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Background Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Methods IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti-TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1–62.3; p=0.0293), and tended to be influenced by COVID-19 infection (139.1, 41.0–472.2; p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA-1273 (90.3 [60.8–134.1]) than for BNT162b2 (39.6 [35.2–44.6], p= 0.0001). Systemic steroids (22.9 [13.9–37.7], p=0.0119), IM (24.2 [18.7–31.4], p Conclusion Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs.

Background EGFR mutation is independently associated with a favorable response in NSCLC patients receiving EGFR-TKIs, regardless of gender or smoking history. However, recent reports have indicated that squamous cell carcinoma patients harboring EGFR mutations show a worse response to EGFR-TKIs than adenocarcinoma patients. We hypothesized that serum CYFRA21-1 is a predictive marker in EGFR-mutated patients treated with EGFR-TKIs. Methods We retrospectively screened 160 NSCLC patients harboring EGFR mutations (exon 19 deletions, L858R in exon 21, or other minor mutations) who received either gefitinib or erlotinib between 1992 and 2011. Patients were screened for histology, sex, age, smoking status, efficacy of EGFR-TKI and tumor markers (CEA/CYFRA21-1) at initial diagnosis. Results Out of 160 eligible patients treated with EGFR-TKIs, 77 patients with a high CYFRA21-1 level (>2 ng/ml) showed statistically shorter progression-free survival (PFS) than 83 patients with a normal CYFRA21-1 level (median PFS 7.5 versus 14.0 months, P = 0.006). No significant difference in PFS was observed between the high CEA group (>5 ng/ml) and the normal CEA group (median PFS 8.6 versus 11.2 months, P = 0.2423). Multivariate analysis revealed that a high CYFRA21-1 level is independently associated with PFS (HR 1.35; P = 0.002) as well as squamous cell carcinoma (HR 1.40; P = 0.020) and performance status 2–4 (HR 2.63; P = 0.003). No statistically significant difference in overall survival (OS) was observed between the high CYFRA21-1 group and the normal group (median OS 24.8 versus 39.1 months, P = 0.104). Conclusions High CYFRA level patients have significantly shorter PFS, which may indicate that this subgroup has a larger squamous component and thus less response to EGFR-TKIs. The serum CYFRA21-1 level is a predictive marker of EGFR-TKIs efficacy and EGFR-mutated patients can be divided into two subgroups according to the CYFRA21-1 level at initial diagnosis.

Chronic empyema, a sequelae of pulmonary tuberculosis, is now a only tuberculosis-related disease which was remained to be treated surgically. The candidates who have basically poor respiratory function are now attained advanced age. Over a 15 years period (1980-95), 22 patients 70 years of age or older underwent surgical intervention for chronic empyema at our hospital. There were 17 men and 5 women, ranging from 70 to 80 years of age (median age 75.0). They were 15.3% of all 145 surgically treated patients during same period. The empyema continued latent from 25 to 58 years (average 39.8 years). On admission they complained of productive cough (9), fever (9), hemosputam (5) and mass on the chest wall. Their Hugh-Johnes classification for dyspnea was I.: 4, II.: 6, III.: 11, IV.: 1 respectively. Their %VC ranged from 31.5 to 79.0 (average 54.8). In fifteen patients, tubercle bacilli (5), aspergillus (3) and other bacteria (9) were discovered in the empyema space. Surgical procedures consisted of 1 pneumonectomy (4.5%), 12 decortication or curettage of empyema wall (54.5%), 4 extraperiosteal air plombage (18%) and 5 other procedures (muscle or omental plombage, thoracoplasty, fenestration and others) (22.7%). There were no operative death and no lethal postoperative complication. In contrast, lethal postoperative complications such as GVIID, MOF and gastrointestinal bleeding occurred in the younger group. There were 2 cases of late respiratory failure in 70 years or older and 6 cases in younger group. Seventy-four years man who, preoperative %VC 33.0, underwent pneumonectomy died of asphyxia 6 month postoperatively. Another 74 years man who, preoperative %VC 76.1, developed respiratory failure after relapse of pulmonary tuberculosis. Four patients of younger group who developed late respiratory failure had all received thoracoplasty as a second operation. Other 2 patients, preoperative %VC 33.0 and 27.4 respectively, had undergone pneumonectomy. The risk of lethal postoperative complication or late respiratory failure were dependent mainly on preoperative respiratory function or surgical procedure selected rather than the age of patients.

