- Daratumumab resistance is frequent in advanced stage multiple myeloma patients irrespectively of CD38 expression, and is related to dismal prognosis. [Journal Article]
- EJEur J Haematol 2018 Feb 17
- CONCLUSIONS: Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short lived, stressing the administration of this agent should be early in the course of the disease. This article is protected by copyright. All rights reserved.
- [Application of endoscope assisted curved laryngoscopy technique in transoral laryngopharyngeal minimally invasive surgery]. [Journal Article]
- ZEZhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018 Jan 07; 53(1):45-48
- Objective: To explore the possibility of endoscope assisted curved laryngoscopy technique applied in transoral laryngopharyngeal minimally invasive surgery and evaluate the advant...
Objective: To explore the possibility of endoscope assisted curved laryngoscopy technique applied in transoral laryngopharyngeal minimally invasive surgery and evaluate the advantages of this technique.Methods:Eight patients with huge benign lesions in larynx and pharynx undergoing transoral microsurgery at Peking University Third Hospital between February 2016 and February 2017 were enrolled in this study.The diagnosis included cyst at the base of tongue in two patients, cysts in the epiglottis in two patients, hemangioma in two patients, multiple masses of the hypopharynx and amyloidosis in supraglottic area in one patient each.The time and exposure during surgery, occurrence rate of complication and conditions of following-up were recorded.Results:The mean time of surgery was 20 min, the exposure was satisfying.There was no obvious complication after surgery.No residual or recurrent lesion was observed after 1 to 12 months follow-up(mean time 4.5 months).Conclusion:The endoscope assisted curved laryngoscopy technique has advantages in shortening the time of surgery, improving exposure and reducing the rate of complication and recurrence.
- Diffuse Peritoneal and Bowel Wall Infiltration by Light Chain-AL Amyloidosis with Omental Calcification Mimicking Abdominal Carcinomatosis - An Elderly Female with Incidental Finding of Light Chain Monoclonal Gammopathy of Undetermined Significance (LC-MGUS). [Case Reports]
- AJAm J Case Rep 2017 Nov 25; 18:1247-1250
- CONCLUSIONS: This case report illustrates that in an era of evidence based medicine, it is important to show through case reports the association of GIT AL amyloidosis with LC-MGUS, as the literature on this topic is lacking. It also points to the importance of timely intervention that can greatly enhance, not only the only the chances of remission but also prevention of further complications such as malignant transformation.
- Case for diagnosis. Systemic light chain amyloidosis with cutaneous involvement. [Case Reports]
- ABAn Bras Dermatol 2017 Sep-Oct; 92(5):731-732
- Systemic light chain amiloydosis is a rare disease. Due to its typical cutaneous lesions, dermatologists play an essential role in its diagnosis. Clinical manifestations vary according to the affecte...
Systemic light chain amiloydosis is a rare disease. Due to its typical cutaneous lesions, dermatologists play an essential role in its diagnosis. Clinical manifestations vary according to the affected organ and are often unspecific. Definitive diagnosis is achieved through biopsy. We report a patient with palpebral amyloidosis, typical bilateral ecchymoses and cardiac involvement, without plasma cell dyscrasia or lymphomas. The patient died shortly after the diagnosis.
- Dermal Hyperneury and Multiple Sclerotic Fibromas in Multiple Endocrine Neoplasia Type 2A Syndrome. [Case Reports]
- JDJAMA Dermatol 2017 Dec 01; 153(12):1298-1301
- CONCLUSIONS: Dermal hyperneury and multiple sclerotic fibromas should be added to the list of cutaneous manifestations of patients with the familial MTC type of MEN 2A syndrome.
- Spectrum of orocutaneous disease associations: Genodermatoses and inflammatory conditions. [Review]
- JAJ Am Acad Dermatol 2017; 77(5):809-830
- The oral cavity and cutaneous organ systems share a close embryologic origin. Therefore, there are numerous dermatologic conditions presenting with concomitant oral findings of which the dermatologis...
The oral cavity and cutaneous organ systems share a close embryologic origin. Therefore, there are numerous dermatologic conditions presenting with concomitant oral findings of which the dermatologist must be aware. The second article in this continuing medical education series reviews inflammatory orocutaneous conditions and a number of genodermatoses. It is essential for dermatologists to be familiar with oral cavity manifestations associated with dermatologic diseases for prompt diagnosis, management, and appropriate referral to stomatology and dentistry.
- Common molecular pathogenesis of disease-related intrinsically disordered proteins revealed by NMR analysis. [Review]
- JBJ Biochem 2018 Jan 01; 163(1):11-18
- Intrinsically disordered proteins (IDPs) are either completely unstructured or contain large disordered regions in their native state; they have drawn much attention in the field of molecular patholo...
Intrinsically disordered proteins (IDPs) are either completely unstructured or contain large disordered regions in their native state; they have drawn much attention in the field of molecular pathology. Some of them substantially tend to form protein self-assemblies, such as toxic or non-toxic aggregates and fibrils, and have been postulated to relate to diseases. These disease-related IDPs include Aβ(1-42) [Alzheimer's disease (AD)], Tau (AD and tauopathy), α-synuclein (Parkinson's disease) and p53 (cancer). Several studies suggest that these aggregation and/or fibril formation processes are often initiated by transient conformational changes of the IDPs prior to protein self-assembly. Interestingly, the pathological molecular processes of these IDPs share multiple common features with those of protein misfolding diseases, such as transmissible spongiform encephalopathy (PrPsc) and AL-amyloidosis (VL-domain of γ-immunoglobulin). This review provides an overview of solution NMR techniques that can help analyse the early and transient events of conformational equilibrium of IDPs and folded proteins.
