Improved long-term survival rate in the responders to bortezomib, cyclophosphamide, dexamethasone induction therapy in a transplant-eligible cohort of predominantly middle-age multiple myeloma patients.

BACKGROUND: Multiple myeloma (MM) represents the second most common hematologic malignancy (15%). Induction with bortezomib, cyclophosphamide, and dexamthasone VCd (d: low dose dexamthasone) regimen is widely used due to its high effectiveness, low toxicity and good tolerability, particularly with renal impairment. Real-world data on the use of VCD in clinical practice is lacking. OBJECTIVES: Evaluate the real-world experience of the VCD regimen. DESIGN: Retrospective. SETTING: Tumor registry database of tertiary cancer care center. PATIENTS AND METHODS: newly diagnosed MM patients who received VCD induction and underwent autologous stem cell transplant (ASCT) from July 2007 to July 2020. MAIN OUTCOME MEASURES: response evaluation, progression-free survival (PFS) and overall survival (OS). SAMPLE SIZE: 87 patients. RESULTS: Of 102 patients who started induction with VCd, 87 patients experienced a partial response or more overall response rate of 85%). The median age of these 87 patients at diagnosis was 52 years, of which 29.9% presented with renal impairment and 60.3% of patients had stage 2 by the Revised International Staging System (R-ISS). Patients with a standard cytogenetic risk achieved a better response compared to those with a poor cytogenetic risk (P=.044). The post-induction response rates were 6.9% stringent complete remission (sCR), 35% complete remission (CR); 41.4% very good partial response (VGPR), and 16.1% partial response (PR), respectively; the response rates became greater for sCR and CR post-transplantation at day 100 with 16.1% sCR, 35.6% CR, 32.2% VGPR and 16.1% PR, respectively. The median PFS was 49 months and 5 years OS was 84%. PFS was better in patients who achieved sCR vs PR (83 vs 35 months, P=.037). High LDH, high-risk cytogenetic and stage 3 R-ISS showed a worse median PFS and OS. CONCLUSIONS: VCD induction in newly diagnosed MM is highly effective, convenient, tolerable and affordable regimen, especially in low and middle-income countries with limited resources, also with favorable outcomes and survival. while those who did not respond successfully shifted to VRD or VTD. LIMITATIONS: The usual limitations of a retrospective analysis using registry-level data, no data on quality of life.

Unveiling Lethal Risks Lurking in Hot Tub Baths: A Review of Tragic Consequences.

Heat therapy, including saunas, jacuzzi, and hot tub bathing, has gained global popularity. However, the escalating incidents of injuries and fatalities associated with hot tub activities are a significant public health concern. This study aims to comprehensively review and analyze the pathophysiological factors contributing to hot tub-related deaths, addressing the need for awareness and mitigation strategies. A comprehensive search of electronic databases, PubMed and Science Direct, was conducted to identify articles relevant to bath-related deaths. Eligible studies were exported to the Rayyan (Qatar Computing Research Institute, Qatar) software for data analysis. The data extracted from the 18 studies were compiled to elucidate the mechanisms underlying hot tub bath-related deaths and to advocate for the adoption of potential mitigation strategies and future directions to prevent such incidents in the future. The review revealed insights into the current trend of fatalities linked to hot tub bathing. A detailed analysis of pathophysiological aspects, encompassing hemodynamics, electrolyte disturbances, serum glucagon alterations, and the impact of alcohol and substance abuse during hot tub use, was conducted. Furthermore, we explored the effects of temperature and conducted a thorough discussion of postmortem evidence analysis concerning deaths related to bathtub usage. Finally, the paper discusses mitigation strategies to prevent fatalities attributed to hot tub bathing. In conclusion, our review highlights growing public health concerns surrounding injuries and fatalities related to hot tub activities. Through an examination of the incidence rates, pathophysiological factors, and proposed mitigation strategies, we provide crucial insights for enhancing safety and addressing the escalating risks associated with hot tub bathing.

Comparative Study of Frequency of Alveolar Osteitis, with and without using Platelet-Rich Fibrin in Mandibular Third Molar Surgery.

