RESUMEN
BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Mieloma Múltiple , Supervivencia sin Progresión , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Bortezomib/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Neoplasia Residual , Estimación de Kaplan-Meier , Análisis de SupervivenciaRESUMEN
OBJECTIVE: The aim of this study was to determine optimal radiological parameters for assessment of the round window approach in cochlear implantation surgery. MATERIALS AND METHODS: Patients undergoing cochlear implantation at the Department of Otolaryngology in Szczecin, between 2015 and 2022 inclusive, were eligible for the study. Radiological assessments were performed according to eight parameters (seven proposed in the literature) and visibility clinical assessments were made intra-operatively on a scale of 1 to 5 (1 - not visible, 5 - fully visible). Visibility assessments of the round window niche (RWN) and round window membrane (RWM) allowed the difference (RWN minus RWM) to be used as a clinical assessment of the size of the overhang over the round window. RESULTS: Computed tomography images of 57 ears from 52 patients were analyzed in terms of round window access. The study group included 26 females and 26 males, ranging in age from 1 year to 80 years, with a median age of 41 years. In clinical assessment, round window visibility was rated as 5, after removal of the bone overhang, in 69% of patients. Cochlear access through the round window was achieved in 39 (68%) cases, extended access through the round window in 13 (23%) cases and cochleostomy was performed in 5 (9%) cases. Statistically significant ordinal correlations with round-window access were found using one parameter from the literature (Chen_Angle) and from our proposal (RWM_prediction). From parameters describing the bone overhang of the round window, positive correlations (using Kendall rank tests) were found using parameters from the literature (Sarafraz_OH and Mehanna_OH). CONCLUSIONS: Radiological measurements describing access to the round window which determine the angle based on the anatomy of the posterior wall of the auditory canal and the position of the facial nerve were found to be of the highest value. CLINICAL RELEVANCE STATEMENT: In the future, the use of algorithms for computed tomography evaluation and robot-assisted surgery will require parameters for assessing round window access, for surgery planning and choice of electrode. The parameters proposed by various authors are summarized, allowing researchers to assess their usefulness in further clinical practice.
RESUMEN
Brain-derived neurotrophic factor (BDNF) is a protein with a potent influence on several aspects of neuronal and blood vessel functions. However, its prognostic potential and functional role in multiple myeloma (MM) remain largely unknown. In this study, we investigated the influence of BDNF on the risk of chemotherapy-induced peripheral neuropathy (CIPN) and clinical outcome. Study group consisted of 91 newly-diagnosed MM patients treated with bortezomib and/or thalidomide-based chemotherapy. Detection of BDNF in serum was performed using ELISA. Polyneuropathy was assessed according to the CTCAE Criteria v5. We observed that BDNF concentration correlated with the severity of polyneuropathy (P = 0·0463). Higher BDNF values were noted in patients who responded to treatment (P = 0·0326), and BDNF proved to be a useful marker to predict lack of response after eight cycles of treatment (sensitivity - 100%, specificity - 61·5%, P = 0·0142). Moreover this marker showed significant diagnostic usefulness in diagnosis of CIPN (sensitivity - 76%, specificity - 71·43%; area under the curve (AUC)= 0·77, 95%, confidence interval (CI): 0·64-0·88; P < 0·0001). Low BDNF was an independent, unfavourable prognostic factor associated with reduced overall survival (OS) (hazard ratio (HR) = 2·79, P = 0·0470). In conclusion, BDNF level may play a prognostic role and constitute a useful biomarker in predicting CIPN in MM patients.
Asunto(s)
Biomarcadores de Tumor/sangre , Bortezomib , Factor Neurotrófico Derivado del Encéfalo/sangre , Mieloma Múltiple , Polineuropatías , Talidomida , Adulto , Anciano , Anciano de 80 o más Años , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Polineuropatías/sangre , Polineuropatías/inducido químicamente , Polineuropatías/mortalidad , Tasa de Supervivencia , Talidomida/administración & dosificación , Talidomida/efectos adversosRESUMEN
Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are considered as laboratory markers of inflammation. They can be potentially useful in predicting the course of multiple neoplasms including selected hematological cancers. The aim of the study was to assess the value of NLR and PLR in predicting the effects of therapy and prognosis in multiple myeloma patients treated with thalidomide-based regimen. The study group consisted of 100 patients treated with the first line CTD (cyclophosphamide, thalidomide, and dexamethasone) chemotherapy. The NLR and PLR were calculated before treatment. High NLR was observed in patients with higher stage of the disease, with poor performance status, hypercalcemia, and high CRP. High PLR was associated with low BMI and high CRP. In patients with high NLR, significantly shorter PFS was observed (17 vs. 26 months, p = 0.0405). In addition, high values of NLR and PLR were associated with significantly shorter OS (38 vs. 79 months, p = 0.0010; 40 vs. 78 months, p = 0.0058). Summarizing, NLR and PLR have a significant independent prognostic value for multiple myeloma patients. Furthermore, the NLR can be a predictive marker for the outcome of thalidomide-based chemotherapy.
