RESUMEN
Mandibular fractures are very common in maxillofacial trauma surgery. While previous studies have focused on possible risk factors related to post-operative complications, none have tried to identify pre-existing conditions that may increase the risk of mandibular fractures. We hypothesized, through clinical observation, that anatomical conditions involving poor dental contacts, such as malocclusions, may increase the risk of mandibular fractures. This work was subdivided into two parts. In the first part, Digital Imaging and Communications in Medicine (DICOM) data of four healthy patients characterized by different dentoskeletal occlusions (class I, class II, class III, and anterior open bite) have been used to develop four finite element models (FEMs) that accurately reproduce human bone structure. A vertical and lateral impact have been simulated at increasing speed on each model, analyzing the force distribution within the mandibular bone. Both vertical and lateral impact showed higher level of stress at the impact point and in the condylar area in models characterized by malocclusion. Specifically, the class III and the open bite models, at the same speed of impact, had higher values for a longer period, reaching critical stress levels that are correlated with mandibular fracture, while normal occlusion seems to be a protective condition. In the second part of this study, the engineering results were validated through the comparison with a sample of patients previously treated for mandibular fracture. Data from 223 mandibular fractures, due to low-energy injuries, were retrospectively collected to evaluate a possible correlation between pre-existing malocclusion and fracture patterns, considering grade of displacement, numbers of foci, and associated CFI score. Patients were classified, according to their occlusion, into Class I, Class II, Class III, and anterior open bite or poor occlusal contact (POC). Class I patients showed lower frequencies of fracture than class II, III, and open bite or POC patients. Class I was associated with displaced fractures in 16.1% of cases, class II in 47.1%, class III in 48.8% and open bite/POC in 65.2% of cases (p-value < 0.0001). In class I patients we observed a single non-displaced fracture in 51.6% of cases, compared to 12.9% of Class II, 19.5% of Class III and 22.7% of the open bite/POC group. Our analysis shows that class I appears to better dissipate forces applied on the mandible in low-energy injuries. A higher number of dental contacts showed a lower rate of multifocal and displaced fractures, mitigating the effect of direct forces onto the bone. The correlation between clinical data and virtual simulation on FEM models seems to point out that virtual simulation successfully predicts fracture patterns and risk of association with different type of occlusion. Better knowledge of biomechanics and force dissipation on the human body may lead to the development of more effective safety devices, and help select patients to plan medical, orthodontic/dental, and/or surgical intervention to prevent injuries.
RESUMEN
Long-term kinetics of antibody (Ab) and cell-mediated immune (CMI) response to full anti-SARS-CoV-2 vaccine schedule and booster doses in Multiple Myeloma (MM) patients remain unclear. We prospectively evaluated Ab and CMI response to mRNA vaccines in 103 SARS-CoV-2-naïve MM patients (median age 66, 1 median prior line of therapy) and 63 health-workers. Anti-S-RBD IgG (Elecsys®assay) were measured before vaccination and after 1 (T1), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months from second dose (D2) and 1 month after the introduction of the booster dose (T1D3). CMI response (IGRA test) was evaluated at T3 and T12. Fully vaccinated MM patients displayed high seropositivity rate (88.2%), but low CMI response (36.2%). At T6 the median serological titer was halved (p=0.0391) in MM patients and 35% reduced (p=0.0026) in controls. D3 (94 patients) increased the seroconversion rate to 99% in MM patients and the median IgG titer in both groups (up to 2500 U/mL), maintained at T12. 47% of MM patients displayed a positive CMI at T12 and double-negativity for humoral and CMI (9.6% at T3) decreased to 1%. Anti-S-RBD IgG level ≥346 U/mL showed 20-times higher probability of positive CMI response (OR 20.6, p<0.0001). Hematological response ≥CR and ongoing lenalidomide maintenance enhanced response to vaccination, hindered by proteasome inhibitors/anti-CD38 monoclonal antibodies. In conclusion, MM elicited excellent humoral, but insufficient cellular responses to anti-SARS-CoV-2 mRNA vaccines. Third dose improved immunogenicity renewal, even when undetectable after D2. Hematological response and ongoing treatment at vaccination were the main predictive factors of vaccine immunogenicity, emphasizing the role of vaccine response assessment to identify patients requiring salvage approaches.
RESUMEN
Background: The anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019. Methods: We conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs. Results: A total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol. Conclusions: Our findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion.
