Venetoclax Plus Azacitidine as a Bridge Treatment to Allogeneic Stem Cell Transplantation in Unfit Patients with Acute Myeloid Leukemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely recommended for unfit patients with newly diagnosed acute myeloid leukemia (AML). Patient survival can improve with venetoclax plus azacitidine (VEN plus AZA). However, the long-term outcome of this treatment strategy is still unsatisfactory. The high response and low treatment toxicity rates of patients receiving VEN plus AZA can provide an opportunity for HSCT among unfit patients. Nevertheless, the outcomes and complications of VEN plus AZA, followed by HSCT, remain unclear. METHODS: This single-center retrospective study aimed to compare patients with newly diagnosed AML receiving VEN plus AZA as induction therapy (n = 27) to those receiving the conventional I3A7 regimen as induction therapy (n = 34). RESULT: The 1-year overall survival, relapse, and non-relapse mortality rates in the two groups were similar. The cytogenetic risks and the hematopoietic cell transplantation-specific comorbidity index are the most significant predictive factors of overall survival. CONCLUSION: In older patients unfit for intensive chemotherapy, a low-intensity regimen with VEN plus AZA is a suitable bridge therapy. Furthermore, allo-HSCT is feasible and can be a curative option.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy.

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC (J Clin Oncol 2019; 37: 3223-3233), NCT04165772 (N Engl J Med 2022; 386: 2363-2376), and PROSPECT (N Engl J Med 2023; 389: 322-334). In this review, we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Neoadjuvant Chemotherapy With/Without Radiotherapy for Locally Advanced Rectal Cancer: A Nationwide Retrospective Cohort Study.

BACKGROUND/AIM: The role of neoadjuvant radiotherapy in the management of patients with locally advanced rectal cancer (LARC) who have undergone neoadjuvant systemic therapy has been the subject of recent debate. PATIENTS AND METHODS: We identified eligible rectal cancer patients diagnosed between 2011 and 2020 using data from the Taiwan Cancer Registry. In our primary analysis, we applied propensity score weighting (PSW) to balance observable potential confounders. We then compared the hazard ratio (HR) of death the neoadjuvant concurrent chemoradiotherapy (nCCRT) group and the neoadjuvant chemotherapy without radiotherapy (nCT) group. Additionally, we conducted a comprehensive assessment of other outcomes and performed various supplementary analyses. RESULTS: The primary analysis included 2,298 patients. The overall survival did not exhibit statistically significant differences, with a PSW-adjusted HR of 0.72 (95% confidence interval=0.33-1.56, p=0.40) when comparing the nCCRT group to the nCT group. These findings were consistent with those of other long-term outcomes and supplementary analyses. CONCLUSION: In patients with LARC who have undergone neoadjuvant systemic therapy, the addition of radiotherapy did not yield statistically significant differences in long-term clinical outcomes.

Enzalutamide Prior to Radium-223 Is Associated with Better Overall Survival in Metastatic Castration-Resistant Prostate Cancer Patients Compared to Abiraterone-A Retrospective Study.

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months, p = 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%, p = 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003-0.231, p = 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis.

First report of Robbsia andropogonis causing bacterial leaf spot of bougainvilleas in Taiwan.

Bougainvilleas (Bougainvillea spp.) are popular ornamentals commonly grown as bushes, vines, or trees worldwide (Kobayashi et al. 2007). Leaf spot symptoms were observed on a bougainvillea hedge located in North District, Taichung, Taiwan during August of 2022. The lesions were brown, necrotic and had yellow halos (Fig. S1). All the plants at the location showed similar symptoms. Leaf samples were collected from five plants and symptomatic tissues were minced in 10 mM MgCl2. The samples were streaked onto nutrient agar (NA) and after culturing at 28°C for 2 days, small, round, creamy white colonies were consistently isolated from all the samples. A total of five strains (BA1 to BA5) were obtained; each of them was isolated from a different plant. All five strains induced hypersensitive response in tobacco leaves. Amplification and sequencing of the isolated strains' 16S rDNA using primers 27F and 1492R (Lane 1991) revealed that all five strains shared identical sequences (GenBank accession no. OQ053015) with Robbsia andropogonis LMG 2129T (formerly Burkholderia andropogonis and Pseudomonas andropogonis; GenBank accession no. NR104960; 1,393/1,393 bp). Further testing of BA1 to BA5's DNA samples using the pathogen's species-specific primers Pf (5'-AAGTCGAACGGTAACAGGGA-3') and Pr (5'-AAAGGATATTAGCCCTCGCC-3'; Bagsic et al. 1995) successfully amplified the expected 410-bp amplicon in all five samples; the sequences of the PCR products completely matched to those of BA1 to BA5's 16S rDNA. Strains BA1 to BA5 also tested negative for arginine dihydrolase and oxidase activity, and failed to grow at 40°C, all of which are consistent with descriptions of R. andropogonis (Schaad et al. 2001). Pathogenicity of the isolated bacteria was confirmed by spray inoculation. Three representative strains, BA1 to BA3, were used for the assay. Bacterial colonies were scraped from NA plates and suspended in 10 mM MgCl2 added with 0.02% Silwet L-77. The concentrations of the suspensions were adjusted to 4.4-5.8 x 108 cfu/ml. The suspensions were sprayed onto three-month-old, cutting-propagated bougainvillea plants (to runoff). Controls were treated with bacteria-free solutions. Three plants were used for each treatment group (and the controls). The plants were placed in a growth chamber (27/25°C, day/night; 14-hour photoperiod) and bagged for three days. Within 20 days post inoculation, brown, necrotic lesions resembling those observed in the sampling site were observed on all inoculated plants, but not on the controls. One strain was re-isolated for each treatment group and the re-isolated strains all shared the same colony morphology and 16S rDNA sequence with BA1 to BA5. Additional PCR testing of these re-isolated strains using Pf and Pr also produced the expected amplicon. This is the first formal report of R. andropogonis affecting bougainvilleas in Taiwan. The pathogen has been reported causing diseases of betel palm (Areca catechu), corn and sorghum in Taiwan (Hseu et al. 2007; Hsu et al. 1991), some of which are economically important (Lisowicz 2000; Navi et al. 2002). As such, infected bougainvilleas could potentially serve as an inoculum source for these diseases.