Asunto(s)
Plaquetas/metabolismo , Linfocitos/metabolismo , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Neutrófilos/metabolismo , Talidomida/uso terapéutico , Anciano , Plaquetas/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Recuento de Linfocitos/métodos , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Neutrófilos/efectos de los fármacos , Recuento de Plaquetas/métodos , Pronóstico , Tasa de Supervivencia/tendencias , Talidomida/farmacología , Resultado del TratamientoRESUMEN
OBJECTIVE: Introduction: Hip osteoarthritis is a disabling disease which become substantial health-related, social, and economic issue. The aim: To assess short term quality of life in male population with hip ostheoarthritis, after total hip arthroplasty. PATIENTS AND METHODS: Material and methods: 118 male patients were included in the study, age range from 31 to 79 year-old, who underwent total hip arthroplasty. Patients quality of life was assessed using questioners: abbreviated version of WHOQoL-BREF, as well as EQ-5D-5L, and SF-36 scale. Patients condition was investigated before surgery, 6 weeks and 6 months after the surgery. RESULTS: Results: The results from WHOQoL-BREF questionnaire demonstrated a statistically significant improvement of quality of life after the surgery - 6 weeks after the procedure by 4% and 21% (p<0.001), after 6 months by 13% and 42% (p<0.001), respectively. The most significant improvement was found in the somatic domain - by 5% after 6 weeks, and by 6% after 6 months (p<0.001). The quality of life according to the EQ-5D-5L questionnaire revealed statistically significant improvement after 6 weeks, by 18-24% (p<0.001), after 6 months by 41-48% (p<0.001). Substantial improvement was achieved in reducing pain and improving mobility. SF-36 questionnaire showed statistically significant improvement after 6 months from the surgery in both physical (by 44%), and mental condition (by 54%) (p<0.001). CONCLUSION: Conclusions: Improvement of the quality of life - mainly less severe pain and better mobility after total hip arthroplasty in the investigated group of men was proven in 6 weeks after the procedure, while the further progress was more noticeable 6 months after the procedure.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Osteoartritis de la Cadera , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/cirugía , Calidad de Vida , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Thalidomide is commonly used in treatment of multiple myeloma (MM). This study aimed to analyse the influence of clinical and molecular factors - single nucleotide polymorphisms (SNPs) of the CRBN gene: rs6768972 and rs1672753, on the risk of adverse effects (AEs) of thalidomide-based chemotherapy in patients with MM. The study group included 82 patients receiving CTD (thalidomide, cyclophosphamide, dexamethasone) as first line treatment. The intensity of haematological and non-haematological AEs was assessed according to the Common Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that patients with the CRBN CC genotype (rs1672753) had more than a 14-fold higher risk of peripheral polyneuropathy compared to patients with other variants of the investigated SNP [odds ratio (OR) = 14·29]. Carriers of this genotype were burdened with significantly (about 17-fold) higher risk of diarrhoea during treatment (OR = 16·67). The presence of CRBN AA (rs6768972) or TT (rs1672753) genotypes was associated with about 333-fold and 250-fold lower risk of constipation in the course of therapy (OR = 0·003; OR = 0·004, respectively). Selected CRBN SNPs may be useful in assessing the probability of AEs in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM.
