Breast Implant-Associated Anaplastic Large Cell Lymphoma: Where Hematology and Plastic Surgery Meet.

Breast implant insertion for breast reconstruction or breast augmentation is a developing procedure, with high demand worldwide-being the second most common plastic surgery in the US as of 2022. Breast-implant-associated anaplastic large cell lymphoma (BIA-ALCL) is T-cell, non-Hodgkin lymphoma, typically CD30+, ALK-, presenting with fluid collection in the inner aspect of the peri-implant capsule in most patients, with the onset exceeding 1-year after implantation. The mean time between breast implant insertion and BIA-ALCL development is 7-10 years. The main risk factor is the use of textured implants because of their susceptibility to triggering local inflammation and immune stimulation finally leading to lymphoproliferation. Genetic predispositions to hereditary breast cancer increase the risk of disease development as well. BIA-ALCL seems to be underestimated in many countries and the initial symptom-seroma might be overlooked and misdiagnosed. Despite its rarity, the awareness of the disease should be improved among patients and medical professionals. This paper summarizes epidemiology, etiopathogenesis, differential diagnosis, and treatment-both surgical and hematological approaches.

A Panoramic X-ray as a Supportive Diagnostic Tool for the Screening of Osteoporosis in Patients with Hemophilia A and B.

BACKGROUND: Hemophilia is associated with an increased risk of developing osteoporosis and osteopenia. The aim of the study was to interpret the usefulness of fractal analysis of the trabecular bone of the mandible (FD) and selected radiomorphic indices (the antegonial index (AI) and Klemetti index (KI)) to assess the risk of reduced bone mineral density (BMD) in patients with hemophilia A/B. METHODS: The study group consisted of 50 patients with type A/B hemophilia. The control group consisted of 25 males without congenital bleeding disorders. The patients had a panoramic radiograph taken with the same X-ray machine (Vistapano S, Durr Dental, Bietigheim-Bissingen, Germany). The AudaXCeph software (Audax d.o.o., Ljubljana, Slovenia) was used to evaluate the AI index, and the ImageJ, software with a specially prepared script, was used to evaluate the FD. The mandibular cortex was assessed distal to the mental foramen using the Klemetti index. RESULTS: There were no statistically significant differences between the AI, KI and FD values between the study group and the control group. CONCLUSIONS: This study indicated the lack of usefulness of AI, KI and fractal analysis in identifying patients with hemophilia at risk of reduced bone mass.

Assessment of Oral Health and Healthy Habits in Adult Patients with Congenital Hemophilia.

OBJECTIVES: The objective of our study was to assess the current knowledge, the oral health status, and the pro-health needs of patients with hemophilia. MATERIALS AND METHODS: The study included 77 patients with known hemophilia. The study included the assessment of dental indicators related to caries incidence (decayed, missing, and filled teeth [DMFT] and decayed, missing, and filled permanent teeth or surfaces [DMFS]), caries treatment (treatment index), oral hygiene status (Approximal Plaque Index [API] and simplified oral hygiene index [OHI-S]), and periodontal status (bleeding on probing [BoP]). A questionnaire addressed symptoms of hemorrhagic diathesis and health-promoting habits. The influence of routine management ("on-demand" vs. prophylactic therapy), type of hemophilia (A, B), and severity of clotting factor deficiency (mild, moderate, or severe) on oral health was assessed. STATISTICAL ANALYSIS: The tests used in the study were Shapiro-Wilk, Mann-Whitney, Kruskal-Wallis, and Dunn's tests. The level of significance was set at p < 0.05. RESULTS: Patients with hemophilia showed a higher prevalence of caries compared with patients without hemorrhagic diathesis (DMFT 14 and 9, and DMFS 30 and 15, respectively), and they also presented a higher bleeding index value during probing and worse effectiveness of hygienic interdental procedures. The type of therapy and secondary prophylaxis used and the type and severity of hemophilia did not affect the oral health status. CONCLUSIONS: Patients with hemophilia have an increased risk of developing dental caries. Undertaking educational activities related to the prevention of oral diseases is necessary to improve oral health.

