Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.

Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant. Twelve of 25 patients (48%) improved their depth of response after a median (range) of 4·3 (1·9-9·7) months of panobinostat. In responders, T-lymphocyte histone acetylation increased after both three cycles (P < 0·05) and six cycles (P < 0·01) of panobinostat when compared to baseline, with no differences in non-responders. The reduction in the proportion of CD127+ CD8+ T cells and CD4:CD8 ratio was significantly greater, after three and six cycles of panobinostat compared to pre-transplant, in non-responders when compared to responders. Whole marrow RNA-seq revealed widespread transcriptional changes only in responders with baseline differences in genes involved in ribosome biogenesis, oxidative phosphorylation and metabolic pathways. This study confirmed the efficacy of panobinostat as a single agent in multiple myeloma and established acetylation of lymphocyte histones, modulation of immune subsets and transcriptional changes as pharmacodynamic biomarkers of clinical benefit.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Healthcare resource utilisation and sickness absence in newly diagnosed multiple myeloma patients who did not undergo autologous stem cell transplantation: Trends in Sweden with the changing treatment landscape.

OBJECTIVES: The introduction of novel drugs has significantly improved outcomes for multiple myeloma (MM) patients. This study describes survival, healthcare resource utilisation and sickness absence in association with the changing MM treatment landscape over time, focussing on patients who did not undergo autologous stem cell transplantation (ASCT). METHODS: Population-based, retrospective registry study in Sweden, where 7012 non-ASCT patients diagnosed between 2001 and 2015 were stratified into diagnosis periods 2001-2005 (n = 2053), 2006-2010 (n = 2372) and 2011-2015 (n = 2587). RESULTS: Median survival increased from 2.5 to 3.4 years from 2001-2005 to 2011-2015. During the first 3 years of follow-up, patients diagnosed during 2011-2015 spent 29% and 12% less time in health care (55 days; inpatient admissions and outpatient visits) than patients diagnosed during 2001-2005 (78 days) and 2006-2010 (63 days), respectively. This was associated with less inpatient and more outpatient healthcare usage. Average 3-year sickness absence (362 days) was 31% and 12% less than for patients diagnosed during 2001-2005 (522 days) and 2006-2010 (410 days), respectively. CONCLUSIONS: These findings of improved survival, reduced healthcare needs and greater productivity in non-ASCT MM patients with access to improved treatment practices and novel drugs provide important real-world cost-benefit insights for the continued development and introduction of treatments for MM.

Does Choice of Reconstruction Type Affect Survival in Patients With Metastatic Breast Cancer?

BACKGROUND: To compare the breast cancer-specific survival (BCSS) and overall survival (OS) between patients who underwent implant or tissue reconstruction after mastectomy with distant metastatic breast cancer (MBC). MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, we enrolled 371 female MBC cases diagnosed during the years 2004-2014. Patients were subdivided into implant (176) and tissue groups (195) for survival comparison between the two groups. The end points were BCSS and OS. Comparisons of the distribution of clinicopathologic characteristics were evaluated by chi-square test and Fisher exact test. Survival outcomes were compared by Kaplan-Meier model and multivariate Cox regression model for known clinicopathologic variables in both the entire population and in the reconstruction cohorts. RESULTS: In the entire cohort, patients with implant exhibited distinctly better BCSS (log rank, P = 0.002) and OS (log rank, P = 0.001) than patients with tissue reconstruction. Multivariate Cox regression model revealed that patients, who received prosthetic implants, were married, and progesterone receptor-positive group showed better survival rates in BCSS and OS. In addition, after stratification of the implant group and tissue groups according to clinicopathologic variables, the survival rate of patients in the implant group was higher than that in the tissue reconstruction group under the influence of factors, such as married, estrogen receptor-negative, nonradiotherapy, and chemotherapy. CONCLUSIONS: Our study provides further survival evidence supporting the practice of mastectomy with prosthetic implant reconstruction in patients with MBC under certain conditions.

A comparative analysis of the efficacy of anterior cruciate ligament reconstruction with autologous ligament grafting at different time points.