To prevent flail chest after chest wall resection, chest wall reconstruction was performed to 74 primary lung cancer patients during the period between 1975 and 1994, out of 1,435 resected lung cancer patients, while in 29 cases, chest wall resection were performed without reconstruction. Numbers of ribs resected were from 1 to 5, mean 2.7, median 3. Chest wall reconstructions were performed in 66.7% of the patients for 2 ribs resected cases, 83.8% for 3 ribs cases, and 90.9% for more than 4 ribs cases. For chest wall reconstruction double layered Marlex mesh was used since 1982, while Dacron or Teflon felt was used until 1984. There was no flail chest, wound infection or operative death in the patients with chest wall resection and reconstruction. Survival curve of the p-T 3 N 0, 1 M 0 received chest wall reconstruction was compatible to the stage II cases out of 1,435 resected lung cancer patients (47.1% and 43.0% at 5 years). There is no need to perform chest wall reconstruction in cases like 1st to 3rd rib resection, or whose chest wall defect is covered with scapula. If the chest wall defect is lower than that and also lateral or anterior, chest wall reconstruction is indicated, even if resected ribs are less than 3. We should not hesitate to remove chest wall in order to get complete resection of the tumor, if tumor invasion is suspected surgically. Because we can reconstruct the chest wall with satisfactorily low risk of complications.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly post-translational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand–glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

MIBG-myocardial SPECT was performed on patients with dilated cardiomyopathy (DCM) undergoing treatment with beta blocker (Nipradilol). The findings of MIBG-myocardial SPECT were compared with the changes in cardiac function obtained by echocardiograms. The patients enrolled in the study were seven males who has been diagnosed as definitely suffering from DCM according to diagnostic guidelines provided by the Ministry of Health and Welfare. The patients were aged 57.5 +/- 10.2 years. Following intravenous administration of 111 MBq (3 mCi) of MIBG, myocardial SPECT was taken 20 minutes, and 4 hours later. The washout rate of the left ventricular wall was higher in the unchanged group (40.7 +/- 1.2%) than in the improved group (30.3 +/- 6.1%). Both the early and delayed images showed higher extent and severity scores for the unchanged group than for the improved group. A correlation of LVEF with the washout rates was demonstrated (r = -0.819, p0.05). A correlation was also observed between the variations in LVEF before and after beta blocker therapy with the washout rates (r = -0.969, p0.01), MIBG-myocardial SPECT suggested possibility of the evaluation of severity and prognosis in the patients with DCM.

We describe a case of carcinosarcoma of the lung in a 60-year-old female who was admitted with complaints of productive cough and an abnormal shadow in the chest X-ray. Sputum cytology showed both squamous cell carcinoma and adenocarcinoma cells. Malignant nonepithelial cells were identified in the needle biopsy specimen. Right middle and lower lobectomy was performed to reveal a carcinosarcoma by microscopic and immunohistochemical examination. This case was histologically unusual because it presented multiple carcinomatous elements (squamous cell carcinoma and adenocarcinoma). It was classified as peripheral type according to the clinical classification, showing an extremely poor prognosis. The histogenesis and clinical features of this rare tumor are discussed.

For the last ten years we had 56 patients operated for the empyema which occupied almost all the thoracic cavity. We evaluated their postoperative pulmonary functions and their sequelae. The pathological features of the resected lung and empyema wall were also examined. Surgical procedures consisted of 25 extraperiostal air plombage, 14 pleuropneumonectomy, 8 decortication, and 9 other procedures (lobectomy, muscle-flap, omental flap, and others). Preoperative %VC of patients with extraperiostal air plombage, those with pleuropneumonectomy, those with decortications and those with other procedures were 59.6 +/- 12.6, 46.4 +/- 11.1, 63.0 +/- 10.1, and 53.8 +/- 11.7 respectively. Of 11 patients who developed severe respiratory impairments (%VC less than 40 and/or FEV 1/VC predicted less than 30) post operatively, 4 had extraperiostal air plombage, 4 had pleuropneumonectomy, and 3 had other procedures. In general, degree of respiratory impairment was more severe in patients who underwent multiple surgical procedures. Of 18 patients who survived 5 years or more, %VC was under 50% in 9, and of those nine patients five had 30% decrease in VC compared to the preoperative values and there were 2 patients with extraperiostal air plombage in whom extreme shrinkage and deformity of hemithorax were observed though they had neither additional surgeries nor recurrences. Hemangioma was often seen on the walls of empyema and in some they became so large as to cause mediastinal shift. There were patients with round atelectasis, which, we thought, could have caused abscess or inflammatory granuloma.

