NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. PATIENTS AND METHODS: This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). RESULTS: During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.

A challenging case of pigmented Bowen's disease and differential diagnosis of pagetoid pigmented skin lesions.

We report a singular case of pigmented pagetoid Bowen's disease showing transitional features between extramammary Paget's disease and in situ squamous cell carcinoma.^ieng

Differentiation of pagetoid cutaneous neoplasms can be very challenging on hematoxylin and eosin-stained sections.

Follicular occlusion tetrad in a male patient with pachyonychia congenita: clinical and genetic analysis.

The case of a 24-year-old male patient affected by follicular occlusion tetrad (acne conglobata, hidradenitis suppurativa, pilonidal cyst and dissecting cellulitis of the scalp) associated with clinical signs of pachyonychia congenita (PC)-2 (focal palmoplantar keratoderma, plantar pain, onycodystrophy and multiple cysts) is reported. The diagnosis was supported by genetic analysis that showed heterozygous mutation within the exon 1 of KRT17 gene. This case may reflect different expressions of a phenotypic spectrum induced by a common genetic alteration.

Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines.

Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.

Pancreatic panniculitis.

Pancreatic panniculitis (PP) is a rare variant of panniculitis characterized by subcutaneous fat necrosis, that affects 0.3-3% of patients across a range of different pancreatic disorders. It presents with painful, tender, erythematous to violaceous nodules that may undergo spontaneous ulceration and discharge of an oily brown, viscous material, resulting from liquefactive necrosis of adipocytes. These lesions usually involve the lower extremities, although may also spread over the buttocks, trunk, arms and scalp. In addition to the skin, fat necrosis may involve periarticular, abdominal and intramedullary adipose tissue. In 40% of cases, skin manifestations can precede by 1 to 7 months the abdominal symptoms of pancreatic disease, which include mostly acute and chronic pancreatitis, pancreatic carcinoma, more frequently of acinar cell type, and pancreatic abnormalities. Histopathologically, PP shows characteristic features of mostly lobular panniculitis with marked necrosis of adipocytes. The necrotic adipocytes with finely granular and basophilic material in the cytoplasm due to calcium deposits are known as "ghost adipocytes". The treatment of pancreatic panniculitis is directed to the underlying pancreatic disease. The prognosis is poor in cases associated with pancreatic carcinoma. When there is widespread and persistent disease, frequent relapses, or ulceration, the possibility of an occult carcinoma of the pancreas should be always considered. While describing three patients seen at the Dermatology Section of the University of Genova from 1990 to 2012, we highlight that, in addition to the rarity of the disease, the precise diagnosis requires adequate samples consisting in large-scalpel incisional biopsies of fully developed lesions.

Isolation of novel microsatellite loci in the black goby Gobius niger and cross-amplification in other gobiid species (Perciformes, Gobiidae).

Twelve microsatellite loci were isolated from and characterized for the black goby Gobius niger. These loci were tested on a total of 48 individuals from two geographically distant locations (Orbetello and Cattolica) and the number of alleles ranged from two to 18, with expected (H(e)) and observed (H(o)) heterozygosities ranging from 0.042 to 0.941 and from 0.042 to 0.917, respectively. The loci described were used to cross-amplify other gobiid species belonging to Gobius, Zosterisessor, Lesueurigobius and Aphia.

Pili annulati coincident with alopecia areata, autoimmune thyroid disease, and primary IgA deficiency: case report and considerations on the literature.

Pili annulati is a rare autosomal dominant hair disorder clinically characterized by a pattern of alternating bright and dark bands of the hair, the bright bands appearing dark if observed by transmitted light. This pattern is due to the periodic occurrence of air-filled cavities along the hair cortex which scatter and reflect the light while precluding its transmission. A susceptibility region, including a possibly responsible Frizzled gene, has been mapped to the telomeric region of chromosome 12q, although a specific mutation has not been identified. The condition has sometimes been observed in concurrence with alopecia areata, and in this paper we report a case in whom the concomitant severe alopecia areata was associated with autoimmune thyroid disease and primary IgA deficiency - a quadruple complex which, to our knowledge, has never been previously described. The occurrence of multiple immune disorders in the same patient affected by pili annulati could represent a key to understanding the high prevalence of alopecia areata in this condition. Specifically, in individuals predisposed to autoimmune disease, the molecular alterations that cause the anatomical changes of pili annulati could prompt the immune response against the hair root that underlies alopecia areata.

Postsurgical paracicatricial cutaneous satellitosis of giant cell tumour of the tendon sheath, localized type.