BACKGROUND: This study was performed to compare the clinical efficacies of anterior cruciate ligament (ACL) reconstruction with autologous ligament grafting at different time points. METHODS: Eighty-five patients with ACL were categorized into two groups: Group A (GA, n = 45), who underwent early-stage (≤3 weeks) surgery, and Group B (GB, n = 40), who underwent advanced-stage (>3 weeks) surgery. Perioperative conditions, knee joint functions, activity and stability before and at 6 months postoperatively, changes in quality of life (QOL), good and excellent rates of knee joint functions, and incidence of complications were compared between the two groups. RESULTS: In both groups, there was an increase in the International Knee Documentation Committee (IKDC) score, Lysholm score, and QOL and a decrease in the knee joint angle flexion limitation, angle of spread limitation, positive rates in the anterior drawer test (ADT), and Lachman test score (P < .05) after surgery. At 6 months postoperatively, the IKDC score, Lysholm score, and QOL were higher in GA than in GB (P < .05). The good and excellent rates of knee joint functions were higher in GA than in GB (93.33% vs. 77.50%) (P < .05). CONCLUSION: Anterior cruciate ligament reconstruction with autologous ligament grafting can achieve good effects whether performed in the early or advanced stage; however, the improvements in patients' knee joint functions and QOL are better in the early stage. Therefore, early ACL reconstruction with autologous ligament grafting is suggested.

Quadriceps tendon vs. patellar tendon autograft for ACL reconstruction using a hardware-free press-fit fixation technique: comparable stability, function and return-to-sport level but less donor site morbidity in athletes after 10 years.

INTRODUCTION: The use of quadriceps tendon-patellar bone (QTB) autograft for anterior cruciate ligament (ACL) reconstruction is gaining momentum. Yet, long-term results that compare this procedure with established methods are lacking. The aim of this study was to report and compare long-term results of ACL reconstruction using QTB autografts versus bone-patellar tendon-bone (BPTB) autografts, both anchored using a hardware-free press-fit fixation technique. MATERIALS AND METHODS: 60 athletes (Tegner score ≥6) with primary ACL rupture were prospectively randomized into two groups. 56 patients were evaluated after a mean duration of 12.2 ± 1.9 months (range 10-14) and 43 patients after 10.3 ± 0.2 years (range 10-11). RESULTS: On final follow-up, 90% of patients scored very good and good results in the functional Lysholm score (mean 99 ± 7.1, range 74-100 points). Normal or almost normal IKDC score was reported by 84% of the patients (mean 97 ± 9.5, range 60-100 points). The activity level decreased in the Tegner score from median of 7 before injury to 6 after 10 years. The KT-1000 arthrometer showed a difference in the anterior translation of less than 3 mm (mean 1.0 ± 1.2, range - 1 to 5 mm) in 91% of the patients. Significant degeneration was radiologically detected in one patient per group. No tunnel widening was seen in any patient. Up to 97% of all patients were satisfied with the operative procedure. No significant differences were found in the mentioned parameters between the two groups and also in comparison with the 1-year results. The only significant difference was in the donor site morbidity. Significantly more patients in the BPTB group had complaints during kneeling both at 1 (p < 0.001) and 10 years (p = 0.019). Squatting was also subjectively more problematic in the BPTB group than in the QTB group both after 1 (p = 0.003) and 10 years (p = 0.046). CONCLUSIONS: This study shows equally good functional, clinical and radiological long-term results for both hardware-free methods of ACL reconstruction. These results clinically confirm the safety of press-fit anchoring after 10 years. The failure rate in this study was very low, with only one re-rupture in 10 years. The increased donor site morbidity when using the BPTB autograft compared to the QTB autograft supports already reported data. It was also seen in this study for the implant-free press-fit techniques. STUDY DESIGN: Prospective and randomized, level of evidence 2.

Bilateral posterior fracture dislocation of the shoulders : review of case reports and treatment.

Bilateral Posterior Fracture Dislocation (BPFD) of the shoulder is an uncommon but not rare presentation. We describe etiology, diagnostics, treatments and outcome and give a historic review and with a current approach of this pathology. We reviewed 55 cases (110 shoulders), mostly men (49/55), with a mean age of 49.2 years, mean follow up 21.9 months, mean delay until diagnose of 12.7 days (0-112 days), with a seizure as the cause in 80.0% . Other causes are electrocution, trauma or other. If the mechanism is not clear an epileptic insult should be considered the cause until proven otherwise. Closed reduction or mini open reduction is common in the more dated literature, but gives a overall good outcome. Arthroplasty is the prefered method in the more recent literature. Autografts from the shoulder treated with arthroplasty can be used to reconstruct the articular surface of the contralateral shoulder. High index of suspicion is important and a CT is most important diagnostic tool.

