Effects of antineoplastic agents on the peripheral nerves under a surgical tissue expansion procedure: an experimental study

BACKGROUND: Elongation of peripheral nerve by the use of a tissue expander is helpful to repair nerve defects. This study was designed to investigate the effects of some antineoplastic agents on the peripheral nerves under a surgical tissue expansion procedure. MATERIALS AND METHODS: Twenty-five Wistar rats were used in this study. Following the exposition of the sciatic nerve and placement of two 10/0-nylon sutures in the epineurium 20 mm apart, a tissue expander was then placed under it. Inflation of the expander was immediately accomplished by the separate percutaneous injections of 6, 6, and 8 ml for every 3 min under general anesthesia. The expander was fully deflated at the end of each 3 min The distance between two sutures was measured 1 h later to measure the rate of elongation. Rats were randomly divided into five groups (according to the administered drugs), each consisting of five rats (10 sciatic nerves). Normal saline (1 ml) in the control group (group I), cyclophosphamide (15 mg/kg) in the group II, cisplatinum (3 microg/kg) in the group III, mitomycin-C (0.5 mg/kg) in the group IV and 5-fluorouracil (10 mg/kg) in the group V were injected intravenously. Intravenous injections of drugs were performed via the tail vein 30 min before expansion, 48 and 96 h after removal of expander. The incision was reopened on the third and seventh postoperative days, and five sciatic nerves of each group were exposed and then the pinching test was performed to measure regeneration distance. Electroneurographic changes were recorded. The expanded portion of the sciatic nerve between two sutures was harvested for histological evaluation. RESULTS: There is no significant difference between the elongation rates of all groups (P < 0.05). Histologic evaluation showed that inflammatory changes, vacuolization, intraneural edema, demyelination, axonal changes in the control group, the cisplatinum group, and the mitomycin-C group. These changes were significantly decreased in the cyclophosphamide group and the 5-fluorouracil group. In the cyclophosphamide group and the 5-fluorouracil group, the amplitude of compound action potential (CAP) values were significantly higher and the latency was significantly shorter (P > 0.05). CONCLUSION: We believed that cyclophosphamide and 5-fluorouracil may be helpful in tissue expansion of peripheral nerves, by decreasing the effects of the ischemia-reperfusion injury on the expanded peripheral nerves.     

Effects of Peritoneal Lavage with Scolicidal Agents on Survival and Adhesion Formation in Rats

Intraoperative irrigation of the peritoneal cavity with scolicidal agents is frequently recommended when dealing with traumatic or spontaneous rupture of hydatid cysts. The present experimental study was designed to examine the influence of various scolicidal agents on adhesion formation and survival. A total of 149 rats were randomly allocated to nine groups. Peritoneal lavage through a median laparotomy was performed with the following scolicidal agents. Group 1 (0.9% saline: controls), group 2 (20% hypertonic saline), group 3 (0.04% chlorhexidine gluconate), group 4 (3% hydrogen peroxide), group 5 (0.5% silver nitrate), group 6 (1% polyvinylpyrrolidone-iodine, or PVP-I ), group 7 (5% PVP-I), group 8 (0.5% cetrimide/0.05% chlorhexidine), and group 9 (10% PVP-I). The surviving animals were sacrificed on postoperative day 15. Adhesion formation was macroscopically graded by the Nair criteria. The severity of adhesion formation was evaluated microscopically using the fibrosing scoring criteria and the strain test. Group 9 (10% PVP-I) was excluded from the adhesion evaluation because all of the rats died in this group. The mortality rate was significantly higher in groups 5 and 7 than in groups 1, 2, 3, 4, 6, and 8. Adhesion scores were significantly lower in groups 1, 2, 3, and 4 than in groups 5, 6, 7, and 8. The lowest adhesion score was found in group 3 and the highest in the group 7. These results indicate that 0.04% chlorhexidine gluconate, the most potent scolicidal agent in vitro and in vivo, was associated with the lowest adhesion formation and mortality among various scolicidal agents in this experimental study.     

Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers

Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all cases had mutations in either IDH1 (14/16) or IDH2 (2/16). In addition, we discovered somatic mutations and insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16 tumours. These discovery set mutations were validated by deep sequencing of 13 additional tumours, which revealed seven others with CIC mutations, thus bringing the overall mutation rate in oligodendrogliomas in this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas and oligoastrocytomas without 1p/19q loss revealed that CIC alterations were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon 5 within an annotated DNA-interacting domain and three were in exon 20 within an annotated protein-interacting domain. The remaining nine were found in other exons and frequently included truncations. CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we observed no differences in the clinical outcomes of CIC mutant versus wild-type tumours, in a background of 1p/19q co-deletion, hemizygous CIC mutations are likely important. We hypothesize that the mutant CIC on the single retained 19q allele is linked to the pathogenesis of oligodendrogliomas with IDH mutation. Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion.     

Case Report: Homicide by a 10-Year-Old Girl with Autistic Disorder

This case study presents a 10-year-old girl with a diagnosis of Autistic Disorder, who killed her 6-month-old sister by throwing her out of a window. Her aggressive–impulsive behavior had a persistent pattern. She had a history of epilepsy, and was frequently exposed to physical abuse. She never attended a structured treatment program. Here, we discuss the possible risk factors including history of epilepsy, unsupervised—disorganized home environment, existence of physical abuse—neglect and lack of appropriate treatment program leading to violent behavior.     

Long-term results of brentuximab vedotin in relapsed and refractory Hodgkin lymphoma: multi-center real-life experience

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4–84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05–0.22) and 26% (95% CI, 0.16–0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13–0.54) and 60% (95% CI, 0.33–0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.     

Correction: Thrombotic and bleeding events,mortality, and anticoagulant use among 546,656 hospitalized patients with COVID‑19 in the United States: a retrospective cohort study

Journal of Thrombosis and Thrombolysis -