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We report a middle-aged man, without occupational or environmental exposure to asbestos, who presented with spontaneous pneumothorax. Computed tomography showed a 13-mm right apical mass. He underwent tumorectomy and was diagnosed with malignant pleural mesothelioma. A local recurrence with multiple and diffuse pleural involvement later appeared. The patient eventually underwent panpleuropneumonectomy, recovered well, and has been doing well for 18 months. [ABSTRACT FROM AUTHOR]

Purpose The relationship between the height of the V wave in the central venous pressure (CVP) waveform and the severity of tricuspid regurgitation (TR) is well known. Their diagnostic ability is unconfirmed. This study explored CVP waveform variations with TR. Methods All patients who underwent preoperative echocardiography and CVP waveform measurements before surgery at our institution were included. Indices were created to capture each feature of the CVP waveform. The median value for each case was obtained and statistically analyzed according to the severity of TR. A deep learning technique, Transformer, was used to handle the complex features of CVP waveforms. Results This study included 436 cases. The values for C wave - Y descent, X descent - Y descent, and V wave - Y descent differed significantly in the Jonckheere-Terpstra test (p = 0.0018, 0.027, and 0.077, respectively). The area under the receiver operating characteristic (ROC) curve (AUC) for X descent - Y descent in two groups, none to moderate TR and severe TR, was 0.83 (95% confidence interval (CI) [0.68, 0.98]). For Transformer, the accuracy of the validation dataset was 0.97. Conclusions The shape of the CVP waveform varied with the severity of TR in a large dataset., (© 2024. The Author(s).)

The use of the laryngeal mask airway (LMA), which offers the benefits of ease in insertion and prevention of tracheal damage, is associated with a risk of flow leakage. This study analyzed our extensive database to compare leakage associated with the use of LMA and endotracheal tube (ETT). Adult patients who underwent chest wall, abdominal wall, inguinal region, limb, transurethral, or transvaginal surgery and received either LMA or ETT between January 2007 and March 2020 were included. The leak fraction was calculated as (inspiratory tidal volume-expiratory tidal volume)/(inspiratory tidal volume) × 100% every minute during intraoperative stable positive pressure ventilation. The median leak fraction was calculated for each case. The leak fraction in the LMA group demonstrated a left-skewed distribution with a larger proportion of excessive leak fraction. The leak fraction in the LMA group (median, 7.9%; interquartile range, 4.8-11.4%) was significantly lower than that in the ETT group (median, 9.1%; interquartile range: 5.5-12.4%; P < 0.001). This tendency was consistent across subgroups divided by sex, age, type of surgery, and ventilation mode. We propose that LMA provides leakage comparable to or less than ETT in most cases if stable positive pressure ventilation is achieved., (© 2024. The Author(s).)

Purpose: The purpose of this study was to investigate whether ex-vivo MRI enables accurate estimation of the invasive component of lung adenocarcinoma., Methods: We retrospectively reviewed 32 patients with lung adenocarcinoma who underwent lung lobectomy. The specimens underwent MRI at 1.5T. The boundary between the lesion and the normal lung was evaluated on a 5-point scale in each three MRI sequences, and a one-way analysis of variance and post-hoc tests were performed. The invasive component size was measured histopathologically. The maximum diameter of each solid component measured on CT and MR T1-weighted (T1W) images and the maximum size obtained from histopathologic images were compared using the Wilcoxon signed-rank test. Inter-reader agreement was evaluated using intraclass correlation coefficients (ICC)., Results: T1W images were determined to be optimal for the delineation of the lesions (P < 0.001). The histopathologic invasive area corresponded to the area where the T1W ex-vivo MR image showed a high signal intensity that was almost equal to the intravascular blood signal. The maximum diameter of the solid component on CT was overestimated compared with the maximum invasive size on histopathology (mean, 153%; P < 0.05), while that on MRI was evaluated mostly accurately without overestimation (mean, 108%; P = 0.48). The interobserver reliability of the measurements using CT and MRI was good (ICC = 0.71 on CT, 0.74 on MRI)., Conclusion: Ex-vivo MRI was more accurate than conventional CT in delineating the invasive component of lung adenocarcinoma.

