Cure Research Articles

ALLG APML5: Bioavailability and safety of oral arsenic trioxide assessed during consolidation therapy for APL.

The prognosis for patients with acute promyelocytic leukemia (APL) has improved dramatically since the introduction of all-trans retinoic acid (ATRA) and intravenous arsenic trioxide (ATO). However, ATO administration requires daily infusions over several months, representing an onerous burden for hospitals and patients. We evaluated the bioavailability of a novel encapsulated oral ATO formulation in APL patients in first complete remission during standard-of-care consolidation. After a pilot study exploring the likely oral dose requirement, total arsenic pharmacokinetics were evaluated in 20 patients after both intravenous and oral ATO 0.15 mg/kg/d, with exposure to oral ATO restricted to the first week in 2 of the 4 ATO cycles. The primary endpoint was bioequivalence of area under the curve from 0-24 hours (AUC0-24), with bioequivalence of maximum concentration achieved (Cmax) as the key secondary endpoint. The 90% confidence intervals (CI) around point estimates of the geometric means of the oral/intravenous ratios for AUC0-24 and Cmax were compared with bioequivalence limits specified by the European Medicines Agency (0.80-1.25). The estimated oral/intravenous ratios and 90% CI for AUC0-24 in whole blood and plasma were 0.993 (0.954-1.034) and 1.030 (0.977-1.087) respectively; data for Cmax also satisfied bioequivalence requirements. Exploratory studies of arsenic species in plasma showed bioequivalence for AUC0-24 with As(III) (oral/intravenous ratio 0.966 (0.879-1.063)). The adverse event profiles of oral and intravenous ATO were comparable for cycles commencing with the IV and oral formulations. In conclusion, this novel oral ATO formulation is bioequivalent with intravenous ATO and offers a convenient alternative for patients with APL. Accession Number: ACTRN12616001022459.

Rationale and design of the HOVON 170 DLBCL-ANTICIPATE trial: preventing anthracycline-induced cardiac dysfunction with dexrazoxane

BackgroundDexrazoxane has been studied for its ability to prevent anthracycline-induced cardiac dysfunction (AICD) in several trials but its use in clinical practice remains limited. This is related to the low to moderate quality of the generated evidence, safety concerns and restricted prescribing indications. Additional randomized trials are needed before this drug can be routinely integrated into cardio-oncology clinical practice.ObjectivesTo describe the rationale and design of the HOVON 170 DLBCL – ANTICIPATE trial. This trial aims to establish the efficacy and safety of dexrazoxane for the primary prevention of AICD in patients diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL) treated with six cycles R-CHOP21 chemo-immunotherapy.MethodsThis is a multicenter, parallel-group, open-label, phase III trial, randomizing 324 patients between either no cardioprotective treatment or dexrazoxane from the first R-CHOP cycle. The primary and co-primary endpoints are the incidence of AICD within 12 months of registration and the percentage of patients with complete metabolic remission at the end-of-treatment PET-CT respectively. The trial is registered at the EU Clinical Trials Register (EU-CT number 2023-505377-32) and ClinicalTrials.gov (NCT06220032).ResultsThe medical research ethics committee approved the trial in May 2024. Recruitment has started in September 2024 and is expected to last for three years.ConclusionsThis trial is poised to contribute crucial evidence concerning the efficacy and safety on the use of dexrazoxane in the primary prevention of AICD. The trial is anticipated to address critical knowledge gaps and offer important insights into the value of dexrazoxane in cardio-oncology practice.

