Tumoral non-amyloidotic monoclonal immunoglobulin light chain deposits ('aggregoma'): presenting feature of B-cell dyscrasia in three cases with immunohistochemical and biochemical analyses

Tumoral monoclonal immunoglobulin (Ig) light chain non-fibrillar deposits ('aggregomas'), which can be considered analogous to solitary light chain amyloidomas, are a rare presenting feature of B-cell dyscrasias. It is not certain if they are truly localized or if in reality they represent an initial expression of a silent systemic non-amyloid light chain deposition disease (LCDD). This report describes three patients, two of whom presented with cervical masses and the third with a solitary lung nodule, each comprising granular aggregates of monoclonal kappa light chain. Extracted deposits from the lymph node of one patient were shown by N-terminal amino acid sequence analysis to belong to the variable-region kappa I (Vkappa I) light chain subgroup, the first reported kappa-LCDD protein encoded by the L9 gene and the first report of an expressed protein related to this gene. Extracted deposits from the lung nodule of the second patient belonged to the Vkappa IV light chain subgroup encoded by the B3 germ line gene. The N-terminal amino acid sequences of the light chains from the aggregomas were compared with the related germ line sequences and to the N-terminal amino acid sequences of the nine other known kappa-LCDD light chains reported thus far from patients with systemic LCDD.     

Auto-induced eosinophilic panniculitis: a diagnostic dilemma

Eosinophilic panniculitis is characterized by a prominent infiltration of subcutaneous fat with eosinophils. The clinical spectrum of lesions that display pathologic changes of eosinophilic panniculitis is diverse, but nodular lesions are the most common. The factitial eosinophilic panniculitis are exceptional, show a pleomorphic pattern of findings and are associated with personality disorders. Its main challenge is to establish the correct diagnostic. We report an unusual case of factitial nodular febrile panniculitis of the left forearm and proximal arm in an 16 year-old girl. She admitted that the lesions were self-inflicted by autoinjection of several farming products as attempted suicide. We describe the clinical, radiological and histopathological features as well as the differential diagnosis of this type of panniculitis.     

Comparison of stent versus balloon angioplasty for pulmonary vein stenosis complicating pulmonary vein isolation

Introduction: Pulmonary vein stenosis (PVS) is a rare but significant complication of pulmonary vein isolation (PVI). Dilation and stent angioplasty have been described but not compared.
Methods and Results: All percutaneous interventions for PVS complicating PVI between December 2000 and March 2007 were reviewed. Acute success, defined as post-intervention stenosis ≤30%, and long-term outcome of dilation versus stent angioplasty were compared. Freedom from restenosis was defined as freedom from repeat intervention. Overall outcome for all interventions was examined. We studied 34 patients with 55 stenotic veins followed for a mean of 25 months. Dilation was performed in 39 veins and stenting in 40 veins (16 primarily, 24 after dilation restenosis). Acute success and restenosis rates were 42% and 72% for dilation versus 95% (P < 0.001) and 33% for stenting. Time to restenosis was greater for stent angioplasty (P = 0.003). Stents ≥10 mm in diameter had lower restenosis than smaller stents. Risk factors for restenosis included small reference vessel diameter and longer time from PVI to intervention for PVS. All but two patients experienced improvement (n = 10) or resolution of symptoms (n = 22). The mean percent stenosis decreased from 82% to 21% for the entire cohort and mean flow to the lung quadrant increased from 10% to 17%.
Conclusion: Stent angioplasty results in less restenosis than dilation, particularly for stents ≥10 mm. Early referral may improve long-term patency by minimizing reference vessel atrophy. Most patients with PVS post-PVI can be improved symptomatically with catheter intervention.     

The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G₂/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1–3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle.     

Tromboembolismo pulmonar en pacientes con COVID-19: estudio de prevalencia en un hospital terciario

IntroductionSARS-CoV-2, the virus responsible for the current pandemic, predominantly affects the respiratory tract, and a growing number of publications report the predisposition of patients with COVID-19 to develop thrombotic phenomena.ObjectiveTo determine the prevalence of pulmonary embolism in patients with COVID-19; to determine the possible relationship between the severity of pulmonary involvement and D-dimer levels; to analyze the location of pulmonary embolisms in patients with COVID-19 and to compare it with the location in patients without COVID-19.MethodsThis retrospective study analyzed all CT angiograms of the pulmonary arteries done in patients with suspected pulmonary embolisms between March 15 and April 30, 2020 and compared them with studies done in the same period one year earlier.ResultsWe included 492 pulmonary CT angiograms (342 (69.9%) in patients with COVID-19 and 147 (30.1%) in patients without COVID-19). The prevalence of pulmonary embolisms was higher in patients with COVID-19 (26% vs. 16.3% in patients without COVID-19, p=0.0197; relative risk=1.6). The prevalence of pulmonary embolisms in the same period in 2019 was 13.2%, similar to that of the group of COVID-19-negative patients in 2020 (p=0.43). There were no significant differences in D-dimer levels or the location of pulmonary embolisms between the two groups. CT showed moderate or severe pulmonary involvement in 78.7% of the patients with COVID-19.ConclusionsPatients with COVID-19 have an increased prevalence of pulmonary embolisms (26%), and most (78.7%) have moderate or severe lung involvement on CT studies. The location of pulmonary embolisms and the degree of elevation of D-dimer levels does not differ between patients with COVID-19 and those without.     

A Novel Regulatory Defect in the Branched‐Chain α‐Keto Acid Dehydrogenase Complex Due to a Mutation in the PPM1K Gene Causes a Mild Variant Phenotype of Maple Syrup Urine Disease

This article describes a hitherto unreported involvement of the phosphatase PP2Cm, a recently described member of the branched‐chain α‐keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease‐causing mutation was identified in a patient with a mild variant phenotype, involving a gene not previously associated with MSUD. SNP array‐based genotyping showed a copy‐neutral homozygous pattern for chromosome 4 compatible with uniparental isodisomy. Mutation analysis of the candidate gene, PPM1K, revealed a homozygous c.417_418delTA change predicted to result in a truncated, unstable protein. No PP2Cm mutant protein was detected in immunocytochemical or Western blot expression analyses. The transient expression of wild‐type PPM1K in PP2Cm‐deficient fibroblasts recovered 35% of normal BCKDH activity. As PP2Cm has been described essential for cell survival, apoptosis and metabolism, the impact of its deficiency on specific metabolic stress variables was evaluated in PP2Cm‐deficient fibroblasts. Increases were seen in ROS levels along with the activation of specific stress‐signaling MAP kinases. Similar to that described for the pyruvate dehydrogenase complex, a defect in the regulation of BCKDH caused the aberrant metabolism of its substrate, contributing to the patient's MSUD phenotype—and perhaps others.