Asunto(s)
Inmunosupresores/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Talidomida/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Enfermedades del Sistema Nervioso Periférico/mortalidad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Tasa de Supervivencia , Talidomida/administración & dosificaciónRESUMEN
PURPOSE: The aim of the study was to identify and analyze non-modifiable risk factors for recurrence after a first-time post-traumatic dislocation of the shoulder in the entire Polish population. METHODS: The entire Polish population was included in a cohort study. Patients diagnosed with primary post-traumatic dislocation of the shoulder between January 1st, 2010 and December 31st, 2011 were identified and followed up from January 1st, 2010 to December 31st, 2014. Incidence and recurrence rates and odds ratios (OR) were calculated. Demographic data were obtained from Poland's Central Statistical Office. Data on the number of patients with primary post-traumatic shoulder dislocation were drawn from the National Health Fund database. RESULTS: A total of 21,739 patients (14,466 males and 7273 females) with a primary shoulder dislocation in Poland were identified in 2010 and 2011. There were 3341 (15.4%) recurrences. Increased risk of recurrence was associated with male gender (OR = 1.92, 95% CI 1.76-2.09, p < 10-10) in the age range of 20-29 years (OR = 2.59, 95% CI 2.38-2.83, p < 10-10). The highest risk of first-time shoulder dislocation was revealed among females in the age group ≥ 80 years (OR = 24.1, 95% CI 22.6-25.7, p < 10-10). The risk of recurrence in the same group was significantly decreased (OR = 0.41, 95% CI 0.32-0.51, p < 10-10). CONCLUSION: Male gender and age range 20-29 years are highest population risk factors for recurrence after primary shoulder dislocation. Female gender and age ≥ 80 years are highest risk factors for the first-time post-traumatic dislocation of the shoulder joint and protective factors for recurrences after the first-time shoulder dislocation. LEVEL OF EVIDENCE: III.
Asunto(s)
Luxación del Hombro/epidemiología , Adolescente , Adulto , Factores de Edad , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Inestabilidad de la Articulación/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polonia/epidemiología , Recurrencia , Factores de Riesgo , Factores Sexuales , Adulto JovenRESUMEN
PURPOSE: The aim of this study was to evaluate five-year prevalence of recurrent shoulder dislocation in the entire Polish population. METHODS: The study involved the entire Polish population between 01 January 2010 and 31 December 2014. Demographic data were retrieved from the Central Statistical Office of Poland. Data on the number of shoulder joint dislocations were retrieved from the database of the National Health Fund. RESULTS: We identified 32,253 Polish residents with shoulder instability. About 0.1% of Polish residents suffered from recurrent shoulder dislocation. Males suffered almost two times more often than females (66% and 34%, respectively), and male gender was recognized as a risk factor of instability (OR = 2.07, p <10-10). Females in their eighth decade of life had the highest risk of recurrent shoulder dislocation (OR = 3.33, p <10-10). In males the highest risk of recurrences was noted for the third decade of life (OR = 1.78, p <10-10). CONCLUSION: The period prevalence rate of recurrent shoulder dislocation in Poland is 83.7 per 100,000 persons per five years. The rate of recurrent shoulder dislocation for the general Polish population is 0.1%. Males suffered from recurrent shoulder dislocation almost twice as frequently as females (OR = 2.07).
Asunto(s)
Luxación del Hombro/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Prevalencia , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Lesiones del Hombro , Adulto JovenRESUMEN
INTRODUCTION: Tumours connected with head and neck comprise about 5% of all tumours. The most frequent histological type of laryngeal carcinoma is squamous cell carcinoma. Different research projects suggest that the role of T lymphocytes might be significant in tumour development. iNKT cells are a new subpopulation of T cells and show cytotoxic activity against tumours. iNKT cells participate in modulating the function of other cells which have anti-tumour properties and secrete cytokines, which have pro-inflammatory and anti-inflammatory effects. In animal models the significance of iNKT cells in various diseases including cancer was shown. AIM OF THE STUDY: The aim of this study was to determine the percentages of iNKT cells, CD161+ cells, CD161- cells, iNKT CD4+ cells, and iNKT CD8+ cells, NK cells, NKT-like cells, and T cells subsets present in peripheral blood of patients with laryngeal cancer before and two months after the tumour resection, in comparison to healthy volunteers. MATERIALS AND METHODS: This study included material from laryngeal patients who were treated at the Department of Otolaryngology and Laryngological Oncology (Medical University of Lublin) between 2012 and 2013. A total of 50 patients (40 men and 10 women) aged between 45 and 77 years (median age: 60 years) were enrolled. Based on the TNM classification, the patients were classified as having stage I-IV laryngeal cancer. The control group was composed of 15 healthy volunteers (12 men and three women) aged between 43 and 82 years (median age: 61 years). The protocol of the study was approved by the Local Bioethical Committee at the Medical University of Lublin.Peripheral blood samples (15 ml) from the basilic vein were collected by venipuncture using sterile, sodium heparin-treated tubes (20 units per ml of blood) and used for cytometric analyses. RESULTS: iNKT cells were analysed among T CD3+ cells. The percentage of CD3+ and CD3+CD4+ T cells before tumour resection was higher than in the control group, but the increase of CD3+ T cells was not significant. The T CD3+CD4+ / T CD3+CD8+ cell ratio was significantly higher than in healthy donors. After tumour resection a decreased percentage of CD3+CD4+ T cells but an increased percentage of CD8+CD3+T cells was noted. The T CD3+CD4+ / T CD3+CD8+ cell ratio was significantly higher in patients before and after the surgery than in the control group. The amount of NKT-like cells increased after resection and was significantly higher than in the control group. CONCLUSIONS: Our study exhibited the change in percentage of iNKT, NK, NKT-like cells, and T lymphocytes after tumour resection in patients with laryngeal cancer. The research explains the contribution of those cells in immunological response against tumour.