P-68 A CHALLENGING CASE OF HYPOTHYROIDISM

Abstract Introduction Hypothyroidism is a common disease. L thyroxine once reached the stomach, undergoes disintegration and dissolution, and the active ingredient must reach the actual site of absorption. Disintegration is highly affected by the type of the formulation, the fasted or fed state, the gastric residence time, and the gastric motor function. The dissolution process consists of the release of solute molecules from the solid phase to the liquid one. Gastric juice pH. food, drugs and H pylori can affect L thyroxine absorption. Clinical Case IAA; A 54 y old female patient, known case of follicular thyroid carcinoma (FTC) since 2013, managed with total thyroidectomy, multiple radioactive iodine doses due to residual tissue. Post operative hypocalcemia that was resolved within a year. She was doing well on L- thyroxine suppressive dose of 200mcg/d. In 2018; she was operated for breast carcinoma, received chemotherapy and tamoxifen tablets. She was doing well on L thyroxine suppressive dose 250 mcg/d taken one hour before breakfast on an empty stomach, and was in complete remission regarding FTC. She lost to follow up for nearly one year. Her investigations: TSH= 39.7 mu/l, FT4= 6 (normal= 6.5-22 pmol/l), hemoglobin= 10.7 g/dl, calcium 8.7 mg/dl (normal= 8.4-10.5mg/dl not on calcium tab), celiac and H pylori serological screening were negative. TSH after 3 months =12.8 mu/l, She denied non compliance, Dose of L- thyroxine increased and gluten free diet was tried and did not work, dose increased to 400mcg/d. She was lost to follow up and came after one year,TSH =80 mu/l. L-thyroxine absorption test was performed; and L thyroxine mal-absorption was confirmed. She was advised to crush L-thyroxine 400 mcg/day and take it with water. TSH after two months was =13, free T4 =14 (normal=6.5-22 pmol/l). Gastroscopy showed pan moderate edematous gastritis and moderate erosive duodenitis. Duodenal biopsy showed chronic inflammation, negative celiac disease or malignancy. Conclusion Thyroid hormone is important for growth of intestinal mucosa. Selective L thyroxine malabsorption in the present case could be related to poor drug compliance and chronically uncontrolled thyroid status lead to intestinal edema and malabsorption. The other explanation was that gastritis caused inability of the stomach to properly dissolve tablet preparations to yield the active ingredient. The good response to crushed L thyroxine, which was a method of giving the drug to infants, suggested L thyroxine malabsorption problem started from the stomach.

Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study)

BackgroundEven though major improvements have been made in the treatment of myeloma, the majority of patients eventually relapse or progress. Patients with multiple myeloma who relapse after initial high-dose chemotherapy with autologous stem cells have a median progression free survival up to 2–3 years, depending on risk factors such as previous remission duration. In recent years, growing evidence has suggested that allogeneic stem cell transplantation could be a promising treatment option for patients with relapsed or progressed multiple myeloma. However, prospective randomized trials including allogeneic stem cell transplantation as second-line therapy do not exist to date and therefore urgently needed to demonstrate the value of this therapy in the overall setting of patients with multiple myeloma.MethodsThis clinical trial is a national, multicenter, randomized, open labeled phase III study conducted in 30 hospitals spread all over Germany. After study inclusion, all patients will receive 3 cycles of salvage therapy with one of the currently approved triplet regimens for first relapse. After 3 cycles of salvage therapy, remission status will be assessed. If the patient achieves at least stable disease, partial or complete remission and an HLA compatible stem cell donor could be identified, he/she will be randomized (1:1) to the control or interventional study arm. Approximately 400 patients will be enrolled to enable a randomization of 280 patients. The primary endpoint is overall survival at five years after randomization. The main secondary objectives and endpoints are progression-free survival rate, time-to first occurrence of an infection with CTCAE grade 3–5, non-relapse mortality rate and incidence of acute and chronic graft-versus-host disease after allogeneic stem cell transplantation.DiscussionThe present clinical study is designed to evaluate the superiority of allogeneic stem cell transplantation compared to conventional therapy (triplet chemotherapy) for the difference in overall survival at 5 years, toxicity and quality of life in patients with multiple myeloma who have relapsed or progressed after first-line autologous stem cell therapy.Trial registrationClinicalTrials.gov (NCT05675319) registered on January 9, 2023.

Orbital emphysema and medial orbital wall fracture after nose-blowing: a case report and review of literature

Nose-blowing is commonly known as the harmless act of expelling nasal mucus by exhaling forcefully through the nose. We report a case of orbital emphysema in a 49-year-old female patient, who suffered from fractures of the medial orbital wall after forcefully blowing her nose. The patient presented to our emergency department with acute right sided periorbital swelling and pain as well as an unremarkable endoscopic examination of the nose. Prior to the event, a common cold with signs of acute sinusitis had been reported. A trauma to the eye was credibly denied, which is consistent with the medical imaging pattern. A CT-scan confirmed the diagnosis and showed air trapped into the orbit as well as multiple fractures of the lamina papyracea with displaced bone fragments. Visual acuity and extraocular muscle motility were intact. The patient was treated conservatively with prophylactic antibiotics and was instructed not to blow her nose. Follow-up examination after seven days showed a complete remission.

