Ketamine uropathy: Clinical experience in a high prevalence center.

OBJECTIVES: Ketamine uropathy causes inflammatory changes to the urothelium, manifesting as significant lower urinary tract symptoms, small bladder capacity, and pelvic pain. Upper tract involvement and hydronephrosis can occur. Data from UK centers are limited, and no formal treatment guidelines exist. PATIENTS AND METHODS: All patients with ketamine uropathy presenting to our unit over an 11-year period were identified through operative and clinic lists, emergency presentations, and a prospectively collected local database. Demographic data, biochemical findings, imaging techniques, and both medical and surgical management were recorded. RESULTS: A total of 81 patients with ketamine uropathy were identified from 2011 to 2022; however, a large proportion presented from 2018 onwards. The average age at presentation was 26 years (interquartile range [IQR]: 27-34), 72.8% were male, and average follow-up time was 34 months (IQR: 8-46). Therapeutic interventions included anticholinergic medication, cystodistension, and intravesical sodium hyaluronate. Hydronephrosis was present in 20 (24.7%) patients and nephrostomy insertion was required in six. One patient underwent bladder augmentation surgery. Serum gamma-glutamyl transferase and length of follow-up were significantly higher in patients with hydronephrosis. Adherence to follow-up was poor. CONCLUSIONS: We present a large cohort of patients with ketamine uropathy from a small town in the UK which is unusual. The incidence appears to be rising, in-keeping with increasing recreational ketamine use and should be of concern to urologists. Abstinence is a key aspect of management, and a multi-disciplinary approach works best particularly as many patients are lost to follow-up. The development of formal guidance would be helpful.

Systematic review and meta-analysis of ketamine-associated uropathy.

INTRODUCTION: This systematic review and meta-analysis focused on the literature regarding ketamine-associated uropathy to summarise its clinical manifestations, the results of urological assessments, and current management. METHODS: A literature search was conducted using keywords and MeSH terms related to ketamine abuse, urinary tracts, and urological examinations. Databases including Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched up to 26 June 2020. RESULTS: In total, 1365 articles were retrieved; 45 articles (4921 patients) were included in the analysis of patient demographics, clinical manifestations, examination results, and treatments. Frequency was the most common manifestation (pooled prevalence 77.1%, 95% confidence interval [CI]=56.9%-92.2%), followed by urgency (69.9%, 95% CI=48.8%-87.3%) and suprapubic pain (60.4%, 95% CI=35.3%-82.9%). Upper urinary tract involvement was less common; the pooled prevalence of hydronephrosis was 30.2% (95% CI=22.0%-39.2%). Further workup revealed a pooled functional bladder capacity of 95.23 mL (95% CI=63.57-126.88 mL), pooled voided volume of 113.31 mL (95% CI=59.44- 167.19 mL), and pooled maximum urine flow rate of 8.69 mL/s (95% CI=5.54-11.83 mL/s). Cystoscopic examinations and bladder biopsy revealed frequent urothelial denudation, inflammatory changes, and inflammatory cell infiltration. Treatments included oral medications for symptomatic relief, intravesical therapy, and surgery (eg, hydrodistension and bladder reconstruction), but ketamine abstinence was necessary for improvement. CONCLUSION: Ketamine-associated uropathy frequently involves frequency, urgency, and suprapubic pain; upper urinary tract involvement is less common. Affected patients showed reductions in bladder capacity and urine flow rate. Endoscopic and histological analyses often revealed cystitis. Despite variations in treatment, ketamine abstinence is important for all patients with ketamine-associated uropathy.

Evolving Role of Silodosin for the Treatment of Urological Disorders - A Narrative Review.