Purpose: While a wide variety of platelet-rich plasma (PRP) solutions has been developed, innovation continues. In this case, the freeze-dried platelet factor concentrate (PFC-FD) represents another step in PRP refinement. The preparation of PFC-FD at a central laboratory with freeze drying for shelf stabilization should provide additional quality improvements if clinical effectiveness can be demonstrated. Therefore, this study was undertaken to assess the safety and effectiveness of PFC-FD in a prospective open-label trial of patients suffering from knee osteoarthritis (OA)., Methods: 312 consecutive knee OA patients (67% female, mean age 63 ± 10 years), were prospectively recruited in an outpatient knee clinic in Japan. Of these, 10 (3.2%) were lost to follow-up at < 12 months and 17 (5.5%) sought additional knee therapy during the follow-up period. The primary outcome of interest was achievement of the OMERACT-OARSI responder criteria with secondary outcomes of adverse events and PROMs scores 1, 3, 6, 12 months following a single PFC-FD injection., Results: 285 patients (91%) completed 12 month PROMs. The 17 who sought additional therapy were considered failures leaving an effective sample size of 302 for our primary outcome in which 62% of patients achieved OMERACT-OARSI responder status by 12 months. This varied by OA class with Kellgren-Lawrence grade 4 patients 3.6 times less likely to be responders than grade 1-2 patients. 6% of patients experienced a non-serious adverse event, primarily pain or swelling at the injection site., Conclusions: PFC-FD provides an observable clinical improvement in 62% of knee OA patients at 12 months post-injection with very little risk of any clinically relevant adverse event. Of course, nearly 40% of patients did not experience an observable clinical improvement, primarily among those with worse KL grades., Level of Evidence: Therapeutic, Level II., (© 2023. The Author(s).)

A typical electroencephalogram (EEG) change induced by general anesthesia is anteriorization-disappearance of occipital alpha oscillations followed by the development of frontal alpha oscillations. Investigating the quantitative relationship between such a specific EEG change and the level of anesthesia has academic and clinical importance. We quantified the degree of anteriorization and investigated its detailed relationship with the level of anesthesia. We acquired 21-electrode EEG data and bispectral index (BIS) values of 50 patients undergoing surgery from before anesthesia induction until after patient arousal. For each epoch of a 10.24-s window with 1-s offsets, we calculated frontal alpha power [Formula: see text], occipital alpha power [Formula: see text], and their difference [Formula: see text] to quantify anteriorization. We calculated Spearman's rank correlation coefficients between these values and the BIS value. We used locally weighted regression to estimate [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] at each BIS value. Thirty-six patients (26 females and 10 males aged 24-85 years) were analyzed. The 95% confidence intervals for the mean of Fisher transformations of Spearman's rank correlation coefficients between [Formula: see text], [Formula: see text], and [Formula: see text] and BIS value were [- 0.68, - 0.26], [0.02, 0.62], and [- 1.11, - 0.91], respectively. The change in [Formula: see text] and [Formula: see text] with BIS value showed different patterns by the type of anesthetic agent, whereas that in [Formula: see text] was more consistent with smaller individual variance. Anteriorization, quantified by the difference between frontal and occipital alpha powers, continuously developed in conjunction with general anesthesia. Quantifying anteriorization may provide an objective indicator of the level of anesthesia., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Cumulative dose effects, which are one of the main causes of errors that occur when an implantable cardiac pacemaker (ICP) is irradiated with ionizing radiation, induce permanent failure in ICPs. Although flattening filter free (FFF) beams, which are often used in stereotactic radiotherapy, are known to have different characteristics from conventional (with flattening filter [WFF]) beams, the cumulative dose effects on ICPs with FFF beams have been under-investigated. This study investigates ICP failure induced by cumulative dose effects of FFF beams. When the ICP placed in the center of the irradiation field was irradiated with 10 MV-FFF at 24 Gy/min, the cumulative dose at which failure occurred was evaluated on the basis of the failure criteria associated with high cumulative dose as described in the American Association of Physicists in Medicine Task Group 203. The ICP failures such as a mild battery depletion at a cumulative dose of 10 Gy, pacing-output voltage change >25% at a cumulative dose of 122 Gy, and the loss of telemetry capability at cumulative dose 134 Gy were induced by cumulative dose effects. The cumulative doses by which the cumulative dose effects of FFF beams induced ICP failure were not very different from those reported in previous studies with WFF beams. Therefore, radiotherapy with FFF beams (and WFF beams) for patients with ICP requires appropriate management for minimizing the cumulative dose effects., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS. To characterize cellular function of PMCs in BHDS patients (BHDS-PMCs), during surgery for pneumothorax, we established the flow cytometry-based methods of isolating high-purity PMCs from pleural lavage fluid. BHDS-PMCs showed impaired cell attachment and a significant decrease in proliferation and migration, but a significant increase in apoptosis compared with PMCs from primary spontaneous pneumothorax (PSP) patients (PSP-PMCs). Microarray analysis using isolated PMCs revealed a significant alteration in the expression of genes belonging to Gene Ontology terms "cell-cell adhesion junction" and "cell adhesion molecule binding". Gene set enrichment analysis demonstrated that CDH1, encoding E-cadherin, was identified in the down-regulated leading edge of a plot in BHDS-PMCs. AMPK and LKB1 activation were significantly impaired in BHDS-PMCs compared with PSP-PMCs. Our findings indicate that FLCN haploinsufficiency may affect the E-cadherin-LKB1-AMPK axis and lead to abnormal cellular function in BHDS-PMCs.