Transfusion of fibrinogen concentrate before dental extractions in patients with afibrinogenemia: a narrative review supported by a case report with a proposed treatment protocol.

Afibrinogenemia is a coagulation disorder that occurs with a frequency of 1-2 cases/1,000,000 population and is characterized by a lack of capacity to synthesize fibrinogen. The predominant symptoms related to fibrinogen deficiency are mucocutaneous bleeding, bleeding from the gastrointestinal tract, genital tract or other vascularized tissues as well as excessive bleeding after minor injuries or accidental cuts. Thromboembolic complications and impaired wound healing may also occur. Due to the rarity of the disease, there are no recommendations about fibrinogen substitution before dental procedures (including dental surgery). The purpose of this review is to discuss the indications for the transfusion of a coagulation factor in the preparation of a patient with afibrinogenemia for dental extraction. The article is a narrative review with a proposed management protocol for the dental procedure. The authors have included information from previously published case reports, research studies, and review papers as well as their own case report.

Emicizumab: a novel drug in hemophilia A prophylaxis - a narrative review.

INTRODUCTION: Hemophilia A is a genetically conditioned disease leading to hemostatic disorders due to factor VIII (FVIII) deficiency. The treatment of hemophilia has evolved throughout the past years and has significantly changed. One of the newest drugs for prophylactic treatment is the humanized bispecific IgG antibody - emicizumab, which binds with factor IXa and factor X, bridging those factors and thus mimicking the activity of factor VIII. AREAS COVERED: The literature search was done via the PubMed database, with the emphasis on clinical trials and case reports, describing the off-label emicizumab use. This review presents an extensive summary and considers the advantages and disadvantages (side-effects) of emicizumab, describing additional clinical situations, where emicizumab has been successfully used. In our review, we cover information about the mechanisms of action, indications, and efficacy and discuss some chosen case reports about off-label emicizumab use. EXPERT OPINION: Its convenient administration method (subcutaneous) and frequency of injections (from once a week to once a month) makes it a more comfortable treatment, limiting injection-site reactions, hospital stays, costs of prophylaxis, and significantly increasing patients' quality of life. Adverse effects are scarce and rarely serious - the most common ones are reactions at the injection-site and upper respiratory tract infections.

The Profile of Markers of Bone Turnover, Inflammation and Extracellular Neutrophil Traps on Bone Mass in Haemophilia and the Development of Haemophilic Arthropathy.

BACKGROUND: The aim of the study is to evaluate selected biomarkers of bone turnover, inflammation, neutrophil trap and factors predisposing haemophiliacs to bone loss, and to analyse their relationship with clinical features, treatment and complications. METHODS: The levels of interleukin 6 (IL-6); citrullinated histone (CH3); osteocalcin (BGLAP); bone alkaline phosphatase (BALP); N-terminal procollagen type I propeptide (P1NP); and C-terminal collagen type I telopeptide (C1CP) were examined in 60 patients with haemophilia. RESULTS: The cut-off value for BGLAP is 26.41 ng/mL, and 929.7 pg/mL for CH3. There is a statistically significant difference between BGLAP, BALP, C1CP and CH3 concentrations, depending on the prophylaxis used. The median concentration of BGLAP in patients taking the factor on demand is 28.0 ng/mL, BALP 322.5 U/L, C1CP 191.2 ng/mL and CH3 1114.4 pg/mL. In patients taking recombinant coagulation factor VIII/IX as prophylaxis of bleeding, the median BGLAP concentrations are 35.9 ng/mL, BALP 280.9 U/L, C1CP 161.6 ng/mL and CH3 952.5 pg/mL. BGLAP and BALP concentrations are dependent on the development of haemophilic arthropathic. CONCLUSIONS: The concentrations of selected markers of bone turnover and NETs may help to identify patients at particular risk of developing haemophilic arthropathy and bone metabolic turnover abnormalities.