Venetoclax Plus CyBorD Induction Therapy and Venetoclax Maintenance Treatment for Immunoglobulin Light Chain Amyloidosis with t(11;14) Translocation

Background: A total of 50% of patients with AL amyloidosis have t(11;14) translocation, allowing us to use the selective oral BCL-2 inhibitor venetoclax in their treatment. Case presentation: Our patient was admitted to the gastroenterology department due to weight loss and abdominal pain. An abdominal CT scan revealed some enlarged lymph nodes; therefore, he was referred to the hematology department. A bone marrow biopsy showed massive amorphous amyloid deposition. The sample was positive on Congo red staining and exhibited double refraction under a polarized light microscope. Serum-free light chains and the difference between involved and uninvolved free light chains (dFLCs) were elevated. Using fluorescent in situ hybridization, we detected t(11;14) translocation. Further examinations confirmed the involvement of the liver, colon and heart. Stage II AL amyloidosis was confirmed. Our patient received combined induction therapy with CyBorD and venetoclax due to the presence of the t(11;14) translocation. After six cycles, the patient achieved complete remission. Autologous stem cell transplantation (ASCT) was performed. At 100 days post-ASCT, the patient had complete hematologic remission. Venetoclax maintenance treatment was initiated. The follow-up examinations showed that the patient is in very good partial remission. Conclusions: In the case of our AL amyloidosis patient with t(11;14) translocation, the combined treatment with CyBorD and venetoclax was well tolerated and effective.

Bayesian design of clinical trials with multiple time-to-event outcomes subject to functional cure

ABSTRACT With the continuous advancement of medical treatments, there is an increasing demand for clinical trial designs and analyses using cure rate models to accommodate a plateau in the survival curve. This is especially pertinent in oncology, where high proportions of patients, such as those with melanoma, lung cancer, and endometrial cancer, exhibit usual life spans post-cancer detection. A Bayesian clinical trial design methodology for multivariate time-to-event outcomes with cured fractions is developed. This approach employs a copula to jointly model the multivariate time-to-event outcomes. We propose a model that uses a Gaussian copula on the population survival function, irrespective of cure status. The minimum sample size required to achieve high statistical power while maintaining reasonable control over the type I error rate from a Bayesian perspective is identified using point-mass sampling priors. The methodology is demonstrated in simulation studies inspired by an endometrial cancer trial.

The role of adenoidectomy and/or tonsillectomy in the treatment of nocturnal enuresis in OSA children: a single-arm meta-analysis.

To evaluate the efficacy of tonsillectomy and/or adenoidectomy for the treatment of nocturnal enuresis (NE) in children with obstructive sleep apnea (OSA). PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to December 2023. We included all studies of children with OSA and NE who underwent adenoidectomy and/or tonsillectomy. Risk of bias assessment and meta-analyses of included studies were performed. The sources of heterogeneity were explored through subgroup analyses. The combined overall remission (OR), complete remission (CR), and partial remission (PR) were 67%, 57%, and 4%, respectively, in NE children who underwent adenoidectomy and/or tonsillectomy. Therein, the pooled OR and CR of primary nocturnal enuresis in children with OSA were 67% and 59%, respectively. The pooled OR and CR of children who were treated with adenotonsillectomy (T&A) were 72% and 65%, respectively. The pooled OR and CR of children with OSA aged > 5years were 67% and 58%, respectively. The pooled OR and CR of postoperative follow-up of ≤ 3months were 64% and 52%, respectively. The pooled OR and CR of NE based on RCT studies were 37.3%. The remission rate of NE children who underwent adenoidectomy and/or tonsillectomy was more than half. While the remission rate was significantly lower when RCT studies were included. This suggested that the actual NE remission rate may be lower than expected. Further studies with large sample sizes and control groups are expected to confirm the position of adenoidectomy and/or tonsillectomy in NE treatment.

Differentiation of stem cells into chondrocytes and their potential clinical application in cartilage regeneration.

