Treatment with bortezomib‐based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib‐based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL‐pPCL and 17 with secondary PCL‐sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR‐group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow‐up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow‐up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity. Am. J. Hematol. 89:145–150, 2014. © 2013 Wiley Periodicals, Inc.     

European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma

Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk disease and preferably in the context of a clinical trial (2B). Thalidomide (1B) or lenalidomide (1A) maintenance increases progression-free survival and possibly overall survival (2B). Bortezomib-based regimens are a valuable consolidation option, especially for patients who failed excellent response after autologous stem cell transplantation (2A). Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide are the standards of care for transplant-ineligible patients (1A). Melphalan-prednisone-lenalidomide with lenalidomide maintenance increases progression-free survival, but overall survival data are needed. New data from the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone reached its primary end point of a statistically significant improvement in progression-free survival as compared to melphalan-prednisone-thalidomide and provides further evidence for the efficacy of lenalidomide-low-dose dexamethasone in transplant-ineligible patients (2B).     

Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism. The incidence of venous thromboembolism among COVID-19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions. D-dimer might help in early recognition of these high-risk patients and also predict outcome. Preliminary data show that in patients with severe COVID-19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis-induced coagulopathy criteria or with markedly elevated d-dimer. Recent recommendations suggest that all hospitalized COVID-19 patients should receive thromboprophylaxis, or full therapeutic-intensity anticoagulation if such an indication is present.     

Salivary alkaline phosphatase activity and chronological age as indicators for skeletal maturity

Objectives:To investigate the relationship between salivary alkaline phosphatase activity (ALP), protein concentration, and chronological age with cervical vertebral maturation stages (CVMS) as noninvasive biomarkers for skeletal maturity assessment.Materials and Methods:This cross-sectional study included 79 subjects (48 females, 31 males; 7 to 23 years old) categorized into five CVMS based on lateral cephalographs evaluated by three examiners. ALP activity and protein concentration in unstimulated whole saliva were compared among five CVMS. The association between age and CVMS was assessed and five multinomial logistic regression models were utilized to predict CVMS based on salivary ALP activity, protein concentration, and chronological age.Results:Salivary ALP reached the peak at early pubertal stage and then declined with a significant difference between CVMS I and CVMS II (P < .001) and between CVMS I and CVMS V (P = .004). A significant positive correlation between age and CVMS was found (r_s = 0.763, P < .001). The models'' overall correct classification rates for predicting CVMS were 32.9% using protein concentration, 35.4% using ALP activity, and 53.2% using both ALP activity and age.Conclusions:The combination of salivary ALP activity and chronological age may provide the best CVMS prediction.     

Comparison of Gastrojejunal Anastomosis Techniques in Laparoscopic Roux-en-Y Gastric Bypass: Gastrojejunal Stricture Rate and Effect on Subsequent Weight Loss

Background

Different gastrojejunal anastomotic (GJA) techniques have been described in laparoscopic Roux-en-Y gastric bypass (LRYGB). There is conflicting data on whether one technique is superior to the other. We aimed to compare hand-sewn (HSA), circular-stapled (CSA) and linear-stapled (LSA) anastomotic techniques in terms of stricture rates and their impact on subsequent weight loss.

Methods

A prospectively collected database was used to identify patients undergoing LRYGB surgery between March 2005 and May 2012. Anastomotic technique (HSA, CSA, LSA) was performed according to individual surgeon preference. The database recorded patient demographics, relevant comorbidities and the type of GJA performed. Serial weight measurements and percentage excess weight loss (%EWL) were available at defined follow-up intervals.

Results

Included in the data were 426 patients, divided between HSA (n?=?174, 40.8 %), CSA (n?=?110, 25.8 %) and LSA (n?=?142, 33.3 %). There was no significant difference in the stricture rates (HSA n?=?17, 9.72 %; CSA n?=?9, 8.18 %; LSA n?=?8, 5.63 %; p?=?0.4006). Weight loss was similar between the three techniques (HSA, CSA and LSA) at 3 months (40.6 %?±?16.2 % vs 35.92 %?±?21.42 % vs 48.21 %?±?14.79 %; p?=?0.0821), 6 months (61.48 %?±?23.94 % vs 58.16 %?±?27.31 % vs 60.18 %?±?22.26 %; p?=?0.2296), 12 months (72.94 %?±?19.93 % vs 69.72?±?21.42 % vs 66.05 %?±?17.75 %; p?=?0.0617) and 24 months (73.29 %?±?22.31 % vs 68.75 %?±?24.71 % vs 69.40 %?±?23.10 %; p?=?0.7242), respectively. The stricture group lost significantly greater weight (%EWL) within the first 3 months compared to the non-stricture group (45.39 %?±?16.82 % vs 39.22 %?±?21.93 %; p?=?0.0340); however, this difference had resolved at 6 months (61.29 %?±?18.50 % vs 59.79 %?±?23.03 %; p?=?0.8802) and 12 months (71.59 %?±?18.67 % vs 68.69 %?±?22.19 %; p?=?0.5970).

Conclusions

There was no significant difference in the rate of strictures between the three techniques, although the linear technique appears to have the lowest requirement for post-operative dilatation. The re-intervention rate will, in part, be dictated by the threshold for endoscopy, which will vary between units. Weight loss was similar between the three anastomotic techniques. Surgeons should use techniques that they are most familiar with, as stricture and weight loss rates are not significantly different.     

Levels of Evidence for the Outcome of Regenerative Endodontic Therapy

Introduction

The aim of this systematic review was to assign levels of evidence (LOEs) to existing clinical articles related to the outcome of regenerative endodontic therapy and to evaluate the clinical and radiographic outcomes of this treatment modality.

Methods

Electronic search was executed in PubMed, Scopus, and Cochrane databases by using appropriate Medical Subject Headings terms covering the period from January 1993 to December 2013. Additional publications from hand-searching and reference section of each relevant article enriched the article list. The LOE of each article was assessed according to guidelines provided by the Oxford Centre of Evidence-Based Medicine. Quality assessment of the observational studies was executed by using the Newcastle-Ottawa scale.

Results

Fifty-one relevant publications were included in this review. There were 2 high-level cohort studies (LOE 2), 8 case series (LOE 4), and 41 case reports (LOE 5). The vast majority of the treated teeth in those publications showed resolution of clinical signs, symptoms, and periapical radiolucencies at follow-up period. Furthermore, the majority of treated teeth presented further increase in root length and root wall thickness and apical closure at the follow-up period. However, because of lack of sufficient high-level evidence it was not possible to answer totally the review question and determine definitely the outcome of regenerative endodontic therapy.

Conclusions

The lack of adequate high-level studies that could possibly strengthen the satisfactory current data and allow practicing more evidence-based dentistry constitutes a significant knowledge gap in the endodontic literature. However, the current best available evidence undeniably allows clinicians to provide this treatment modality safely to patients.     

Sleep Deprivation: Effects on Weight Loss and Weight Loss Maintenance

This narrative review presents the findings from intervention studies on the effects of sleep deprivation on eating habits, metabolic rate, and the hormones regulating metabolism, and discusses their relevance to weight loss efforts. Disturbed sleeping patterns lead to increased energy intake, partly from excessive snacking, mainly on foods high in fat and carbohydrates. The studies focused mainly on the effects of sleep duration, but also of sleep quality, on dietary intake during weight loss trials, and on weight loss maintenance. It is important to explore sleep routines that could enhance the efforts of obese and overweight people to lose weight, maintain their weight loss, and improve their overall health.