case Presentation: A 69-year-old man was injured in a motor vehicle accident and suffered from left hemothorax and multiple rib fractures near the heart. A comprehensive assessment raised suspicions of lacerated pericardium and myocardial injury. Consequently, a thoracoscopy was performed 9 h after injury. A penetrating cardiac injury was detected and surgically treated via video-assisted thoracoscopic surgery. The patient recovered uneventfully and was discharged on postoperative day 16. Conclusion: Exploratory video-assisted thoracoscopic surgery may play a key role in the primary diagnosis of patients with high-energy chest traumas with cardiac injury and simultaneously allow for the appropriate surgical interventions.

Multi-frequency forced oscillation technique using impulse oscillations: can it give mechanical information about the lung periphery?

Forced oscillation techniques (FOTs) using sine curved oscillatory waves are used for assessing the lung periphery, but measure only overall respiratory mechanics. Therefore, mathematical models of the respiratory system serve as vehicles to obtain detailed mechanics. Although the simplest model of respiratory mechanics is a simple 3-element series (RIC) model, the constant phase (CP) model is recently used for characterizing respiratory mechanics, which has the advantage of partitioning of respiratory mechanics into airway and tissue components. Meanwhile, FOTs using non-sine curved oscillatory waves are easily applied in patients with severe respiratory diseases because they do not require voluntary apnea. If the latter type of FOTs is as informative as the former, the question arises whether a FOT using non-sine curved oscillatory waves (IOS) could be used to study mechanical properties of the lung periphery. And the CP model should fit the impedance spectra. To answer this, subjects with lymphangioleiomyomatosis (LAM) were recruited as a cohort of patients with lung parenchymal disease. Impedance spectra obtained by the IOS were fitted to the CP and RIC models. Mean values of goodness of fit from the CP and RIC models were 0.978 ± 0.022 and 0.968 ± 0.026, respectively. The extra sum-of-squares F test was used to compare the two mathematical models. The F ratio was 2.37 ± 1.40 and the p-value was 0.29 ± 0.21. Unfortunately, there was no compelling evidence for adopting the CP model for the evaluation of impedance spectra obtained by IOS. This result might relate to the uncertainty of IOS for detecting mechanical properties of the lung periphery.

Time dependency and unique etiology of barotrauma in COVID-19: A retrospective cohort study with landmark analysis and pathological approach.

BACKGROUND: Barotrauma frequently occurs in coronavirus disease 2019. Previous studies have reported barotrauma to be a mortality-risk factor; however, its time-dependent nature and pathophysiology are not elucidated. To investigate the time-dependent characteristics and the etiology of coronavirus disease 2019-related-barotrauma. METHODS AND FINDINGS: We retrospectively reviewed intubated patients with coronavirus disease 2019 from March 2020 to May 2021. We compared the 90-day survival between the barotrauma and non-barotrauma groups and performed landmark analyses on days 7, 14, 21, and 28. Barotrauma within seven days before the landmark was defined as the exposure. Additionally, we evaluated surgically treated cases of coronavirus disease 2019-related pneumothorax. We included 192 patients. Barotrauma developed in 44 patients (22.9%). The barotrauma group's 90-day survival rate was significantly worse (47.7% vs. 82.4%, p < 0.001). In the 7-day landmark analysis, there was no significant difference (75.0% vs. 75.7%, p = 0.79). Contrastingly, in the 14-, 21-, and 28-day landmark analyses, the barotrauma group's survival rates were significantly worse (14-day: 41.7% vs. 69.1%, p = 0.044; 21-day: 16.7% vs. 62.5%, p = 0.014; 28-day: 20.0% vs. 66.7%, p = 0.018). Pathological examination revealed a subpleural hematoma and pulmonary cyst with heterogenous lung inflammation. CONCLUSIONS: Barotrauma was a poor prognostic factor for coronavirus disease 2019, especially in the late phase. Heterogenous inflammation may be a key finding in its mechanism. Barotrauma is a potentially important sign of lung destruction.