Cartilage diseases and injuries are considered difficult to treat owing to the low regenerative capacity of this tissue. Using stem cells (SCs) is one of the potential methods of treating cartilage defects and creating functional cartilage models for transplants. Their ability to proliferate and to generate functional chondrocytes, a natural tissue environment, and extracellular cartilage matrix, makes SCs a new opportunity for patients with articular injuries or incurable diseases, such as osteoarthritis (OA). The review summarizes the most important scientific reports on biology and mechanisms of SC-derived chondrogenesis and sources of SCs for chondrogenic purposes. Additionally, it focuses on the genetic mechanisms, microRNA (miRNA) regulation, and epigenetic processes steering the chondrogenic differentiation of SCs. It also describes the attempts to create functional cartilage with tissue engineering using growth factors and scaffolds. Finally, it presents the challenges that researchers will have to face in the future to effectuate SC differentiation methods into clinical practice for treating cartilage diseases.

Efficacy of Apheresis in the Remission of Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis.

Sudden sensorineural hearing loss (SSHL) is an abrupt hearing loss, often of unknown cause. Apheresis is a treatment option aimed at improving blood hemorheology by removing pathogenic blood components. There are currently no previous meta-analyses on its efficacy. Therefore, the aim of this study was to evaluate the efficacy of apheresis in achieving total, complete, and partial remission of SSHL, as well as remission outcomes based on the type of apheresis used. A systematic search was performed in PubMed, Scopus, Web of Science, and the Cochrane Library until March 2024. Random-effects models were used to calculate pooled estimates of treatment success rates (TSR) and their respective 95% CI to analyze the efficacy of apheresis in the remission of SSHL. Subgroup analyses were performed by type of apheresis (HELP-apheresis and rheopheresis). The systematic review included 12 studies (10 in the meta-analysis) involving 786 adults with SSHL. The effect of apheresis showed significant total remission (TSR: 0.55; 95% CI: 0.47, 0.64), complete remission (TSR: 0.21; 95% CI: 0.11, 0.30), and partial remission (TSR: 0.43; 95% CI: 0.37, 0.48). Subgroup analysis revealed significant remission rates for HELP-apheresis (TSR: 0.58; 95% CI: 0.52, 0.64) and rheopheresis (TSR: 0.51; 95% CI: 0.30, 0.72). These findings support apheresis as an equally or more effective treatment for SSHL, particularly in cases where corticosteroid therapy fails. However, due to the unknown etiology of SSHL, further clinical trials with larger, diverse populations are essential to confirm these results.

Revumenib: a new era in acute leukemia treatment.

The AUGMENT-101 clinical trial reported that the use of revumenib led to improved overall survival (OS) and complete remission (CR)/CR with partial hematologic recovery (CRh) in patients with acute leukemias and has released updated data with longer follow-up of Phase 2 results. Additionally, revumenib has received FDA approval for its use in relapsed or refractory (r/r) lysine methyltransferase 2A rearranged (KMT2A-r) acute leukemias.

Prevention of bleeding after endoscopic resection of early esophageal neoplasia in patients with esophageal varices: a systematic review.

Background Although endoscopic resection (ER) is recommended as first-choice treatment for early esophageal neoplasia, patients with esophageal varices are considered a high-risk group due to an increased bleeding risk. This systematic review aimed to evaluate the effectiveness and safety of ER in this specific patient category. Methods We searched for studies reporting on clinical outcomes of ER in presence of esophageal varices, irrespective of study design or follow-up time. Endpoints included the incidence of prophylactic measures to reduce the risk of variceal hemorrhage, radical and curative resection rates, and adverse events. Results After screening a total of 2,371 studies, 42 studies with a total sum of 186 subjects were included in this systematic review. Endoscopic band ligation (72/186; 39%) and endoscopic injection sclerotherapy (22/186; 12%) were reported as most widely adopted prophylactic measures to eradicate varices prior to ER. Other frequently described prophylactic measures included direct varix coagulation during ER (18/186; 10%) and the placement of a transjugular intrahepatic portosystemic shunt prior to ER (9/186; 5%). While the radical and curative resection rates were high (86% and 72%, respectively), the periprocedural and delayed bleeding risk were reported to be relatively low (6% and 3%, respectively). In all studies, no procedure-related mortality was observed. Conclusions ER appears to be a safe and effective treatment option in selected patients with concurrent early esophageal neoplasia and esophageal varices, provided that a tailored approach of adequate prophylactic measures is applied to prevent bleeding.

