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Clinical Lymphoma, Myeloma & Leukemia May 2022With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in... (Review)
Review
With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50%-90% and 50%-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 34879994
DOI: 10.1016/j.clml.2021.10.014 -
Diagnostic and Interventional Radiology... Nov 2021Bone tracers have been validated for many years in detecting transthyretin cardiac amyloidosis (TTR-CA). However, several new studies suggest conflicting results. Our... (Meta-Analysis)
Meta-Analysis
PURPOSE
Bone tracers have been validated for many years in detecting transthyretin cardiac amyloidosis (TTR-CA). However, several new studies suggest conflicting results. Our study aimed to systematically evaluate the accuracy of bone radiotracers for diagnosis and differentiation of TTR-CA via a systematic review and meta-analysis.
METHODS
We retrieved articles assessing the performance of bone tracer in diagnosing and differentiating TTR-CA from PubMed, the Cochrane Library, ScienceDirect, and DOAJ databases, dating up to 10 July 2020. The meta-analysis was conducted through Stata 16 software, and the risk of bias for the included studies was assessed by the QUADAS-2 tool. Moreover, we made a comprehensive review.
RESULTS
Fourteen articles were included in the systematic review, and 9 in the meta-analysis. The pooled sensitivity was 0.97 (95% confidence interval [95% CI] 0.85-0.99) with heterogeneity (I2=73.5, 95% CI 55.6-91.2), and the specificity was 0.92 (95% CI 0.82-0.96) with heterogeneity (I2=42.0, 95% CI 0.0-86.9). The pooled positive and negative likelihood ratios were 11.49 (95% CI 5.07-26.0) and 0.03 (95% CI 0.01-0.18), respectively. The diagnostic odds ratio was 341 (95% CI 53-2194), and the area under the receiver operating characteristic curve was 0.96 (95% CI 0.94-0.97).
CONCLUSION
The findings evidence that the bone radiotracer is a valuable noninvasive approach that provides high accuracy for diagnosing TTR-CA and plays a modest role in differentiating TTR-CA from immunoglobulin amyloid light-chain cardiac amyloidosis. 99mTc-HMDP may be more accurate than 99mTc-PYP, 99mTc-DPD, and 18F-NaF in the TTR-CA detecting process, and 18F-NaF is a promising bone tracer to diagnose and differentiate TTR-CA.
Topics: Amyloidosis; Bone and Bones; Heart; Humans; Prealbumin; Radionuclide Imaging
PubMed: 34792038
DOI: 10.5152/dir.2021.20662 -
Oxidative Medicine and Cellular... 2021Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still... (Meta-Analysis)
Meta-Analysis
Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still absent in the literature. Kefir is fermented milk resulting from the metabolism of a complex microbiota in symbiosis. Recent researches have investigated the bioactive compounds responsible for the preventive and therapeutic effects attributed to kefir. However, differences in functional potential between industrial and artisanal kefir are still controversial. Firstly, we identified differences in the microbial composition among both types of kefir. Available evidence concerning the action of different bioactive compounds from kefir on health, both from and studies, was subsequently summarized to draw a primary conclusion of the dose and the intervention time for effect, the producer microorganisms, the precursor in the milk, and the action mechanism. Meta-analysis was performed to investigate the statistically significant differences ( < 0.05) between intervention and control and between both types of kefir for each health effect studied. In summary, the bioactive compounds more commonly reported were exopolysaccharides, including kefiran, bioactive peptides, and organic acids, especially lactic acid. Kefir bioactive compounds presented antimicrobial, anticancer, and immune-modulatory activities corroborated by the meta-analysis. However, clinical evidence is urgently needed to strengthen the practical applicability of these bioactive compounds. The mechanisms of their action were diverse, indicating that they can act by different signaling pathways. Still, industrial and artisanal kefir may differ regarding functional potential-OR of 8.56 (95% CI: 2.27-32.21, ≤ .001)-according to the observed health effect, which can be associated with differences in the microbial composition between both types of kefir.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Biological Products; Fermentation; Humans; Immunomodulating Agents; Kefir; Milk
PubMed: 34745425
DOI: 10.1155/2021/9081738 -
Pacing and Clinical Electrophysiology :... Dec 2021Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure, characterized by extracellular deposition of insoluble protein fibrils leading to...
Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure, characterized by extracellular deposition of insoluble protein fibrils leading to progressive myocardial dysfunction. The most common types of cardiac amyloidosis are immunoglobin light-chain (AL) and transthyretin (ATTR). Conduction abnormalities are commonly encountered among patients with cardiac amyloidosis and are an important cause of morbidity and mortality. Abnormalities range from infra-Hisian intraventricular conduction delay and bundle branch block to complete atrioventricular block. Pacemaker placement in CA patients follows established guidelines, similar to those for patients without CA, with generally good efficacy. The role and appropriate timing of pacemakers for primary prevention of brady-arrhythmias in CA remains uncertain. While biventricular (BiV) pacing has been shown to improve clinical outcomes in patients with systolic heart failure without CA, there are few data examining the utility of BiV pacing in patients with CA. With the advent of effective treatments for AL and ATTR, appropriate application of pacing is important to support patients with CA and conduction disease through therapeutic trials. This systematic review summarizes the current literature examining the utility of pacing in CA.