Tenosynovial giant cell tumour (localized type) is a tumour of tendon sheaths and interphalangeal joints, affecting the digits and arising from the synovium. It is characterized by a proliferation of mononuclear cells and osteoclast-like polykaryocytes. Its propagation to the skin is an exceptional event, which can take place either in localized form in the fingertips (localized type) or in the rare diffuse form called giant cell tumour of the tendon sheath (diffuse type). We report here a case of giant cell tumour with cutaneous satellites, which appeared close to and around the surgical scar following the excision of the primary lesion, in a 9-year-old boy. In the cutaneous satellites, a few signs of transformation could be observed, consisting of the lack of stroma and pronounced cellularity characterized by sheets of rounded synovial-like cells admixed with multinucleated giant cells and xanthoma cells. No relapse was observed 1 year after a plastic surgery procedure (complete replacement of the involved skin). Diffuse lesions usually represent a diagnostic problem in comparison with their localized counterparts. The malignant transformation of an originally typical tenosynovial giant cell tumour is a rare but well-documented event. Our case seems to represent a typical example because the pronounced cellularity might wrongly lead to a diagnosis of malignancy.

A clinical case of necrotizing sialometaplasia and conjunctival hemorrhage.

The first case reported in the literature of a rare disease called necrotizing scialometaplasia (NS), dates back to 1973 when Abrams et al. described the main histological features of this disease. In this article we describe the rare clinical case of a young woman came to our observation for a double ulcer in the middle portion of the hard palate, aching, that histological examination showed compatible with a diagnosis of NS and preceded his appearance a haemorrhagic conjunctival suffusion left. We have provided a complete description of all the investigations in which the patient underwent and its treatment. We have also outlined the major etiological hypotheses of SN, histological features that point to a correct diagnosis, clinical features and prognostic and finally we reflected on the rare and interesting overlap in clinical manifestations palatal and conjunctival those trying to find a possible explanation.

Characterisation of a GC-rich telomeric satellite DNA in Eumeces schneideri Daudin (Reptilia, Scincidae).

A hitherto undescribed satellite DNA family (AvaII satDNA) has been isolated and characterised in Eumeces schneideri, a squamate reptile belonging to the family Scincidae. AvaII satDNA is characterised by a monomer length of 208 bp, a GC content of 59% and exhibits a certain degree of CpG methylation. FISH experiments with AvaII satDNA probe produced bright signals (i) at the end of the short arms of all subtelocentric chromosomes except for pair 14, in which the signal was at the end of the long arms, (ii) at the ends of both arms of the small metacentric chromosomes 12, and (iii) in a terminal position on the acrocentric chromosomes 11 and 13. AvaII satDNA repeats were not found in the metacentric pair 3, whereas only a weak interstitial signal occurred in the metacentric pairs 1 and 2. C-banding showed that this satellite represents most of the constitutive heterochromatin in the genome of this skink, and chromomycin A(3) staining produced a clear signal overlapping with the satellite, except for NOR-associated heterochromatin. In addition, quantitative dot blot analysis showed that these repetitive sequences constitute about 3% of the genomic DNA of this lizard. AvaII satDNA sequence analysis revealed the occurrence of short guanine residue stretches for which a function in structural stability of these sequences and a role in recombination with telomeric sequences can be hypothesised. Fibre FISH experiments showed that on some chromatin fibres telomeric sequences and AvaII satellite DNA repeats are intermingled or overlapping.

Chromosomal study of native and hatchery trouts from Italy (Salmo trutta complex, Salmonidae): conventional and FISH analysis.

A cytogenetic analysis was carried out using conventional staining, banding techniques and fluorescence in situ hybridization (FISH) in Italian populations of brown trout (Salmo truttacomplex). All individuals analysed, belonging to the Atlantic (At), Marmoratus (Ma), Adriatic (Ad) and Mediterranean (Me) lineages, showed remarkable karyotype uniformity, with diploid complement of 2n = 80 chromosomes, arm number (NF) of 102 and invariable karyotype composition. Such uniformity was also observed with respect to the location of 5S rDNA and the active, i.e. silver-positive NOR sites. On the contrary, FISH with 28S ribosomal probe and fluorescent staining with CMA3 revealed that inactive NOR sites are more numerous in Ad and Me than in At and Ma lineages. A centromeric sequence was successfully isolated from Salmo trutta individuals by polymerase chain reaction (PCR)-based cloning, using primers designed from published Atlantic salmon (Salmo salar) satellite DNA sequences. This sequence had high AT content (65.3%) and short consensus motif (A/T)(G/C)AAA(T/C) similar to other centromeric satellite repeats. The isolated satellite DNA clones were localized with FISH in the centromeric regions of the brown trout chromosomes, showing lineage-specific patterns. Because it is well known that AT-rich sequences can induce a pronounced DNA curvature, which in turn would promote faster and higher chromatin spiralization, it may be hypothesised that the wide distribution of this satellite in the S. trutta genome may have played a role in its karyotype stability. The presence of this sequence in other salmonid species was also tested by Southern blot hybridization and used to analyze its evolution within salmonids.

