Metronomic therapy is an effective salvage treatment for heavily pre-treated relapsed/refractory multiple myeloma

Relapsed/refractory multiple myeloma represents a major challenge in multiple myeloma therapy. For patients with relapsed/refractory multiple myeloma, we developed a treatment schema of metronomically scheduled drug therapy. We identified 186 patients who had been treated with metronomic therapy between March 2004 and January 2012 with a median follow up of 24.2 months. Median age was 61 years (range 36–83). Median number of prior therapies was 14 (range 1–51). Median number of completed metronomic therapy cycles was 1 (range 1–5), while 45 of 186 (25%) received 2 or more cycles. Responses included complete remission in 11 of 186 patients (6%), very good partial remission in 12 of 186 (7%), partial remission in 65 of 179 (36%), and minimal response in 29 of 186 (16%), for an overall response rate of 63% (117 of 186). Median overall survival and progression-free survival were 11.2 and 3.6 months, respectively. Hematologic toxicity grading was problematic as 146 of 186 (78%) of patients presented with at least grade 2 thrombocytopenia within 90 days prior to starting metronomic therapy. Grade 4 leukopenia, anemia, and/or thrombocytopenia following metronomic therapy occurred in 108 of 186 (58%), 12 of 186 (6%), and 147 of 186 (79%) patients, respectively. Incidence of grade 3–4 neutropenic fever was 4 of 186 (2%). Most patients (177 of 186, 95%) were treated in an outpatient unit and secondary admissions due to regimen-related toxicity occurred in 37 of 186 (20%). Treatment-related mortality was evident in 2 of 186 (1%). In conclusion, metronomic therapy is an effective late salvage treatment in relapsed/refractory multiple myeloma, with a high overall response rate and a favorable toxicity profile.     

Flavanol monomer-induced changes to the human faecal microflora

We have investigated the bacterial-dependent metabolism of ( - )-epicatechin and (+)-catechin using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal region of the human large intestine. Incubation of ( - )-epicatechin or (+)-catechin (150 mg/l or 1000 mg/l) with faecal bacteria, led to the generation of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, 5-phenyl-gamma-valerolactone and phenylpropionic acid. However, the formation of these metabolites from (+)-catechin required its initial conversion to (+)-epicatechin. The metabolism of both flavanols occurred in the presence of favourable carbon sources, notably sucrose and the prebiotic fructo-oligosaccharides, indicating that bacterial utilisation of flavanols also occurs when preferential energy sources are available. (+)-Catechin incubation affected the growth of select microflora, resulting in a statistically significant increase in the growth of the Clostridium coccoides-Eubacterium rectale group, Bifidobacterium spp. and Escherichia coli, as well as a significant inhibitory effect on the growth of the C. histolyticum group. In contrast, the effect of ( - )-epicatechin was less profound, only significantly increasing the growth of the C. coccoides-Eubacterium rectale group. These potential prebiotic effects for both (+)-catechin and ( - )-epicatechin were most notable at the lower concentration of 150 mg/l. As both ( - )-epicatechin and (+)-catechin were converted to the same metabolites, the more dramatic change in the growth of distinct microfloral populations produced by (+)-catechin incubation may be linked to the bacterial conversion of (+)-catechin to (+)-epicatechin. Together these data suggest that the consumption of flavanol-rich foods may support gut health through their ability to exert prebiotic actions.     

Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to five years from three centers

OBJECTIVE: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the major criticism, as with all alternative treatments for BPH, was the lack of long-term data. We present the clinical outcome of patients treated by TUNA and followed for 5 years. METHODS: 188 consecutive patients with symptomatic BPH treated with TUNA were followed for five years in three different centers. All patients were treated using the TUNA II or TUNA III catheters under local anesthesia only without general or spinal anesthesia. Baseline and 5-year follow-up evaluation included urinary peak flow, International Prostate Symptom Score (IPSS) and post-void residual urine (PVR). The number of patients requiring additional medical or surgical treatment was recorded. Statistics were performed using the t-test. RESULTS: At a mean follow-up of 63 months, mean urinary peak flow rate increased from 8.6 ml/s to 12.1 ml/s (p<0.01, t-test), IPSS and PVR decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p<0.001, t-test). The percentage of patients who improved by at least 50% their peak uroflow and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively at 5 years, both p values > 0.05, t-test). Two patients died of unrelated comorbidities and 10 were lost for follow-up. Medical treatment was given to 12 patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and 10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up following the original TUNA procedure. CONCLUSIONS: TUNA is effective and provides good long-term clinical improvement at 5-year follow-up. TUNA treatment stands the test of time at 5-year follow-up with low and acceptable failure rates. More than 75% of the patients do not need additional treatment for BPH on the long run.     

Is there a need for weekend face-to-face inpatient assessments by hospital specialist palliative care services? Evaluation of an out-of-hours service

There is an increasing demand for hospital specialist palliative care services to be made more accessible outside of normal working hours. However, it has been argued that extended service provision could be misused and that specialist telephone advisory services are an adequate response to this demand. A 'routine' Saturday face-to-face visiting service was introduced into a hospital palliative care team and the service was evaluated to determine whether it was being utilised appropriately. A retrospective notes review of out-of-hours assessments was undertaken. Anonymised data relating to the nature of the interaction with the palliative care team and the outcome of the consultation were entered into an electronic database. A random sample of routine weekday interactions was also evaluated. A total of 336 Saturday and 93 weekday assessments were analysed. Most of the Saturday assessments resulted in a significant change in management (57%) or were undertaken on patients close to death (10%). There were 39/336 (12%) new referrals assessed on Saturdays. There were few differences between the nature of the Saturday and the weekday service and no evidence of 'inappropriate' referrals. We found clear evidence of the need for a specialist out-of-hours face-to-face inpatient visiting service for hospital palliative care.     

The Natural Course of Radiographic Progression in Ankylosing Spondylitis: Differences Between Genders and Appearance of Characteristic Radiographic Features

Our study set out to analyze the radiographic progression of ankylosing spondylitis (AS) patients based on gender differences. A total of 146 AS patients were retrospectively blindly analyzed in at least 2 time points within 6 years using the modified Stokes AS Spine Score. The mean follow-up time was 3.8 ± 1.7 years, and 114 patients (78%) were male. The overall progression was similar between genders. Females showed higher progression in the cervical spine, and males in the lumbar spine. More females showed new cervical syndesmophytes, and more males showed new lumbar syndesmophytes. More females showed slow radiographic progression, and more males showed fast radiographic progression, while moderate progression was similar for both genders. Dorsal syndesmophytes showed no impact in the prediction of future progression. Female AS patients showed more cervical structural lesions, but male patients overall showed more rapid progress, leading us to conclude that dorsal vertebral edges do not add in depiction of radiographic deterioration in AS patients.