Use of α-androgenic receptor blockers remains a mainstay therapeutic approach for the treatment of urological diseases. Silodosin is recommended over other α-blockers for the treatment of lower urinary tract symptoms (LUTS) and benign prostate hyperplasia (BPH), due to its high α1A uroselectivity. Current research data suggest that silodosin is efficacious in the management of various urological diseases. Thus, we herein review the current evidence of silodosin related to its efficacy and tolerability and appraise the available literature that might ultimately aid in management of various urological conditions at routine clinical practice. Literature reveals that silodosin is beneficial in improving nocturia events related to LUTS/BPH. Silodosin exerts effect on relaxing muscles involved in detrusor obstruction, therefore prolonging the need for patients undergoing invasive surgery. Silodosin treatment, either as a monotherapy or combination, significantly improves International Prostate Symptom Score (IPSS) including both storage and voiding symptoms in patients with BPH/LUTS. Patients on other treatment therapies such as phosphodiesterase 5 inhibitors or other α-blockers are well managed with this drug. Steadily, silodosin has proved beneficial in the treatment of other urological disorders such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), overactive bladder/acute urinary retention (AUR), premature ejaculation (PE), and prostate cancer post brachytherapy-induced progression. In patients with distal ureteral stones, silodosin treatment is beneficial in decreasing stone expulsion time without affecting stone expulsion rate or analgesic need. Moreover, there were significant improvements in intravaginal ejaculation latency time, quality of life scores, and decrease in PE profile among patients with PE. Silodosin has also demonstrated promising results in increasing the likelihood of successful trial without catheter in patients with AUR and those taking antihypertensive drugs. Reports from Phase II studies have shown promising role of silodosin in the treatment of CP/CPPS as well as facilitating ureteral stone passage. From the robust data in this review, further silodosin treatment strategies in the management of different urological conditions need to be focused on.

Bisphenol-A analogs induce lower urinary tract dysfunction in male mice.

Bisphenol-A (BPA), an estrogenic endocrine disrupting chemical, significantly impacts numerous diseases and abnormalities in mammals. Estrogens are known to play an important role in the biology of the prostate; however, little is known about the role of bisphenols in the etiology of prostate pathologies, including benign prostate hyperplasia (BPH) and associated lower urinary tract dysfunction (LUTD). Bisphenol-F (BPF) and bisphenol-S (BPS) are analogs often used as substitutes for BPA; they are both reported to have in vitro and in vivo estrogenic effects similar to or more potent than BPA. The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p < 0.005) and prostate (p < 0.0001) mass, and there was an increased number of prostatic ducts in the prostatic urethra (p < 0.05) and decreased size of the urethra lumen (p < 0.05) compared to negative controls. After two months of bisphenol exposure, mice displayed notable differences in cystometric tracings compared to controls, consistent with LUTD. Treatment of male mice with all bisphenols also induced voiding dysfunction manifested by detrusor instability and histologic changes in the prostatic urethra of male rodents, consistent with LUTD. Our results implicate BPA and its replacements in the development and progression LUTD in mice and provide insights into the development and progression of BPH/LUTS in men.

Dysuria due to benign prostatic hyperplasia of the median lobe with ketamine-associated uropathy in a young male.

BACKGROUND: Benign prostatic hyperplasia (BPH) rarely occurs in children or young males. In this case report, a 29-year-old male patient diagnosed with BPH coexisting with ketamine-associated uropathy was reported to investigate the possible relationship between BPH and ketamine-associated uropathy as well as therapeutic strategies. CASE PRESENTATION: A 29-year-old male patient with a 3-year history of ketamine inhalation, complaining of dysuria with frequency and urgency, was admitted. Hydronephrosis, hydroureters, uneven bladder wall thickening and a tumour located in the outlet of the bladder were detected with computed tomography (CT). The patient agreed to cystoscopy under general anaesthesia. A spherical tumour with a diameter of approximately 2 cm was found to originate from the median lobe of the prostate and follicular lesions were diffusely distributed on the right bladder wall. The tumour and follicular lesions in the bladder were resected successfully, and pathology demonstrated BPH and chronic inflammation of the mucous membranes separately. The patient quit ketamine completely during the one-year follow-up. Dysuria was relieved completely and no tumour or follicular neoplasm recurrence was found. CONTRIBUTION: Inflammation in the urothelium, as a direct or indirect consequence of ketamine, may contribute to the development of BPH. Both surgical interventions to remove obstruction and ketamine cessation are necessary approaches.

Management of complications of ketamine abuse: 10 years' experience in Hong Kong.