Potential Biochemical Markers and Radiomorphometric Indices as Predictors of Reduced Bone Mass in Patients with Congenital Hemophilia.

Background: The study aimed to evaluate radiomorphometric indices derived from panoramic X-rays and selected blood markers of bone turnover and neutrophil extracellular traps, with a view to identifying hemophilic patients at risk of developing osteoporosis. Methods: The study consisted of 50 adult men with hemophilia A and B (mild, moderate, and severe). The control group consisted of 25 healthy adult men. In both groups, blood samples were collected to determine concentrations of citrullinated histone H3 (CH3) and osteocalcin (BGLAP) with ELISA tests, and panoramic X-rays were obtained. Images were imported into AudaXCeph software to calculate two radiomorphometric indices: mental index (MI) and panoramic mandibular index (PMI). Concentrations of BGLAP and CH3 were compared with MI and PMI values in patients with and without hemophilia. Results: There were statistically significant differences in BGLAP, CH3, and PMI between the study and the control group (p < 0.05). Multivariate logistic regression analysis showed a predictive value for PMI, BGLAP, and CH3.The ROC curve with cutoff point (Youden index) at 0.40­PMI was calculated. No correlation was observed for the PMI index in any particular subgroup of patients. No correlation between MI and BGLAP/CH3 was observed. Conclusions: Simultaneous use of PMI value and BGLAP and CH3 levels may allow the identification of patients with hemophilia who requirea detailed diagnosis of osteoporosis with DXA.

Risk Factors for Catheter-Related Thrombosis in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

Background and Objectives: Cancer associated thrombosis (CAT) is a common complication of neoplasms. Multiple myeloma (MM) carries one of the highest risks of CAT, especially in the early phases of treatment. Autologous stem cell transplantation (ASCT) as the standard of care in transplant-eligible patients with MM carries a risk of catheter-related thrombosis (CRT). The aim of this study was identification of the risk factors of CRT in MM patients undergoing ASCT in 2009-2019. Materials and Methods: We retrospectively analyzed patients with MM undergoing ASCT. Each patient had central venous catheter (CVC) insertion before the procedure. The clinical symptoms of CRT (edema, redness, pain in the CVC insertion area) were confirmed with Doppler ultrasound examination. We examined the impacts of four groups of factors on CRT development: (1) patient-related: age, gender, Body Mass Index (BMI), obesity, Charlson comorbidity index, hematopoietic stem cell transplantation comorbidity index, renal insufficiency, and previous thrombotic history; (2) disease-related: monoclonal protein type, stage of the disease according to Salmon-Durie and International Staging System, number of prior therapy lines, and MM response before ASCT; (3) treatment-related: melphalan dose, transplant-related complications, and duration of post-ASCT neutropenia; (4) CVC-related: location, time from placement to removal. Results: Symptomatic CRT was present in 2.5% (7/276) of patients. Univariate analysis showed an increased risk of CRT in patients with a catheter-related infection (OR 2.4, 95% CI; 1.109-5.19, p = 0.026), previous thrombotic episode (OR 2.49, 95% CI; 1.15-5.39, p = 0.021), previous thrombotic episode on initial myeloma treatment (OR 2.75, 95% CI; 1.15-6.53, p = 0.022), and gastrointestinal complications of ASCT such as vomiting and diarrhea (OR 3.87, 95% CI; 1.57-9.53, p = 0.003). In multivariate analysis, noninfectious complications were associated with higher CRT incidence (OR 2.75, 95% CI; 1.10-6.19, p = 0.031). Conclusions: The incidence of symptomatic CRT in ASCT in MM was relatively low. Previous thrombotic events, especially during the induction of myeloma treatment, increased CRT risk during ASCT. Dehydration following gastrointestinal complications may predispose to higher CRT incidence.

Preventing the suspension of dental clinics by minimizing the risk of SARS­CoV­2 transmission during dental treatment.