Disparities in Access to Autologous Breast Reconstruction.

Background and objectives: This study aimed to determine if age, race, region, insurance, and comorbidities affect the type of breast reconstruction that patients receive. Materials and methods: This analysis used the Florida Inpatient Discharge Dataset from 1 January 2013 to 30 September 2017, which contains deidentified patient-level administrative data from all acute care hospitals in the state of Florida. We included female patients, diagnosed with breast cancer, who underwent mastectomy and a subsequent breast reconstruction. We performed an χ2 test and logistic regression in this analysis. Results: On the multivariable analysis, we found that age, race, patient region, insurance payer, and Elixhauser score were all variables that significantly affected the type of reconstruction that patients received. Our results show that African American (odds ratio (OR): 0.68, 95%CI: 0.58-0.78, p < 0.001) and Hispanic or Latino (OR: 0.82, 95%CI: 0.72-0.93, p = 0.003) patients have significantly lower odds of receiving implant reconstruction when compared to white patients. Patients with Medicare (OR: 1.57, 95%CI: 1.33-1.86, p < 0.001) had significantly higher odds and patients with Medicaid (OR: 0.61, 95%CI: 0.51-0.74, p < 0.001) had significantly lower odds of getting autologous reconstruction when compared to patients with commercial insurance. Conclusions: Our study demonstrated that, in the state of Florida over the past years, variables, such as race, region, insurance, and comorbidities, play an important role in choosing the reconstruction modality. More efforts are needed to eradicate disparities and give all patients, despite their race, insurance payer, or region, equal access to health care.

Evaluation of Parathyroid Glands with Indocyanine Green Fluorescence Angiography After Thyroidectomy.

BACKGROUND: Indocyanine green fluorescence angiography (ICGA) is a new adjunct that has been used in surgical procedures to assess blood flow. This study evaluated the utility of ICGA compared to visual inspection to predict parathyroid function, guide autotransplantation and potentially decrease permanent hypoparathyroidism. METHODS: This was a retrospective study of patients who underwent total or near-total thyroidectomy (T-NT) between January 2015 and March 2018. Patients with preoperative hyperparathyroidism and those undergoing reoperation were excluded. Patients who had ICGA were compared to T-NT patients without ICGA. Data were analyzed to assess the frequency of autotransplantation and incidence of hypoparathyroidism between groups. RESULTS: In total, 210 patients underwent T-NT: 86 with ICGA and 124 without. Autotransplantation was more common in the ICGA group at 36% compared to 12% in the control (p = 0.0001). There was no correlation with at least one normal parathyroid gland on ICGA and postoperative PTH levels (p = 0.75). There was a difference in having normal postoperative PTH when there were at least two normal parathyroid glands (n = 50) compared to patients with less than two normal ICGA glands (n = 36, p = 0.044). Visual assessment and ICGA assessment of vascularity were in agreement, 245/281 (87%). There were 19 glands (6.8%) that would have undergone autotransplant based on visual inspection that had adequate blood supply on ICGA. Transient hypoparathyroidism was present in 45 out of 124 controls (36%) and 32 out of 86 (37%) in the ICG group. CONCLUSIONS: ICGA is a novel technique that may improve the assessment of parathyroid gland blood supply compared to visual inspection. ICGA can guide more appropriate autotransplantation without compromising postoperative parathyroid function. At least two vascularized glands on ICGA may predict postoperative parathyroid gland function.

Impact of the affordability of novel agents in patients with multiple myeloma: Real-world data of current clinical practice in Mexico.

