Incidence of gastrointestinal perforation associated with bevacizumab in combination with neoadjuvant chemotherapy as first-line treatment of advanced ovarian, fallopian tube, or peritoneal cancer: analysis of a Japanese healthcare claims database

[Objective] To assess the incidence of bevacizumab-associated gastrointestinal (GI) perforation during first-line treatment of patients with ovarian, fallopian tube, or peritoneal cancer receiving neoadjuvant chemotherapy (NAC) in Japanese real-world clinical practice. [Methods] A retrospective study was conducted using a healthcare claims database owned by Medical Data Vision Co., Ltd. (study period, 2008–2020). Patients who initiated first-line treatment of ovarian, fallopian tube, or peritoneal cancer were identified and divided into NAC and primary debulking surgery (PDS) groups. The incidence of bevacizumab-associated GI perforation was compared within the NAC group and between the groups. [Results] Paclitaxel + carboplatin (TC) was most commonly used as first-line treatment (39.5% and 59.6% in the NAC and PDS groups, respectively). TC + bevacizumab was used in 9.3% and 11.6% of patients in the NAC and PDS groups, respectively. In the NAC group receiving TC, the proportion of patients with risk factors for GI perforation was lower among patients with versus without concomitant bevacizumab. The incidence of GI perforation in the NAC group was 0.38% (1/266 patients) in patients receiving TC + bevacizumab and 0.18% (2/1, 131 patients) in patients receiving TC without bevacizumab (risk ratio=2.13; 95% confidence interval [CI]=0.19 to 23.36; risk difference=0.20; 95% CI=−0.58 to 0.97). None of the 319 patients in the PDS group receiving TC + bevacizumab had GI perforation. [Conclusion] No notable increase was observed in GI perforation associated with NAC containing bevacizumab. We conclude that bevacizumab is prescribed with sufficient care in Japan to avoid GI perforation

Dynamics of rheumatoid joint

In the present communication the recent works done by the Rheumatism Research Group of Department of Orthopedic Surgery, Okayama University, are described. The principal findings may briefly be summarized as follows. 1. Pathohistological pictures of the synovial membrane are classified into six types. Among them, Fibrinoid type and Follicular-Fibrosis type are the representative ones of chronic rheumatoid arthritis. 2. For the evaluation of the systemic as well as the local activities in rheumatoid arthritis and for judging the therapeutic effect, some indices have been established. 3. Injection of steroid hormones into the local joints fails to give satisfactory results in advanced, chronic rheumatoid arthritis. In such instances the flushing of the joint with physiological saline solution is effective. 4. In the case of chronic rheumatoid arthritis where the inflammation of hand and phalangeal joints is marked, RA-test gives rapid and more intense reaction, and most of such cases are of Follicular-Fibrosis type. 5. When lymph follicles appearing in the synovial membrane are stained when methyl green pyronine, the arrangement of lymphoid cells and plasma cells becomes distinctly clear. By micro-autoradiographic observations it can be seen that ³H-thymindine injected into the joint cavity is mostly ingested by the lymphoid cells in lymph follicles. 6. In the observation by the fluorescent antibody method multinuclear leucocytes found in the joint fluid and in the peripheral blood react with 19S and 7S-gamma-globulins. 7. When the serum and the joint fluid of the patient with rheumatoid arthritis are fractionated, they separate into three peaks at 19S, 7S, and 4S. Both S. S. C. A.-test and L. F. T. tests reveal the peak at 19S. The serum of chronic hepatitis positive to RA-test and the serum of rheumatoid arthritis are found to react immunologically the same to anti-&#946;2 M globulin sheep serum. 8. When the reticulo-endothelial system of rat is blocked by 900,000 molecules of poly-vinyl-pyrroridon, the ability of antibody production is diminished. 9. Chemical synovectomy of injecting osmic acid is effective to FibrinoidCoating type. Its action mechanism lies in the complete cleaning of the surface of synovial membrane. 10. By radiating synovectomy with 193Au a fairly good result can be expected. 198Au is ingested by those cells in the surface layer of the synovial membrane and also by histiocytes in the synovial membrane. When 5 mc of 198Au are injected into the knee joint, a marked necrosis of the synovial membrane occurs. When 198Au is added to the ascites cells of rabbit during the tissue culture, in the concentration of over 14 &#956;C degeneration of these cells can be recognized. 11. From the examination results of prognosis on those 25 cases with 41 rheumatoid knee joints after surgical synovectomy, it is considered that this method is indicated for Follicular-Fibrosis type. Ones with rheumatoid knee joint of Fibrinoid-Coating type gold sol treatment should be resorted to. In the cases of hand joints, surgical synovectemy is to be recommended at a relatively early stage.</p

Studies on the biological toxicity of several hydrocarbon pollutants of the environment Report 3. The metabolites and excretion rates of brominated benzenes

Metabolites of brominated benzenes in rabbits, rats and mice after a single oral administration were examined with ECD-GC and MS-GC. The major metabolites found in the urine of the three kinds of animals were bromophenol, mercapturic acid, thiophenylacetic acid and sulphuric methylates. A significant increase in mercapturic acid and thiophenylacetic acid was found in urine after administration of low brominated benzenes, whereas remarkable sulphuric methylate excreation was observed after administration of tribromobenzene. Unchanged bromobenzenes were remarkable in the urine of highbrominated benzene-administered animals. Debromination from which debrominated bromobenzenes and bromophenols in excretions result are best ascertained by an enzymatic reaction of the mixed function oxygenase system. The biological half life of each metabolite and unchanged bromobenzene correlated with the number of the substituted aromatic bromine atoms

Intake of brominated hydrocarbons in gold fish

Transfer to gold fish of brominated hydrocarbons (1-2-dibromoethane, bromoform, 1-1-2-2-tetrabromoethane) from rearing water was examined. The concentration of brominated hydrocarbons in fish flesh reached the first steady state 5 hours after fish were placed in rearing water. The concentration factors (cont. in gold fish/cont. in rearing water at steady state) of brominated hydrocarbons for gold fish were in the decreasing order of: bromoform 1-1-2-2-tetrabromoethane 1-2-dibromoethane

Studies on the biological toxicity of several hydrocarbon pollutants of the environment Report 2. The effect of halogenated hydrocarbons on oxidative phosphorylation and potassium compartmentalization of rat liver mitochondria.