Due to a high risk of the transmission of severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) during dental work, the coronavirus disease 2019 (COVID­19) pandemic has had a considerable influence on the functioning of dental clinics. The elevated risk of transmission is related to the production of aerosol containing secretions from the upper respiratory tract that is produced during dental procedures.The purpose of this narrative review was to present the current knowledge concerning COVID­19 and to propose methods for reducing the spread of the virus. Dental staff should follow the current guidelines and ensure safety at work through the use of personal protective equipment (PPE), including FFP2/FFP3 filter masks, the implementation of the screening protocols and telephone consultations as well as the appropriate preparation of dental practices and patient waiting areas. In addition, it is essential to reduce the number of people simultaneously occupying one building by effectively planning visiting times or discouraging patients from accompanied visits. Procedures that may contribute to production of the aerosol should also be limited.

Autoimmune hemolytic anemia: current knowledge and perspectives.

Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.

Practical Recommendations for Treatment of Dental Patients with Congenital Bleeding Disorders during the Covid-19 Pandemic: A Narrative Review.

At the end of 2019, a new disease -COVID-19-was identified, and a few months later, the World Health Organization announced a pandemic. It is now known that SARS-CoV-2 is highly contagious and most confirmed infections are mild to moderate. The situation is particularly difficult for dentists due to the high risk of virus transmission in the dental surgery. Complications including, but not limited to, problems with the respiratory and cardiovascular systems have been reported in patients with SARS-CoV-2. Several changes in the coagulation system, such as lower platelet numbers or increased prothrombin time, as well as increased D-dimer and fibrinogen, were observed. This review is intended to systematize the knowledge on the treatment of patients with congenital bleeding disorders (CBD) during the SARS-CoV-2 pandemic. Extensive literature research was conducted into COVID-19 and the general medical and dental treatment of patients with CBD. Case studies, research results and recommendations of international societies were used in the study. The results of this research are presented in the form of recommendations for the treatment of patients with coagulopathies. It should be remembered that the impact of COVID-19 on the health condition of patients with CBD is unknown to date.

Selected Hematological Biomarkers to Predict Acute Mortality in Emergency Department Patients. Recent Polish Hospital Statistics.

BACKGROUND: Complete blood count (CBC), red cell distribution width (RDW), mean platelet volume (MPV), mean corpuscular volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), or platelet (PLT) count are referred as predictors of adverse clinical outcomes in patients. The aim of the research was to identify potential factors of acute mortality in Polish emergency department (ED) patients by using selected hematological biomarkers and routine statistical tools. METHODS: The study presents statistical results on patients who were recently discharged from inpatient facilities within one month prior to the index ED visit. In total, the analysis comprised 14,881 patients with the first RDW, MPV, MCV, MCH, MCHC, or PLT biomarkers' measurements recorded in the emergency department within the years 2016-2019 with a subsequent one month of all-cause mortality observation. The patients were classified with the codes of the International Statistical Classification of Diseases and Related Health Problems after 10th Revision (ICD10). RESULTS: Based on the analysis of RDW, MPV, MCV, MCH, MCHC, and PLT on acute deaths in patients, we establish strong linear and quadratic relationships between the risk factors under study and the clinical response (P < 0.05), however, with different mortality courses and threats. In our statistical analysis, (1) gradient linear relationships were found for RDW and MPV along an entire range of the analyzed biomarkers' measurements, (2) following the quadratic modeling, an increasing risk of death above 95 fL was determined for MCV, and (3) no relation to excess death in ED patients was calculated for MCH, MCHC, and PLT. CONCLUSION: The study shows that there are likely relationships between blood counts and expected patient mortality at some time interval from measurements. Up to 1 month of observation since the first measurement of an hematological biomarker, RDW and MPV stand for a strong relationship with acute mortality of patients, whereas MCV, MCH, MCHC, and PLT give the U-shaped association, RDW and MPV can be established as the stronger predictors of early deaths of patients, MCV only in the highest levels (>95 fL), whereas MCH, MCHC, and PLT have no impact on the excess acute mortality in ED patients.

