Transcatheter arterial embolization of abnormal neovessels in a swine model of knee arthritis

BackgroundIn recent years, transcatheter arterial embolization (TAE) using imipenem/cilastatin (IPM/CS) has attracted attention as a treatment for relieving osteoarthritis (OA) pain. However, IPM/CS is not approved by Japanese medical insurance for use as an embolic material. Therefore, it is necessary to develop new embolic materials for TAE to relieve OA pain. The purpose of this study was to develop a swine model of knee arthritis and embolize abnormal neovessels (ANs) using two different embolic materials. We compared the embolic effects and tissue damage in knees.MethodsKnee arthritis was induced by intra-articular injection of papain into 12 knees in six female swine. The swine were divided into two groups of three swine each (six knees per group) for embolization of ANs in the knees with either IPM/CS or soluble gelatin sponge particles (SGSs). Three days after embolization, we compared the embolic effects using angiography and the tissue damage histopathologically.ResultsANs were observed in all 12 knees at 42 days after papain injection. The ANs disappeared and the patent arteries were recanalized 3 days after TAE in all 12 knees. Histopathological evaluation revealed synovitis changes, such as synovial thickening and inflammatory cell infiltration, in all 12 knees. There was no evidence of skin or muscle necrosis in either group. The appearance of ANs, recanalization of the parent arteries, and histopathological outcomes were not significantly different between the two groups.ConclusionSGSs were as safe as IPM/CS for TAE of ANs in this swine model of knee arthritis.     

Técnicas de imagen híbridas en cardiopatía isquémica

Hybrid imaging for ischemic heart disease refers to the fusion of information from a single or usually from multiple cardiovascular imaging modalities enabling synergistic assessment of the presence, the extent, and the severity of coronary atherosclerotic disease along with the hemodynamic significance of lesions and/or with evaluation of the myocardial function. A combination of coronary computed tomography angiography with myocardial perfusion imaging, such as single-photon emission computed tomography and positron emission tomography, has been adopted in several centers and implemented in international coronary artery disease management guidelines. Interest has increased in novel hybrid methods including coronary computed tomography angiography-derived fractional flow reserve and computed tomography perfusion and these techniques hold promise for the imminent diagnostic and management approaches of patients with coronary artery disease. In this review, we discuss the currently available hybrid noninvasive imaging modalities used in clinical practice, research approaches, and exciting potential future technological developments.     

HLA Antigens Shed from the Surface of Synthetic or Naturally Occurred Platelet-Derived Microparticles During Storage of Platelet Concentrate

The demand for standard platelet concentrates (PCs) has continued to increase in the recent years. Infusible platelet membranes (IPM) prepared from new or outdated human platelets have been developed as an alternative to standard PCs, with the additional advantage of long shelf life and increased viral safety. Reduction of HLA antigens on the IPM has been assigned as one of the probable advantages of this product. In re-examining this issue, we studied the existence of HLA class I on the surface of IPM microparticles. In comparison we also surveyed HLA expression on the surface of the naturally occurred platelet-derived microparticles (nPMPs) during 7 days storage. Intended for producing IPM, PCs obtained from Iranian blood transfusion organization were lysed; virally inactivated with wet heat in the presence of a heat stabilizer and then sonicated. IPMs were separated using centrifugation and liquid-stored in 4°C. The expression of HLA class I antigens was surveyed using flow cytometry technique. HLA molecules were present on the microparticles. Shedding of HLA antigens was demonstrated from the surface of the both liquid-stored IPM and nPMPs during storage. Storage of IPM in 4°C was accompanied with significant reduction of HLA molecules. It seemed that achievement of HLA-free IPM could be impossible unless chloroquine treated platelets were used to prepare these microvesicles.     

Effect of sodium mercaptoacetic acid on different antimicrobial disks in the sodium mercaptoacetic acid double disk synergy test for detection of IMP-1 metallo-β-lactamase-producing Pseudomonas aeruginosa isolates in Japan