Closure of ventricular septal defect in children with trisomy 18: perioperative events and long-term survival.

This retrospective study aimed to investigate the feasibility of surgical closure of ventricular septal defect in children with trisomy 18 by assessing perioperative events and long-term survival. From April 2008 to March 2024, 41 consecutive patients were referred to us for ventricular septal defect surgery. The defect was closed in 35 patients at the end (median age, 16 months; median body weight, 5.7 kg), 31 out of 37 patients after the preceding pulmonary artery banding according to our staged surgery policy, and 4 patients without the banding. Sixty-five significant non-cardiac lesions existed concurrently and 14 patients underwent tracheostomy before closure. The investigation was conducted by checking medical records and contacting the primary physician. Four patients died during the inter-stage after banding to closure (10.8%). Two of them were awaiting closure. Concomitant surgeries, 15 right ventricular muscle resections, or 1 arch repair, were performed along with closure. Arrhythmia was the most common adverse event (51.4%). Three patients required extracorporeal membrane oxygenation support. Transient but severe hepatic injury occurred in 11 patients (31.4%). There were 2 hospital death (5.7%) due to severe respiratory insufficiency or fulminant sepsis. Five patients died after discharge, 3 pneumonia and 2 sudden death, resulting in a 5-year estimated survival of 79.5%. Three hepatoblastoma and 1 hepatoangioma developed, but complete remission was achieved in all patients. Although further studies are mandatory, surgical closure of ventricular septal defect may be an effective treatment option even for children with trisomy 18.

Imaging characteristics and treatment of recurrent germinoma.

An MRI protocol for germinoma surveillance after complete remission has not been established. Moreover, the standard treatment for recurrent or refractory germinoma has not been determined. In this study, the authors explored the imaging characteristics of recurrent germinoma and discuss their institution's experience with multidisciplinary treatment of this malignancy. The medical records of 16 patients (14 male, 2 female) with recurrent germinoma and 62 patients (52 male, 10 female) without recurrence who were treated at the authors' institution between 1989 and 2023 were retrospectively examined. Data including diagnostic imaging, tumor markers, treatment at diagnosis and recurrence, and overall survival were collected from patients' medical records and statistically analyzed. No patients with recurrence received craniospinal irradiation (CSI) as an initial therapy, and local irradiation was a significant risk factor of recurrence (p = 0.0072). The period between the start of first-line treatment and confirmation of the first recurrence ranged from 4.2 to 272 months (median 66.8 months). Among the recurrences, 13 tumors occurred outside the radiation field, including 6 cases of spinal cord/canal recurrence. One-third of patients did not exhibit elevated tumor marker levels in the serum. Fourteen patients had contrast-enhanced recurrent lesions. In the 2 patients with non-contrast-enhanced lesions, recurrence was detected by high signal intensity on diffusion-weighted imaging (DWI) and elevated tumor marker levels in CSF. Fifteen patients received chemotherapy for the first recurrence, and 14 received radiation therapy, with 9 receiving CSI. The patients who received CSI survived without further recurrence during the study period. However, the median progression-free survival and overall survival after the first recurrence among patients who did not undergo CSI were 12.2 and 37.4 months, respectively, which were shorter than those for patients treated with CSI (both p < 0.01, log-rank test). Spinal MRI for surveillance in patients with recurrent germinoma, especially for those who do not receive CSI, is recommended. DWI might be useful for detecting recurrent germinoma. Aggressive treatment at the time of recurrence is crucial, and even if remission is achieved with chemotherapy, CSI for consolidation is important to prevent further recurrence.

Total marrow irradiation as part of autologous stem cell transplantation for patients with multiple myeloma.