Introduction: Alveolar ostitis (AO) is the dissolution of blood clot due to enhanced local fibrinolysis and is caused by trauma to the jaw (direct) or because of bacterial involvement (indirect), which result in the activation of plasminogen pathway. Platelet-rich fibrin (PRF) is a platelet concentrate that comprises numerous autologous growth factors, and immune cells hence has the potential to expedite the healing process. The objective of the study was to determine the efficacy of PRF in the surgically extracted third molar in the context of its potential progress to AO. Materials and Methods: A total of 180 patients of 18-65 years with unilateral painful mandibular third molars due to caries, failed endodontics treatment, and pericoronitis were included in the study. Exclusion criteria were patients who were medically compromised, smokers, alcoholic, poor oral hygiene, third molar having associated periapical pathology, and receiving antibiotic regime in the last 2 weeks. Before starting surgical procedure, patients were randomly divided into two groups using lottery method. Group I received PRF in the extraction socket, while in Group II, the extraction site was left for normal healing as practiced in a standard procedure. Pain was assessed in terms of pain score, and it was recorded on a 10 mm visual analog scale on the first and third postoperative days. Results: Mean age of the patients was 41.35 ± 9.87 years. The mean age in Group I was 42.84 ± 10.52 years, and in Group II, it was 40.54 ± 9.52 years. Out of 180 patients, 90 (50.0%) were male and 90 (50.0%) were female, with a male-to-female ratio of 1 : 1. Frequency of AO following mandibular third molar surgery in Group I receiving PRF was 2.22% and in non-PRF group 12.22% (p-value = 0.010). Conclusion: The incidence of AO following mandibular third molar surgery was lower when PRF was used.

Intensification of Biodiesel Processing from Waste Cooking Oil, Exploiting Cooperative Microbubble and Bifunctional Metallic Heterogeneous Catalysis.

Waste resources are an attractive option for economical the production of biodiesel; however, oil derived from waste resource contains free fatty acids (FFA). The concentration of FFAs must be reduced to below 1 wt.% before it can be converted to biodiesel using transesterification. FFAs are converted to fatty acid methyl esters (FAMEs) using acid catalysis, which is the rate-limiting reaction (~4000 times slower than transesterification), with a low conversion as well, in the over biodiesel production process. The study is focused on synthesizing and using a bifunctional catalyst (7% Sr/ZrO2) to carry out esterification and transesterification simultaneously to convert waste cooking oil (WCO) into biodiesel using microbubble-mediated mass transfer technology. The results reveal that a higher conversion of 85% is achieved in 20 min using 7% Sr/ZrO2 for biodiesel production. A comprehensive kinetic model is developed for the conversion of WCO in the presence of a 7% Sr/ZrO2 catalyst. The model indicates that the current reaction is pseudo-first-order, controlled by the vapor-liquid interface, which also indicates the complex role of microbubble interfaces due to the presence of the bifunctional catalyst. The catalyst could be recycled seven times, indicating its high stability during biodiesel production. The heterogeneous bifunctional catalyst is integrated with microbubble-mediated mass transfer technology for the first time. The results are unprecedented; furthermore, this study might be the first to use microbubble interfaces to "host" bifunctional metallic catalysts. The resulting one-step process of esterification and transesterification makes the process less energy-intensive and more cost-efficient, while also reducing process complexity.

Improved survival in adolescents and young adults (AYA) patients aged 14-55 years with acute lymphoblastic leukemia using pediatric-inspired protocol - a retrospective analysis of a real-world experience in 79 of patients treated at a national tertiary care referral center.

BACKGROUND: Treating adolescents and young adults (AYA) patients with acute lymphoblastic leukemia (ALL) using pediatric-inspired protocols have shown improvement in outcomes. Most data available in the literature of such protocols is derived from well-controlled clinical trials. This report aims to provide a real-world experience from using a pediatric-inspired protocol in ALL-AYA population in larger number of patients treated at a national tertiary care referral center. METHODS: Newly diagnosed Philadelphia negative ALL-AYA patients ages between 14 and 55 years of age were treated on an institutional protocol (AYA-15 protocol) adopted from a modified version of Children's Cancer Group (CCG) 1900 protocol. At the time of this publication, a total of 79 patients were treated using the AYA-15 protocol between 2015 and 2020). Event-free survival (FFS), disease-free survival (DFS), and overall survival (OS) were analyzed using cumulative incidence and Kaplan-Meier methods. RESULTS: The median age at diagnosis was 18 years (14-51 years) with 63% male patients. Complete remission (CR) at day 28 of induction was achieved in 88.6% of which 73.4% were minimal residual disease (MRD) negative. At a median follow up of 5 years, EFS, DFS and OS were 57.5%, 69.2% and 75.8% respectively. Toxicities were within the expected range with infections and transaminitis being the most common adverse events. CONCLUSION: Our single-center experience real-world data in treating AYA-ALL patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18-55 years.

Cold-stored whole blood and platelet counts in severe acute injury: A comparison of four retrospective cohorts.