Ringed fluorodeoxyglucose uptake predicted poor prognosis after resection of pulmonary pleomorphic carcinoma.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a relatively rare and poorly differentiated non-small cell carcinoma. This study aimed to investigate the clinicopathological features including programmed cell death ligand 1 (PD-L1) expression status in patients with PPC who underwent curative resection. METHODS: We retrospectively studied 29 consecutive patients who had undergone anatomical lung resections for PPC. Perioperative and pathological variables, including radiological findings, were investigated to define prognostic factors. RESULTS: Overall survival (OS) rates were 71.8% at 1 year and 60.0% at 5 years. Disease-free survival (DFS) rates were 54.8% at 1 year and 43.6% at 5 years. Univariate analysis revealed that ringed fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) (p = 0.003), a cavity in the tumor on CT (p = 0.004), and tumor size (> 40 mm) (p = 0.014) were poor prognostic factors for OS. Regarding DFS, ringed FDG uptake (p = 0.002), a cavity on CT (p < 0.001), tumor size (p = 0.007), and pleural invasion (p = 0.014) were poor prognostic factors. PD-L1 expression was not a prognostic factor. CONCLUSION: This study showed for the first time that ringed FDG uptake on PET/CT is a poor prognostic factor of PPC. PD-L1 expression status was not related to the prognosis. Trial registration The study was approved by the Kobe City Medical Center General Hospital's ethics board (No. 20112) on August 20, 2020.

Structure-function relations in an elastase-induced mouse model of emphysema.

Emphysema is a progressive disease characterized by the destruction of peripheral airspaces and subsequent decline in lung function. However, the relation between structure and function during disease progression is not well understood. The objective of this study was to assess the time course of the structural, mechanical, and remodeling properties of the lung in mice after elastolytic injury. At 2, 7, and 21 days after treatment with porcine pancreatic elastase, respiratory impedance, the constituents of lung extracellular matrix, and histological sections of the lung were evaluated. In the control group, no changes were observed in the structural or functional properties, whereas, in the treatment group, the respiratory compliance and its variability significantly increased by Day 21 (P < 0.001), and the difference in parameters decreased with increasing positive end-expiratory pressure. The heterogeneity of airspace structure gradually increased over time. Conversely, the relative amounts of elastin and type I collagen exhibited a peak (P < 0.01) at Day 2, but returned to baseline levels by Day 21. Structure-function relations manifested themselves in strong correlations between compliance parameters and both mean size and heterogeneity of airspace structure (r(2) > 0.9). Similar relations were also obtained in a network model of the parenchyma in which destruction was based on the notion that mechanical forces contribute to alveolar wall rupture. We conclude that, in a mouse model of emphysema, progressive decline in lung function is sensitive to the development of airspace heterogeneity governed by local, mechanical, force-induced failure of remodeled collagen.

A prospective naturalistic multicentre study of intravenous medications in behavioural emergencies: haloperidol versus flunitrazepam.

A prospective naturalistic multicentre study for deep sedation was conducted in intensive care with continuous electrocardiogram (ECG) monitoring. Clinical purpose was enough sedation, which made uncooperative and disrupted patients receive brain computed tomography (CT), magnetic resonance imaging (MRI), or fluid therapy, with minimum drug doses. A first infusion was either haloperidol (HAL group) or flunitrazepam (FNP group). If enough sedation was not achieved, a second infusion, which was the opposite drug to the first infusion, was given. The proportion requiring a second infusion was higher in the HAL group than in the FNP group (82% vs. 36%, P<0.0001). The mean reduction of the Excited Component for Positive and Negative syndrome scale at 15 min was greater for the FNP first group (FNP+HAL group) than the HAL first group (HAL+FNP group) (68% [S.D. 17] vs. 54% [S.D. 31], P=0.02). The mean dose of flunitrazepam in the HAL+FNP group was significantly lower than that in the FNP+HAL-group (1.3 mg vs. 3.5 mg, P=0.0003). Thus, in terms of monotherapy and speed of action, flunitrazepam has advantages over haloperidol as a first infusion for deep sedation. Regarding drug dosages, haloperidol has an advantage over flunitrazepam as a first infusion in safety.

Forced oscillation technique as a non-invasive assessment for lung transplant recipients.

We usually use spirometry for the medical follow-up of respiratory mechanics after lung transplantation. However, especially in the first few post-operative weeks, it is easily affected by postoperative pain and the patient's co-operation during forced breathing effort. To avoid missing out on assessing pulmonary function, we perform non-invasive forced oscillation techniques on the patients who cannot perform forced breathing maneuvers. In this paper, we discuss the application of forced oscillation techniques on a patient with suspicion of acute lung rejection, whose spirometry could not be correctly performed and seemed to be unreliable. The respiratory impedance measurements had good correlation with the patient's clinical symptoms before and after steroid therapy. Thus, postoperative pulmonary function follow-up using forced oscillation technique was useful in assessing peripheral airway condition in critically ill patients, and may be able to detect acute rejection.