Pelvic Neoadjuvant Radiotherapy for Stage M1a Rectal Adenocarcinoma Patients Treated With Systemic Therapy Followed by Proctectomy and Metastasectomy: A Nationwide Retrospective Cohort Study.

BACKGROUND/AIM: The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures. PATIENTS AND METHODS: The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses. RESULTS: Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses. CONCLUSION: nRT was associated with improved OS in our study population.

Chondrosarcoma of Ureter in an Elderly Patient: A Case Report.

Chondrosarcoma is a rare type of cancer that can affect the upper urinary tract. Because of its rarity, the clinical presentation of chondrosarcoma can be similar to other urinary tract conditions, such as renal colic, hematuria, and urothelial carcinoma. The primary treatment for chondrosarcoma is the surgical removal of the tumor, and radiation or chemotherapy may be used for advanced cases. However, because of the limited number of patients with this condition, there are no established guidelines for chemotherapy, and the outcomes are unclear. In this case, we present a 71-year-old female patient who was diagnosed with ureteral chondrosarcoma. She presented with abdominal pain and hydronephrosis, and a tumor was found beneath a small stone. The patient underwent nephroureterectomy and received oral fluorouracil chemotherapy due to the advanced stage of the disease. Fortunately, the patient survived, and at the 7 months post-operative follow-up there was no evidence of recurrence. In conclusion, the chondrosarcoma of the upper urinary tract is a rare condition that can be difficult to diagnose due to its similarity to other urinary tract conditions. Treatment typically involves the surgical removal of the tumor, with radiation or chemotherapy reserved for advanced cases. However, because of the limited number of patients, there are no established guidelines for chemotherapy, and the outcomes of treatment are unclear.

An External Coincidence Model for the Lunar Cycle Reveals Circadian Phase-Dependent Moonlight Effects on Coral Spawning.

Many marine organisms synchronously spawn at specific times to ensure the success of external fertilization in the ocean. Corals are famous examples of synchronized spawning at specific lunar phases, and two distinct spawning patterns have been observed in two dominant taxa: merulinid corals spawn at regular lunar phases, several days after the full moon, whereas Acropora corals spawn at more irregular lunar phases around the full moon. Although it has been suggested that the two coral taxa have different responses to moonlight and seawater temperature, their spawning times have never been analyzed by integrating the two environmental factors, resulting in an incomplete understanding of the regulatory mechanisms of spawning. In this study, we developed a new predictive model of coral spawning days by integrating moonlight and temperature effects based on the external coincidence model for the lunar cycle. We performed model fitting using a 10-year monitoring record of coral spawning time in Taiwan. Our model successfully demonstrated the synergistic effects of moonlight and temperature on coral spawning time (days) and provided two testable hypotheses to explain the different spawning patterns regarding the preparation (maturation) process for spawning and the sensitivity to moonlight at different circadian phases: (1) Acropora corals may have an earlier onset and longer period of preparation for spawning than merulinid corals; and (2) merulinid corals may use moonlight signals near sunset, while Acropora corals may have a similar onset at approximately midnight. This is the first study to indicate the difference in circadian phase-dependent moonlight sensitivities between coral taxa, providing a basis for underlying coral spawning mechanisms for rhythmic studies.