Topics: Amyloidosis; Cardiac Pacing, Artificial; Heart Block; Heart Conduction System; Humans
PubMed: 34632598
DOI: 10.1111/pace.14375 -
Lasers in Medical Science Mar 2022With the investigation of the efficacy of laser therapy in primary localized amyloidosis(PLCA) only recently starting to materialize, we aimed to review the currently... (Review)
Review
With the investigation of the efficacy of laser therapy in primary localized amyloidosis(PLCA) only recently starting to materialize, we aimed to review the currently available studies of laser therapy in the management of the disease. We searched PubMed, Scopus, Embase, Web of Science, Cochrane, and ProQuest online databases with a specified search strategy, assessed the quality of each study, and then extracted the eligible data. Five RCTs(randomized controlled trials), one non-randomized controlled trial, three case series, and nine case reports(18 in total) were included. Overall, carbon dioxide (CO2), neodymium-doped:yttrium aluminum garnet (Nd:YAG), pulsed dye (PDL), Er (Erbium):YAG, and yttrium/erbium fiber were the studied lasers. One hundred fifty-five cases in total underwent laser therapy, with CO2 being the most frequent laser. Almost all studies demonstrated significantly desirable outcomes, while only mild and transient side effects were noted. Even though the studies' results were significant, we noticed that implementing a consistent methodology and a standardized objective assessment method was missing. Therefore, we recommend that future studies be conducted with less heterogeneous data for a more definite conclusion.
Topics: Humans; Amyloidosis, Familial; Laser Therapy; Lasers, Solid-State; Skin Diseases, Genetic; Randomized Controlled Trials as Topic
PubMed: 34611800
DOI: 10.1007/s10103-021-03429-4 -
Heart Failure Reviews Mar 2022Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that... (Review)
Review
Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that stabilizes TTR, has been used as an off-label therapeutic for ATTR-CM. Given limited data surrounding the use of diflunisal, a systematic review of the literature is warranted. We searched the PubMed, MEDLINE, and Embase databases for studies that reported on the use of diflunisal therapy for patients with ATTR-CM. We included English language studies which assessed the effect of diflunisal in adult patients with ATTR-CM who received diflunisal as primary treatment and reported clinical outcomes with emphasis on studies that noted the safety and efficacy of diflunisal in cardiac manifestations of ATTR amyloidosis. We excluded studies which did not use diflunisal therapy or used diflunisal therapy for non-cardiac manifestations of TTR amyloidosis. We also excluded case reports, abstracts, oral presentations, and studies with fewer than 10 subjects. Our search yielded 316 records, and we included 6 studies reporting on 400 patients. Non-comparative single-arm small non-randomized trials for diflunisal comprised 4 of the included studies. The 2 studies that compared diflunisal versus no treatment found improvements in TTR concentration, left atrial volume index, cardiac troponin I, and global longitudinal strain. Overall, diflunisal use was associated with decreased mortality and number of orthotopic heart transplant in ATTR-CM patients. Although a smaller number of patients had to stop treatment due to gastrointestinal side effects and transient renal dysfunction, there were no severe reactions reported in the studies included in our review. This systematic review supports the use of diflunisal for ATTR-CM. Additional long-term analyses and randomized clinical trials are needed to confirm these results.
Topics: Adult; Amyloid Neuropathies, Familial; Diflunisal; Humans; Myocardium; Prealbumin
PubMed: 34272629
DOI: 10.1007/s10741-021-10143-4 -
Scandinavian Journal of Gastroenterology Sep 2021Peripheral autonomic neuropathy, including enteric neuropathy, may be subtle and unrecognized for several years. Diagnosis of enteric neuropathy demands complicated...
PURPOSE
Peripheral autonomic neuropathy, including enteric neuropathy, may be subtle and unrecognized for several years. Diagnosis of enteric neuropathy demands complicated examinations such as full-thickness bowel biopsy. We hypothesized that knowledge about simultaneous occurrence of different types of neuropathy would lead to faster recognition and diagnosis of autonomic/enteric neuropathy. The aim of the present systematic review was to increase the awareness of disease groups causing autonomic and enteric neuropathy along with sensorimotor neuropathy.
METHODS
A systematic search strategy was used in PubMed, Embase and Web of Science. First, 4978 articles were identified. Review of titles/abstracts rendered exclusion of animal studies, articles not written in English or full-length, case reports, conference abstracts and duplicates until 357 articles remained. The full-length evaluation resulted in 35 studies (27 non-systematic reviews) which described objectively verified peripheral autonomic, enteric and sensorimotor neuropathy within the same disease.
