Search

Abstract Background Navigated endodontics is a cutting-edge technology becoming increasingly more accessible for dental practitioners. Therefore, it is necessary to clarify the ideal technical parameters of this procedure to prevent collateral damage of the surrounding tissues. There is a limited number of studies available in published scientific literature referencing the possible collateral thermal damage due to high-speed rotary instruments used in guided endodontic drilling. The aim of our study was to investigate the different drilling parameters and their effect upon the temperature elevations measured on the outer surface of teeth during guided endodontic drilling. Methods In our in vitro study, 72 teeth with presumably narrow root canals were prepared using a guided endodontic approach through a 3D-printed guide. Teeth were randomly allocated into six different test groups consisting of 12 teeth each, of which, four parameters affecting temperature change were investigated: (a) access cavity preparation prior to endodontic drilling, (b) drill speed, (c) cooling, and (d) cooling fluid temperature. Temperature changes were recorded using a contact thermocouple electrode connected to a digital thermometer. Results The highest temperature elevations (14.62 °C ± 0.60 at 800 rpm and 13.76 °C ± 1.24 at 1000 rpm) were recorded in the groups in which drilling was performed without prior access cavity preparation nor without a significant difference between the different drill speeds (p = 0.243). Access cavity preparation significantly decreased temperature elevations (p

Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.

Abstract Background Cardiac tumors are very uncommon compared to other cardiac diseases. Their clinical symptoms can vary from absent to non-specific. The most common symptoms are arrhythmias, blood flow obstruction due to valvular dysfunction, shortness of breath, systemic embolization, and accumulation of pericardial fluid. Hereby, we describe a very rare case of a diffuse large B cell lymphoma patient who presented with the symptoms and signs of acute coronary syndrome (ACS) but the patient’s complaints were caused by his intramyocardial lymphoma metastasis. Case presentation Forty-eight-year-old diffuse large B cell lymphoma patient was admitted to our emergency department with chest pain, effort dyspnea, and fever. The patient had normal blood pressure, blood oxygen saturation, sinus tachycardia, fever, crackles over the left lower lobe, novum incomplete right bundle branch block with Q waves and minor ST alterations, elevated C-reactive protein, high-sensitivity troponin-T, and d-dimer levels. Chest X-ray revealed consolidation on the left side and enlarged heart. Bed side transthoracic echocardiography showed inferior akinesis with pericardial fluid. Coronary angiography showed no occlusion or significant stenosis. Chest computed tomography demonstrated the progression of his lymphoma in the myocardium. He was admitted to the Department of Hematology for immediate chemotherapy and he reached complete metabolic remission, followed by allogeneic hematopoietic stem cell transplantation. Unfortunately, about 9 months later, he developed bone marrow deficiency consequently severe sepsis, septic shock, and multiple organ failure what he did not survive. Conclusions Our case demonstrates a very rare manifestation of a heart metastasis. ACS is an unusual symptom of cardiac tumors. But our patient’s intramyocardial lymphoma in the right atrium and ventricle externally compressed the right coronary artery and damaged the heart tissue, causing the patient’s symptoms which imitated ACS. Fortunately, the quick diagnostics and immediate aggressive chemotherapy provided the patient’s remission and suitability to further treatment.

Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma ( p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS . PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lovas, Obajed Al-Ali, Varga, Szita, Alizadeh, Plander, Rajnics, Illés, Szemlaky, Mikala and Váróczy.)