In order to investigate the influence of various environmental pollutants on living organisms, the effects of hlogenated hydrocarbons on the mitochondrial membrane were examined. The results obtained were as follows: 1) Monohalogenated benzenes decrease state 3 respiration and increase state 4 respiration, resulting in a decrease in both respiratory control (RCI) and the ADP/O ratio. 2) The above activity is in the decreasing order of iodobenzene, bromobenzene, chlorobenzene and fluorobenzene. This order of activity is parallel to that of potassium releasing activity. 3) Similarly to the effect of monohalogenated benzenes, brominated hydrocarbons also decrease both RCI and the ADP/O ratio. The activity is in the decreasing order of tribromobenzene, dibromobenzene, boron carbide, monobromobenzene and bromoform, which parallels the potassium releasing activity

Studies on the biological toxicity of several brominated benzene pollutants of the environment Report 4. Biological fate of brominated benzenes in animals

Movement of brominated benzenes in rats and mice was investigated. The concentration of o-dibromobenzene in several tissues and organs reached the highest value within 10 hours of a single oral administration and then decreased rapidly. The accumulation of o-dibromobenzene in tissues and organs was in the descending order of adipose tissue, liver (=pectoral muscle), kidney, brain and blood. A similar tendency was observed in mono-and tribromobenzene administered animals. The concentration of hexabromobenzene following continuous intraperitoneal administration reached the highest value 16.3 (liver) to 28.8 days (brain) after the administration. The biological half life of hexabromobenzene ranged from 2.0 (kidney) to 4.1 days (brain) in the first phase of excretion, and from 5.2 (kidney) to 7.3 days (adipose tissue) in the second phase of excretion. Accumulation of hepatic triglyceride due to administration of brominated benzenes occurred. A decrease in the percentage of arachidonic acid among total fatty acids was observed after the administration of brominated benzenes. It is suggested that accumulativeness of brominated benzenes becomes higher with the number of bromine atoms. Clonic toxicity induced by these compounds needs to be investigated in this connection

Studies on the biological toxicity several brominated benzene pollutants of the environment Report 5. Metabolism of 1.3.5-tribromobenzene

The formative mechanism of debrominated compounds was investigeted. The excretion rate of tribromobenzene metabolites into the rat urine was enhanced by pretreatment with phenobarbital, and the amount of debrominated bromophenol in urine was greater than that of sulfur containing compounds after phenobarbital pretreatment. on the other hand, sulfur containing compounds were predominant in the urine of rats pretreated with glutathione. Incubation of tribromobenzene with the 10,000g supernatant of rat liver homogenate from rats pretreated with phenobarbital resulted in an increase in 3.5-dibromophenol. The above effect was accelerated remarkably by NADH and NADPH. These results demonstrate two metabolic pathways in the debromination of tribromobenzene: one to sulfur containing compounds and another to bromophenol bodies

Studies on the biological toxicity of several brominated benzene pollutants of the environment Report 4. Biological fate of brominated benzenes in animals

Movement of brominated benzenes in rats and mice was investigated. The concentration of o-dibromobenzene in several tissues and organs reached the highest value within 10 hours of a single oral administration and then decreased rapidly. The accumulation of o-dibromobenzene in tissues and organs was in the descending order of adipose tissue, liver (=pectoral muscle), kidney, brain and blood. A similar tendency was observed in mono-and tribromobenzene administered animals. The concentration of hexabromobenzene following continuous intraperitoneal administration reached the highest value 16.3 (liver) to 28.8 days (brain) after the administration. The biological half life of hexabromobenzene ranged from 2.0 (kidney) to 4.1 days (brain) in the first phase of excretion, and from 5.2 (kidney) to 7.3 days (adipose tissue) in the second phase of excretion. Accumulation of hepatic triglyceride due to administration of brominated benzenes occurred. A decrease in the percentage of arachidonic acid among total fatty acids was observed after the administration of brominated benzenes. It is suggested that accumulativeness of brominated benzenes becomes higher with the number of bromine atoms. Clonic toxicity induced by these compounds needs to be investigated in this connection

Skid Control of a Small Electric Vehicle with Two In-Wheel Motors: Simulation Model of ABS and Regenerative Brake Control

Due to the space limitation at the driving tyre, some of the small electric vehicles (EVs) with two in-wheel motors employed a mechanical braking system rather than the hydraulic braking system. Although the mechanical braking system is compact, its rigidness and the response performance are lower than the hydraulic braking system. In this paper, we propose a combination of anti-lock braking system (ABS) and regenerative brake control to improve the braking performance of the small EVs. The hydraulic unit of ABS is installed at the front tyre, while an in-wheel motor at the rear tyre will be an actuator of ABS to control the regenerative braking torque at the rear tyre. During braking on an icy road, the operational of ABS and regenerative brake control can prevent the tyre lock and vehicle from skidding. The simulation result shows that our proposed model can improve the safety and stability of the vehicle