BACKGROUND: The treatment of multiple myeloma (MM) has become costly and difficult to access for patients living in low-income to middle-income countries. METHODS: The current retrospective study included 148 patients in Mexico with newly diagnosed MM, and was performed to compare the outcomes of patients with and without access to novel agents. The records of 77 patients admitted to a public hospital (PubC) and 71 patients cared for within private health systems (PrivC) from November 2007 to July 2016 were reviewed. RESULTS: Compared with those treated in PrivC, patients receiving care at PubC were more likely to be diagnosed with advanced disease. A thalidomide-based regimen was the most common induction treatment used at PubC, whereas a bortezomib-based regimen was used most often in PrivC. The median follow-up was 41 months. Patients in PrivC demonstrated better response rates and survival; 65% of patients treated in PrivC versus 41% treated at PubC achieved a very good partial response or better (P = .005). The median progression-free survival and median overall survival were 23 months and 51 months, respectively, for patients treated at PubC and 41 months and 79 months, respectively, for those treated in PrivC (P<.001). More patients underwent autologous stem cell transplantation in PrivC. When adjustments were made for covariates, patients treated at PubC experienced a higher risk of death compared with patients receiving care in PrivC (hazard ratio, 2.0; 95% confidence interval, 1.0-4.3 [P = .04]). CONCLUSIONS: Stage at diagnosis, induction regimen, and autologous stem cell transplantation were found to be contributors to survival disparities between patients with MM treated at PubC compared with PrivC in Mexico. These findings underscore the need to improve access to novel agents and stem cell transplantation in public health systems. Cancer 2018;124:1946-53. © 2018 American Cancer Society.

Hispanics have the lowest stem cell transplant utilization rate for autologous hematopoietic cell transplantation for multiple myeloma in the United States: A CIBMTR report.

BACKGROUND: Race/ethnicity remains an important barrier in clinical care. The authors investigated differences in the receipt of autologous hematopoietic cell transplantation (AHCT) among patients with multiple myeloma (MM) and outcomes based on race/ethnicity in the United States. METHODS: The Center for International Blood and Marrow Transplant Research database was used to identify 28,450 patients who underwent AHCT for MM from 2008 through 2014. By using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 registries, the incidence of MM was calculated, and a stem cell transplantation utilization rate (STUR) was derived. Post-AHCT outcomes were analyzed among patients ages 18 to 75 years who underwent melphalan-conditioned peripheral cell grafts (N = 24,102). RESULTS: The STUR increased across all groups from 2008 to 2014. The increase was substantially lower among Hispanics (range, 8.6%-16.9%) and non-Hispanic blacks (range, 12.2%-20.5%) compared with non-Hispanic whites (range, 22.6%-37.8%). There were 18,046 non-Hispanic whites, 4123 non-Hispanic blacks, and 1933 Hispanic patients. The Hispanic group was younger (P < .001). Fewer patients older than 60 years underwent transplantation among Hispanics (39%) and non-Hispanic blacks (42%) compared with non-Hispanic whites (56%). A Karnofsky score <90% and a hematopoietic cell transplantation comorbidity index score >3 were more common in non-Hispanic blacks compared with Hispanic and non-Hispanic whites (P < .001). More Hispanics (57%) versus non-Hispanic blacks (54%) and non-Hispanic whites (52%; P < .001) had stage III disease. More Hispanics (48%) versus non-Hispanic blacks (45%) and non-Hispanic whites (44%) had a very good partial response or better before transplantation (P = .005). Race/ethnicity did not impact post-AHCT outcomes. CONCLUSIONS: Although the STUR increased, it remained low and was significantly lower among Hispanics followed by non-Hispanic blacks compared with non-Hispanic whites. Race/ethnicity did not impact transplantation outcomes. Efforts to increase the rates of transplantation for eligible patients who have MM, with an emphasis on groups that underuse transplantation, are warranted. Cancer 2017;123:3141-9. © 2017 American Cancer Society.

Epidemiology of Acute Respiratory Distress Syndrome Following Hematopoietic Stem Cell Transplantation.

