Overweight/Obesity and Monoclonal Gammopathy of Undetermined Significance

BackgroundObesity and high body mass index (BMI) are associated with increased incidence of multiple myeloma (MM). MM usually evolves from a precursor asymptomatic disease, namely monoclonal gammopathy of undetermined significance (MGUS). MGUS progresses to MM at a 1% annual rate; however, risk factors predisposing to MGUS are not completely understood. We conducted a systematic review to assess the relationship between obesity and high BMI with MGUS prevalence and progression to MM. To our knowledge, this is the first systematic review evaluating the role of obesity in MGUS.Patients and MethodsWe searched the Medline database and ClinicalTrials.gov for studies investigating BMI and obesity association with MGUS incidence and progression. The algorithm consisted of a predefined combination of the words “obesity,” “obese,” “body mass index,” “overweight,” “diet,” “nutrition,” “food,” “dietary,” “adiponectin,” “monoclonal gammopathy,” and “MGUS”.ResultsOverall, 12 articles were retrieved, including 11 eligible articles and 1 clinical trial. More than 57,068 patients were evaluated in this systematic review. Discrepancies between the identified studies were noted. Multiple studies support the notion that obesity or high BMI are positively linked to MGUS prevalence and transition to MM. In contrast, other studies revealed no such association. Visceral adipose tissue metabolic activity and decreased adiponectin concentrations were identified as biomarkers of MGUS progression to MM.ConclusionObesity and increased BMI seem to be implicated both in MGUS development and progression to MM. Further studies should be designed to confirm this hypothesis.     

The Gram-negative bacteria-binding protein gene family: its role in the innate immune system of anopheles gambiae and in anti-Plasmodium defence

Gram-negative bacteria-binding proteins (GNBPs) are pattern recognition receptors which contribute to the defensive response against Plasmodium infection in Anopheles . We have characterized the GNBP gene family in Anopheles gambiae at the molecular level, and show that they are functionally diverse components of the A. gambiae innate immune system. GNBPB4 is a major factor in the defence against a broad range of pathogens, while the other GNBP s have narrower defence specificities. GNBPB4 is associated with the regulation of immune signalling pathways and was found to interact with the Gram-negative Escherichia coli and weakly co-localized with Plasmodium berghei ookinetes in the mosquito midgut epithelium.     

羟乙基淀粉溶液在复苏肠缺血再灌注休克中的作用

目的　比较不同剂量羟乙基淀粉溶液 ( HES)对兔肠缺血再灌注损伤所致休克的复苏作用。方法　 32只新西兰白兔随机分为 4组 :模型对照、乳酸林格液复苏组 ( L RS,2 0 m l· kg- 1 · h- 1 ) ,小剂量 HES复苏组 ( HES2 ml· kg- 1· h- 1 L RS18m l· kg- 1· h- 1 ) ,大剂量 HES复苏组 ( HES2 0 ml· kg- 1· h- 1 )。采用肠系膜上动脉夹闭 6 0 m in后松夹行再灌注制备肠缺血再灌注休克模型 ,松夹再灌注时同步进行液体复苏。观测各时间点的血流动力学参数 (平均动脉压、心率、心排血量、肠系膜上动脉血流 ) ,并通过测定肠黏膜CO2 分压和动脉血 CO2 分压的差值 (动脉二氧化碳间隙 )、肠黏膜 p H值、动脉血乳酸浓度和氧输送等指标间接评估组织氧合情况。实验结束后累计动物死亡数。结果　 HES能明显提高肠缺血再灌注休克时的血流动力学参数 ,与对照组和 L RS组比较差异均有显著性 ( P均 <0 .0 5 ) ;小剂量 HES比大剂量 HES改善血流动力学参数的作用更平稳 ( P均 <0 .0 5 ) ,且较其他 3组能明显降低血乳酸浓度和动脉二氧化碳间隙 ,减轻 p Hi的降低 ( P均 <0 .0 5 ) ;而大剂量 HES对上述参数的影响不明显 ,并可见动物口鼻出血及死亡 ;小剂量或大剂量HES与其他两组比较均能使氧输送回升 ( P均 <0 .0 5 )。结     

Evolving chemotherapy options for the treatment of myeloma kidney: a 40-year perspective

Kidney impairment (KI) at the time of initial diagnosis is common in myeloma. The improvement of kidney function and the reversal of KI are of utmost importance. Recent advances have made it possible to reverse acute kidney damage due to myeloma in most patients, at least if treatment is immediately implemented. Immediate antimyeloma therapy and appropriate hydration are the most commonly used treatment modalities for the management of acute KI related to myeloma. Mechanical approaches can only temporarily reduce the free light-chain load, and without effective chemotherapy they are probably not able to significantly improve kidney function. However, the role of mechanical approaches together with effective chemotherapy is still being explored. Thalidomide, lenalidomide, and bortezomib have improved the survival of myeloma patients, but they have also improved the outcome of patients presenting with KI. Thalidomide is safe to use on patients with KI without dose adjustments. Lenalidomide needs dose modification, but it can improve kidney function in many patients. Bortezomib seems to be the agent of choice for most patients presenting with KI without dose modifications. This review focuses on the management of patients presenting with "myeloma kidney" using modern chemotherapy approaches, especially novel agents.     

