Autoantibody Response to Islet Transplantation in Type 1 Diabetes

Islet allotransplantation into patients with autoimmune type 1 diabetes represents a reexposure to autoantigen. Here, measurement of antibodies to GAD and IA-2 autoantigens before and after islet transplantation in 36 patients (33 receiving islet plus kidney grafts with cyclosporin and steroid-based immunosuppression, and 3 receiving solitary islet transplants with mycophenolate but cyclosporin-free immunosuppression) demonstrated marked rises in GAD antibodies within 7 days posttransplantation in 5 patients (3 receiving islet after kidney transplants, and 2 receiving solitary islet transplants) and within 30 days in the third patient receiving solitary islet transplantation. GAD antibodies were of the IgG1 subclass, against major autoantigenic epitopes, and in cases of islet after kidney transplants, the responses were short-lived and not accompanied by HLA antibodies. Two of these patients had subsequent marked rises of IA-2 antibodies, and an additional patient had a marked rise in IgM-GAD antibodies 3 years after transplantation. Insulin independence was not achieved in patients with autoantibody elevations and was significantly less frequent in these patients. These data are consistent with a reactivation of autoimmunity that may be dependent on immunosuppression therapy and is associated with impaired graft function

Small Subcutaneous Soft Tissue Tumors (<5 cm) Can Be Sarcomas and Contrast-Enhanced Ultrasound (CEUS) Is Useful to Identify Potentially Malignant Masses

Subcutaneous masses smaller than 5 cm can be malignant, in contrast with the international guidelines. Ultrasound (US) and magnetic resonance imaging (MRI) are useful to distinguish a potentially malignant mass from the numerous benign soft tissue (ST) lesions. Contrast-enhanced ultrasound (CEUS) was applied in ST tumors, without distinguishing the subcutaneous from the deep lesions. We evaluated CEUS and MRI accuracy in comparison to histology in differentiating malignant from nonmalignant superficial ST masses, 50% smaller than 5 cm. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) with their 95% confidence intervals (CI) were calculated. Of malignant cases, 44.4% measured &le;5 cm. At univariate analysis, no statistically significant differences emerged between benign and malignant tumors in relation with clinical characteristics, except for relationship with the deep fascia (p = 0.048). MRI accuracy: sensitivity 52.8% (CI 37.0, 68.0), specificity 74.1% (CI 55.3, 86.8), PPV 73.1% (CI 53.9, 86.3), and NPV 54.1% (CI 38.4, 69.0). CEUS accuracy: sensitivity 75% (CI 58.9, 86.3), specificity 37% (CI 21.5, 55.8), PPV 61.4% (CI 46.6, 74.3), and NPV 52.6% (CI 31.7, 72.7). CEUS showed a sensitivity higher than MRI, whereas PPV and NPV were comparable. Also, masses measuring less than 5 cm can be malignant and referral criteria for centralization could be revised

The rs1001179 SNP and CpG methylation regulate catalase expression in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an extremely variable clinical course. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course. Elucidating mechanisms regulating CAT expression in CLL is preeminent to understand disease mechanisms and develop strategies for improving its clinical management. In this study, we investigated the role of the CAT promoter rs1001179 single nucleotide polymorphism (SNP) and of the CpG Island II methylation encompassing this SNP in the regulation of CAT expression in CLL. Leukemic cells harboring the rs1001179 SNP T allele exhibited a significantly higher CAT expression compared with cells bearing the CC genotype. CAT promoter harboring the T -but not C- allele was accessible to ETS-1 and GR-β transcription factors. Moreover, CLL cells exhibited lower methylation levels than normal B cells, in line with the higher CAT mRNA and protein expressed by CLL in comparison with normal B cells. Methylation levels at specific CpG sites negatively correlated with CAT levels in CLL cells. Inhibition of methyltransferase activity induced a significant increase in CAT levels, thus functionally validating the role of CpG methylation in regulating CAT expression in CLL. Finally, the CT/TT genotypes were associated with lower methylation and higher CAT levels, suggesting that the rs1001179 T allele and CpG methylation may interact in regulating CAT expression in CLL. This study identifies genetic and epigenetic mechanisms underlying differential expression of CAT, which could be of crucial relevance for the development of therapies targeting redox regulatory pathways in CLL

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Significance of a single pulmonary nodule in patients with previous history of malignancy.

none5OBJECTIVES: To determine the diagnosis, treatment and follow-up in patients with a solitary lung nodule and a previous primary extrapulmonary neoplasm. METHODS: The authors evaluated the charts of 45 patients with an extrapulmonary malignant neoplasm and a solitary pulmonary nodule. The histologic characteristics of the nodule were correlated with those of the extrapulmonary neoplasm. RESULTS: The histology of the nodule was not known preoperatively in 43 cases (93.5%); in the remaining three cases cytologic examination had shown the presence of atypical cells. The majority of pulmonary lesions (73.9%) were found during the follow-up of the previous tumour, but a significant percentage of nodules (17.4%) were found incidentally. Pre- or intraoperative localisation of the nodule was done in 19 cases (41.3%), and was successful in nine cases (47.4%). Thoracoscopy was performed in 44 patients (95.6%). The coincidence between the pathology of the previous tumour and that of the nodule was 41.3% (19/46). The coincidence rate was 100% for the tumours of ovary, prostate, and sarcomas. CONCLUSIONS: The advent of minimally invasive surgical techniques has made a definitive diagnosis likely, providing also therapy with a less painful engagement for the patient and a less cost for the community.noneSORTINI A.; CARCOFORO P; ASCANELLI S; SORTINI D; POZZA ESortini, Andrea; Carcoforo, Paolo; Ascanelli, Simona; Sortini, Davide; Pozza, Enz

ONE WOUND "MUPPETS SHOW_MAN TECHNIQUE" LAPAROSCOPIC CHOLECYSTECTOMY

none6------openNAVARRA G.; CARCOFORO P.; OCCHIONORELLI S.; ASCANELLI S.; POLEDRELLI M.; POZZA E.Navarra, Giuseppe; Carcoforo, Paolo; Occhionorelli, Savino; Ascanelli, Simona; Poledrelli, M.; Pozza, Enz