Despite the introduction of novel agents, multiple myeloma remains incurable for most patients, necessitating further therapeutic options. Venetoclax, a selective BCL-2 inhibitor, had shown promising results in patients with translocation t(11;14), but questions remain open about its optimal use. We have contacted all Hungarian haematology centers for their experience treating t(11;14) myeloma patients with venetoclax. 58 patients were reported. 37 received venetoclax in the relapsed/refractory setting with few or no other therapeutic options available. 21 patients started venetoclax as salvage after failing to achieve satisfactory response to first line therapy. In the relapsed/refractory setting objective response rate (ORR) was 94%, median progression-free survival (PFS) 10.0 months and median overall survival (OS) 14.6 months. In reinduction patients, ORR was 100%, median PFS and OS were not reached. Importantly, we found no adverse effect of high risk features such as deletion 17p or renal failure, in fact renal failure ameliorated in 42% of the cases, including three patients who became dialysis independent. Our study also reports the highest number of plasma cell leukemia cases successfully treated with venetoclax published in literature, with refractory plasma cell leukemia patients achieving a median PFS of 10.0 and a median OS of 12.2 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Szita, Mikala, Kozma, Fábián, Hardi, Alizadeh, Rajnics, Rejtő, Szendrei, Váróczy, Nagy, Illés, Vályi-Nagy, Masszi and Varga.)

In Hungary, the cost of lenalidomide-based therapy is covered only for relapsed multiple myeloma (MM) patients, therefore lenalidomide is typically used in the second-line either as part of a triplet with proteasome inhibitors or as a doublet. Lenalidomide-dexamethasone is a standard treatment approach for relapsed/refractory MM, and according to recent large randomized clinical trials (RCT, the standard arm of POLLUX, ASPIRE, TOURMALINE), the progression-free survival (PFS) is expected to be approximately 18 months. We surveyed ten Hungarian centers treating MM and collected data of 278 patients treated predominantly after 2016. The median age was 65 years, and patients were distributed roughly equally over the 3 international staging system groups, but patients with high risk cytogenetics were underrepresented. 15.8% of the patients reached complete response, 21.6% very good partial response, 40.6% partial response, 10.8% stable disease, and 2.5% progressed on treatment. The median PFS was unexpectedly long, 24 months, however only 9 months in those with high risk cytogenetics. We found interesting differences between centers regarding corticosteroid type (prednisolone, methylprednisolone or dexamethasone) and dosing, and also regarding the choice of anticoagulation, but the outcome of the various centers were not different. Although the higher equivalent steroid dose resulted in more complete responses, the median PFS of those having lower corticosteroid dose and methylprednisolone were not inferior compared to the ones with higher dose dexamethasone. On multivariate analysis high risk cytogenetics and the number of prior lines remained significant independent prognostic factors regarding PFS ( p < 0.001 and p = 0.005). Our results show that in well-selected patients Lenalidomide-dexamethasone can be a very effective treatment with real-world results that may even outperform those reported in the recent RCTs. This real world information may be more valuable than outdated RCT data when treatment options are discussed with patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Varga, Dávid Tóth, Réka Szita, Csukly, Hardi, Gaál-Weisinger, Nagy, Altai, Rencsik, Plander, Szendrei, Kórád, Radványi, Rottek, Deák, Szaleczky, Schneider, Kohl, Kosztolányi, Alizadeh, Lengyel, Modok, Borbényi, Lovas, Váróczy, Illés, Rajnics, Masszi and Mikala.)

A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression-free survival (PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old. Median PFS for patients <70 years old was 28·6 months for the carfilzomib group versus 17·6 months for the control group [hazard ratio (HR), 0·701]. Median PFS for patients ≥70 years old was 23·8 months for the carfilzomib group versus 16·0 months for the control group (HR, 0·753). For patients <70 years the overall response rate (ORR) was 86·0% (carfilzomib group) and 66·9% (control group); for patients ≥70 years old the ORR was 90·3% (carfilzomib group) and 66·1% (control group). Within the carfilzomib group, grade ≥3 cardiovascular adverse events occurred more frequently among patients ≥70 years old compared with patients <70 years old. Carfilzomib-lenalidomide-dexamethasone has a favourable benefit-risk profile for patients with RMM, including elderly patients ≥70 years old., Trial Registration: clinicaltrials.gov identifier: NCT01080391., (© 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)

Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide. Treatment with KRd led to a 12-month improvement in median PFS vs Rd after first relapse (HR 0.713) and a 9-month improvement after ⩾2 previous lines of therapy (HR 0.720). Treatment with KRd led to an approximate 8-month improvement vs Rd in median PFS in bortezomib-exposed patients (HR 0.699), a 15-month improvement in thalidomide-exposed patients (HR 0.587) and a 5-month improvement in lenalidomide-exposed patients (HR 0.796). Objective response and complete response or better rates were higher with KRd vs Rd, irrespective of previous treatment. KRd had a favorable benefit-risk profile and should be considered an appropriate treatment option for patients with 1 or ⩾2 previous lines of therapy and those previously exposed to bortezomib, thalidomide or lenalidomide.