Unexplained anemia in the elderly - a real life analysis of 981 patients.

INTRODUCTION: We aimed to analyze the prevalence of unexplained anemia (UA) and assess its characteristics, potential causes and impact on survival in an elderly population. MATERIAL AND METHODS: Medical files of 981 patients aged ≥ 60 years consulted in one primary medical clinic in Poland in 2013-2014 were retrospectively analyzed. Anemia, defined according to WHO criteria, diagnosed during either hospitalization or outpatient treatment, from the age of 60, was included. Unexplained anemia was diagnosed if, based on available clinical data and laboratory tests and other assessments in medical records, none of the well-known types of anemia were identified. RESULTS: Of 981 patients with anemia, UA was found in 48 (28.4%) patients (4.9% of those studied) and incidence increased with age (≥ 80 years, 12.3%). In 81.3% no full hematological diagnostics were performed. Patients with UA, as with those with defined anemia, when compared to the group without anemia were older, had more co-morbidities, were more frequently hospitalized, more frequently had dementia syndrome and obtained lower Barthel scores (p < 0.0001). In the groups of patients with UA and defined anemia, there were more deaths than in those without anemia (10% vs. 13% vs. 2%, p < 0.0001) with significant differences in survival rates observed during 3-year follow-up. CONCLUSIONS: The increasing incidence with age of UA in the elderly population, insufficient diagnosis and the higher mortality of patients with UA in comparison to the group without anemia indicate the need to develop recommendations for its management by primary care physicians.

Red Blood Cells Mean Corpuscular Volume (MCV) and Red Blood Distribution Width (RDW) Parameters as Potential Indicators of Regenerative Potential in Older Patients and Predictors of Acute Mortality - Preliminary Report.

This study presents the statistical results of patients who had been recently discharged from hospital within one month after their treatment in the emergency department (ED). Using routine (14,881) MCV and RDW measurements and statistical tools, we could predict acute mortality in these patients (N = 1158), adjusted for age. It is likely that an increase in the MCV and RDW parameters may correlate in some of our older patients with a poor prognosis with an increased level of circulating IGF-I, which affects red blood cell parameters. The research presents the prognostic statistics of the analyzed clinical factors as well as speculates on the potential correlation of these parameters with the regenerative potential of stem-cell compartment. Analysis shows that both MCV and RDW are statistically significant (Area Under Curve [AUC], lower CI 95% >50%) predictors of acute mortality in ED patients. The classification of patients based on their MCV threshold (= 92.2 units) indicates a proper clinical prognosis in nearly 6 of 10 subjects (AUC >58%), whereas taking into account RDW (=13.8%) indicates a proper clinical prognosis in no more than 7 of 10 individuals. The report concludes that by employing strongly fitting (95%) quadratic modeling of the ORs against the biomarkers studied, one can notice a similar relationship between MCV and RDW as diagnostic tools to predict regenerative potential and clinical outcomes in older patients. Although RDW alone had a 10% higher diagnostic value in terms of predicting early death in the emergency department in patients that were admitted to the ED and subsequently hospitalized, also taking the MCV measurement improved accuracy in predicting clinical outcomes by 2.5% compared to RDW alone.

Acquired Aplastic Anemia as a Clonal Disorder of Hematopoietic Stem Cells.

Aplastic anemia is rare disorder presenting with bone marrow failure syndrome due to autoimmune destruction of early hematopoietic stem cells (HSCs) and stem cell progenitors. Recent advances in newer genomic sequencing and other molecular techniques have contributed to a better understanding of the pathogenesis of aplastic anemia with respect to the inflammaging, somatic mutations, cytogenetic abnormalities and defective telomerase functions of HSCs. These have been summarized in this review and may be helpful in differentiating aplastic anemia from hypocellular myelodysplastic syndrome. Furthermore, responses to immunosuppressive therapy and outcomes may be determined by molecular pathogenesis of HSCs autoimmune destruction, as well as treatment personalization in the future.