Ketamine is an N-methyl-d-aspartate receptor antagonist, a dissociative anaesthetic agent and a treatment option for major depression, treatment-resistant depression, and bipolar disorder. Its strong psychostimulant properties and easy absorption make it a favourable candidate for substance abuse. Ketamine entered Hong Kong as a club drug in 2000 and the first local report of ketamine-associated urinary cystitis was published in 2007. Ketamine-associated lower-urinary tract symptoms include frequency, urgency, nocturia, dysuria, urge incontinence, and occasionally painful haematuria. The exact prevalence of ketamine-associated urinary cystitis is difficult to assess because the abuse itself and many of the associated symptoms often go unnoticed until a very late stage. Additionally, upper-urinary tract pathology, such as hydronephrosis, and other complications involving neuropsychiatric, hepatobiliary, and gastrointestinal systems have also been reported. Gradual improvement can be expected after abstinence from ketamine use. Sustained abstinence is the key to recovery, as relapse usually leads to recurrence of symptoms. Both medical and surgical management can be used. The Youth Urological Treatment Centre at the Prince of Wales Hospital, Hong Kong, has developed a four-tier treatment protocol with initial non-invasive investigation and management for these patients. Multidisciplinary care is essential given the complex and diverse psychological factors and sociological background that underlie ketamine abuse and abstinence status.

Histopathological characteristics of ketamine-associated uropathy and their clinical association.

AIM: To investigate the histopathological findings in ketamine-associated uropathy (KU) and their clinical association. METHODS: Thirty-eight KU patients had received history investigation and video urodynamic study. Twelve of them were clinically mild KU who were admitted for cystoscopic hydrodistention. The other 26 patients were severe KU who were admitted for enterocystoplasty with or without ureter reimplantation. Bladder and ureter specimens were harvested during operation, and a single pathologist reviewed all specimens under hematoxylin and eosin stain. The severity of histopathological findings was graded with a 4-point scale (0: none, 1: mild, 2: moderate, and 3: severe) RESULTS: Inflammatory cells infiltrations and nerve hyperplasia were found in the mucosa, muscle, and subserosal layers of KU bladders and ureter. In the mild KU bladder mucosa, the predominant component of the infiltrating inflammatory cells was lymphocytes. In contrast, neutrophils, eosinophils, lymphocytes, and plasma cells infiltration were noted in the mucosa of almost all severe KU bladders. Clinical severe KU was significantly correlated with severe to moderate lymphocytes, plasma cells, neutrophils, eosinophils infiltration, and nerve hyperplasia in bladder mucosa. KU patients with moderate or severe neutrophils or lymphocytes infiltration in bladder mucosa had significantly more severe bladder pain and smaller bladder capacity. CONCLUSION: The histological findings of KU showed whole-layer inflammation and nerve hyperplasia in bladder mucosa. The severity of inflammatory cell infiltration in the bladder mucosa is associated with clinical symptoms. A histopathological examination might be a useful tool to discriminate the KU severity in patients.

Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine.

OBJECTIVE: Evaluations of upper gastrointestinal toxicity from ketamine abuse are uncommon. This study investigated the clinical pattern of upper gastrointestinal symptoms in patients inhaling ketamine. METHODS: In a cross-sectional study of 611 consecutive patients who were seeking treatment for ketamine uropathy in a tertiary hospital setting between August 2008 and June 2016, their clinical pattern of upper gastrointestinal symptoms was evaluated and compared with a control population of 804 non-users. RESULTS: A total of 168 (27.5%) patients abusing ketamine (mean age 26.3 years, 58.9% female) reported the presence of upper gastrointestinal symptoms. These symptoms were significantly more prevalent in patients inhaling ketamine than in those who were not (27.5% vs 5.2%, P < 0.001). Their mean duration of ketamine abuse before symptom presentation was 5.0 ± 3.1 years. The presenting symptoms included epigastric pain (n = 155, 25.4%), recurrent vomiting (n = 48, 7.9%), anemia (n = 36, 5.9%) and gastrointestinal bleeding (n = 20, 3.3%). Uropathy symptoms were preceded by upper gastrointestinal symptoms for 4.4 ± 3.0 years in 141 (83.9%) patients. Logistic regression showed that elder age (odds ratio [OR] 1.06, P = 0.04), active abuser status (OR 1.60, P = 0.04) and longer duration of ketamine abuse (OR 1.00, P = 0.04) were independent factors associated with upper gastrointestinal toxicity. CONCLUSIONS: Although epigastric symptoms are unusual in the young population, upper gastrointestinal toxicity was highly prevalent in those inhaling ketamine. Enquiries about ketamine abuse are recommended when assessing young patients with epigastric symptoms.

