METHODS: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder.
RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys.
CONCLUSION: Oral ketamine caused pathological changes in the urinary tract, similar to that described in exposure to parenteral ketamine. The changes in the urinary bladder were reversible after short-term exposure.
METHODS: This is a cross-sectional study where patients with haematological cancers attending two major hospitals were recruited. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression scale (HADS). Quality of life (QoL) of these patients was measured using the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30). An overall summary QoL score in combination with financial difficulty score and global health score were used for analysis.
RESULTS: A total of 319 patients were recruited. Thirty-three percent of patients had anxiety symptoms, 23.5% had depression symptoms. In summary the overall score of QoL is significantly lower in patients with higher scores for depression and anxiety, (p<0.05). Patients who exhibit anxiety symptoms were more frequently female, still undergoing treatment whereas patients who had higher depression scores were older and had acute leukemias or myeloproliferative neoplasms. Patients who have depression are significantly associated with a higher financial difficulty score, p<0.05.
CONCLUSION: The poor quality of life in patients who have anxiety and depression should raise awareness amongst the health professions treating them so that additional support can be provided.
SUMMARY: Background Mutation of the growth factor-independent 1B (GFI1B) fifth DNA-binding zinc-finger domain causes macrothrombocytopenia and α-granule deficiency leading to clinical bleeding. The phenotypes associated with GFI1B variants disrupting non-DNA-binding zinc-fingers remain uncharacterized. Objectives To determine the functional and phenotypic consequences of GFI1B variants disrupting non-DNA-binding zinc-finger domains. Methods The GFI1B C168F variant and a novel GFI1B c.2520 + 1_2520 + 8delGTGGGCAC splice variant were identified in four unrelated families. Phenotypic features, DNA-binding properties and transcriptional effects were determined and compared with those in individuals with a GFI1B H294 fs mutation of the fifth DNA-binding zinc-finger. Patient-specific induced pluripotent stem cell (iPSC)-derived megakaryocytes were generated to facilitate disease modeling. Results The DNA-binding GFI1B variant C168F, which is predicted to disrupt the first non-DNA-binding zinc-finger domain, is associated with macrothrombocytopenia without α-granule deficiency or bleeding symptoms. A GFI1B splice variant, c.2520 + 1_2520 + 8delGTGGGCAC, which generates a short GFI1B isoform that lacks non-DNA-binding zinc-fingers 1 and 2, is associated with increased platelet CD34 expression only, without quantitative or morphologic platelet abnormalities. GFI1B represses the CD34 promoter, and this repression is attenuated by different GFI1B zinc-finger mutations, suggesting that deregulation of CD34 expression occurs at a direct transcriptional level. Patient-specific iPSC-derived megakaryocytes phenocopy these observations. Conclusions Disruption of GFI1B non-DNA-binding zinc-finger 1 is associated with mild to moderate thrombocytopenia without α-granule deficiency or bleeding symptomatology, indicating that the site of GFI1B mutation has important phenotypic implications. Platelet CD34 expression appears to be a common feature of perturbed GFI1B function, and may have diagnostic utility.
MATERIALS AND METHODS: Eighteen facilities in 10 Asian countries participated in this prospective, interventional, single-arm study. The study included two independent regimens: hypofractionated whole-breast irradiation (WBI) for patients who had undergone breast-conserving surgery and hypofractionated PMRT for patients who had undergone total mastectomy at a dose of 43.2 Gy in 16 fractions. In the hypofractionated WBI group, patients with high-grade factors received additional 8.1 Gy boost irradiation sessions for the tumour bed in three fractions.
RESULTS: Between February 2013 and October 2019, 227 and 222 patients were enrolled in the hypofractionated WBI and hypofractionated PMRT groups, respectively. The median follow-up periods in the hypofractionated WBI and hypofractionated PMRT groups were 61 and 60 months, respectively. The 5-year locoregional control rates were 98.9% (95% confidence interval 97.4-100.0) and 96.3% (95% confidence interval 93.2-99.4) in the hypofractionated WBI and hypofractionated PMRT groups, respectively. Regarding adverse events, grade 3 acute dermatitis was observed in 2.2% and 4.9% of patients in the hypofractionated WBI and hypofractionated PMRT groups, respectively. However, no other adverse events were observed.
CONCLUSION: Although further follow-up is required, hypofractionated radiotherapy regimens for postoperative patients with breast cancer in East and Southeast Asian countries are effective and safe. In particular, the proven efficacy of hypofractionated PMRT indicates that more patients with advanced breast cancer can receive appropriate care in these countries. Hypofractionated WBI and hypofractionated PMRT are reasonable approaches that can contain cancer care costs in these countries. Long-term observation is required to validate our findings.