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Morgana is a ubiquitous HSP90 co-chaperone protein coded by the CHORDC1 gene. Morgana heterozygous mice develop with age a myeloid malignancy resembling human atypical myeloid leukemia (aCML), now renamed MDS/MPN with neutrophilia. Patients affected by this pathology exhibit low Morgana levels in the bone marrow (BM), suggesting that Morgana downregulation plays a causative role in the human malignancy. A decrease in Morgana expression levels is also evident in the BM of a subgroup of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients showing resistance or an incomplete response to imatinib. Despite the relevance of these data, the mechanism through which Morgana expression is downregulated in patients' bone marrow remains unclear. In this study, we investigated the possibility that Morgana expression is regulated by miRNAs and we demonstrated that Morgana is under the control of four miRNAs (miR-15a/b and miR-26a/b) and that miR-15a may account for Morgana downregulation in CML patients., (© 2024. The Author(s).)

Acute myeloid leukemia (AML) is a complex hematologic malignancy with high morbidity and mortality. Nucleophosmin 1 (NPM1) mutations occur in approximately 30% of AML cases, and NPM1-mutated AML is classified as a distinct entity. NPM1-mutated AML patients without additional genetic abnormalities have a favorable prognosis. Despite this, 30-50% of them experience relapse. This study aimed to investigate the potential of total RNAseq in improving the characterization of NPM1-mutated AML patients. We explored genetic variations independently of myeloid stratification, revealing a complex molecular scenario. We showed that total RNAseq enables the uncovering of different genetic alterations and clonal subtypes, allowing for a comprehensive evaluation of the real expression of exome transcripts in leukemic clones and the identification of aberrant fusion transcripts. This characterization may enhance understanding and guide improved treatment strategies for NPM1mut AML patients, contributing to better outcomes. Our findings underscore the complexity of NPM1-mutated AML, supporting the incorporation of advanced technologies for precise risk stratification and personalized therapeutic strategies. The study provides a foundation for future investigations into the clinical implications of identified genetic variations and highlights the importance of evolving diagnostic approaches in leukemia management.

It is well known by surgeons that patient positioning is fundamental to exposing the organs when performing an operation via laparoscopy, as gravity can help move the organs and facilitate the exposure of the surgical site. But is it also important for endoscopic procedures? This paper examines various types of endoscopic operations and addresses the issue of the patient's position. The patient's position can be changed not only by rotating the patient along the head-toe axis but also by tilting the surgical bed, as is undertaken during laparoscopic surgical procedures. In particular, it is useful to take into account the effect of gravity on lesion exposure, tumour traction during dissection, crushing by body weight, risk of sample drop, risk of damage to adjacent organs, and anatomical exposure for procedures with radiological support. The endoscopist should always keep in mind the patient's anatomy and the position of the endoscope during operative procedures, not limited to considering only intraluminal vision.

Background: Collateral damage to surrounding healthy tissues has been reported in patients who undergo radiation therapy for pelvic malignancies. This study aimed to evaluate the safety, efficacy and cost efficiency of endoscopic diode laser therapy in patients diagnosed with chronic radiation proctitis (CRP)., Methods: The data of 24 patients (median age 78, range 67-90 years) who presented rectal bleeding and were diagnosed with CRP after undergoing high-dose radiotherapy for prostatic cancer and underwent diode laser therapy were evaluated retrospectively. Non-contact fibers were used in the patients who underwent the procedure without sedation in an outpatient setting., Results: The patients underwent a median of two sessions; overall, a mean of 1591 J of laser energy per session was used. No complications were noted during or after the procedures. Bleeding was completely resolved in 21/24 (88%) patients, and two patients showed improvement (96%). It was not necessary to suspend antiplatelet (six patients) or anticoagulant (four patients) therapy during the treatment course. The mean cost per session was EUR 473.4., Conclusions: The study findings demonstrated that endoscopic non-contact diode laser treatment in CRP patients is safe, effective and cost efficient. For this procedure, antiplatelet and anticoagulant therapy suspension, intraprocedural sedation and hospital admission are not required.