E-cigarettes and Urologic Health: A Collaborative Review of Toxicology, Epidemiology, and Potential Risks.

CONTEXT: Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. OBJECTIVE: To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks. EVIDENCE ACQUISITION: A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out. EVIDENCE SYNTHESIS: We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks. CONCLUSIONS: ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events. PATIENT SUMMARY: While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear.

Clinical Significance of Hematuria in Atrial Fibrillation With Oral Anticoagulation Therapy.

BACKGROUND: Hematuria is a common and important complication in atrial fibrillation (AF) patients on oral anticoagulation therapy (OAT). This study evaluated the clinical significance of hematuria and its relationship with genitourinary disease in AF patients receiving OAT.Methods and Results:Among 20,456 consecutive AF patients who visited a tertiary hospital from January 2005 to April 2015, 5,833 had hematuria. Of these 5,833 patients, 3,798 were on OAT (OAT(+) group) and 2,035 were not (OAT(-) group). A total of 1,785 patients from each group were then matched on propensity score analysis. The prevalence of cancer and other diseases in the genitourinary tract was evaluated. While there was no difference in the prevalence of genitourinary stones or urinary tract infection, genitourinary cancer was significantly more common in the OAT(+) group than in the OAT(-) group (1.6% vs. 0.7%, P=0.011). Bladder cancer was the most common genitourinary malignancy, and it was significantly more common in the OAT(+) group (1.2% vs. 0.5%, P=0.019). Subjects on warfarin were more likely to have bladder cancers of lower pathologic grade (63.6% vs. 33.3%, P=0.124). CONCLUSIONS: OAT was associated with a higher prevalence and early detection of genitourinary cancer in AF patients with hematuria. Meticulous evaluation of the cause of hematuria is necessary in AF patients with hematuria receiving OAT.

Adverse urinary effects of allopurinol in dogs with leishmaniasis.

OBJECTIVE: The objective of this study was to describe the adverse effects of allopurinol on the urinary system during treatment of canine leishmaniasis. METHODS: Retrospective case series of 42 dogs that developed xanthinuria while receiving allopurinol treatment for leishmaniasis. RESULTS: Of 320 dogs diagnosed with leishmaniasis, 42 (13%) developed adverse urinary effects. Thirteen (of 42) dogs (31%) developed xanthinuria, renal mineralisation and urolithiasis; 11 (26·2%) showed xanthinuria with renal mineralisation; 9 (21·4%) had xanthinuria with urolithiasis and 9 (21·4%) developed xanthinuria alone. Urinary clinical signs developed in 19 dogs (45·2%). CLINICAL SIGNIFICANCE: This study demonstrates that urolithiasis and renal mineralisation can occur in dogs receiving allopurinol therapy. Dogs receiving therapy should be monitored for the development of urinary adverse effects from the beginning of treatment.

[Influence of drugs on urological diseases]. / Einfluss von Medikamenten auf urologische Krankheiten.

A number of drugs prescribed for the treatment of various diseases can induce urological symptoms as side effects. Antihypertensive drugs (particularly alpha blockers) can result in stress incontinence, whereas selective serotonin reuptake inhibitors (SSRI) can cause urge incontinence and estrogen promotes both forms. A wide range of drugs with anticholinergic activity, among them neuroleptics, tricyclic antidepressants and certain drugs used in airway disorders are associated with urinary retention. Only very few drugs bear a relevant risk for urolithiasis, i. e. the diuretic triamterene and protease inhibitors, such as indinavir; however, the widely used combination of calcium and vitamin D supplementation for prevention of osteoporosis may be an underdiagnosed cause of renal calculi. Drug-induced sexual dysfunction is a frequent side effect of antihypertensive treatment, particularly with beta adrenoceptor blockers and diuretics. The SSRI and some neuroleptics can also impair sexual function.