We determined the optimal antimicrobial in the sodium mercaptoacetic acid double disk synergy test (SMA-DDST) for the detection of IMP-1-producing Pseudomonas aeruginosa isolates in Japan and evaluated the performance of the test.Fifty-four P. aeruginosa clinical isolates were tested, including 39 IMP-1 producers and 15 non-metallo-β-lactamase (MBL)-producing carbapenem- and ceftazidime (CAZ)-resistant isolates. The SMA-DDST was performed with CAZ, cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), or biapenem (BIPM)-containing disks. The sensitivity of the SMA-DDST with CAZ, CFPM, IPM, MEPM, DRPM, and BIPM was 39/39 (100%), 36/39 (92%), 18/39 (46%), 8/39 (21%), 19/39 (49%), and 36/39 (92%), respectively. The specificity was 15/15 (100%) for all SMA-DDSTs. This suggests that the isolates may have a resistance mechanism other than MBL production for IPM, MEPM, or DRPM. Since the CAZ resistance mechanism in P. aeruginosa is the same as that of CFPM, but differs from that of carbapenems, we conclude that combining CAZ with BIPM SMA-DDSTs can prevent any failure in the detection of IMP-1-producing P. aeruginosa.     

寄生虫抗药性及应对措施

长期使用化学杀虫剂,使寄生虫对药物产生了抗药性。目前抗药性问题成为寄生虫防治所面临的最严峻的问题之一。本文对寄生虫的抗药性及其产生机制进行了描述,着重论述了寄生虫的综合治理方案(IPM),旨在为寄生虫的防治开辟一条新途径。     

A Randomized Trial Comparing Imipenem/Cilastatine Alone with Latamoxef Plus Tobramycin in Febrile Neutropenic Patients with Lung Cancer

We conducted a randomized trial to compare the efficacy of imipenem/cilastatine(IPM/CS) monotherapy with thatof a combination of latamoxef(LMOX) and tobramycin (TOB) in the initial management of feverand neutropenia in patients with lung cancer. Leukocytopenicfebrile patients(<3,000 leukocytes perµl; temperature>38°C) with lung cancer given induction therapy wererandomly assigned to receive intravenous treatment with either1g IPM/CS twice daily or 2g LMOX plus 90 mg TOB twice daily.A total 101 febrile episodes were studied. Fifty-one episodeswere treated with IPM/CS and 50 with LMOX+TOB. Fifty-nine ofthe febrile episodes were bacteriologically confirmed, whilean organism could not be isolated despite the presence of obviousclinical infection in the remaining 42. The response rate was82% with IPM/CS and 80percent; with combination therapy. Thisdifference was not statistically significant. The response rateregarding gram-negative infections was 10 out of 14 (71%) inthe IPM/CS group and seven out of 12(58%) in the LMOX+TOB group.This differnce was also not significant (P=0.484). The responserate in severely neutropenic patients (neutrophils <100/µl)was low (P=0.078). Three patients in the IPM/CS group were withdrawnfrom the study due to skin rash and vomiting. Therapy with IPM/CSmonotherapy was as effective as a combination regimen     

Comparison of drug susceptibility between Escherichia coli detected in stool cultures of patients undergoing transrectal prostate needle biopsy and Escherichia coli in hospital-wide urine antibiograms

A prostate biopsy is essential for prostate cancer diagnosis. However, infections are one of the biopsy-associated complications, and post-biopsy fever is estimated to occur in approximately 1% of all cases. It may thus be beneficial to perform a rectal swab culture before a transrectal prostate biopsy to confirm the presence of resistant bacteria and select preventive antibacterial agents according to the drug susceptibility results. This study aimed to determine whether there is a difference between the drug susceptibility of bacteria detected in the stool of patients who were scheduled to undergo prostate biopsy and the hospital-wide urine antibiogram. Patients suspected of having prostate cancer who underwent transrectal prostate biopsy via transrectal ultrasonography between August 1, 2016, and June 30, 2020, were included in this study. Stool samples were collected and cultured before biopsy. Overall, 99 patients underwent prostate biopsy, and of these, culture results were available for 81 patients (81.8%). Escherichia coli was detected in 74.0% (60 samples) of the stool culture samples, of which 4 samples were extended-spectrum β-lactamase-producing types. We found greater susceptibility of Escherichia coli to ampicillin, fluoroquinolones, sulfamethoxazole/trimethoprim, and cefixime in the stool culture antibiogram than in the hospital-wide urine antibiogram. We also found a significantly low incidence of ESBL-positive Escherichia coli in the stool culture antibiogram with p-values of 0.009, 0.007, and 0.03 compared to the hospital-wide urine antibiograms for 2017, 2018, and 2019, respectively. Stool culture of prostate cancer patients undergoing biopsy may provide useful information for selecting prophylactic antimicrobial agents.     

Clinical Outcomes of Transcatheter Arterial Embolization for Adhesive Capsulitis Resistant to Conservative Treatment

Purpose

To evaluate clinical outcomes of transcatheter arterial embolization (TAE) for adhesive capsulitis resistant to conservative treatments.

