Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated ...when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd
3+
) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.
Cepharanthine (CEP) is a naturally occurring alkaloid extracted from the plant Stephania cepharantha Hayata. It has been widely used in Japan for more than 40 years to treat a wide variety of acute ...and chronic diseases. CEP inhibits tumor necrosis factor (TNF)-α-mediated NFκB stimulation, plasma membrane lipid peroxidation and platelet aggregation and suppresses cytokine production. It has also been shown to scavenge free radicals and to have a protective effect against some of the responses mediated by pro-inflammatory cytokines such as TNF-α, interleukin (IL)-1β and IL6. CEP has successfully been used to treat a diverse range of medical conditions, including radiation-induced leukopenia, idiopathic thrombocytopenic purpura, alopecia areata, alopecia pityrodes, venomous snakebites, xerostomia, sarcoidosis, refractory anemia and various cancer-related conditions. No safety issues have been observed with CEP, and side effects are very rarely reported.
Background
There is growing evidence that failure to rescue (FTR) is an important factor of postoperative mortality (POM) after rectal cancer surgery and surgical approach modified post-operative ...outcomes. However, the impact of laparoscopy on FTR after proctectomy for rectal cancer remains unknown. The aim of this study was to compare the rates of postoperative complications and FTR after laparoscopy
vs
open proctectomy for cancer.
Methods
All patients who underwent proctectomy for rectal cancer between 2012 and 2016 were included. FTR was defined as the 90-day POM rate among patients with major complications. Outcomes of patients undergoing open or laparoscopic rectal cancer surgery were compared after 1:1 propensity score matching by year of surgery, hospital volume, sex, age, Charlson score, neoadjuvant chemotherapy, tumor localization and type of anastomosis.
Results
Overall, 44,536 patients who underwent proctectomy were included, 7043 of whom (15.8%) developed major complications. The rates of major complications, POM and FTR were significantly higher in open compared to laparoscopic procedure (major complications: 19.2% vs 13.7%,
p
< 0.001; POM: 5.4% vs 2.3%,
p
< 0.001; FTR: 13.6% vs 8.3%,
p
< 0.001; respectively). After matching, open and laparoscopic groups were comparable. Multivariate analysis showed that age, Charlson score, sphincter-preserving procedure and surgical approach were predictive factors for FTR. Open proctectomy was found to be a risk factor for FTR (OR 1.342, IC95% 1.066; 1.689,
p
= 0.012) compared to laparoscopic procedure.
Conclusion
When complications occurred, patients operated on by open proctectomy were more likely to die.
Background: Noscapine, a non-toxic alkaloid and common constituent of cough medicine, stabilises tubulin. It inhibits the
growth of several human and murine neoplasms, with no significant toxicity. ...Its effect on prostate cancer has not been evaluated.
Materials and Methods: Noscapine was administered orally (300 mg/kg per day) for 56 days to PC3 human prostate cancer-bearing
immunodeficient mice (n=10). Immunodeficient control mice (n=10) received only diluent in an identical regimen. Results: Mean
total tumour weight was 0.42±0.23 g and 0.97±0.31 g (p<0.001) in the noscapine-treated group and the control group, respectively,
without evidence of toxicity. Metastases occurred less frequently in the treatment than the control group (30% vs. 90%; p<0.05).
Conclusion: Oral administration of noscapine limited tumour growth and lymphatic metastasis of PC3 human prostate cancer in
this mouse model, supporting its therapeutic potential as a nontoxic and easily administered treatment for metastatic cancer.
This is the first report of an early association between elevated fibrinogen and asymptomatic unicentric Castleman's disease (CD). A 49-year-old asymptomatic female who was serving as a normal ...control in an unrelated study was incidentally found to have significantly elevated levels of plasma fibrinogen. Upon further investigation with computer tomography scans and magnetic resonance imaging, the woman was found to have a mobile mass in the abdominal region which was surgically removed. Based on histological analysis, a diagnosis of CD was made. At four-month follow-up, no additional signs of CD were present and fibrinogen levels returned to the normal range. This report, therefore, signifies the importance for physicians to consider unicentric CD in the differential diagnosis when patients present with elevated levels of plasma fibrinogen. Awareness of this diagnostic possibility may lead to increased early diagnosis of CD before symptoms become apparent, and provide a marker candidate for CD activity that may assist in monitoring treatment success. J Clin Exp Hematop 54(1): 85-88, 2014
Tranilast (N-3,4-dimethoxycinnamoyl-anthranilic acid; Rizaben®) is an anti-allergy drug approved for use in Japan and South Korea, also used against asthma, autoimmune diseases, and atopic and ...fibrotic pathologies. The antitumor potential of tranilast is attracting considerable interest. This review summarizes recent evidence concerning the effect of tranilast on different tumor types and discusses the drug's possible mode of action in this area. In vivo and in vitro studies are covered, as well as evidence from clinical trials, in which tranilast was evaluated in various models of proliferative disorders. The findings presented in this report, demonstrate the excellent potential of tranilast in the management of certain types of tumor, and provide a strong rationale for the initiation of controlled clinical trials in this area.