Mitochondrial DNA variation of an isolated population of the Adriatic brook lamprey Lampetra zanandreai (Agnatha: Petromyzontidae): phylogeographic and phylogenetic inferences.

Two mitochondrial genes were examined to compare an isolated population of the Adriatic brook lamprey Lampetra zanandreai in central Italy with other populations in the species range (Po plain) and with parasitic and freshwater lampreys. A single haplotype, identical to one in a Venetian sample, was found in 10 individuals from the isolated population. The reduced variability is consistent with a history of dispersal after the Pleistocene expansion of the Po basin. The results support the hypothesis of an origin of L. zanandreai and L. fluviatilis-L. planeri from a common anadromous ancestor.

Skinks (Reptilia: Scincidae) have highly conserved karyotypes as revealed by chromosome painting.

Skinks represent the most diversified squamate reptiles with a great variation in body size and form, and are found worldwide in a variety of habitats. Their remarkable diversification has been accompanied by only a few chromosome rearrangements, resulting in highly-conservative chromosomal complements of these lizards. In this study cross-species chromosome painting using Scincus scincus (2n = 32) as the source genome, was used to detect the chromosomal rearrangements and homologies between the following skinks: Chalcides chalcides (2n = 28), C. ocellatus (2n = 28), Eumeces schneideri (2n = 32), Lepidothyris fernandi (2n = 30), Mabuya quinquetaeniata (2n = 32). The results of this study confirmed a high degree of chromosome conservation between these species. The main rearrangements in the studied skinks involve chromosomes 3, 5, 6 and 7 of S. scincus. These subtelocentric chromosomes are homologous to the p and q arms of metacentric pair 3 and 4 in C. chalcides, C. ocellatus, L. fernandi, and M. quinquetaeniata, while they are entirely conserved in E. schneideri. Other rearrangements involve S. scincus 11 in L. fernandi and M. quinquetaeniata, supporting the monophyly of Lygosominae, and one of the chromosomes S. scincus 12-16, in M. quinquetaeniata. In conclusion, our data support the monophyly of Scincidae and confirm that Scincus-Eumeces plus Chalcides do not form a monophyletic clade, suggesting that the Scincus-Eumeces clade is basal to other members of this family. This study represents the first time the whole genome of any reptile species has been used for cross-species chromosome painting to assess chromosomal evolution in this group of vertebrates.

Oligoartritis como forma de presentación temprana de sarcoma granulocítico / Oligoarthritis as inicial manifestation of granulocytic sarcoma

La literatura médica refiere bastamente la asociación de neoplasia y enfermedad reumática pero, en general, de una manera poco consistente. Neoplasmas sólidos, linfomas, mielomas y leucemias pueden causar enfermedad reumática por infiltración o por mecanismos inmunológicos, pero en la mayoría de los casos es difícil demostrar causalidad.1 Numerosos autores debaten este tema, existen muchas publicaciones internacionales al respecto citándose diferentes tipos de cáncer en el contexto de varios síndromes de naturaleza autoinmune. 2,3 Síndromes autoinmunes paraneoplásicos se observan también en pacientes con enfermedad mielodisplásica. Una revisión de casos individuales y pequeñas series sugieren que alrededor del 10% de estos pacientes puede experimentar varios síndromes autoinmunes, incluyendo como manifestaciones clínicas más frecuentes vasculitis cutáneas y sistémicas, fiebre, artritis, infiltrados pulmonares, polineuropatía periférica, enfermedad intestinal inflamatoria y glomerulonefritis que habitualmente responden también al tratamiento inmunosupresor o esteroideo

High frequency of subtelomeric rearrangements in a cohort of 92 patients with severe mental retardation and dysmorphism.

About 5-10% of patients with dysmorphisms, severe mental retardation, and normal standard karyotype are affected by subtelomeric chromosome rearrangements. Sequence homology between different chromosomes and variability between homologs make these regions more susceptible to breakage and reunion. We analyzed the telomeric regions of 92 of these patients, selected with strict clinical criteria. Fifteen individuals (16.3%) had subtelomeric rearrangements. Nine had a unique anomaly, which in one case had been inherited from a balanced parent. Six subjects had double segmental imbalances, including three de novo imbalances. This study provides further evidence for the plasticity of subtelomeric regions, which often results in cryptic rearrangements, and recommends stringent criteria for selecting patient candidates to telomere analysis.