Direct irradiation may cause malfunctioning of cardiac implantable electronic devices (CIEDs). Therefore, a treatment plan that does not involve direct irradiation of CIEDs should be formulated. However, CIEDs may be directly exposed to radiation because of the sudden intrafractional movement of the patient. The probability of CIED malfunction reportedly depends on the dose rate; however, reports are only limited to dose rates ≤8 Gy/min. The purpose of this study was to investigate the effect of X-ray dose rates >8 Gy/min on CIED function. Four CIEDs were placed at the center of the radiation field and irradiated using 6 MV X-ray with flattening filter free (6 MV FFF) and 10 MV X-ray with flattening filter free (10 MV FFF). The dose rate was 4-14 Gy/min for the 6 MV FFF and 4-24 Gy/min for 10 MV FFF beams. CIED operation was evaluated with an electrocardiogram during each irradiation. Three CIEDs malfunctioned in the 6 MV FFF condition, and all four CIEDs malfunctioned in the 10 MV FFF condition, when the dose rate was >8 Gy/min. Pacing inhibition was the malfunction observed in all four CIEDs. Malfunction occurred simultaneously along with irradiation and simultaneously returned to normal function on stopping the irradiation. An X-ray dose rate >8 Gy/min caused a temporary malfunction due to interference. Therefore, clinicians should be aware of the risk of malfunction and manage patient movement when an X-ray dose rate >8 Gy/min is used for patients with CIEDs., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Clinical anesthesiologists, particularly residents, work in stressful environments. However, evidence-based physiological and psychological tests to evaluate stress are still lacking. In this single-center study of 33 residents, we investigated the relationship between heart rate variability (HRV), which had the potential to screen residents' stress levels using Holter electrocardiography (ECG) and psychological mood as assessed by the Profile of Mood States (POMS) questionnaire. HRV analysis revealed 2 findings. Firstly, standard deviation of the average of 5-min normal-to-normal R-R intervals (SDANN) was significant lower than that of same-aged healthy volunteers (69.3 ± 27.9 vs. 137.0 ± 43.0 ms, P < 0.05), which indicated suppression of autonomic nervous system activity throughout their work. Secondly, at induction of anesthesia, significant higher low frequency/high frequency ratio (LF/HF ratio: 1.326 vs. 0.846; P < 0.05) and lower HF (3326 vs. 5967 ms 2 ; P < 0.05) and lower standard deviation of normal-to-normal R-R intervals (SDNN: 50.5 vs. 79.4 ms; nervous system was suppressed at the induction of anesthesia: expected to be the most stressful period of their work. On the other hand, deviation scores of POMS questionnaire elucidated that all the residents were within normal range of psychological mood, and without any significant diurnal changes with respect to total mood disturbance deviation (TMD) scores (48 vs. 47; P = 0.368). HRV elucidated physiological stress among anesthesiology residents quantitatively by evaluating autonomic nervous activities, especially at induction of anesthesia. These changes in HRV could be observed regardless of psychological mood.

Tumor-associated macrophages affect tumor progression and resistance to immune checkpoint therapy. Here, we identify the chemokine signal regulator FROUNT as a target to control tumor-associated macrophages. The low level FROUNT expression in patients with cancer correlates with better clinical outcomes. Frount-deficiency markedly reduces tumor progression and decreases macrophage tumor-promoting activity. FROUNT is highly expressed in macrophages, and its myeloid-specific deletion impairs tumor growth. Further, the anti-alcoholism drug disulfiram (DSF) acts as a potent inhibitor of FROUNT. DSF interferes with FROUNT-chemokine receptor interactions via direct binding to a specific site of the chemokine receptor-binding domain of FROUNT, leading to inhibition of macrophage responses. DSF monotherapy reduces tumor progression and decreases macrophage tumor-promoting activity, as seen in the case of Frount-deficiency. Moreover, co-treatment with DSF and an immune checkpoint antibody synergistically inhibits tumor growth. Thus, inhibition of FROUNT by DSF represents a promising strategy for macrophage-targeted cancer therapy.