Purpose: We report a case of a symptomatic, inflamed pterygium treated nonsurgically with topical dipyridamole and followed for 12 months. Case Report: A 35-year-old woman presented with a stage II ...to III, V3, C3, K2, P1 (using Johnston, Williams & Sheppard's classification) pterygium in her right eye. She complained of a foreign body sensation, dryness, burning, and persistent uncontrolled blinking. A raised lesion was observed on the nasal conjunctiva that was 1.5 mm in size. It extended slightly onto the nasal cornea. There was moderate vascularity of the lesion that obscured the underlying scleral vessels. Moderate conjunctival hyperemia was detected at and medial to the pterygium. The cornea, anterior chamber, and external anatomy were otherwise unremarkable. The eye was initially treated twice daily with a topical application of dipyridamole in a normal saline solution, which was later reduced to once daily. Results: There was a marked improvement in both the pterygium and the patient's symptoms. The tissue regressed from the limbal region of the cornea, had decreased in length from 1.5 to 1.0 mm, and decreased in height from approximately 1.0 to approximately 0.3 mm. Conjunctival hyperemia and vascularization resolved completely, and the underlying scleral vessels could once again be visualized. At 12 months, the pterygium was graded as stage 0 to I, V0, C2, K0, P0. Conclusions: To our knowledge, this is the first case of successful management of a pterygium and associated symptoms using topical dipyridamole. Further investigation is required to clarify the potential role of dipyridamole in the treatment of pterygia and pingueculae.
Real-world drug repurposing-the immediate "off-label" prescribing of drugs to address urgent clinical needs-is a widely overlooked opportunity. Off-label prescribing (ie, for a nonapproved ...indication) is legal in most countries and tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, health crises may mean that real-world repurposing is the only realistic source for solutions. Optimal real-world repurposing requires a track record of safety, affordability, and access for drug candidates. Although thousands of such drugs are already available, there is no central repository of off-label uses to facilitate immediate identification and selection of potentially useful interventions during public health crises. Using the current coronavirus disease (COVID-19) pandemic as an example, we provide a glimpse of the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and targeted toward the underlying pathophysiology that makes COVID-19 so deadly. This paper briefly summarizes why cimetidine or famotidine, dipyridamole, fenofibrate or bezafibrate, and sildenafil citrate are worth considering for patients with COVID-19. Clinical trials to assess efficacy are already underway for famotidine, dipyridamole, and sildenafil, and further trials of all these agents will be important in due course. These examples also reveal the unlimited opportunity to future-proof our health care systems by proactively mining, synthesizing, cataloging, and evaluating the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs.
OBJECTIVE:To identify the impact of hospital volume according to Charlson Comorbidity Index (ChCI) on postoperative mortality (POM) after rectal cancer surgery.
BACKGROUND:A volume–outcome ...relationship has been established in complex surgical procedures. However, little is known regarding the impact of hospital volume on POM according to patients’ comorbidities after rectal cancer surgery.
METHODS:All patients undergoing proctectomy for cancer from 2012 to 2016 were identified in the French nationwide database. Patient condition was assessed on the basis of the validated ChCl and was stratified into 3 groups according to the score (0–2, 3, and ≥4). Chi-square automatic interaction detector (CHAID) was used to identify the cut-off values of the annual proctectomy caseload affecting the 90-day POM. The 90-day POM was analyzed according to hospital volume (low<10, intermediate10–40, and high≥41 cases/yr) and ChCI.
RESULTS:Among 45,569 rectal cancer resections, the 90-day POM was 3.5% and correlated to ChCI (ChCI 0–21.9%, ChCI 34.9%, ChCI ≥45.8%; P < 0.001). There was a linear decrease in POM with increasing hospital volume (low5.6%, intermediate3.5%, high1.9%; P < 0.001). For low-risk patients (ChCl 0–2), 90-day POM was significantly higher in low and intermediate hospital volume compared with high hospital volume centers (3.2% and 1.8% vs 1.1%; P < 0.001). A significant decrease in postoperative hemorrhage complication rates was observed with increasing center volume (low13.3%, intermediate11.9%, and high9.4%; P < 0.001). After multivariable analysis, proctectomy in low odds ratio (OR) 2.1, 95% confidence interval (CI) 1.71–2.58, P < 0.001 and intermediate (OR 1.45, 95% CI 1.2–1.75, P < 0.001) hospital volume centers were independently associated with higher risk of mortality.
CONCLUSION:The POM after proctectomy for rectal cancer is strongly associated with hospital volume independent of patients’ comorbidities. To improve postoperative outcomes, rectal surgery should be centralized.
Abstract Crohn's disease (CD) is a debilitating condition which still requires improvement in its management. There is a need for alternatives to anti-tumour necrosis factor drugs which are costly ...and beneficial in less than 50% of patients. Intravenous immunoglobulin (IVIG) has been used in the management of aminosalicylate- and steroid-resistant CD for more than 20 years, although the published literature available is limited. A literature search identified 17 relevant publications since 1969, including five case reports of single patients, two abstracts, three conference papers, one review paper and six book or journal articles. No randomised controlled trials of IVIG in CD have been published. A review of the evidence identified indicates that IVIG can induce a rapid and significant improvement in aminosalicylate- and steroid-resistant CD, often within days of the initial administration. Data from longer-term studies show that maintenance of remission over the medium term is also possible. These encouraging findings provide a rationale for the initiation of larger randomised controlled trials of IVIG in CD with the aim of providing further treatment options for this difficult-to-manage condition.
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