Plasmablastic lymphoma (PBL) is a rare and clinically aggressive neoplasm that typically occurs in immunocompromised individuals, including those with HIV infection and solid organ allograft ...recipients. Most prior studies have focused on delineating the clinicopathologic features and genetic attributes of HIV-related PBLs, where MYC deregulation and EBV infection, and more recently, mutations in JAK/STAT, MAP kinase, and NOTCH pathway genes have been implicated in disease pathogenesis. The phenotypic spectrum of post-transplant (PT)-PBLs is not well characterized and data on underlying genetic alterations are limited. Hence, we performed comprehensive histopathologic and immunophenotypic evaluation and targeted sequencing of 18 samples from 11 patients (8 males, 3 females, age range 12-76 years) with PT-PBL; 8 de novo and 3 preceded by other types of PTLDs. PT-PBLs displayed morphologic and immunophenotypic heterogeneity and some features overlapped those of plasmablastic myeloma. Six (55%) cases were EBV+ and 5 (45%) showed MYC rearrangement by fluorescence in situ hybridization. Recurrent mutations in epigenetic regulators (KMT2/MLL family, TET2) and DNA damage repair and response (TP53, mismatch repair genes, FANCA, ATRX), MAP kinase (KRAS, NRAS, HRAS, BRAF), JAK/STAT (STAT3, STAT6, SOCS1), NOTCH (NOTCH1, NOTCH3, SPEN), and immune surveillance (FAS, CD58) pathway genes were observed, with EBV+ and EBV- cases exhibiting similarities and differences in their mutational profiles. Clinical outcomes also varied, with survival ranging from 0-15.9 years postdiagnosis. Besides uncovering the biological heterogeneity of PT-PBL, our study highlights similarities and distinctions between PT-PBLs and PBLs occurring in other settings and reveals potentially targetable oncogenic pathways in disease subsets.
Benzoate (Bz), 2,4-dichlorobenzoate (BzDC), and p- and o-hydroxybenzoate (p- and o-BzOH) anions with antimicrobial activity have been intercalated into Zn(0.65)Al(0.35)(OH)(2)(NO(3))(0.35).0.6H(2)O, ...layered double hydroxide (LDH), via anion-exchange reactions. The composition of the obtained intercalation compounds, determined by chemical, thermogravimetric, and ion chromatographic analyses, indicates that benzoate and benzoate derivative anions replace the nitrate counteranions, almost completely. Information on the interactions of the intercalated anions with the inorganic layer have been obtained from Fourier transform IR absorption spectroscopy and powder X-ray diffraction of the samples. It has been found that both the nature and the position of the aromatic ring substituents affect the value of the basal distance and the host-guest hydrogen bond network. Knowledge of the chemical composition, basal distance, and van der Waals dimensions of the guests has finally allowed the proposal of structural models of the intercalation compounds that have been used as fillers of poly(caprolactone), a biodegradable polymer. Films of polymeric composites were obtained by hot-pressing the powders of polymer and filler previously milled by a high-energy ball milling procedure. X-ray diffraction analysis and optical and scanning electron microscopy of the composites indicate that the LDH samples containing BzDC anions are delaminated into the polymeric matrix, whereas those containing p-BzOH anions maintain for the most part the crystal packing and give rise to microcomposites. Intermediate behavior was found for LDH modified with Bz and o-BzOH anions because exfoliated and partly intercalated composites were obtained. Preliminary antimicrobial tests indicate that the composites are able to inhibit the Saccharomyces cerevisiae growth of 40% in comparison with the growth in a pure culture medium. The composites can be studied as the model for "active packaging" systems because of the antimicrobial properties of the anions anchored to the LDH layer.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure in adult life. Rarely, ADPKD can be diagnosed in utero or in infancy, and the genetic mechanism ...underlying such severe presentation has been shown to be related to reduced gene dosage. Biallelic
variants are often identified in early onset ADPKD, with one main pathogenic variant and a modifier hypomorphic variant showing an in trans configuration. We describe two unrelated individuals with early onset cystic kidney disease and unaffected parents, where a combination of next-generation sequencing of cystic genes including
,
and
allowed the identification of biallelic
variants. Furthermore, we review the medical literature in order to report likely
hypomorphic variants reported to date and estimate a minimal allele frequency of 1/130 for this category of variants taken as a group. This figure could help to orient genetic counseling, although the interpretation and the real clinical impact of rare
missense variants, especially if previously unreported, remain challenging.
Aorto-esophageal fistula (AEF) is an uncommon but usually fatal disorder. Surgery with resection of an aneurysm and esophagus, in situ reconstruction of the descending aorta and omental flap ...installation offers the gold standard for the reduction of infections, but it is burdened by high intraoperative and perioperative mortality rates. We report our experience with a combined minimally invasive approach for the multi-stage treatment of three cases of aorto-esophageal fistula caused by thoracic aneurysm rupture. In all of the patients, the aneurysm was treated with thoracic endovascular aortic repair and the esophageal lesion was treated with esophageal endoprosthesis placement. According to our experience, the combined strategy of thoracic endovascular aortic repair (TEVAR) and esophageal less invasive endoscopic treatments represents an alternative solution in frail patients with high surgical risk.
The treatment of renal artery aneurysms located from the mid to distal portion of the vessel is challenging. The complexity is related to the frequent involvement of side branches and to the risk of ...postoperative renal impairment. We report five cases of multidisciplinary treatment of distal renal artery aneurysms, adopting in situ reconstruction technique and renal perfusion with Custodiol solution, with satisfactory early and mid-term outcomes.
Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the
gene, which encodes for a subunit of caseinkinase
involved in neuronal growth and synaptic ...transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of
.
Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of
mutation.
We reported nine unrelated patients with heterozygous de novo mutations of the
gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of
that have not been reported previously.
Although it was not possible to assess a genotype-phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the
gene.
An extracranial carotid artery aneurysm (ECAA) is a rare condition. The major complications are rupture and thromboembolism. Therefore, treatment is generally recommended. We report the case of a ...young woman affected by an ECAA, with a cervical pulsatile mass. A multidisciplinary evaluation was performed to ensure the best treatment in terms of safety and efficacy, and the patient underwent hybrid treatment. The 6-month computed tomography angiogram revealed patency of the carotid artery stents and the venous graft, in the absence of any relevant complications. An ECAA is a serious clinical condition. The treatment is challenging, and a multidisciplinary evaluation and precise planning are recommended.
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