The aim of this study was to evaluate the safety and efficacy of the endoscopic sleeve gastroplasty (ESG) procedure. Patients ineligible for bariatric surgery due to comorbidities or low Body Mass Index (BMI) were offered ESG. Gastric tubularization was carried out via multiple multi-bite sutures across the greater curvature of the stomach. The patients underwent a water-soluble swallow test on post-operative day 1 (POD-1) to assess gastric emptying and were placed on a soft diet if upper GI tract function was confirmed. From January 2019 to March 2022, 27 patients underwent ESG: 14 for severe obesity with comorbidities, including liver transplant, end-stage kidney disease, severe cardiovascular and respiratory diseases. The mean BMI before treatment was 36 ± 9 kg/m 2 . Two patients (7%) who developed gastric bleeding were successfully treated with packed red blood cells (PRBC) transfusions. After a mean follow-up of 18 months, the percentage of total body weight loss (%TBWL) and the percentage of excess weight (%EWL) were 11 ± 7 and 39 ± 27, respectively. The latter was significantly higher in the patients with an initial BMI < 40 kg/m 2 (50 vs 22, p < 0.05). The patients whose gastric sleeve extended for more than a third of the length of the stomach (p < 0.05) had better results. ESG was found to be effective and safe in high-risk surgical patients whose initial BMI was (< 40). Studies characterized by larger number of patients and longer follow-up periods will be able to confirm these results., (© 2022. The Author(s).)

Background: Palmitoylethanolamide is reported to solve pain and neuroinflammation in different models of chronic and neurodegenerative diseases. Some concerns have been illustrated for cautiously interpreting the available literature on the topic. Specifically, there is a lack of evidence about palmitoylethanolamide and female chronic pelvic pain. Concerns will be best solved by randomized trials. The present study was aimed at finding the best responders to micronized palmitoylethanolamide in female patient with chronic pelvic pain, using the existing literature at individual patient level, to help further randomized trial planning., Methods: After a systematic research, eligible studies (the ones enrolled female patients treated for chronic pelvic pain or for dyspareunia, dysuria, dyschezia, and dysmenorrhea with or without chronic pelvic pain) were assessed at individual patient data level. Conditional probabilities were calculated to assess variables conditioning the rates of good responders (pain score points more or equal to 3 reduction), poor responders (2 pain score reduction), and nonresponders at a three-month follow-up., Results: Only cases treated with palmitoylethanolamide comicronized with polydatin for a short period can be assessed. Good responders are more than 50%. In chronic pelvic pain, there is a 19.0% conditional probability to find good responders among patients with pain score at enrolment of 6 to 8 and of 6.8% to find poor responders among patients with a pain score at enrolment of 6 to 8. Painful disease does not matter on responders' rates., Conclusion: Best responders to comicronized palmitoylethanolamide/polydatin are patients with pain score higher than 6 at enrolment, irrespective of other variables., Competing Interests: All authors disclose no conflict of interest., (Copyright © 2022 Ugo Indraccolo et al.)

Mutations in SF3B1 are found in 20% of myelodysplastic syndromes and 5-10% of myeloproliferative neoplasms, where they are considered important for diagnosis and therapy decisions. Sanger sequencing and NGS are the currently available methods to identify SF3B1 mutations, but both are time-consuming and expensive techniques that are not practicable in most small-/medium-sized laboratories. To identify the most frequent SF3B1 mutation, p.Lys700Glu, we developed a novel fast and cheap assay based on PNA-PCR clamping. After setting the optimal PCR conditions, the limit of detection of PNA-PCR clamping was evaluated, and the method allowed up to 0.1% of mutated SF3B1 to be identified. Successively, PNA-PCR clamping and Sanger sequencing were used to blind test 90 DNA from patients affected by myelodysplastic syndromes and myeloproliferative neoplasms for the SF3B1 p.Lys700Glu mutation. PNA-PCR clamping and Sanger sequencing congruently identified 75 negative and 13 positive patients. Two patients identified as positive by PNA-PCR clamping were missed by Sanger analysis. The discordant samples were analyzed by NGS, which confirmed the PNA-PCR clamping result, indicating that these samples contained the SF3B1 p.Lys700Glu mutation. This approach could easily increase the characterization of myelodysplastic syndromes and myeloproliferative neoplasms in small-/medium-sized laboratories, and guide patients towards more appropriate therapy.