OBJECTIVES: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic, Rochester, MN. PATIENTS: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell transplantation (5.0%). Acute respiratory distress syndrome developed in 75 patients (15.6%) undergoing allogeneic hematopoietic stem cell transplantation and 58 patients (2.7%) undergoing autologous hematopoietic stem cell transplantation. Median time to acute respiratory distress syndrome development was 55.4 days (interquartile range, 15.1-139 d) in allogeneic hematopoietic stem cell transplantation and 14.2 days (interquartile range, 10.5-124 d) in autologous hematopoietic stem cell transplantation. Twenty-eight-day mortality was 46.6%. At 12 months following hematopoietic stem cell transplantation, 89 patients (66.9%) who developed acute respiratory distress syndrome had died. Only 7 of 133 acute respiratory distress syndrome cases met criteria for engraftment syndrome and 15 for diffuse alveolar hemorrhage. CONCLUSIONS: Acute respiratory distress syndrome is a frequent complication following hematopoietic stem cell transplantation, dramatically influencing patient-important outcomes. Most cases of acute respiratory distress syndrome following hematopoietic stem cell transplantation do not meet criteria for a more specific post-transplantation pulmonary syndrome. These findings highlight the need to better understand the risk factors underlying acute respiratory distress syndrome in this population, thereby facilitating the development of effective prevention strategies.

Autologous stem cell transplantation for multiple myeloma: Long-term results.

BACKGROUND: Survival of myeloma patients has improved considerably in the past decade. However, limited data are available on their long-term outcome. We analysed the data of 225 consecutive patients who underwent autologous stem cell transplantation (ASCT) at our centre. METHODS: Between April 1990 and December 2013, a total of 225 patients with multiple myeloma (median age 53 years, range 27-67 years, 69.3% men) underwent ASCT. High-dose melphalan 200 mg/m2 was used for conditioning. Before transplant, the patients received induction therapy with novel agents (thalidomide and dexamethasone, or lenalidomide and dexamethasone, or bortezomib and dexamethasone); or vincristine, doxorubicin, dexamethasone; or alkylating agents (vincristine, melphalan, cyclophosphamide and prednisolone; or melphalan and prednisolone). The response to transplant was evaluated using the European Bone Marrow Transplant criteria, and an intention-to-treat analysis was done. RESULTS: Four-fifths (79.6%) of our patients had Durie Salmon Stage (DSS) IIIA and nearly a quarter (24%) of them had International Stage III disease. Before the transplant, 80.4% of patients had chemosensitive disease. The median interval from diagnosis to transplant was 10 months (range 2-128 months). Following ASCT, 197 (87.5%) patients responded. Complete response was obtained in 54.7%, very good partial response in 19% and partial response in 13.8%. At a median follow-up of 90 months (range 18-266 months), the median progression-free survival (PFS) and overall survival (OS) were 32 and 85.5 months, respectively. The estimated PFS and OS at 10 years were 29.7% and 43.6%, respectively. On multivariate analysis, the presence of extramedullary disease (HR 3.05, p < 0.001), and ISS III (HR 0.50, p < 0.02) predicted inferior OS. Extramedullary disease at diagnosis (HR 1.585, p < 0.03), and more than one regimen pre- transplant (HR 0.53, p < 0.02) predicted an inferior PFS. Complete response was a predictor of superior OS and PFS (p < 0.001). CONCLUSION: Complete response following ASCT is associated with good long-term outcome. Alternative treatment strategies are needed to improve results in patients who fail to achieve CR post-transplant and in those with high-risk disease.

Cartilage repair surgery for full-thickness defects of the knee in Germany: indications and epidemiological data from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: Treatment of cartilage defects of the knee remains an important issue with high relevance. In October 2013 the German Cartilage Registry (KnorpelRegister DGOU) was initiated in order to study indications, epidemiology and (clinical) outcome of different cartilage repair techniques. The present evaluation of the registry baseline data was initiated to report common practices of cartilage repair surgery in Germany. MATERIALS AND METHODS: 1065 consecutive patients who underwent surgical cartilage treatment of the knee have been included (complete data sets available in 1027 cases; FU rate 96.4 %) between October 1, 2013 and June 30, 2015. Data collection was performed using a web-based RDE System. All data were provided by the attending physician at the time of arthroscopic or open surgery of the affected knee. RESULTS: In 1027 cartilage repair procedures, single defects were treated in 80 % of the cases with the majority of the defects located on the medial femoral condyle, followed by the patella. Degenerative defects grade III or IV according to ICRS were treated in 60 % of the cases and therefore were found more frequently compared to traumatic or post-traumatic lesions. Autologous chondrocyte implantation (ACI) was the most common technique followed by bone marrow stimulation (BMS) and osteochondral transplantation (OCT). While ACI was performed in defects with a mean size of 4.11 cm(2) SD SD 2.16), BMS and OCT (1.51 cm(2), SD 1.19; p < 0.01) were applied in significantly smaller defects (both p < 0.01). Independent of defect size, the ratio of ACI versus BMS applications differed between different defect locations. ACI was used preferably in defects located on the patella. CONCLUSION: The present analysis of data from the German Cartilage Registry shows that the vast majority of cartilage repair procedures were applied in degenerative, non-traumatic cartilage defects. Experts in Germany seem to follow the national and international guidelines in terms that bone marrow stimulation is applied in smaller cartilage defects while cell-based therapies are used for the treatment of larger cartilage defects. In patellar cartilage defects a trend towards the use of cell-based therapies has been observed.