Role of Bladder Neck and Urethral Sphincter Dysfunction in Men with Persistent Bothersome Lower Urinary Tract Symptoms after α-1 Blocker Treatment.

OBJECTIVE: To analyze the video-urodynamic results of voiding dysfunction in men of all ages with bothersome lower urinary tract symptoms (LUTS) after α-1 adrenoceptor blocker therapy. METHODS: A total of 930 consecutive men over 45 years of age with LUTS who were failure treated with α-1 blocker therapy for at least one month were retrospectively studied. Patients underwent video-urodynamic studies to evaluate the cause of lower urinary tract dysfunction (LUTD). Clinical symptoms, prostatic measurements, and video-urodynamic findings were compared among different LUTD groups. RESULTS: After video-urodynamic studies, 653 (70.2%) men were diagnosed with voiding dysfunction and 277 (29.8%) were with bladder dysfunction. Among patients with voiding dysfunction, bladder neck dysfunction (BND) occurred in 242 (37.1%), benign prostatic obstruction (BPO) in 298 (45.6%), and poor relaxation of the external sphincter (PRES) in 113 (17.3%). The symptom score did not differ significantly among the three subgroups. The mean age, total prostate volume (TPV), transition zone index, and prostate-specific antigen were also significantly higher in BPO patients compared with the other two subgroups, but no difference was noted between BND and PRES patients. BPO patients had significantly higher voiding pressure, higher Abrams-Griffiths number, lower Qmax, and a higher rate of detrusor overactivity than did patients in the other two subgroups. CONCLUSION: Bladder neck dysfunction and PRES play important roles in male LUTS. In men younger than 70 years with small TPV and persistent LUTS after α-1 blocker therapy, video-urodynamic studies should be performed to make an accurate diagnosis before invasive surgery is planned.

Imaging of chemotherapy-related iatrogenic abdominal and pelvic conditions.

Oncologic therapy is constantly evolving to improve patient outcomes, especially with regard to chemotherapy. The use of combination therapies and development and implementation of molecular targeted therapy lead to iatrogenic conditions that the radiologist must be aware of in interpreting studies of and caring for the oncologic patient. Knowledge of the chemotherapeutic agents and the imaging appearances of associated toxicities can impact patient management and decrease patient morbidity and mortality.

Ketamine: an update on its abuse.

Ketamine is a dissociative anesthetic and substance of abuse. Numerous effects can result from the abuse of ketamine. Death from acute direct toxicity is rare. Ketamine can alter numerous functions in the brain including color perception, memory, attention, cognition, reaction time, and sense of time and can produce psychological addiction. Chronic ketamine abuse can produce toxicity to the gastrointestinal and urinary tract. Gastrointestinal changes include epigastric pain, hepatic dysfunction, and impaired gallbladder activity. The most common urological condition from ketamine is cystitis but renal failure has been reported.

One-stop clinic for ketamine-associated uropathy: report on service delivery model, patients' characteristics and non-invasive investigations at baseline by a cross-sectional study in a prospective cohort of 318 teenagers and young adults.