Bilateral lacrimal glands and paranasal sinus diffuse large B-cell lymphoma following lung mucosa-associated lymphoid tissue lymphoma in one patient.

We report an atypical case of diffuse large B-cell lymphoma (DLBCL) of bilateral lacrimal glands and paranasal sinus following mucosa-associated lymphoid tissue (MALT) lymphoma of the lung. Bilateral DLBCL is rare in the literature, and only few cases of DLBCL in bilateral lacrimal gland are reported. A 71-year-old male presented with bilateral, slowly enlarging, and swelling of both eyelids. Computed tomography scan images showed bilateral symmetric, hyperdense, circumferential masses over lacrimal glands occupying most of the orbital compartment. Neither optic nerve involvement nor adjacent orbital walls erosion was noted. Bilateral excisional biopsy and pathological examination confirmed the diagnosis of DLBCL. Since DLBCL of bilateral lacrimal gland can occur in case of systemic MALT lymphoma, excision and pathological examination is mandatory, and further metastatic workup is essential.

Antithymocyte globulin plus post-transplant cyclophosphamide combination as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation for hematological malignancies.

BACKGROUND: Post-transplant cyclophosphamide (PT-Cy) and calcineurin inhibitors used in peripheral blood haplo-identical stem cell transplantation (haploSCT) increase the risk of acute/chronic graft-versus-host disease (GVHD). Whether ATG/PT-Cy is feasible for Asian patients undergoing haploSCT is unclear, and an optimal strategy for GVHD prophylaxis is needed. MATERIALS AND METHODS: We retrospectively analyzed 61 hematologic malignancy patients who underwent peripheral blood haploSCT using ATG/PT-Cy from January 2013 to December 2018. We also compared the effects of ATG/PT-Cy (ATG group; n = 61) with historical data from patients who underwent haploSCT using sirolimus/PT-Cy (non-ATG group; n = 22). RESULTS: Cumulative incidences of grades II-IV acute GVHD and moderate to severe chronic GVHD did not differ significantly. The ATG group had higher incidence of Epstein-Barr virus (EBV) reactivation, but neither group had post-transplant lymphoproliferative disorders. The ATG group also had a higher OS rate (2-year OS in ATG group vs. non-ATG group: 43.4% vs. 27.3%, respectively; P = 0.071). CONCLUSION: ATG/PT-Cy is an acceptable strategy for GVHD prophylaxis in Asian patients undergoing haploSCT.

Combination of Durvalumab and Chemotherapy to Potentially Convert Unresectable Stage IV Penile Squamous Cell Carcinoma to Resectable Disease: A Case Report.

Penile squamous cell carcinoma is a rare disease entity with poor overall survival in an advanced stage. Few studies have investigated the role of immunotherapy in advanced penile squamous cell carcinoma. Herein, we report a case of stage IV unresectable penile squamous cell carcinoma presenting with anal bleeding and urethra obstruction who responded dramatically to combination therapy of durvalumab and cisplatin-based chemotherapy. The patient had HPV-positive penile squamous cell carcinoma, cT3N3M0, with concomitant anus squamous cell carcinoma. After 2 months of the combination treatment, almost all bulky inguinal lymph nodes shrank, and the main tumor of the anus and penis responded completely. A durable response was seen 16 months after initiating the combination therapy. This case report highlights the potential role of the combination of immunotherapy and chemotherapy in patients with advanced penile cancer. The promising results of this combination resulted in the conversion of unresectable disease to a potentially curable disease.

Moonrise timing is key for synchronized spawning in coral Dipsastraea speciosa.

Synchronized mass coral spawning typically occurs several days after a full moon once a year. It is expected that spawning day is determined by corals sensing environmental change regulated by the lunar cycle (i.e., tide or moonlight); however, the exact regulatory mechanism remains unknown. Here, we demonstrate how moonlight influences the spawning process of coral, Dipsastraea speciosa When corals in the field were shaded 1 and 3 d before the full moon or 1 d after the full moon, spawning always occurred 5 d after shading commenced. These results suggest moonlight suppresses spawning: a hypothesis supported by laboratory experiments in which we monitored the effects of experimental moonlight (night-light) on spawning day. Different night-light treatments in the laboratory showed that the presence of a dark period between day-light and night-light conditions eliminates the suppressive effect of night-light on spawning. In nature, moonrise gets progressively later during the course of the lunar cycle, shifting to after sunset following the day of the full moon. Our results indicate that this period of darkness between sunset and moonrise triggers synchronized mass spawning of D. speciosa in nature.

An Indo-Pacific coral spawning database.