Cost-Effectiveness of Autologous Hematopoietic Stem Cell Transplantation for Elderly Patients with Multiple Myeloma using the Surveillance, Epidemiology, and End Results-Medicare Database.

In the past decade, the number of autologous hematopoietic stem cell transplants (Auto HSCT) for older patients with multiple myeloma (MM) has increased dramatically, as has the cost of transplantation. The cost-effectiveness of this modality in patients over age 65 is unclear. Using the Surveillance, Epidemiology, and End Results-Medicare database to create a propensity-score matched sample of patients over age 65 between 2000 and 2007, we compared the survival and cost for those who received Auto HSCT to those who did not undergo transplantation but survived at least 6 months after diagnosis, and we calculated an incremental cost-effectiveness ratio (ICER). Two hundred seventy patients underwent transplantation. Median overall survival from diagnosis in those who underwent transplantation was significantly longer than in patients who did not (58 months versus 37 months, P < .001). For patients living longer than 2 years, the median monthly cost during the first year was significantly different, but the middle and last year of life costs were similar. The median cost of the first 100 days after transplantation was $60,000 (range, $37,000 to $85,000). The resultant ICER was $72,852 per life-year gained. Survival after transplantation was comparable to that in those who underwent transplantation patients under 65 years and significantly longer than older patients who did not undergo transplantation. With an ICER less than $100,000/life-year gained, Auto HSCT is cost-effective when compared with nontransplantation care in the era of novel agents and should be considered, where clinically indicated, for patients over the age of 65.

Cumulative birth rates with linked assisted reproductive technology cycles.

BACKGROUND: Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure. METHODS: We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment. RESULTS: The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used. CONCLUSIONS: Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).

Patient mobility for bone marrow transplant: the experience of the Perugia Hospital, years 2000-2013.

INTRODUCTION: Patient mobility, driven by patient preference is an indirect indicator of perception of hospital quality. Patients' choices depend on their previous healthcare experiences, the reputation of the hospital staff and the network of relationships between the patient, hospital doctors, general practitioners/reference specialists, etc. Therefore, the analysis of patient preferences provides an idea of hospital quality as well as qualitative and quantitative lack of services. The aim of the present research was to describe and analyze patient mobility for bone marrow transplantation regarding the Hospital of Perugia, which represents the second most important structure for bone marrow transplant in Italy. METHODS: Data have been collected from hospital discharge records in the ordinary regime related to the Diagnosis Related Group 481 "bone marrow transplant" since 2000 to 2013. We included autologous and allogenic transplant, in the adult and the child. Analysis of escaped, attracted and resident patients flows was undertaken using Gandy's nomogram which detects, through repeated time investigations, patients' movement inside and outside their catchment area. RESULTS: Between 2000 and 2013, 1782 patients were admitted to hospital with a DRG 481 "bone marrow transplant". Nine hundred and nineteen (51,5%) were resident in Umbria region, 799 (44,8%) in other regions, 64 (0,3%) abroad. Escapes were 158. The high percentage of admissions represented by patients that live out of Umbria, shows a high attractive power of the hospital. For "distant regions" this situation was maintained from 2000 to 2003, with a mild decrease from 2004 and, from 2010, the situation is stable. Only for "bordering regions" the attraction, which was stable up to 2010, seems to decrease. Gandy's nomogram shows also that the hospital was able to satisfy the health needs of the Umbria residents between 2004 and 2009 with a reductions in the escapes; then, in the last four years there is an increase in Umbria residents who seek care outside the catchment area and, in the last two years a reduction in the attraction power also. CONCLUSIONS: During the analyzed period of time, the Hospital of Perugia has been a choice for patients needing a bone marrow transplant. In the last period of the analysis it seems that patients preferences have changed. The increased availability of new hematologic centers explains two phenomena: on the one hand patients tend to not move for the examined DRG, so that there is a reduction in incoming patients from bordering regions; on the other hand the competition to attract patients from the catchment area leads to an increase in the quality of the service.