RESUMEN
BACKGROUND The incidence of shoulder joint dislocation has been estimated at 11-26 per 100 000 population per year. In our opinion, basic epidemiological data need to be continually updated in studies of large populations. To study the incidence of posttraumatic dislocation of the shoulder joint in the Polish population. MATERIAL AND METHODS We retrospectively investigated the entire Polish population between 1 January 2010 and 1 January 2015. To identify the study group, data collected in the electronic database of the National Health Fund were used. The study group was divided into subgroups to detect possible differences in the incidence of shoulder dislocation with regard to age, sex, and season of the year (month) when the dislocation occurred. RESULTS The cumulative size of the study sample was 192.72 million over the 5 years of the study. We identified 51 409 patients with first posttraumatic shoulder dislocation, at a mean age of 50.83 years (SD 21.12), from 0 to 104 years. The incidence of traumatic shoulder dislocations for the entire study group ranged from 24.75/100 000/year (number of posttraumatic shoulder dislocations per 100 000 persons per year) to 29.09/100 000/year, for a mean of 26.69/100 000/year. CONCLUSIONS In this study, the overall incidence of first-time posttraumatic shoulder dislocations in the Polish general population was 26.69 per 100 000 persons per year. These results are higher than estimates presented by other authors. It is necessary to study, regularly update, and monitor this problem in the general population.
Asunto(s)
Luxación del Hombro/epidemiología , Lesiones del Hombro , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Incidencia , Inestabilidad de la Articulación , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Recurrencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Shoulder instability is an important clinical problem. Arthroscopic surgery is an established treatment modality in shoulder instability, but it continues to be associated with a high rate of recurrences and complications. The purpose of the study was to analyze late outcomes of arthroscopic repair of Bankart lesions in patients with post-traumatic anterior shoulder instability and non-engaging Hill-Sachs lesion, with special focus on the incidence and causes of recurrences and complications. MATERIAL AND METHODS: We investigated 92 patients (92 shoulders) who underwent surgery on account of post-traumatic anterior shoulder instability. The duration of follow-up ranged from 6 to 12.5 years (mean: 8.2 years). All patients were operated on in the lateral decubitus position using FASTak 2.8-mm suture anchors (FASTak, Arthrex, Naples, Florida). Treatment outcomes were evaluated using the Rowe and University of California at Los Angeles rating system (UCLA). RESULTS: According to Rowe scores, there were 71 (81.5%) excellent, 12 (12.6%) good, 5 (5.3%) satisfactory, and 2 (2.1%) poor results. Rowe scores improved in a statistically significant manner (p=0.00) post-surgery, to a mean of 90 (range: 25-100). Treatment outcomes measured as UCLA scores improved in a statistically significant manner (p=0.00), reaching post-operative levels of 12-35 (mean: 33.5). There were 9 recurrences, 1 case of axillary nerve praxia, and 1 case of anchor loosening. CONCLUSIONS: With rigorous criteria for qualifying patients for surgery, arthroscopic treatment of post-traumatic anterior shoulder instability produces good outcomes and low recurrence and complication rates irrespective of the number of previous dislocations, age, or sex.