Age-related changes in the trachea in healthy adults.

To investigate age-related changes in the shape of trachea, normal male volunteers (n = 83, mean +/- SD: 47.7 +/- 20.2 years old) underwent inspiratory CT scans at full inspiration and lung function tests. Subjects who showed VC < 80% predicted or FEV1 < 80% predicted on lung function tests were excluded. The CT data, which is located at 2.0 cm above the aortic arch, were transferred to a personal computer. The tracheal area (St) and two parameters, Tracheal index (Ti) and Circularity (Ci) indicating the shape of the trachea, were automatically calculated. Ti was defined the ratio of the coronal to the sagittal diameter of the trachea, and the Ci (Ci = 4piS/L2, S: tracheal area, L: tracheal perimeter) was used to indicate the roundness of the trachea. A Ci value of less than 1 indicated the distortion of the roundness. Both St and St/BSA (body surface area) showed a significant correlation with age (r = 0.37, r = 0.52; p = 0.0006, p < 0.0001). Ti was not correlated with age (r = -0.20; p = 0.0697), whereas Ci was significantly correlated with age (r = -0.32; p = 0.00364). There were measurable age related changes of the trachea both in the area and the shape. Aging results in the increased tracheal area and a distortion of the roundness.

Three-dimensional measurement of alveolar airspace volumes in normal and emphysematous lungs using micro-CT.

In pulmonary emphysema, the alveolar structure progressively breaks down via a three-dimensional (3D) process that leads to airspace enlargement. The characterization of such structural changes has, however, been based on measurements from two-dimensional (2D) tissue sections or estimates of 3D structure from 2D measurements. In this study, we developed a novel silver staining method for visualizing tissue structure in 3D using micro-computed tomographic (CT) imaging, which showed that at 30 cmH20 fixing pressure, the mean alveolar airspace volume increased from 0.12 nl in normal mice to 0.44 nl and 2.14 nl in emphysematous mice, respectively, at 7 and 14 days following elastase-induced injury. We also assessed tissue structure in 2D using laser scanning confocal microscopy. The mean of the equivalent diameters of the alveolar airspaces was lower in 2D compared with 3D, while its variance was higher in 2D than in 3D in all groups. However, statistical comparisons of alveolar airspace size from normal and emphysematous mice yielded similar results in 2D and 3D: compared with control, both the mean and variance of the equivalent diameters increased by 7 days after treatment. These indexes further increased from day 7 to day 14 following treatment. During the first 7 days following treatment, the relative change in SD increased at a much faster rate compared with the relative change in mean equivalent diameter. We conclude that quantifying heterogeneity in structure can provide new insight into the pathogenesis or progression of emphysema that is enhanced by improved sensitivity using 3D measurements.

Prevalence of i.v. thiopental use in psychiatric emergency settings in Japan.

AIM: Because i.v. barbiturates such as thiopental carry the risk of apnea and laryngeal spasm in asthmatic patients, reducing the use of barbiturate in emergency situations is important. The purpose of the present study was therefore to investigate the prevalence of i.v. thiopental as a choice of sedation in behavioral emergency settings, we conducted a cross-sectional multicenter study. METHODS: Psychiatric emergency departments of seven hospitals were studied during a 4-month period. Patients with a score >15 on the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) who received i.v. medication were included in the study. Drugs were chosen according to the Japanese guidelines, in which the first injection was either haloperidol or benzodiazepine in accordance with clinical requirements. A second injection, which was the opposite drug to the first injection was administered as needed. Only when excitement obviously increased following the first injection, which was considered uncontrollable without thiopental according to expert experience, was thiopental given as a second injection. A total of 137 patients were included. The mean age was 40.4 years (SD 13.1), and the rate of male gender, drug-naïve, and F2 (schizophrenia, schizotypal and delusional disorders) on the ICD-10 were 48.9%, 29.9%, and 65.7%, respectively. RESULTS: The rate of patients treated with thiopental as a second injection was 8.0% (n = 11). All of the first injections in patients treated with thiopental were not haloperidol but benzodiazepines (P = 0.0072). CONCLUSION: Because this multicenter study has an epidemiological character, the prevalence of i.v. thiopental use in psychiatric emergency settings in Japan is considered to be 8.0%.