Transfusions in autologous breast reconstructions: an analysis of risk factors, complications, and cost.

PURPOSE: Free tissue transfer requires lengthy operative times and can be associated with significant blood loss. The goal of our study was to determine independent risk factors for blood transfusions and transfusion-related complications and costs. METHODS: We reviewed our prospectively maintained free flap database and identified all patients undergoing breast reconstruction receiving blood transfusions. These patients were compared with those not receiving a postoperative transfusion. We examined baseline patient comorbidities, preoperative and postoperative hemoglobin (HgB) levels, intraoperative and postoperative complications, and blood transfusions. Factors associated with transfusion were identified using univariate analyses, and multivariate logistic regression was used to determine independently associated factors. RESULTS: A total of 70 (8.2%) patients received postoperative blood transfusions. Multivariate analysis revealed associations between length of surgery (P=0.01), intraoperative arterial thrombosis [odds ratio (OR), 6.75; P=0.01], major surgical complications (OR, 25.9; P<0.001), medical complications (OR, 7.2; P=0.002), and postoperative HgB levels (OR, 0.2; P<0.001). Transfusions were independently associated with higher rates of medical complications (OR, 2.7; P=0.03). A significantly lower rate of medical complications was observed when a restrictive transfusion (HgB level, <7 g/dL) was administered (P=0.04). A cost analysis demonstrated that each blood transfusion was independently associated with an added $1,500 in total cost. CONCLUSIONS: Several key perioperative factors are associated with allogenic transfusion, including intraoperative complications, operative time, HgB level, and postoperative medical and surgical complications. Blood transfusions were independently associated with greater morbidity and added hospital costs. Overall, a restrictive transfusion strategy (HgB level, <7 g/dL or clinically symptomatic) may help minimize medical complications. LEVEL OF EVIDENCE: Prognostic/risk category, level III.

Hematopoietic stem cell transplantation activity in Europe.

PURPOSE OF REVIEW: This review describes the current use of hematopoietic stem cell transplantation (HSCT) and aims to assess recent trends, to analyze factors associated with use and trends, and to discuss potential implications of such developments on future use. RECENT FINDINGS: The one millionth HSCT worldwide was announced in early 2013. More than 35 000 HSCT (40% allogeneic and 60% autologous) were reported in 2011 to the European Group for Blood and Marrow Transplantation, with more than 60 000 worldwide. Total numbers increased in Europe over the last 10 years by 50%, with the highest increase being for allogeneic HSCT from an unrelated donor. Change in HSCT numbers was different for each indication with novel indications emerging. There were significant differences in absolute numbers and increase in transplant rates between countries concerning main indication, donor type, and stem cell source or transplant technology. Trends showed a widening gap between countries with high or low national income. The high costs of HSCT impact on its use; availability of resources, presence of a national registry, and numbers of registered donors are the most closely associated with unrelated donor transplant rates. SUMMARY: Timely and comprehensive data on HSCT activity reveal trends and provide essential information for decision making to patients, physicians, healthcare administrators, or competent authorities alike.

[STATE OF DEVELOPMENT OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE EUROPE AND WORLD].

In this review, we summarize information about the current trends in hematopoietic stem cells transplantation (HSCT) in Europe and world. HSCT has represented one of the most innovative and highly expensive method of treatment for a set of malignant and non-malignant disorders. Differences in the number of HSCT and transplant rates (number of HSCT per 10 million inhabitants), indications and types of transplantations between countries have been reported. They were attributed mainly to differences in the economic situation of the countries and differences in prevalence of certain types of diseases. The gross national income per capita, health care expenditures per capita, number of transplant teams per 1 million inhabitants and team experience are the main impact factors influencing on transplant activity. These data provide a basis for health care planning, preparation of normative acts and future research in Ukraine for rapid expansion HSCT