Preclinical activity of palifosfamide lysine (ZIO-201) in pediatric sarcomas including oxazaphosphorine-resistant osteosarcoma

Purpose  Oxazaphosphorines, such as ifosfamide (IFA), are frequently used in the treatment of pediatric sarcomas. They are pro-drugs and undergo hepatic metabolism into the active moiety and potentially toxic by-products such as acrolein and chloracetaldehyde, which may cause hemorrhagic cystitis and encephalopathy, respectively. In addition, resistance to oxazaphosphorines can be mediated by overexpression of enzymes involved in their catabolism. Isophosphoramide mustard (IPM, palifosfamide) is the active moiety of IFA. In the current study, the activity of palifosfamide lysine (ZIO-201), a stable form of palifosfamide, was evaluated in a panel of sarcoma cell lines and tumor xenografts including oxazaphosphorine-resistant xenografts. Methods  The cytotoxic effect of palifosfamide lysine was studied in osteosarcoma (OS), Ewing’s sarcoma (ES) and rhabdomyosarcoma (RMS) cell lines using the MTT assay. In vivo, the maximum tolerated dose (MTD) of palifosfamide lysine was determined in SCID mice based on a 3-day intravenous (IV) administration schedule. The effect on tumor growth and event-free survival was assessed at the MTD in all three sarcoma xenografts. In OS, cyclophosphamide (CPA)-resistant and -sensitive xenografts (OS31 and OS33, respectively) were evaluated for palifosfamide lysine activity. ALDH1A1 and ALDH3A1 gene expression data for the OS xenografts were mined from the Pediatric Preclinical Testing Program gene expression data. ALDH3A1 enzyme levels were compared between the CPA-resistant and -sensitive xenografts. Results  Palifosfamide lysine was cytotoxic against all the cell lines tested with the IC₅₀ ranging from 0.5 to 1.5 μg/ml except for OS222, which had an IC₅₀ of 7 μg/ml. The IV MTD of palifosfamide lysine in mice was 100 mg/kg per day for three consecutive days. Tumor growth inhibition was seen in both OS31 and OS33 xenografts and the RMS xenograft resulting in a significant difference in event-free survival between the control and the treated groups. Differential gene expression of ALDH3A1 but not ALDH1A1 was noted in the OS31 xenograft. This was confirmed by RT-PCR and the ALDH3A1 enzyme assay. ALDH3A1 enzyme activity was measured at 100 mIU/mg of protein in OS31 xenograft but no significant activity was seen in the OS33 xenograft. Conclusions  We conclude that palifosfamide lysine has broad activity in a panel of sarcoma cell lines. It inhibits tumor growth in OS and RMS xenografts. Furthermore, it is active against the CPA-resistant, ALDH3A1 overexpressing, OS xenograft suggesting that it might have the potential of overcoming this resistance mechanism against oxazaphosphorines and may be an active agent in resistant/relapsed sarcomas in patients.     

Disseminated Mycobacterium abscessus subspecies massiliense infection and subsequent prosthetic joint infection in a hemodialysis patient: A case report

A 74-year-old man with diabetic nephropathy undergoing dialysis after total knee arthroplasty presented to our hospital with dyspnea and abnormal behavior such as wearing his pants on his head. The patient was in shock with ventricular tachycardia. Urine and blood cultures showed MAM with sterile pyuria. We administered amikacin and imipenem cilastatin, but repeated cultures were persistently positive. Although we initially chose not to administer azithromycin because of a higher risk of fatal arrhythmia, we had no choice but to administer azithromycin because of treatment failure. Upon close monitoring, we observed no arrhythmia, and the blood cultures became negative. The patient was discharged on day 106 without any symptoms. However, 2 months after discontinuation of antibiotics, he was readmitted and diagnosed with prosthetic joint infection due to MAM. He could not undergo total knee arthroplasty resection because of his low tolerance to surgery. We re-administered same antibiotics, and repeated draining and cleaning of his left knee for several weeks. The inflammation in the knee joint gradually improved, and the patient was discharged while treatment with azithromycin and amikacin was continued. After being discharged, the patient did not experience recurrent disease for at least 6 months.Our case suggests that MAM can cause sterile pyuria and infection in a patient with diabetic nephropathy. The macrolide agent is a key drug for MAM infection, and repeated joint lavage in addition to administering antibiotics may be an alternative treatment for prosthetic joint infection in patients with intolerance to surgery.