The ross-konno procedure as reoperative treatment in a young adult with congenital aortic stenosis

Mechanical and biological prostheses are valid options when aortic valve replacement is necessary. The Ross procedure is also an alternative solution, especially for young patients.We describe the case of a young patient with congenital aortic stenosis and bicuspid aortic valve who presented with dyspnea on exertion. An open commissurotomy was performed, and within 8 months the patient developed recurrent symptoms of severe aortic stenosis. He underwent redo sternotomy and a Ross-Konno procedure with an uneventful recovery.     

Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2

A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β(2)-microglobulin level and International Staging System stages II and III, incorporating high β(2)-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.     

Prophylactic antibiotics for the prevention of neutropenic fever in patients undergoing autologous stem-cell transplantation: results of a single institution, randomized phase 2 trial

One hundred and fifty-seven patients undergoing high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) for hematopoietic malignancies and solid tumors were randomly assigned to receive (Group A) or not (Group B) prophylaxis with ciprofloxacin, orally, and vancomycin, intravenously. Prophylactic antibiotics were given from day 0 until resolution of neutropenia or the appearance of a febrile event. Furthermore, patients in both groups received once a day fluconazole, orally. The primary end-point of our study was the incidence of neutropenic febrile episodes attributed to infection. One hundred and twelve (71.3%) patients developed neutropenic fever, 50 (56.2%) in Group A and 62 (91.2%) in Group B (P < 0.001) with the majority (82%) of patients developing fever of unknown origin. Patients on prophylactic antibiotics had a significantly lower rate of bacteremias (5.6%) than did those randomized to no prophylaxis (29.4%) (P = 0.005) and, when developing neutropenic fever, they had a lower probability of response to first-line empirical antibiotics (P = 0.025). Prophylactic administration of ciprofloxacin and vancomycin reduced the incidence of neutropenic fever in patients receiving HDT with ASCT, however, without affecting the total interval of hospitalization, time to engraftment, or all-cause mortality. Therefore, our results do not support the use of antibiotic prophylaxis for patients undergoing HDT and ASCT.     

An update on the use of lenalidomide for the treatment of multiple myeloma

Introduction: Lenalidomide, an immunomodulatory agent with unique mechanism of action, represents the cornerstone in the treatment of patients with multiple myeloma (MM) providing rapid and sustained control of the disease with a manageable safety profile.

Areas covered: This review article, synthesizing all available data coming from trials and evaluating the efficacy and safety of lenalidomide in patients with MM, tries to provide to the clinicians with an easy-to-grasp synopsis of recent and clinically meaningful advances on the field.

Expert opinion: Lenalidomide combined with dexamethasone is a safe and effective option for newly diagnosed MM patients ineligible for autologous stem cell transplantation (ASCT). Long-term administration of the agent as continuous treatment for ineligible for ASCT patients or maintenance therapy after ASCT has documented unprecedented progression-free survival improvements, whereas lenalidomide in combination with dexamethasone has shown deep and durable remissions for patients with relapsed and/or refractory disease.     

Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity

BACKGROUNDVascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation.AIMTo evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity.METHODSForty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO₂, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34⁺/CD45^-/CD133⁺, CD34⁺/CD45^-/CD133⁺/VEGFR₂ and CD34⁺/CD133⁺/vascular endothelial growth factor receptor 2 (VEGFR₂)] and two subgroups of circulating endothelial cells (CD34⁺/CD45^-/CD133^- and CD34⁺/CD45^-/CD133^-/VEGFR₂). Patients were divided in two groups of severity according to the median value of peak VO₂ (18.0 mL/kg/min), predicted peak VO₂ (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/10⁶ enucleated cells.RESULTSPatients with lower peak VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133^- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/10⁶ enucleated cells, P < 0.001], while patients with higher VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD133⁺/VEGFR₂ [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/10⁶ enucleated cells, P < 0.01], CD34⁺/CD45^-/CD133^- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/10⁶ enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05).CONCLUSIONOur study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.