- Immunoparesis defined by heavy+light chain suppression is a novel marker of long-term outcomes in cardiac AL amyloidosis. [Journal Article]
- BJBr J Haematol 2017; 179(4):575-585
- Cardiac involvement and presenting dFLC (difference between involved and uninvolved free light chains) are independent predictors of outcome in systemic AL amyloidosis. These markers have limited pro...
Cardiac involvement and presenting dFLC (difference between involved and uninvolved free light chains) are independent predictors of outcome in systemic AL amyloidosis. These markers have limited prognostic utility in patients surviving the initial months following diagnosis. Here we assessed immunoparesis, as determined by novel heavy+light chain (HLC) immunoassays, as a prognostic marker for survival in AL amyloidosis. HLC measurements identified immunoparesis of at least one immunoglobulin (Ig) isotype in 145 (85%) patients; and severe immunoparesis (≥2 Ig isotypes suppressed by >50% below normal levels) in 29 (17%) patients. Median overall survival (OS) on intention to treat (ITT) analysis was 26·2 months. In the ITT cohort, dFLC >180 mg/l was associated with shorter OS (P = 0·05); whereas HLC immunoparesis was not prognostic. On a landmark analysis of 127 patients alive at 6 months, presenting dFLC was not prognostic for OS (P = 0·33) and severe HLC immunoparesis trended towards poorer survival (20·2 vs. 42·8 months; P = 0·09). In the subset of patients with cardiac involvement, severe HLC immunoparesis conferred very poor outcome (median OS 8·8 vs. 29·9 months, P = 0·007). In conclusion, severe HLC immunoparesis is an independent marker of long-term poor prognosis in AL patients with cardiac involvement. The pathophysiological significance of this observation needs further study.
- At least partial hematological response after first cycle of treatment predicts organ response and long-term survival for patients with AL amyloidosis receiving bortezomib-based treatment. [Clinical Trial]
- AHAnn Hematol 2017; 96(12):2089-2094
- AL amyloidosis is a rare plasma cell dyscrasia characterized by multi-organ involvement and poor prognosis. We retrospectively evaluated the organ response (OR) and long-term survival of newly diagno...
AL amyloidosis is a rare plasma cell dyscrasia characterized by multi-organ involvement and poor prognosis. We retrospectively evaluated the organ response (OR) and long-term survival of newly diagnosed AL amyloidosis patients who received first-line bortezomib-containing induction therapy, aiming to identify the clinical indication of a 50% reduction in the difference between involved and uninvolved free light chains (dFLC) after first cycle of treatment. Among the 89 patients included, 78.7% had cardiac involvement and 42.7% were diagnosed with 2004 Mayo stage III disease, while 75.3% of patients achieved a hematological response, including 37.1% with complete response and a median response time of 1 month. Cardiac and renal responses were observed in 44.3 and 53.1% of patients, respectively. Sixty-one (68.5%) patients achieved at least 50% reduction in dFLC after the first cycle of therapy. After a median follow-up duration of 12 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 61.3 and 61.7% respectively. At least 50% reduction in dFLC after the first cycle of therapy was predictive of achieving an OR (p = 0.002), as well as superior PFS (HR = 0.119; 95% CI = 0.045-0.313; p < 0.001) and OS (HR = 0.206; 95% CI = 0.078-0.541; p = 0.001). Additionally, the median PFS and OS were not reached for patients with rapid reduction of dFLC. These results demonstrated that early reduction of dFLC after the first cycle of treatment is predictive of achieving an OR and long-term survival in AL patients receiving bortezomib.
New Search Next
- Kinetic stability and sequence/structure studies of urine-derived Bence-Jones proteins from multiple myeloma and light chain amyloidosis patients. [Journal Article]
- BCBiophys Chem 2017; 230:89-98
- It is now accepted that the ability of a protein to form amyloid fibrils could be associated both kinetic and thermodynamic protein folding parameters. A recent study from our laboratory using recomb...
It is now accepted that the ability of a protein to form amyloid fibrils could be associated both kinetic and thermodynamic protein folding parameters. A recent study from our laboratory using recombinant full-length (encompassing the variable and constant domain) immunoglobulin light chains found a strong kinetic control of the protein unfolding for these proteins. In this study, we are extending our analysis by using urine-derived Bence Jones proteins (BJPs) from five patients with light chain (AL) amyloidosis and four patients with multiple myeloma (MM). We observed lower stability in κ proteins compared to λ proteins (for both MM and AL proteins) in agreement with previous studies. The kinetic component of protein stability is not a universal feature of BJPs and the hysteresis observed during refolding reactions could be attributed to the inability of the protein to refold all domains. The most stable proteins exhibited 3-state unfolding transitions. While these proteins do not refold reversibly, partial refolding shows 2-state partial refolding transitions, suggesting that one of the domains (possibly the variable domain) does not refold completely. Sequences were aligned with their respective germlines and the location and nature of the mutations were analyzed. The location of the mutations were analyzed and compared with the stability and amyloidogenic properties for the proteins in this study, increasing our understanding of light chain unfolding and amyloidogenic potential.