The discovery of multi-species synchronous spawning of scleractinian corals on the Great Barrier Reef in the 1980s stimulated an extraordinary effort to document spawning times in other parts of the globe. Unfortunately, most of these data remain unpublished which limits our understanding of regional and global reproductive patterns. The Coral Spawning Database (CSD) collates much of these disparate data into a single place. The CSD includes 6178 observations (3085 of which were unpublished) of the time or day of spawning for over 300 scleractinian species in 61 genera from 101 sites in the Indo-Pacific. The goal of the CSD is to provide open access to coral spawning data to accelerate our understanding of coral reproductive biology and to provide a baseline against which to evaluate any future changes in reproductive phenology.

A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice.

Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1mutation /FLT3- internal tandem duplication (ITD)negative were independent prognostic factors for the entire cohort. Among patients with intermediate-risk cytogenetics, patients with mutations in CEBPAdouble mutation , IDH2, and NPM1 in the absence of FLT3-ITD were associated with improved Overall survival (OS), similar to those with favorable-risk cytogenetics; patients with mutations in TET2, RUNX1, ASXL1, and DNMT3A were associated with reduced OS, similar to those with unfavorable-risk cytogenetics. We concluded that integration of cytogenetic and molecular profiling improves prognostic stratification of patients into three groups with more distinct prognoses (P < 0.001) and significantly reduces the number of patients classified as intermediate risk. In addition, our study demonstrates that next-generation sequencing (NGS)-based multi-gene sequencing is clinically applicable in establishing an accurate risk stratification system for guiding therapeutic decisions.

A Comparative Effectiveness Study of Two Oral Chemotherapy Drugs (UFT vs. Capecitabine) in Neoadjuvant Concurrent Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer.

BACKGROUND/AIM: Capecitabine is the current standard oral chemotherapy used in neoadjuvant concurrent chemoradiotherapy (NCCRT) for locally advanced rectal cancer (LARC) in North America. We compared the effectiveness of another oral chemotherapy agent, UFT (an oral combination of uracil and tegafur), to that of capecitabine. MATERIALS AND METHODS: We identified LARC patients diagnosed from 2007 to 2011 using a population-based registry in Taiwan (Health and Welfare Data Science Center, HWDC) and constructed a propensity score matched cohort to balance observable potential confounders. We compared the hazard ratio (HR) of death between the UFT and capecitabine groups. We performed supplementary analysis (SA) to evaluate the robustness of our finding regarding potential unobserved confounders (SA-1) and the robustness of the result in a subgroup when an additional potential confounder was taken into account (SA-2). RESULTS: Our study population comprised of 200 patients balanced with respect to observed co-variables. UFT lowered the hazard of death significantly more than capecitabine (HR=0.58, 95% confidence interval (CI)=0.35-0.95, p=0.03). Our result was moderately sensitive in SA-1 but not significant in SA-2. CONCLUSION: The effectiveness of UFT in NCCRT for LARC is probably non-inferior to that of capecitabine.

Quantifying the Interactions in the Aggregation of Thermoresponsive Polymers: The Effect of Cononsolvency.

The aggregation kinetics of thermoresponsive core-shell micelles with a poly(N-isopropyl acrylamide) shell in pure water or in mixtures of water with the cosolvents methanol or ethanol at mole fractions of 5% is investigated during a temperature jump across the respective cloud point. Characteristically, these mixtures give rise to cononsolvency behavior. At the cloud point, aggregates are formed, and their growth is followed with time-resolved small-angle neutron scattering. Using the reversible association model, the interaction potential between the aggregates is determined from their growth rate in dependence on the cosolvents. The effect of the cosolvent is attributed to the interaction potential on the structured layer of hydration water around the aggregates. It is surmised that the latter is perturbed by the cosolvent and thus the residual repulsive hydration force between the aggregates is reduced. The larger the molar volume of the cosolvent, the more pronounced is the effect. This framework provides a molecular-level understanding of solvent-mediated effective interactions in polymer solutions and new opportunities for the rational control of self-assembly in complex soft matter systems.

Non-decarbonylative photochemical versus thermal activation of Bu4N[Fe(CO)3(NO)] - the Fe-catalyzed Cloke-Wilson rearrangement of vinyl and arylcyclopropanes.

The base metal complex Bu4N[Fe(CO)3(NO)] (TBA[Fe]) catalyzes the rearrangement of vinyl and arylcyclopropanes both under thermal or photochemical conditions to give the corresponding vinyl or aryldihydrofurans in good to excellent yields. Under photochemical conditions the reaction is performed at room temperature. Spectroscopic investigations show that the metal carbonyl catalyst is not decarbonylated. The best performance was observed at a wavelength of 415 nm. icMRCI+Q analysis of the excited singlet and triplet states of the [Fe(CO)3(NO)] anion was performed and used to calculate the vertical excitation energies which are in good agreement with the experimental data. CASSCF analysis indicates that the Fe center in all excited states of the ferrate becomes more electrophilic while adopting a distorted tetrahedral configuration. Both aspects have a positive synergistic effect on the formation of the initial π-complex with the incoming organic substrate.