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Background : Pathogenic variants in the Polycystic Kidney Disease 2 (PKD2) gene are associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) in approximately 30% of cases. In recent years, the high-throughput sequencing techniques have significantly increased the number of variants identified in affected patients. Here, we described the peculiar effect of a PKD2 splicing variant, the c.1717-2A>G, identified in an Italian male patient with ADPKD. This variant led to the unusual and rare skipping of two consecutive exons, causing a large in-frame deletion. Methods : The genetic evaluation of the patient was performed using the Next-Generation Sequencing (NGS) assay Clinical Exome Solution ® (SOPHiA Genetics). Bioinformatics analysis was performed using the SOPHiA DDM platform (SOPHiA Genetics). Prediction of pathogenicity was carried out by integrating several in silico tools. RNA evaluation was performed to test the effect of the variant on the PKD2 splicing using a Reverse-Transcription PCR coupled with cDNA sequencing. Results : NGS revealed the presence of the PKD2 c.1717-2A>G variant that lies in the canonical splice site of intron 7. This rare variant was predicted to have a significant impact on the splicing, proved by the RNA-based analysis. We identified the presence of a transcript characterised by the simultaneous skipping of exons 8 and 9, with a retained reading frame and the merging of exons 7-10. Conclusions : We described for the first time a dual-exon skip event related to the presence of a single-base substitution in the PKD2 gene in an ADPKD-affected patient. We assumed that the molecular basis of such a rare mechanism lies in the specific order of intron removal. The finding represents novel evidence of an alternative and unusual splicing mechanism in the PKD2 gene, adding insights to the pathogenesis of the ADPKD.

Background: While anabolic hormone deficit is a common finding in heart failure with reduced ejection fraction (HFrEF), few data are available in heart failure with preserved ejection fraction (HFpEF)., Methods: Blood samples were collected for metabolic (total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glucose) and hormonal (IGF-1, DHEA-S, TSH, fT3, fT4, and T) determination, comparing 30 patients with HFpEF and 20 patients with HFrEF. Total antioxidant capacity was evaluated by using the spectrophotometric method using the latency time in the appearance of the radical species of a chromogen (LAG, sec) as a parameter proportional to antioxidant content of the sample. Echocardiographic parameters were also assessed in the two groups., Results: A high prevalence of testosterone (32% in HFrEF and 72% in HFpEF, p < 0.05) and DHEA-S deficiencies was observed in HFpEF patients. Echocardiographic parameters did not correlate with hormone values. A significant direct correlation between T ( r 2  = 0.25, p < 0.05) and DHEA-S ( r 2  = 0.19, p < 0.05) with LAG was observed only in HFpEF., Conclusion: Anabolic hormone deficiency is clearly shown in HFpEF, as already known in HFrEF. Although longitudinal studies are required to confirm the prognostic value of this observation, our data suggest different mechanisms in modulating antioxidants in the two conditions, with possible therapeutic implications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Antonio Mancini et al.)

On the ground of a personal observation of juvenile popliteal obstructive arteriopathy, the Authors have considered, after a brief revision of the literature, the physiopathology and the pathologic anatomy about this pathology which, even if uncommon, must by anyhow taken into consideration among the possible causes of "claudicatio intermittens" in young patients. A right diagnosis can be made only during the surgical intervention, the indications of which are represented either by a clinic objectiveness consistent with a peripheral obstruction with description of chronic or openly acute arterial failure, or by an angiographic checking which shows a stop along the femoropopliteal axis. The prognosis is generally good, as the literature confirms, and particularly in the case observed by the Authors it was quite satisfactory after a follow up of four years.

A series of 38 cases of superficial thrombosis occurring during the period 1-12-1979 to 1-12-1981 was examined. The series included 10 cases of iatrogenic thrombophlebitis of the upper limbs, one case of Mondor's thrombophlebitis, and 27 cases of superficial thrombophlebitis of the lower limbs in subjects with essential varices of the legs. A particular predilection for women and for advanced age was noted, as well as particular frequency in the area of distribution of the Great versus and Small Saphenous Vein, and a sharp prevalence of segments below the knee as compared with the thigh. Treatment was always surgical, mainly directed to preventing any thromboembolic complications, shortening the healing times and eliminating the Varicose Disease, which is well known to constitute the basic aetiopathogenetic moment of superficial thrombophlebitis. In all cases where it was possible to follow this schedule the result was excellent, and no effects on the deep venous system or thromboembolic complications occurred. The 5 patients treated with simple ligature of the Saphenous Vein according to Cross had a recurrence of varicose disease in a period varying from 6 months to 1 years; two of them also had a relapse of the thrombophlebitic process.

The Authors operated on a series of 173 patients with direct, indirect or relapsing hernia and crural hernia by Mc Vay's surgical procedure, of which they outlined the salient aspects. The study led to some statistical considerations with regard to the rate and time of appearance of the various types of subject hernia in the two sexes and also evidenced two cases of post-operative complication very probably due to the technique used. The follow-up evidenced only one case of relapse. Despite the small number of cases and the restricted nature of the follow-up, which varied from two years to six months, the Authors consider that Mc Vay's plastic surgery constitutes a highly reliable technique for treatment of both primitive and relapsing hernias. Particular practical interest attaches to the observation that 90% of patients were operated under epidural anaesthesia, which, given parity of results from the surgical standpoint, involves a considerably lower anaesthesiological risk than other types of anaesthesia.

The authors studied 500 pregnant women suffering from varicose pathology, they had the opportunity to observe in the years 1979, 1980, 1981. The range of age hit was between 18 and 46 years. A higher prevalence occurred in pluriparae (82.8%) in respect of primiparae (17.2%). As to the type of varicose pathology observed, 40% showed diffused teleangectasies; 30% essential varices weighing on small and large saphena; 20% associations of the two former types; 6.4% post-phlebitic syndromes with insufficiency of the deep communicating vessels, and 3.6% pudendae venous ectasies. The medical treatment, aiming to avoid venous stasis and rise in weight, was effected in 94% of cases: in 40% of cases a choice was also done for a pharmacologic treatment with synthetic glucofuranoside compounds, interrupted in 3.5% of the patients for the arising of more or less various symptoms of gastric intolerance. In the remaining 6% of cases, it was essential to adopt the surgical treatment, always performed after the 4th month of pregnancy and in epidural anaesthesia. As to the surgical indications, the authors remarked the higher frequency for the post-phlebitic syndromes with incompetence of the deep communicating vessels and serious tropic alterations, affecting in the rate of 40% the operated patients and 2.4% the varicose pathology they aggregately had the opportunity to observe. The other indications were the surface thrombophlebites (33.4%), varices with remarkable subjective troubles and cutaneous alterations of average and serious importance (6,6%) and larger caliper varices in pluriparae (20%). The authors, in the several middle and long term follow-up, never recorded any relapses in the patients surgically treated.

The Authors refer about a case of rare obstructive arteriopathy of the Hunterian superficial femoral artery, disease better known as Palma's Syndrome.

The AA. propose the utilization of the relaxing incision of the aponeurosis during the Hernioplasty according to McVay's procedure. The main advantage of such a method is the lower tension of the suture of the plasty, with several aspects, which take to a lower incidence of recurrences. Also anaesthesiological aspects tied to such a surgical procedure are considered, after having said precisely the indications of the known methods of anaesthesia.