The isolated left middle lobes of canine lungs were perfused in situ, by stepwise elevation of the blood flow. The weight gain of the lung lobe per initial bloodless dry lung weight (delta w g/min.IdQ1) showed a significant (p less than 0.001) correlation with the blood flow per body weight (F, ml/min.kg) with a regression line of delta w = 8.3 X 10-4F2.3. The pulmonary venous pressure (Pv) correlated significantly (p less than 0.001) with the pulmonary artery pressure (Pa), i.e. Pa = 11.2 + 1.3 Pv, with a constant left atrial pressure (Pla). The total pulmonary vascular resistance [TPVR = (Pa - Pla)/F] and the small pulmonary artery resistance [SR = (Pa-Pv)/F] decreased by steps with a constant pulmonary venous resistance (VR = TPVR-SR), and VR/TPVR increased by steps as the flow was increased. By incremental blood flow through the restricted lung tissue, we conclude that fluid filtration into the interstitium was flow-dependent, the pulmonary capillaries and precapillaries provided a large capacity for blood flow and the resistance to the flow was directed to the postcapillary site.

To determine the lung microvascular pressure profile during hypoxia, we micropunctured the subpleural microcirculation of isolated perfused cat lungs. Our procedures involved exsanguinating a cat, then cannulating its pulmonary artery, left atrium, and trachea. Using the cat's own blood, we perfused the lungs at pulmonary artery and left atrial pressures of 18 and 9 cm water, respectively, to obtain lung blood flow of 81 +/- 29 ml/(kg body weight x min), which we held constant throughout the experiment. We stabilized the lung surface with a vacuum ring and micropunctured 30- to 50-micrometers arterioles and venules to measure microvascular pressure by the servo-null method. During micropuncture, we held the lungs at constant inflation using airway pressure of 8 cm water. We varied the oxygen concentration of the inflation gas from 30% during baseline to 2% during hypoxia. We studied groups with high (more than 7.5) or normal pH. During normoxia, 27, 44, and 29% of the pressure drop occurred in the arterial, capillary and venous segments, respectively. During hypoxia, the increase in pulmonary vascular resistance, which was marked in both groups, was significantly greater in the normal pH group. All segmental pressure drops increased significantly during hypoxia. However, the predominant increase occurred in the arteries where segmental pressure drop increased by 148% and 210%, respectively, in the high and normal pH groups. We conclude that the major site of hypoxic vasoconstriction is in the pulmonary arteries.

We punctured subpleural microvessels in 19 isolated blood-perfused dog lung lobes to determine the effect of 5-hydroxytryptamine (5-HT) on the pulmonary microvascular pressure profile. Maintaining lobe airway pressure at 6 cmH2O and lobe venous pressure at 10 cmH2O we infused saline alone (10 microliter/min) in 10 control lobes and 5-HT in saline solution (100--150 micrograms/min) in 9 lobes. We measured pressures in subpleural microvessels using micropipettes connected to a servo-null system. The 5-HT infusion doubled lobar vascular resistance. In all microvessels upstream from the 150-micrometer venules, pressure was higher than in the control lobes. In contrast to the control lobes, pressure dropped markedly from the lobar artery to the 50-micrometer arterioles and from the venous capillaries to the 50-micrometer venules. We conclude that 5-HT not only constricted arterioles, but also raised lung microvascular pressure by constricting postcapillary venules.

The most important problem during FBS examination in infants is respiratory care. A new ventilation method using the channel of the FBS is proposed for respiratory care during FBS examination in infants. An FBS with a channel of more than 1.2 mm in diameter was directly inserted into the trachea under general anaesthesia without an orotracheal tube. The first step of this ventilation is the flushing of pure O2 into the lung as inspiration through the channel of the FBS. The second step is the aspiration of expiratory gas through the channel by a vacuum pump. Ventilation during the FBS examination is maintained by the repetition of these two steps by the operation of a stop-cock. Experiments in dogs, and clinical use showed that this method of respiratory care is effective and safe with certain limitations. Clinically, inspection with the FBS could be performed continuously for five minutes in most cases.

The sections of the salivary gland chromosomes of Drosophila virilis made by means of supersonic vibration, and treated with the silver impregnation method and examined with the electron microscope show minute structures of chromatin bands and interchromatin bands of the chromosomes. The chromatin band is composed of a multitude of chromomere granules; the interchromatin band appears cocoonshaped or irregularly oval in shape, and contains 64 pairs of chromonemata embedded in the opaque matrix.

The concentration of cefotiam (CTM) in the serum and the bloodless lung with time is discussed. Five patients who were undergone pneumonectomy or lobectomy, were given 1 g of CTM intravenously during the operation. Blood samples and lung samples were collected 15, 30, 60, 90, 120, and 300 minutes after the administration. The CTM levels in the blood and the lung samples were measured by the agar well bioassay. The CTM levels in the lung samples were modified as the CTM levels in the bloodless lung by calculating the contained blood volume, as lung samples were proven to have a mean value of 34.2% of blood in weight. The serum CTM level was 73.3 micrograms/ml at 15 minutes after injection and then decreased gradually. The CTM level in bloodless lung was elevated during the first 60 minutes, became equal to that of the blood during next 30 minutes and then exceeded the serum levels thereafter. These results indicate that the distribution of CTM to the bloodless lung was excellent and a satisfactory preventative effect against postsurgical infection could be expected.