Asunto(s)
Artroscopía/métodos , Inestabilidad de la Articulación/cirugía , Hombro/cirugía , Anclas para Sutura , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Hip resurfacing is a conservative type of total hip arthroplasty but its use is controversial, especially in patients with osteonecrosis. The aim of this study was analysis of the clinical and radiographic outcomes of hip resurfacing in patients with osteonecrosis. MATERIAL/METHODS: Between 2007 and 2008, 30 hip resurfacing arthroplasties were performed due to osteoarthritis secondary to avascular necrosis of femoral head staged as Ficat III and IV. Patients were qualified to resurfacing arthroplasty when the extent of avascular necrosis using Kerboul's method was <200° and the angle between avascular necrosis and head-neck junction was >20°. All patients were evaluated clinically and radiologically before and 60 months after the operation. RESULTS: The mean Harris Hip Score (HHS) score increased from 47.8 to 94.25 (p<0.05). Physical activity level (University of California, Los Angeles activity score--UCLA activity score) improved from 3.7 to 7.55 (p<0.05). No implant migration was observed. CONCLUSIONS: Management of osteonecrosis of the hip with resurfacing arthroplasty seems to be effective in strictly-selected patients.
Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/diagnóstico por imagen , Adulto , Índice de Masa Corporal , Cabeza Femoral/cirugía , Necrosis de la Cabeza Femoral/cirugía , Prótesis de Cadera , Humanos , Masculino , Persona de Mediana Edad , Osteonecrosis/cirugía , Radiografía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Introduction: Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events. Methods: We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia. Results: Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414). Conclusions: Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.
Asunto(s)
Quimiocina CCL2 , Interleucina-8 , Mieloma Múltiple , Factor A de Crecimiento Endotelial Vascular , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factor A de Crecimiento Endotelial Vascular/sangre , Interleucina-8/sangre , Pronóstico , Quimiocina CCL2/sangre , Interleucina-6/sangre , Estudios Prospectivos , Adulto , Anciano de 80 o más Años , Citocinas/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Non-secretory multiple myeloma (NSMM) accounts for approx. 2-3% of multiple myeloma (MM) cases. Due to the rare occurrence and ineligibility of patients with NSMM to participate in clinical trials, we have limited data on treatment efficacy and the clinical course in these patients. Most of the literature consists of case reports and small retrospective studies. OBJECTIVES: The study aimed to analyze patient characteristics, prognostic factors and treatment outcomes in newly diagnosed (ND) NSMM. MATERIAL AND METHODS: This is a multicenter, retrospective analysis of 43 patients with NSMM diagnosed between June 2010 and September 2021, conducted in 8 Polish hematology centers. RESULTS: The median overall survival (OS) was 103 months (95% confidence interval (95% CI): 20-72). The most common cause of death was MM disease progression. The overall response rate (ORR) was 84.6%; complete response (CR), very good partial response (VGPR), partial response (PR), and no response (NR) rates were 20.5%, 46.2%, 17.9%, and 15.4%, respectively. In multivariable analysis, factors contributing to worse OS included International Staging System stage 3 (ISS-3) (p = 0.0277), anemia (Hb <10 g/dL or >2 below upper limit of normal value (ULN), p = 0.0270), renal insufficiency (RI, serum creatinine >2 mg/dL, p = 0.0476), and serum albumin <5.5 mg/L (0.0408). CONCLUSIONS: Non-secretory multiple myeloma is a rare subtype of MM. This small study demonstrates that outcomes are comparable to secretory MM. However, the inclusion of this subset of patients in clinical trials is essential to assess prognosis, treatment efficacy and clinical outcomes.
RESUMEN
Velocities and accelerations are measured and visualized in silicon microchannels using particle tracking velocimetry (PTV). Both pulsatile and stationary flows are generated in channels with different geometry. Distinct differences between flow regimes and geometries are shown. Flow separation occurred at Re = 84 for the channel with an expanded bifurcation shown by streamlines from long exposed images. Moving least squares are used to find the ensemble-averaged positions of the measured velocities from tracking. This is needed to find the local and convective accelerations.
Asunto(s)
Hidrodinámica , Microtecnología/métodos , Reología/métodos , Silicio , AceleraciónRESUMEN
BACKGROUND: The primary objective of this study was to analyze middle ear structures critical for cochlear implantation using computed tomography. MATERIALS AND METHODS: Patients who underwent cochlear implantation at the Department of Otolaryngology in Szczecin between 2015 and 2022 were eligible for the study. We analyzed computed tomography images of 57 ears in 52 patients. The following parameters were assessed: mastoid aeration, tegmen tympani height, sigmoid sinus position, posterior tympanotomy width, the distance between the facial nerve and chorda tympani, modified facial recess distance, and the prediction line described by other authors. RESULTS: In 69% of patients, after the removal of the round window bony overhang, the round window membrane became fully visible. There were no statistically significant correlations found for parameters describing mastoid process anatomy or those rating the width of the posterior tympanotomy concerning round window access. The prediction lines, according to Kashio and Jwair, were found to be relevant. In cases where patients' access to the niche and membrane of the window was rated as good or very good during clinical evaluation, they were more likely to describe the window as being located posteriorly or medially in the radiological evaluation. Using a binary Jwair scale provided a better correlation with the clinical assessment. In cases where the windows were graded as posterior, the clinical assessment indicated better surgical access, especially to the RWM (Round Window Membrane). CONCLUSIONS: Evaluating middle ear anatomy on a computed tomography scan is useful for preparing for middle ear surgery but does not significantly affect the ability to access the round window. For such access, the position of the window in relation to the facial nerve is the most relevant factor, and measurements based on this relationship hold the highest clinical value.