The efficacy and safety of total marrow irradiation (TMI) plus a reduced dose of melphalan as autologous stem cell transplantation (ASCT) preconditioning for multiple myeloma (MM) patients were evaluated. The 11 patients with MM had a median age of 57 (range: 46-75) years; six of them were at standard risk and five of them were at high risk based on the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) standard risk factors. Before ASCT, three patients achieved stringent complete response (sCR), two patients achieved complete remission (CR), and the rest of the patients had either partial response (PR) or progressive disease. Most of the 11 patients were pretreated with melphalan 120-140 mg/m2 and TMI 12Gy. The intravenous infusion median mononuclear cell count (MNC) was 8.13 (4.16-11.84) × 108/kg, and the median CD34+ count was 4.74 (2.51-21.98) × 106/kg. The minimal residual disease (MRD) in the grafts as determined by flow cytometry (FCM) and fluorescence in situ hybridization (FISH) were negative in 10 patients but positive in the progressive patient. All patients stopped maintenance therapy after transplantation, and further observation focused on the efficacy and tolerability of the transplantation. The neutropenic and thrombocytopenia durations were 11 (7-28) and 14 (8-70) days, respectively. The primary acute non-hematological toxicities were mild oral and gastrointestinal mucositis; there were no transplant-related deaths or serious complications. Of the eight patients who did not achieve sCR before transplantation, seven converted to sCR and one converted to VGPR after transplantation. The median follow-up period was 24 (10-57.5) months. Only one patient relapsed, and the progression-free survival (PFS) was 90.9%, while the overall survival (OS) was 100%. Our preliminary results suggest that melphalan 120-140 mg/m2 plus TMI 12Gy/6f as a conditioning regimen is safe and efficient for patients with MM.

Membranous Nephropathy

Membranous nephropathy is a glomerular disease that may be caused by exogenous risk factors in genetically predisposed individuals (primary MN) or may be associated with other autoimmune diseases, drug exposure, or cytotoxic agents (secondary MN). Primary membranous nephropathy (PMN) is an autoimmune disease in which antigens—mainly the phospholipase A2 receptor—are located in the podocytes and are targeted by circulating antibodies, leading to in situ formation of immune complexes that activate the complement system. Clinically, the disease is characterized by nephrotic syndrome (NS) and associated complications. The outcome of PMN can vary, but untreated patients with NS may progress to end-stage kidney disease (ESKD) in 35–40% of cases within 10 years. Treatment primarily aims to prevent NS complications and progression to ESKD. The most commonly used immunosuppressive drugs are rituximab, corticosteroids, cyclophosphamide, and calcineurin inhibitors. Most patients may experience an improvement of proteinuria, which can sometimes be followed by NS relapse. Fewer than 50% of patients with PMN achieve complete and stable remission. In addition to immunosuppressive therapy, antiproteinuric, anti-lipemic, and anticoagulant medicaments are often required.

Blastic plasmacytoid dendritic cell neoplasm: a Swiss case series of a very rare disease and a structured review of the literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease, with unique diagnostic challenges and often dismal outcome. There are no widely accepted treatment guidelines available. Lymphoma-like regimens with or without autologous or allogenic transplantation were the cornerstone of most therapeutic concepts. A few years ago, the CD123-directed immunoconjugate tagraxofusp emerged as a new valuable treatment option. The goal of our research was to collect available data on BPDCN-patients treated at large centres in Switzerland and worldwide and to draw conclusions regarding the incidence, clinical presentation, prognostic factors and therapeutic strategies. We collected data from BPDCN patients from leading Swiss haemato-oncology centres from 2005 to 2022. Furthermore, we reviewed and analysed the published literature (cohorts and case reports in peer-reviewed journals) from 1997 to 2020 (structured review of the literature). We identified 115 international publications including 600 patients from all over the world. Most of them had very small sample sizes (only ten papers with more than ten patients) and all but one were retrospective or observational respectively. Most included patients were Europeans (n = 385, 64%) and Asians (n = 120, 20%), followed by Americans (n = 90, 15%) and patients from Australia/New Zealand (n = 3) and Africa (n = 2). BPDCN was more common in men with a predominance of 3:1. The median age (n = 414) at diagnosis was 66.5 years ranging from one month to 103 years. Newly diagnosed women were significantly younger than men (median: 62 vs 67 years, mean: 53.4 vs 59.3 years, p = 0.027) and less often had bone marrow infiltration and affected lymph nodes. Upfront allogenic transplantation as well as ALL regimens performed best, with response to first-line therapy clearly associated with better overall survival. The Swiss cohort contained 26 patients (23 males and 3 females) over 18 years (2005-2022). The median age at diagnosis was 68.5 years (range: 20-83). Ten patients underwent upfront stem cell transplantation (seven allogenic and three autologous), at least trending towards a better overall survival than other therapies. With a follow-up of 8 years, the median overall survival was 1.2 years. Eight patients in this cohort were treated with tagraxofusp, which became available in 2020 and was approved by Swissmedic in 2023. Our study confirms that BPDCN is a very rare and difficult-to-treat disease. Underdiagnosis and underreporting in the literature pose further challenges. Symptoms at presentation seem to differ slightly between sexes and reaching a complete remission after first-line treatment remains crucial for a prolonged overall survival. Effective treatment protocols in first line include transplantation regimens (mainly allogenic, potentially also autologous) as well as ALL protocols. In order to understand the significance of tagraxofusp as a bridge to transplant or as a continuous monotherapy in elderly patients, further evaluation with longer follow-up periods is required. In general, analysis of the Swiss patients confirmed the results from the worldwide cohort.