Background: Intra-articular injection of adipose-derived stem cells (ASCs) has shown promise for improving symptoms and cartilage quality in the treatment of osteoarthritis (OA). However, while most preclinical studies have been performed with plastic-adherent ASCs, most clinical trials are being conducted with the stromal vascular fraction (SVF), prepared from adipose tissue without prior culture., Purpose: To directly compare clinical outcomes of intra-articular injection with ASCs or SVF in patients with knee OA., Study Design: Cohort study; Level of evidence, 3., Methods: The authors retrospectively compared 6-month outcomes in 42 patients (59 knees) receiving intra-articular injection with 12.75 million ASCs and 38 patients (69 knees) receiving a 5-mL preparation of SVF. All patients had Kellgren-Lawrence grade 2, 3, or 4 knee OA and had failed standard medical therapy. The visual analog scale (VAS) pain score and Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline and 1, 3, and 6 months after injection were considered as outcomes. Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) criteria were also used to assess positive response. A repeated measures analysis of variance was used for comparison between the treatment groups., Results: No major complications occurred in either group. The SVF group had a higher frequency of knee effusion (SVF 8%, ASC 2%) and minor complications related to the fat harvest site (SVF 34%, ASC 5%). Both groups reported improvements in pain VAS and KOOS domains. Specifically, in the ASC group, symptoms improved earlier (by 3 months; P < .05) and pain VAS decreased to a greater degree (55%; P < .05) compared with the SVF group (44%). The proportion of OMERACT-OARSI responders in the ASC group was slightly higher (ASCs, 61%; SVF, 55%; P = .25)., Conclusion: It was observed that both ASCs and SVF resulted in clinical improvement in patients with knee OA, but that ASCs outperform SVF in the early reduction of symptoms and pain with less comorbidity.

Obesity is a risk factor of postoperative complications. We experienced 2 extremely obese patients:a 32-year-old male with coronary artery disease and a 75-year-old female with aortic valve stenosis. Their initial body weights were 133 kg and 88.5 kg, respectively, and their initial body mass indexes (BMIs) were both 41. Their BMIs were reduced to 35.5 and 35, respectively, after preoperative weight reduction. Off-pump coronary artery bypass grafting and aortic valve replacement were performed, respectively. After surgery, the non-invasive positive pressure ventilation( NPPV) support was effective, and their postoperative courses were uneventful. Preoperative weight reduction and NPPV are useful for extremely obese patients who undergo cardiac surgery.

Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although lung fibroblasts play a central role in PF, the key regulatory molecules involved in this process remain unknown. To address this issue, we performed a time-course transcriptome analysis on lung fibroblasts of bleomycin- and silica-treated murine lungs. We found gene modules whose expression kinetics were associated with the progression of PF and human idiopathic PF (IPF). Upstream analysis of a transcriptome network helped in identifying 55 hub transcription factors that were highly connected with PF-associated gene modules. Of these hubs, the expression of Srebf1 decreased in line with progression of PF and human IPF, suggesting its suppressive role in fibroblast activation. Consistently, adoptive transfer and genetic modification studies revealed that the hub transcription factor SREBP-1c suppressed PF-associated gene expression changes in lung fibroblasts and PF pathology in vivo. Moreover, therapeutic pharmacological activation of LXR, an SREBP-1c activator, suppressed the Srebf1-dependent activation of fibroblasts and progression of PF. Thus, SREBP-1c acts as a protective hub of lung fibroblast activation in PF. Collectively, the findings of the current study may prove to be valuable in the development of effective therapeutic strategies for PF.