RESUMEN
Multiple myeloma (MM) is the second most common hematological neoplasm. Cytokines, chemokines, and their receptors, induced by the microenvironment of MM, participate in tumor growth, the attraction of leukocytes, cell homing, and bone destruction. This study aimed to assess the correlation between the pretreatment serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), angiogenic chemokine monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) and the clinical outcomes and survival of patients newly diagnosed with MM. The study group consisted of 82 individuals. The IL-8 concentration was significantly positively correlated with the age of onset (p = 0.007), the International Staging System (ISS) stage (p = 0.03), the Eastern Cooperative Oncology Group (ECOG) performance status (p < 0.001), the degree of anemia before treatment (p < 0.0001), the degree of kidney disease (p < 0.001), and VEGF (p = 0.0364). Chemotherapy responders had significantly lower concentrations of IL-8 (p < 0.001), IL-6 (p < 0.001), and VEGF (p = 0.04) compared with non-responders. Patients with treatment-induced polyneuropathy had significantly higher levels of IL-8 (p = 0.033). Patients with a high level of IL-6 had a 2-fold higher risk of progression-free survival (PFS) reduction (17 vs. 35 months; HR = 1.89; p = 0.0078), and a more than 2.5-fold higher risk of overall survival (OS) reduction (28 vs. 78 months; HR = 2.62; p < 0.001). High levels of IL-6, IL-8, and VEGF demonstrated significant predictive values for some clinical conditions or outcomes of newly diagnosed MM patients. Patients with an early response to chemotherapy had a significantly lower concentration of these cytokines. A high pretreatment IL-6 concentration was an independent negative prognostic marker for newly diagnosed MM patients.
RESUMEN
MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16-3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie-Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high ß2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20-7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.
Asunto(s)
Antineoplásicos , MicroARN Circulante , Hipoalbuminemia , MicroARNs , Mieloma Múltiple , Antineoplásicos/uso terapéutico , Biomarcadores , Bortezomib/uso terapéutico , Humanos , Hipoalbuminemia/complicaciones , Hipoalbuminemia/tratamiento farmacológico , MicroARNs/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Pronóstico , Talidomida/uso terapéuticoRESUMEN
Healthcare workers (HCWs) are on the frontline, struggling with the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To describe recent or past infections, the serological assays enabled the assessment of the immune response developed in coronavirus disease (COVID-19) in the period when testing was hardly available. In this study, we investigated SARS-CoV-2 seroprevalence in HCWs in a Polish teaching hospital and the Regional Occupational Medicine Center after both the first and the second waves. ELISA-based tests for anti-SARS-CoV-2 IgA and IgG were used to determine immune response to SARS-CoV-2 in volunteer HCWs who worked in those institutions in May 2020 (208 participants aged 47.1 ± 12.5, 88% women) and in December 2020 (179 participants aged 45.2 ± 12.4, 86% woman). Risk factors for seropositivity were also assessed using a questionnaire filled out by all participants. We reported a significant increase in seroprevalence after the second wave (22.9%) compared with the first outbreak (2.4%) (OR 12.1; 95%CI 4.6-31.3; p < 0.0001). An association between IgG seroprevalence and severity of infections was noted. Furthermore, we demonstrated that amongst medical personnel, nurses exhibited a proportionally higher SARS-CoV-2 seroprevalence. Moreover, given the high seroprevalence in non-clinical group of HCWs, we suggest that community transmission can play a superior role to workplace exposure.
Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Anticuerpos Antivirales , COVID-19/epidemiología , Femenino , Personal de Salud , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Polonia/epidemiología , Estudios Seroepidemiológicos , VacunaciónRESUMEN
Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; p = 0.027) and CD86 on CD19+ cells (r = 0.6950; p < 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling (p < 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.