RESULTS
Diabetes is the most common disease in society rendering generalized peripheral neuropathy. Accumulation of tissue deposits in amyloidosis, Lewy body disorders and sarcoidosis lead to widespread peripheral neuropathy. Several autoimmune disorders such as systemic sclerosis and primary Sjögren's syndrome present themselves with neuropathy. Paraneoplastic neuropathy may appear prior to symptoms from the malignancy. Both the infection , as well as the autoimmune response to the infection, i.e., Guillain-Barré syndrome, may lead to widespread peripheral neuropathy. Hereditary disorders with disturbed metabolism lead to intermittent attacks of neuropathy.
CONCLUSIONS
The major causes of generalized peripheral neuropathy are diabetes, diseases with tissue deposits, autoimmunity, infections, malignancy and metabolic diseases.
Topics: Animals; Autoimmune Diseases; Guillain-Barre Syndrome; Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases
PubMed: 34214006
DOI: 10.1080/00365521.2021.1942542 -
BMC Musculoskeletal Disorders Jan 2021Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid...
BACKGROUND
Transthyretin and immunoglobulin light-chain amyloidoses cause amyloid deposition throughout various organ systems. Recent evidence suggests that soft tissue amyloid deposits may lead to orthopedic conditions before cardiac manifestations occur. Pharmacologic treatments reduce further amyloid deposits in these patients. Thus, early diagnosis improves long term survival.
QUESTIONS/PURPOSES
The primary purpose of this systematic review was to characterize the association between amyloid deposition and musculoskeletal pathology in patients with common orthopedic conditions. A secondary purpose was to determine the relationship between amyloid positive biopsy in musculoskeletal tissue and the eventual diagnosis of systemic amyloidosis.
METHODS
We performed a systematic review using PRISMA guidelines. Inclusion criteria were level I-IV evidence articles that analyzed light-chain or transthyretin amyloid deposits in common orthopedic surgeries. Study methodological quality, risk of bias, and recommendation strength were assessed using MINORS, ROBINS-I, and SORT.
RESULTS
This systematic review included 24 studies for final analysis (3606 subjects). Amyloid deposition was reported in five musculoskeletal pathologies, including carpal tunnel syndrome (transverse carpal ligament and flexor tenosynovium), hip and knee osteoarthritis (synovium and articular cartilage), lumbar spinal stenosis (ligamentum flavum), and rotator cuff tears (tendon). A majority of studies reported a mean age greater than 70 for patients with TTR or AL positive amyloid.
CONCLUSIONS
This systematic review has shown the presence of amyloid deposition detected at the time of common orthopedic surgeries, especially in patients ≥70 years old. Subtyping of the amyloid has been shown to enable diagnosis of systemic light-chain or transthyretin amyloidosis prior to cardiac manifestations.
LEVEL OF EVIDENCE
Level IV.
Topics: Aged; Amyloid Neuropathies, Familial; Humans; Immunoglobulin Light-chain Amyloidosis; Orthopedic Procedures; Osteoarthritis, Hip; Osteoarthritis, Knee
PubMed: 33419417
DOI: 10.1186/s12891-020-03912-z -
Cardiology and Therapy Jun 2021This study investigates the gender distribution in patients diagnosed with wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt). (Review)
Review
INTRODUCTION
This study investigates the gender distribution in patients diagnosed with wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt).
METHODS
A systematic review and meta-analysis of the male proportion in diagnosed ATTRwt patients were conducted. To avoid overlapping population, pooled estimates in the primary analysis were based on all unique studies. In secondary analyses, we considered predefined subsets of studies based on study sample size, recruitment years, geography, study design, age at diagnosis, and method of diagnosis. Additional meta-regression analyses were tested for potential determinants of gender distribution.
RESULTS
Twenty-eight unique studies (2542 patients) were included in the meta-analysis. Male proportion in patients with ATTRwt was 86.9% (95% confidence interval 81.5-91.6%). Studies, including patients older than 80 years at diagnosis, had a 29.1% (p value < 0.001) lower male proportion compared to studies, including younger patients. After adjusting for age, studies using autopsy as a method of diagnosis had a 21.1% (p value 0.002) lower male proportion compared to other studies.
CONCLUSIONS
Studies conducted to date suggest ATTRwt disproportionally affects males. The proportion of males was significantly impacted by the age at diagnosis and method diagnosis, which may suggest important gender-based differences in the clinical manifestation and diagnostic challenges of ATTRwt in females that warrant future research.
PubMed: 33315233
DOI: 10.1007/s40119-020-00205-3 -
European Journal of Haematology Feb 2021Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab...
OBJECTIVES
Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting.
METHODS
A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations.
RESULTS
Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was ≥ 3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P = .03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4 months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6 ± 7.5% and 90.4 ± 4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n = 517) and 2 clinical trials (n = 62) meeting prespecified criteria.
CONCLUSIONS
Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.
Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Biomarkers; Clinical Trials as Topic; Disease Management; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome
PubMed: 33090552
DOI: 10.1111/ejh.13535