OBJECTIVE: To describe a service delivery model and report the baseline characteristics of patients investigated by a non-invasive approach for ketamine-associated uropathy. PATIENTS AND METHODS: This was a cross-sectional study in a prospective cohort of patients who attended their first visit and underwent non-invasive investigations at a dedicated centre to treat ketamine-associated uropathy in Hong Kong from December 2011 to July 2013. Data on demographics, illicit ketamine use, symptoms scores and voiding function parameters at baseline were prospectively collected. Differences between active abusers and ex-abusers, and risk factors for the most symptomatic group were investigated by univariate and multivariate analysis. RESULTS: In all, 318 patients completed the non-invasive assessment at their first visit and were eligible for inclusion. In all, 174 were female and the mean (sd) age of the entire cohort was 24.4 (3.1) years. Patients had used ketamine for a mean (sd) period of 81 (36) months. The mean (sd) ketamine use per week was 18.5 (15.8) g. In all, 214 patients were active abusers while 104 were ex-abusers but had persistent lower urinary tract symptoms. The mean (sd) voided volume, bladder capacity, and bladder emptying efficiency were 111.5 (110) mL, 152.5 (126) mL and 73.3 (26.9)%, respectively. The ex-abusers had a lower symptom score (19.3 vs 24.1; P < 0.001), a larger voided volume (126 vs 85 mL; P < 0.001), and a larger bladder capacity (204.8 vs 126.7 mL; P < 0.001) compared with active abusers. Multivariate analysis found female gender was associated with a higher symptom score (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.35-4.23; P = 0.003) and a smaller voided volume (OR 1.9; 95% CI 1.1-3.3; P = 0.02). Ketamine taken (g/week) was another risk factor for a higher symptom score (OR 1.03; 95% CI 1.01-1.05; P = 0.002). Status of ex-abuser was the only protective factor associated with fewer symptoms, larger voided volume and bladder capacity. CONCLUSIONS: An effective service model for recruiting patients with ketamine-associated uropathy is possible. With such a service model as a platform, further prospective studies are warranted to investigate the appropriate choice of treatment for this new clinical entity.

Urological complications of illicit drug use.

Illicit drug use is prevalent worldwide; over 24 million people are estimated to have used recreational drugs during the past month in the UK and USA alone. Illicit drug use can result in a wide spectrum of potential medical complications that include many urological manifestations. To ensure optimal care and treatment, urologists need to be cognizant of these complications in their patients, particularly among youths. Ketamine uropathy is thought to affect over one-quarter of ketamine users and can lead to severe lower urinary tract symptoms, as well as upper tract obstruction. Cannabis use has been associated with an increased risk of bladder cancer, prostate cancer and nonseminomatous germ cell tumours in case-control studies. Fournier's gangrene has been reported following injection of heroin and cocaine into the penis. Excessive use of cough medicines can lead to the development of radiolucent stones composed of ephedrine, pseudoephedrine and guaifenesin. As the current evidence is mostly limited to case reports and case series, future epidemiological studies are needed to fully address this issue.

Comparison of the safety of seven iodinated contrast media.

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.

Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes.

The multi-kinase inhibitor rigosertib (ON 01910.Na) induces mitotic arrest and apoptosis in myeloblasts, while sparing normal cells. The purpose of this study was to determine the pharmacokinetic profile, maximum-tolerated dose (MTD), safety, and clinical activity of an oral formulation of rigosertib in patients with myelodysplastic syndromes (MDS). For pharmacokinetic studies, patients received rigosertib in single escalating weekly doses. To determine the MTD, patient cohorts received escalating doses of rigosertib twice daily for 14 d of a 21-d cycle. Overall, 37 patients were treated. Rigosertib exposure increased with escalating oral doses. Mean absolute oral bioavailability ranged from 13·9% (fed) to 34·8% (fasting) in 12 patients treated at the 560 mg b.i.d. dose level. Dose-limiting toxicity (grade 3 dysuria and shortness of breath) occurred at the 700 mg b.i.d. dose. Five patients experienced grade 3 non-haematological toxicity, including symptoms of urothelial inflammation, hypotension and syncope, fatigue and abdominal pain. Encouraging signs of clinical activity included two bone marrow complete remissions in refractory anaemia with excess blasts type 1 patients previously treated with azacitidine. In addition, four patients each achieved transfusion independence and haematological improvements. In conclusion, oral rigosertib is bioavailable and well tolerated, and has clinical activity in patients with MDS.

Postoperative considerations of neuraxial anesthesia.

Spinal and epidural anesthesia and analgesia, and the combination of the two techniques, have been excellent choices for the management of certain surgical procedures and continue to grow in popularity. The demand for increased patient mobility and quicker discharge for both inpatients and outpatients lends itself to the benefits of regional anesthesia. A neuraxial block is indicated for any surgical procedure in which the appropriate sensory level can be accomplished without any adverse outcome. This article outlines the indications and contraindications for these techniques.