The simultaneous occurrence of acute myeloid leukaemia with untreated chronic lymphocytic leukemia is extremely rare. We report a case of a 74-year-old man who was evaluated for macrocytic anaemia. Based on the morphology and immunophenotyping analysis of peripheral blood, a diagnosis of chronic lymphocytic leukemia was established. Subsequently, the bone marrow examination revealed the presence of two distinct, coexisting CLL and AML clones. Cytogenetic and molecular genetic analysis detected deletion 13q14.3 and unmutated immunoglobulin variable heavy-chain in the CLL clone, only. The AML and CLL clones did not share clonality, and the AML did not involve the peripheral blood. A diagnosis of cytogenetically normal de novo AML occurring concurrently with untreated CLL has not been reported previously in English literature., (© 2015 by the Association of Clinical Scientists, Inc.)

Background: Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma., Methods: We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival., Results: Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life., Conclusions: In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

Background: Clostridium perfringens septicaemia with massive hemolysis is well known. The infection induced acute hemolytic attack frequently occur in chronic corpuscular hemolytic anemias. Alterations in mental status are common in septic patients., Case Report: The case of a 39-year-old woman with a history of chronic corpuscular hemolytic anemia, experiencing weakness, pallor, somnolence is presented. Hypothermia and an acute paranoid psychotic episode subsequently developed in the hospital. C. perfringens sepsis was detected from blood cultures. The patient was cured by penicillin and clindamycin. Her symptoms disappeared and there was total resolution of toxic encephalopathy according to the brain MRI after 6 weeks., Conclusion: This report discusses the possible explanation of clostridial sepsis the role of brain MRI in the sepsis-induced organic psychosyndromes and underlines the need for obtain blood cultures in hypothermia suggestive to sepsis.

Using a specialized orthopedic software package, the authors investigated the sagittal spinal shape and the position of the pelvis in the space in patients with isthmic spondylolisthesis and in persons with no such symptoms. Digitized lateral spinal radiographs of 30 healthy volunteers and 48 patients were evaluated. The absolute values and significant correlations between parameters were analyzed. The pelvic parameters correlated well with lordosis, which shows sagittal balance in the asymptomatic group. The hyperlordosis and the horizontally positioned sacrum in isthmic spondylolisthesis enlarge the tensile force component of gravity, which may cause the lysis. Finally, the authors developed a new balance between the pelvis and the spine after slipping of the vertebral body. The degree of slipping correlated well with the sacrofemoral anatomic constant (incidence), which is unique in each person.

The sagittal shape of the spine, particularly its sagittal balance, currently is being extensively investigated. The major purpose of this study is to examine the measurement repeatability of SpineView software, which calculates 13 independent variables, to shorten and facilitate the measurement of lateral spinal radiographs; another purpose is to collect physiological data for nonpathologic spines, which can be used as a reference in future research. This article also presents two new parameters and discusses their possible role in forthcoming investigations. The interobserver repeatability study shows that most of the variables are more repeatable (less than +/-1.5 degrees ) when the operator is experienced. A less (+/-6.5 degrees ) repeatable measurement is T4-T12 kyphosis, which may be because of the poor contrast generally observed on radiographs of the upper thoracic vertebrae. The intraobserver repeatability study also demonstrates that subjective failures do not influence the results significantly, but the quality of the radiographs may have significant effect on long-term repeatability. The mean values were generally different between male and female subjects, and significant differences between the two sexes were only noticed for pelvic thickness and global spinal inclination. Normal range values and correlations between some pelvic and spinal parameters were similar to data found in the literature. The results of the current study provide evidence that the SpineView software is useful for experimental investigation of sagittal spinal alignment.