Tumor-to-Tumor Metastasis: Pulmonary Carcinoid Metastasizing to Solitary Fibrous Tumor.

BACKGROUND Tumor-to-tumor metastasis is an uncommon phenomenon in which a primary tumor metastasizes into another tumor. CASE REPORT An 81-year-old Asian woman was referred to our hospital for evaluation and treatment of a solid mass in the right middle lung lobe that had rapidly enlarged for 1.5 years compared to that observed over the last 5 years. On computed tomography (CT), the mass was 68×60 mm, and 2 different tumors appeared to exist in the upper portion of the mass. Blood examination findings revealed high serum levels of progastrin-releasing peptide and neuron-specific enolase. Based on the radiographic course of the tumor and elevated levels of tumor markers, we suspected that a new malignant tumor, such as a neuroendocrine tumor, had developed dorsally adjacent to the benign tumor. CT-guided percutaneous needle biopsy of the lung indicated a solitary fibrous tumor (SFT), which did not lead to the diagnosis of another tumor adjacent to the original tumor. Therefore, a right middle lobectomy was performed. The resected specimen contained 2 different tumors: an SFT and a typical carcinoid without mitosis or necrosis. On microscopic examination, they were separated from each other by normal alveolar tissue. In addition, a typical carcinoid was also observed inside the SFT lesion, completely enclosed by the SFT tissue. These findings suggested that the carcinoid metastasized to the SFT in the same lung lobe. CONCLUSIONS To the best of our knowledge, this is the first case of a pulmonary typical carcinoid metastasizing to an intraparenchymal SFT.

Association Between Formalin Fixation Time and Programmed Cell Death Ligand 1 Expression in Patients With Non-Small Cell Lung Cancer.

BACKGROUND/AIM: The expression of programmed cell death ligand 1 (PD-L1) determined by immunohistochemistry (IHC) may be associated with tissue formalin fixation time in non-small cell lung cancer (NSCLC) samples. We investigated the association between the PD-L1 expression and formalin fixation time, and clarified the optimal duration of fixation for accurate PD-L1 evaluation. MATERIALS AND METHODS: We collected 55 tumor specimens from resected NSCLC patients. The samples were halved and immediately fixed in 10% buffered formalin for 12-24 h (normal fixation), or 96-120 h (prolonged fixation). Each specimen was stained using two assay systems (22C3 and SP263) for PD-L1. RESULTS: The mean PD-L1 tumor proportion score was not significantly different between normal and prolonged fixation groups for either 22C3 or SP263 (normal fixation: 18.8%; prolonged fixation: 16.3%, p=0.277; normal fixation: 16.2%; prolonged fixation: 17.6%, p=0.560, respectively). CONCLUSION: Formalin fixation duration for up to 120 h does not affect PD-L1 IHC expression. PD-L1 tumor proportion score of tumor specimens can be evaluated by IHC even if these have been fixed in formalin outside the recommended duration in clinical practice.

Olanzapine orally disintegrating tablet vs. risperidone oral solution in the treatment of acutely agitated psychotic patients.

OBJECTIVE: Efficacy and tolerability of risperidone oral solution (RIS-OS) and olanzapine orally disintegrating tablet (OLZ-ODT) were compared for the treatment of acute psychotic agitation. METHOD: During a 2-month period, patients scoring > or =15 on the Excited Component for Positive and Negative Syndrome Scale (PANSS-EC) were assigned to treatment with OLZ-ODT (n=34) or RIS-OS (n=53) on psychiatric emergency situations, and assessed every 15 min. RESULTS: Two (OLZ-ODT and RIS-OS) by five (0-, 15-, 30-, 45- and 60-min time points) repeated-measures analysis of variance revealed only a significant main effect of time course on PANSS-EC (F=82.2, P<.0001). No differences in the number of patients receiving additional injection due to worsening were found (OLZ-ODT, 11.8%; RIS-OS, 9.4%). No differences in rate of extrapyramidal symptoms and patient satisfaction with assigned treatment were found. However, patients in the OLZ-ODT group recovered significantly more from tachycardia than those in the RIS-OS group (t=2.17, P=.03). CONCLUSION: OLZ-ODT and RIS-OS treatments yielded similar improvements in acutely agitated patients who accepted oral medication. However, on one physiological parameter (i.e., tachycardia) OLZ-ODT might be superior to RIS-OS. Physiological indicators may also be useful for measuring levels of agitation.