Knowing a patient's cardiac output (CO) could contribute to a safe, optimized hemodynamic control during surgery. Precise CO measurements can serve as a guide for resuscitation therapy, catecholamine use, differential diagnosis, and intervention during a hemodynamic crisis. Despite its invasiveness and intermittent nature, the thermodilution technique via a pulmonary artery catheter (PAC) remains the clinical gold standard for CO measurements. LiDCOrapid™ (LiDCO, London, UK) and FloTrac/Vigileo™ (Edwards Lifesciences, Irvine, CA) are less invasive continuous CO monitors that use arterial waveform analysis. Their calculations are based on arterial waveform characteristics and do not require calibration. Here, we evaluated LiDCOrapid™ and FloTrac/Vigileo™ during off-pump coronary artery bypass graft (OPCAB) and living-donor liver transplantation (LDLT) surgery. This observational, single-center study included 21 patients (11 OPCAB and 10 LDLT). We performed simultaneous measurements of CO at fixed sampling points during surgery using both devices (LiDCOrapid™ version 1.04-b222 and FloTrac/Vigileo™ version 3.02). The thermodilution technique via a PAC was used to obtain the benchmark data. LiDCOrapid™ and FloTrac/Vigileo™ were used in an uncalibrated fashion. We analyzed the measured cardiac index using a Bland-Altman analysis (the method of variance estimates recovery), a polar plot method (half-moon method), a 4-quadrant plot and compared the widths of the limits of agreement (LOA) using an F test. One OPCAB patient was excluded because of the use of an intra-aortic balloon pumping during surgery, and 20 patients (10 OPCAB and 10 LDLT) were ultimately analyzed. We obtained 149 triplet measurements with a wide range of cardiac index. For the FloTrac/Vigileo™, the bias and percentage error were -0.44 L/min/m 2 and 74.4 %. For the LiDCOrapid™, the bias and percentage error were -0.38 L/min/m 2 and 53.5 %. The polar plot method showed an angular bias (FloTrac/Vigileo™ vs. LiDCOrapid™: 6.6° vs. 5.8°, respectively) and radial limits of agreement (-63.9 to 77.1 vs. -41.6 to 53.1). A 4-quadrant plot was used to obtain concordance rates (FloTrac/Vigileo™ vs. PAC and LiDCOrapid™ vs. PAC: 84.0 and 92.4 %, respectively). We could compare CO measurement devices across broad ranges of CO and SVR using LDLT and OPCAB surgical patients. An F test revealed no significant difference in the widths of the LoA for both devices when sample sizes capable of detecting a more than two-fold difference were used. We found that both devices tended to underestimate the calculated CIs when the CIs were relatively high. These proportional bias produced large percentage errors in the present study.

Varying temperature affects cardiac systolic and diastolic function and the left ventricular (LV) pressure-time curve (PTC) waveform that includes information about LV inotropism and lusitropism. Our proposed half-logistic (h-L) time constants obtained by fitting using h-L functions for four segmental phases (Phases I-IV) in the isovolumic LV PTC are more useful indices for estimating LV inotropism and lusitropism during contraction and relaxation periods than the mono-exponential (m-E) time constants at normal temperature. In this study, we investigated whether the superiority of the goodness of h-L fits remained even at hypothermia and hyperthermia. Phases I-IV in the isovolumic LV PTCs in eight excised, cross-circulated canine hearts at 33, 36, and 38 °C were analyzed using h-L and m-E functions and the least-squares method. The h-L and m-E time constants for Phases I-IV significantly shortened with increasing temperature. Curve fitting using h-L functions was significantly better than that using m-E functions for Phases I-IV at all temperatures. Therefore, the superiority of the goodness of h-L fit vs. m-E fit remained at all temperatures. As LV inotropic and lusitropic indices, temperature-dependent h-L time constants could be more useful than m-E time constants for Phases I-IV.

Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and recurrent pneumothorax. These cysts occupy predominantly the lower-medial zone of the lung field adjacent to the interlobar fissure, and some of them abut peripheral pulmonary vessels. For the surgical management of pneumothorax with BHDS, the conventional approach of resecting all subpleural cysts and bullae is not feasible. Thus, after handling several bullae by using a stapler or performing ligation as a standardized treatment, we applied to a pleural covering technique to thicken the affected visceral pleura and then to prevent recurrence of pneumothorax. We herein report the successful application of a pleural covering technique via thoracoscopic surgery to treat the recurrent pneumothorax of a 30-year-old man with BHDS. This technique is promising for the management of intractable pneumothorax secondary to BHDS.

Background: Myocardial contraction and relaxation are regulated by increases and decreases in cytoplasmic calcium concentration ([Ca(2+)]i). In previous studies, we found that a half-logistic (h-L) function, which represents a half-curve of a symmetrical sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phase and the second half of the descending phase of the [Ca(2+)]i transient curve better than a mono-exponential (m-E) function. In the present study, we investigated the potential application of an h-L function to analyse the first half of the descending phase of CaTC (CaTCIII)., Methods: The [Ca(2+)]i was measured using the Ca(2+)-sensitive aequorin, which was microinjected into 15 isolated mouse left ventricular (LV) papillary muscles. The observed CaTCIII data in the interval from the point corresponding to the peak [Ca(2+)]i to the point corresponding to dCa/dtmin was curve-fitted using the h-L and m-E function equations by the least-squares method., Results: The mean correlation coefficient (r) values of the h-L and m-E function best curve-fits for 11 CaTCIIIs were 0.9986 and 0.9982, respectively. The Z transformation of h-L r (3.64 ± 0.45) was larger than that of m-E r (3.50 ± 0.33) (p < 0.05)., Conclusions: The h-L function can evaluate most CaTCIIIs more accurately than the m-E function in isolated aequorin-injected mouse LV papillary muscle. The three calculated h-L parameters i.e., amplitude constant, time constant, and non-zero asymptote, are more reliable indices than m-E for evaluating the magnitude and time course of the change in the decrease in [Ca(2+)]i., Key Words: Ca(2+) transient; Half-logistic amplitude constant; Half-logistic non-zero asymptote; Half-logistic time constant; Myocardial Ca(2+) handling.

Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Lung macrophages have been reported to regulate both progression and remission of bleomycin-induced diffuse PF. However, it remains unclear how macrophages contribute to silica-induced progressive nodular PF and the associated tissue cell responses in vivo. We found that lack of monocyte-derived macrophages results in the formation of diffuse PF after silica instillation. We found that the proportion and the number of monocyte-derived macrophages were persistently higher in silica-induced progressive PF compared with bleomycin-induced PF. Surprisingly, in Ccr2(-/-) mice, in which monocyte-derived macrophage infiltration is impaired, silica administration induced diffuse PF with loose nodule formation and greater activation of tissue cells. In the diffuse lesions, the distribution of epithelial cells, distribution of myofibroblasts, and architecture of the basement membrane were disrupted. Consistent with the development of diffuse lesions, genes that were differentially expressed in CD45(-) tissue cells from the lung of wild-type and Ccr2(-/-) mice were highly enriched in human diffuse, progressive PF. In gene ontology network analyses, many of these genes were associated with tissue remodeling and included genes not previously associated with PF, such as Mmp14, Thbs2, and Fgfr4. Overall, these results indicate that monocyte-derived macrophages prevent transition from nodular to diffuse silica-induced PF, potentially by regulating tissue cell responses., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Most mediastinal abscesses result from infections after thoracotomy, esophageal perforation or pene- trating chest trauma. This disease is rarely caused by closed blunt chest trauma. All previously reported such cases after closed blunt chest trauma presented with hematoma and sternal osteomyelitis resulting from sternal fracture. Here we report a 15-year-old sumo wrestler who presented with an anterior mediastinal abscess without any mediastinal fracture. The mediastinal abscess resulted from the hematogenous spread of Staphylococcus aureus to a hematoma that might have been caused by a closed blunt chest trauma incurred during sumo wrestling exercises.

Lung volume changes involve the recruitment of collapsed alveoli and the expansion of already opened alveoli. This study aimed to determine the alveolar recruitment function by using a mathematical model from a pressure-volume curve (P-V curve). We assumed a lung model as VL=R(P)V0f(P), where R recruitment function is the fraction of recruited alveoli, V0 is the resting lung volume at FRC of a fully recruited lung, and f(P) corresponds to the normalized compliance function of the lungs open to ventilation. Seven white rabbits were subjected to saline-lavage lung injury, and P-V curves were calculated using the slow inflation technique. We obtained the P-R curve from the P-V curve, and two curves were differently shaped after lung injury. We concluded that the recruitment function was obtained from the P-V curve and that the P-R curve estimated the recruitment and derecruitment status., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The patient was a 68-year-old man who underwent pylorus-preserving pancreaticoduodenectomy for cancer of the pancreatic head in March 2012. Pre-operative chest computed tomography (CT) revealed a scar-like shade approximately 1.5 cm in length in the right middle lobe of the lung, but an active metastasis was not suspected. Adjuvant S-1 was initiated in June the same year at 100 mg/day and reduced to 50 mg/day in October because of neutropenia. The internal structure of the right middle lobe was observed to be uneven on a CT scan obtained in July 2013, and the shading increased to approximately 3 cm in length along with spicula. Brushing and transbronchial lung biopsy(TBLB)were performed. No other distant organ metastases were detected on a whole body search. Diagnosis was between a solitary lung metastasis of pancreatic cancer or cT2N0M0, StageIB primary lung cancer. The right middle lobe of the lung was resected via thoracoscopy along with lymph node dissection in September 2013. Histological examination revealed that the lesion was a well differentiated adenocarcinoma, with negative immunostaining for thyroid transcription factor-1(TTF-1) and Napsin A, and positive staining for cytokeratin (CK)7 and CK20, consistent with a solitary lung metastasis of pancreatic cancer. This report documents a rare case of pancreatic cancer with a solitary, resectable lung metastasis without involvement of other organs.