Preparation of Highly Stable Wood with Fast Curing, Ultraviolet, and Mildew Resistance through Copper-Montmorillonite Nanoparticles Hybridized with Tung Oil.

Wood has a number of undesirable inherent properties that limit its ability to be used in a wider range of applications. For this reason, in this study, copper-montmorillonite nanoparticles were prepared from natural biomass tung oil and the natural mineral montmorillonite by the ion exchange method. Modified wood with tung oil intercalated with copper-montmorillonite was prepared by a simple and environmentally friendly impregnation and natural curing process. The natural curing rate of tung oil was greatly accelerated by the addition of copper-montmorillonite nanoparticles. The surface contact angle of the wood increased from 85.0° to 152.2° after copper-montmorillonite-tung oil treatment, and remarkably, it remained at 144.2° after 180 s. After 192 h of immersion, the water absorption decreased by 90.0% compared with the control group, of which the resistance to swelling was as high as 59.00%, which significantly improved the dimensional stability of the wood. After 15 days of ultraviolet irradiation, the copper-montmorillonite-tung oil-treated wood showed a 68.89% reduction in redness value compared to the control and a significant increase in ultraviolet resistance. Copper-montmorillonite-tung oil-treated wood showed greatly enhanced effectiveness against mildew. On the eighth day of Aspergillus niger infestation, the control wood was already full of mildew, whereas the copper-montmorillonite-tung oil-treated wood was not infested with mildew. In particular, after 28 days of infestation by Penicillium oryzae, the modified wood remained free of the fungus, with 100% mildew prevention efficiency. In addition, after 2 weeks of leaching, the leaching rate of the impregnated material was only 0.22%, facilitating long-term protection of the wood. The present study by the copper-montmorillonite synergistic tung oil treatment strategy provides innovative methods and potential ideas for extending the service life of wood products and high-value utilization of wood and also has the potential to scale up wood protection.

Weibull-Geometric Mixture Cure Rate Models With Applications

This article delves into a parametric survival model tailored for scenarios where the studied population encompasses long-term survivors or individuals with immunity. We initially conceptualized the cure rate model as a mixture model, which included a segment that represented the proportion of immune individuals and a distribution that characterized the lifetimes of susceptible individuals. Our contribution lies in proposing a cure rate model grounded in the Weibull-Geometric Distribution, adept at integrating the influences of risk factors or covariates on the likelihood of an individual becoming a long-term survivor. Cure rate models serve as powerful tools for modeling time-to-event dynamics across diverse contexts. Different methods of estimation are used to estimate the unknown parameters in complete and censored random samples.

A complete response with daratumumab, venetoclax, azacitidine and dexamethasone in a heavily pre-treated, chemo-refractory early T-precursor acute lymphoblastic leukemia/lymphoma patient.

Early T-precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a rare and aggressive subtype of T-cell leukemia with poor prognosis and resistance to standard treatments. We report a 21-year-old male with ETP-ALL/LBL who, after an initial complete remission with the HOELZER protocol, experienced early relapse and was refractory to subsequent FLEND and BFM protocols. Following disease progression and complications, he was treated with a combination of daratumumab, venetoclax, azacitidine, and dexamethasone. This regimen achieved complete remission after one cycle. This case highlights the potential of this combination therapy as an effective treatment for refractory ETP-ALL/LBL, suggesting further research is warranted to validate its efficacy and safety.