ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia.

PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.     

Achieving optimal outcomes after radical prostatectomy.

PURPOSE: The most favorable outcome that can be achieved after radical prostatectomy is complete tumor resection without recurrence and full recovery of continence and potency. Risks of erectile dysfunction, incontinence, and disease recurrence are well described, but in isolation, do not adequately inform patients of the possibility of becoming cancer-free while at the same time returning to their preoperative functional state. We sought to determine the frequency of optimal outcomes after radical prostatectomy and the time to such outcomes. PATIENTS AND METHODS: Patients who underwent radical prostatectomy performed at a tertiary referral center between July 1998 and July 2003 for clinical stage T1 to T3 prostate cancer were identified. Patients were excluded if they were incontinent or impotent preoperatively, or if they had received radiotherapy or neoadjuvant androgen deprivation therapy previously. Six hundred forty-seven patients were analyzed for time to recovery of full continence and potency without cancer recurrence after surgery. Optimal outcome probability was calculated with a Markov state transition model to simulate clinical outcomes in the first 4 years following radical prostatectomy. RESULTS: Mean patient age was 58 years, and mean pretreatment prostate-specific antigen was 6.9 ng/mL. Cancer-free status with full continence and potency was achieved in 30% of men at 12 months, 42% at 24 months, 47% at 36 months, and 53% at 48 months postoperatively. CONCLUSION: Optimal outcomes after radical prostatectomy can be achieved in a small majority of cases. Time to full recovery is primarily dictated by recovery of erectile function. This information is helpful for patients interested in their chances of returning to their preoperative functional state.     

Short-Term Pilot Study to Evaluate the Impact of Salbi Educa Nutrition App in Macronutrients Intake and Adherence to the Mediterranean Diet: Randomized Controlled Trial

Promoting a healthy diet is a relevant strategy for preventing non-communicable diseases. This study aims to evaluate the impact of an innovative tool, the SAlBi educa nutrition app, in primary healthcare dietary counseling to improve dietary profiles as well as adherence to the Mediterranean diet. A multi-center randomized control trial comprising 104 participants was performed. Both control (n = 49) and intervention (n = 55) groups attended four once-weekly sessions focusing on healthy eating habits and physical activity, over one month. As well as attending the meetings, the intervention group used the app, which provides self-monitoring and tailored dietary advice based on the Mediterranean diet model. In a second intervention (one arm trial), the potential of SAlBi educa was evaluated for three months during the COVID-19 pandemic. At 4 weeks, the intervention group had significantly increased their carbohydrate intake (7.7% (95% CI: 0.16 to 15.2)) and decreased their total fat intake (−5.7% (95% CI: −10.4 to −1.15)) compared to the control group. Significant differences were also found for carbohydrates (3.5% (95% CI: −1.0 to 5.8)), total fats (−5.9% (95% CI: −8.9 to −3.0)), fruits and vegetables (266.3 g/day (95% CI: 130.0 to 402.6)), legumes (7.7g/day (95% CI: 0.2 to 15.1)), starchy foods (36.4 g/day (95% CI: 1.1 to 71.7)), red meat (−17.5 g/day (95% CI: −34.0 to −1.1)), and processed meat (−6.6 g/day (95% CI: −13.1 to −0.1)) intakes during the COVID-19 pandemic. SAlBi educa is a useful tool to support nutrition counseling in primary healthcare, including in special situations such as the COVID-19 pandemic. Trial registration: ISRCTN57186362.     

Experimental Testing of the Action of Vitamin D and Silicon Chelates in Bone Fracture Healing and Bone Turnover in Mice and Rats

This study presents findings on the biological action of an integrated supplement containing the following components involved in osteogenesis and mineralization: vitamin D and silicon in the bioavailable and soluble form. A hypothesis that these components potentiate one another’s action and make calcium absorption by the body more efficient was tested. Biological tests of the effect of vitamin D and silicon chelates on bone fracture healing and bone turnover were conducted using ICR mice and albino Wistar rats. Radiographic and biochemical studies show that the supplement simultaneously containing silicon chelates and vitamin D stimulates bone tissue regeneration upon mechanical defects and accelerates differentiation of osteogenic cells, regeneration of spongy and compact bones, and restoration of bone structure due to activation of osteoblast performance. Bone structure restoration was accompanied by less damage to skeletal bones, apparently due to better absorption of calcium from food. The studied supplement has a similar effect when used to manage physiologically induced decalcification, thus holding potential for the treatment of osteomalacia during pregnancy or occupational diseases (e.g., for managing bone decalcification in astronauts).     

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.     

Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.     

Aggressive prolactinomas responsive to temozolomide treatment: Report of two cases

Refractory aggressive prolactinomas are detected after the unresponsiveness to conventional therapies. We report two cases that underwent temozolomide treatment and have been in near‐complete remission ever since. We suggest the pathology techniques for earlier detection and, subsequently, treatment with temozolomide to reduce morbidities and better respond to therapy.