Purpose: Thoracic endometriosis-related pneumothorax (TERP) is a secondary condition specific for females, but in a clinical setting, TERP often is difficult to distinguish from primary spontaneous pneumothorax (PSP) based on a relationship between the dates of pneumothorax and menstruation. The purpose of this study was to clarify the clinical features of TERP compared with PSP., Methods: We retrospectively reviewed the clinical and histopathological files of female patients with pneumothorax who underwent video-assisted thoracoscopic surgery in the Pneumothorax Research Center during the 6-year period from January 2005 to December 2010. We analyzed the clinical differences between TERP and PSP., Results: The study included a total of 393 female patients with spontaneous pneumothorax, of whom 92 (23.4 %) were diagnosed as having TERP and 33.6 % (132/393) as having PSP. We identified four factors (right-sided pneumothorax, history of pelvic endometriosis, age ≥31 years, and no smoking history) that were statistically significant for predicting TERP and assigned 6, 5, 4, and 3 points, respectively, to establish a scoring system with a calculated score from 0 to 18. The cutoff values of a calculated score ≥12 yielded the highest positive predictive value (86 %; 95 % confidence interval (CI) 81.5-90.5 %) for TERP and negative predictive value (95.2 %; 95 % CI 92.3-98 %) for PSP., Conclusions: TERP has several distinct clinical features from PSP. Our scoring system consists of only four clinical variables that are easily obtainable and enables us to suspect TERP in female patients with pneumothorax.

Myeloid cells such as monocytes and monocyte-derived macrophages promote tumor progression. Recent reports suggest that extramedullary hematopoiesis sustains a sizable reservoir of tumor-infiltrating monocytes in the spleen. However, the influence of the spleen on tumor development and the extent to which spleen monocytes populate the tumor relative to bone marrow (BM) monocytes remain controversial. Here, we used mice expressing the photoconvertible protein Kikume Green-Red to track the redistribution of monocytes from the BM and spleen, and mice expressing fluorescent ubiquitination-based cell-cycle indicator proteins to monitor active hematopoiesis in these tissues. In mice bearing late-stage tumors, the BM, besides being the major site of monocyte production, supplied the expansion of the spleen reservoir, replacing 9% of spleen monocytes every hour. Deployment of monocytes was equally rapid from the BM and the spleen. However, BM monocytes were younger than those in the spleen and were 2.7 times more likely to migrate into the tumor from the circulation. Partly as a result of this intrinsic difference in migration potential, spleen monocytes made only a minor contribution to the tumor-infiltrating monocyte population. At least 27% of tumor monocytes had traveled from the BM in the last 24 h, compared with only 2% from the spleen. These observations highlight the importance of the BM as the primary hematopoietic tissue and monocyte reservoir in tumor-bearing mice, despite the changes that occur in the spleen monocyte reservoir during tumor development.

Purpose: The reduction of periosteal compression through the use of a locking plate may minimize disturbances of bone blood supply and may improve the rate of bone union. A single-centre, assessor blinded randomized controlled trial was conducted to compare the clinical effectiveness of a locking plate and a non-locking plate., Methods: A total of 52 patients with AO/OTA 44B lateral malleolar fractures were included in this study. All patients underwent surgical fixation using a lag screw and neutralization plate. An identical treatment protocol was used in all patients, with exception of plate selection. The rate of radiographic bone union, defined as the complete disappearance of fracture lines confirmed through anteroposterior, lateral, and internal oblique views was compared at three, six, and 12 months following surgery. In addition, the Medical Outcomes 36-Item Short-Form Health Survey (SF-36) score, the time required for resolution of tenderness at the fracture site and the complication rate were evaluated., Results: Twenty-three patients were randomly assigned to undergo fixation using a locking plate, and 29 patients were assigned to undergo fixation using a non-locking plate. Intention-to-treat analysis showed no difference in the radiographic bone union rate of fibula, SF-36 score, the time for resolution of tenderness at the fracture site and complication rates., Conclusion: No differences were observed in patients with AO/OTA 44B lateral malleolar fractures undergoing fixation with a locking versus non-locking neutralization plate.