BACKGROUND: Low-titer group O whole blood (LTOWB) is attractive for acute trauma care as it delivers concentrated and balanced hemostatic resuscitation in single large bags. Whether cold-stored LTOWB can sustain platelet counts is unclear. STUDY DESIGN AND METHODS: Four cohorts of trauma patients-three historic, one retrospective-were identified by their urgency of blood use. Admission and all subsequent platelet counts over the first 24 h of care were compared with t-tests. The cohorts were as follows: 1292 patients at Maryland Shock Trauma as described by Stansbury and colleagues in 2013; 35 patients enrolled locally in the 1:1:2 arm of the pragmatic randomized optimal plasma and platelet ratios (PROPPR) trial; 34 patients enrolled locally in the 1:1:1 arm of PROPPR; and 59 patients receiving more than 3 units of LTOWB enroute to or at our Level 1 trauma center, 2019-2020. RESULTS: Mean age of LTOWB units transfused was 9 ± 5 days and mean dose was 5 ± 2 units. All four cohorts were profoundly injured (mean Injury Severity Score ≥ 31), with mean first platelet counts 204-228 K/µ and subsequent counts approximately 100 k/µl lower. Through the first 24 h of care, mean platelet counts decreased least, 79 and 83 103 /µl, in the 1:1:1 PROPPR and LTOWB cohorts. Mean platelet counts in patients transfused with LTOWB remained stable after the third hour of care. DISCUSSION: LTOWB transfusion was associated with lesser mean decrease in platelet counts during the first 24 h after injury, similar to those observed among patients receiving components 1:1:1 component in the PROPPR study.

Rates of delayed hemolytic transfusion reactions observed in a trauma center.

BACKGROUND: Delayed hemolytic transfusion reactions (DHTRs) are reported to be rare occurrences but may be more frequently observed in the trauma setting where patients are heavily transfused, followed over long inpatient admissions, and have frequent subsequent blood counts as they undergo multiple surgical interventions. STUDY DESIGN AND METHODS: We examined the rates of DHTRs on a per transfusion and per patient basis in an academic county hospital with a level 1 trauma center serving a four-state region and over a 3-year period. DHTRs were entered sequentially into a registry as they were observed, and a retrospective review of all new alloantibodies detected was performed to identify any additional DHTRs. The number of units of red blood cells (RBCs), the number of unique patients, types of alloantibodies, and number of transfusions were extracted from blood bank records. RESULTS: Twenty-nine DHTRs were observed from January 1, 2017, through December 31, 2019, from newly observed alloantibodies after a median of 12 red blood cells (RBCs) transfusions per patient. These reactions occurred in response to 24,633 unique transfusions in 6905 unique patients, so the observed rates were about 1:849 RBC transfusions and 1:238 transfused patients. Evidence of delayed hemolysis was seen in five additional patients who were transfused during emergency resuscitation and later found to have had known RBC antibodies. DISCUSSION: We report a higher rate of DHTRs than previously described to demonstrate that DHTRs are not rare in trauma centers.

Educational Case: Partial D Phenotype and Role of RhoGAM.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Evaluation of a New Generation Automated Assay for 25-Hydroxy Vitamin D Based on Competitive Protein Binding.

BACKGROUND: The interest for vitamin D has exponentially increased testing demand for 25-hydroxy vitamin D [25(OH)D]. Consequently, many laboratories are switching from LC-MS/MS methods to automated, high-throughput immunoassays. One of the major potential issues with these assays has been the lack of cross-reactivity with 25(OH)D2. METHODS: We have evaluated the Roche Elecsys vitamin D total II assay for accuracy by comparing 79 patient samples with LC-MS/MS. The cross-reactivity for 25(OH)D2 was evaluated by analyzing samples with high 25(OH)D2 separately and estimating 25(OH)D2 recovery, as well as by spiking of 25(OH)D2. The assay was further evaluated for precision, linearity, sample type, and common interferences. RESULTS: There was mostly good agreement between the Elecsys and LC-MS/MS assays (Deming regression: y = 0.95x + 0.70), with an overall bias of 2.3% (-0.84 ng/mL). However, there were 6 out of 79 (7.6%) discordant samples. The Deming regression for samples with high 25(OH)D2 compared to LC-MS/MS showed similar slope and intercept (y = 0.97x - 1.1). The average recovery of 25(OH)D2 for these samples was 90%. The initial precision studies were in general agreement with the package insert, but long-term clinical use showed higher-than-claimed imprecision (11.7%-14.4% at 12 ng/mL and 6.9%-7.6% at 27 ng/mL; claimed: 7.2% and 5.0%, respectively). We observed 1 falsely high result in plasma, an issue previously addressed by Roche in a medical device correction. CONCLUSIONS: The analytical performance of the Roche Vitamin D assay was acceptable, and the assay had a good cross-reactivity for 25(OH)D2.