Recent investigations of the role of large infusions of concentrated serum albumin on the acute pulmonary edema caused by hydrochloric acid (HCl) aspiration have produced contradictory results. We used the open thorax anesthetized dog with weighed lung lobe as well as completely isolated perfused weighed lobes. The results were the same with both preparations. Instillation of 0.1 N HCl (2 ml/kg) caused small increases in pulmonary artery pressure, and the rate of lung weight gain increased from 1.2 to 2.5 g/h to 22.2 to 30.2 g/h. Addition of 25% human serum albumin, either before or after acid instillation, had no significant effect on the rate of lobe weight gain. Additional experiments showed that after HCl the rate of lobe weight gain was exquisitely sensitive to pulmonary arterial pressure. Albumin therapy is without benefit in the prevention or treatment of the pulmonary edema caused by HCl aspiration.

Reducing sugars induced alkali-labile sites in DNA. The DNA reacted with D-fructose 6-phosphate or D-fructose in the presence of Cu2+ was cleaved by the treatment with aqueous piperidine at 90 degrees C for 30 min. Alkali-labile sites were induced frequently at the pyrimidine residues, especially at the pyrimidine residues in pyrimidine-purine (5'----3') sequences. Transition metal ions such as Cu2+ and oxygen radicals such as hydrogen peroxide were possibly involved in the induction of alkali-labile sites.

Amoxicillin tablets (50 mg (potency)/tablet) were administered to 14 cases of acute tympanitis and one case of acute tonsillitis, and the following results were obtained. (1) Of 15 cases in total, 3 cases were remarkably improved, 11 improved, and one not improved; that is, the effective rate was 93%. (2) Acute simple tympanitis: 6 cases, effective rate 100%. Acute suppurative tympanitis: 8 cases, effective rate 88%. Acute tonsillitis: 1 case, improved. (3) There was one case of diarrhea which appeared to be a side effect of this drug.

Forty-seven patients were pathologically studied in order to identify the kind of local tumoral spread occurring in lung cancer with particular reference to direct infiltration, intra and peribronchial metastasis and multicentricity. The potential absolute and relative criteria for bronchoplasty for lung cancer are discussed. Eighty-three patients were treated over a five-year period with bronchoplasty for malignancy. Survival data show that bronchoplasty can cure some patients with an absolute indication and save lobar function or improve surgical radicality in patients with relative indications.

Using 14 anesthetized dogs with lymph flowing through right lymph duct, we observed dynamic insufficiency of lung lymph flow during acute left atrial pressure loading. Net pulmonary microvascular fluid filtration pressure (sigma p) was defined as the difference between pulmonary microvascular pressure (Pmv) and oncotic gradient through the capillaries (pi mv - pi pmv). Pulmonary extravascular water content (PEVW) was well correlated with sigma p in either mild edema or gross edema (PEVW = 0.19 sigma p + 2.15, r = 0.813, 0.001 less than p less than 0.002). Percent increase in lymph flow (% Qlym) was well correlated with both PEVW (% Qlym = 130.8 PEVW - 376.5, r = 0.886, 0.005 less than p less than 0.01) and sigma p (% Qlym = 11.0 sigma p + 34.7, r = 0.853, 0.02 less than p less than 0.05) in mild edema. However, in gross edema compared with mild edema, % Qlym as a function of PEVW or sigma p was significantly low. We concluded that in gross edema with PEVW, over 6 g/g of bloodless dry lung and sigma p over 20 mmHg, lymph flow from right lymph duct becomes dynamically insufficient and can neither transport enough fluid from the pulmonary interstitium nor tracheobronchial trees to relieve the edema process.

Fifteen patients operated on for medullary thyroid carcinoma with elevated postoperative serum calcitonin (CT) levels underwent serial measurements of serum CT and carcinoembryonic antigen (CEA) levels. Both CT and CEA levels showed an exponential increase in 12 patients and a slight decrease in three. CEA levels manifested less fluctuation than CT levels. The doubling time of these tumor marker levels calculated from the regression line in each patient showed a strong correlation with three-year survival, recurrence within five years, and the time interval between surgery and recurrence of the tumor, allowing quantitative prediction of the prognosis. However, the doubling time of CEA was longer than that of CT in most patients.