Background: Myocardial contraction and relaxation are regulated by increases and decreases in intracellular cytoplasmic calcium (Ca(2+)) concentration ([Ca(2+)]i). In previous studies, we found that a half-logistic (h-L) function, which represents a half-curve of a symmetrical sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phase (CaTI) and the second half of the descending phase of the [Ca(2+)]i transient curve (CaTIV) better than a mono-exponential (m-E) function. In the present study, we investigated the potential application of an h-L function to the analysis of the second half of the ascending phase of the [Ca(2+)]i transient curve (CaTII)., Methods: The [Ca(2+)]i transient was measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into 15 isolated left ventricular (LV) papillary muscles of mice. The observed CaTII data during the time duration from the point corresponding to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dtmax) to the point corresponding to the peak Ca(2+) concentration was curve-fitted by the least-squares method using the h-L and m-E function equations., Results: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for CaTII were 0.9996 and 0.9984, respectively. The Z transformation of h-L r was larger than that of m-E r (p < 0.0001). H-L residual mean square (RMS) was smaller than m-E RMS (p < 0.001)., Conclusions: The h-L function tracks the magnitudes and time courses of CaTII more accurately than the m-E function in isolated aequorin-injected mouse LV papillary muscle. Compared with the m-E time constant, the h-L time constant of CaTII is a more reliable index for evaluating the time duration of the change in the increase in [Ca(2+)]i during the combination of the middle part of the contraction process and the early part of the relaxation process. CaTII can be assessed by the h-L function model in cardiac muscles. The h-L approach may provide a more useful model for studying each process in myocardial Ca(2+) handling., Key Words: Calcium handling; Calcium transient; Curve-fit; Half-Logistic function; Time constant.

ddY mice spontaneously develop IgA nephropathy (IgAN) with a variable age of disease onset. Establishing a model with early-onset IgAN could aid the investigation of mechanisms that underlie the pathogenesis of this disease. On the basis of histologic grading in serial biopsies, we previously classified ddY mice into early-onset, late-onset, and quiescent groups. Here, we selectively mated mice with the early-onset phenotype for >20 generations and established "grouped ddY" mice that develop IgAN within 8 weeks of age. Similar to human IgAN, the prognosis was worse for male mice than females. These mice homogeneously retained genotypes of four marker loci previously associated with the early-onset phenotype, confirming a close association of these loci with early-onset IgAN in ddY mice. Grouped ddY mice comprised two sublines, however, which had distinct genotypes at a susceptibility locus for high serum IgA levels, which maps within the Ig heavy-chain gene complex. The subline bearing the Igh-2(a) IgA allotype had a more rapid course of fatal disease and lower oligosaccharide content, suggesting that aberrant IgA glycosylation may promote the progression of murine IgAN. Taken together, these data indicate that grouped ddY mice may be a useful model for the identification of susceptibility genes and the underlying molecular mechanisms involved in the pathogenesis of human IgAN.

Purpose: Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. In an earlier study, we found that (1) a half-logistic (h-L) function, which represents a half-curve of a sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phases of the isometric myocardial tension and isovolumic left ventricular (LV) pressure waveforms better than a mono-exponential (m-E) function and (2) the h-L time constants are useful as inotropic indices. We report here our investigation of the potential application of an h-L function to the analysis of the first half of the ascending phase of the Ca(2+) transient curve (faCaT) that precedes and initiates myocardial contraction and the increase in LV pressure., Methods: Ca(2+) transients (CaT) were measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into seven isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The faCaT data from the beginning of twitch stimulation to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dt(max)) was curve-fitted by the least-squares method using h-L and m-E function equations., Results: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for the faCaTs were 0.9740 and 0.9654 (P < 0.05) in the rabbit and 0.9895 and 0.9812 (P < 0.0001) in the mouse., Conclusion: The h-L curves tracked the amplitudes and time courses of the faCaTs in cardiac muscles more accurately than m-E functions. Based on this result, we suggest that the h-L time constant may be a more reliable index than the m-E time constant for evaluating the rate of CICR from the SR in myocardial Ca(2+) handling. The h-L approach may provide a more useful model for the study of CICR during the contraction process induced by anesthetic agents.

Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10(-25)), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control.

Cell chemotaxis has been characterized as the formation of a front-back axis that is triggered by a gradient of chemoattractant; however, chemotaxis is accompanied by more complicated behaviors. These include migration in a straight line with a stable axis [the stable single-axis (SSA) pattern] and repeated splitting of the leading edge of the cell into two regions, followed by the "choice" of one of these as the new leading edge [the split and choice (S&C) pattern]. Indeed, transition between these two behaviors can be observed in individual cells. However, the conceptual framework of the network of signaling molecules that generates these patterns remains to be clarified. We confirmed theoretically that a system that has positive and negative feedback loops involving the reciprocal cycling between the membrane and the cytosol of molecules that promote membrane protrusion or retraction generates SSA and S&C patterns of migratory behavior under similar conditions. We also predicted properties of the instabilities of such a system, which are essential for the generation of these behaviors, and we verified their existence in chemotaxing cells. Our research provides a simple model of network structure for chemotactic behaviors, including cell polarization.