Sulfamethoxazole-trimethoprim for pneumocystis pneumonia prophylaxis, causes of discontinuation and thrombocytopenia observed during administration: A single-center retrospective study.

INTRODUCTION: The development of pneumocystis pneumonia (PCP) has recently become a growing concern; thus, its prevention has become increasingly important. Sulfamethoxazole-trimethoprim (ST) is a cost-effective first-line and prophylactic treatment for PCP. However, ST administration criteria for PCP prophylaxis remain unclear and are often discontinued because of adverse events (AEs). In this study, we aimed to investigate the causes of ST discontinuation and the associated AEs using objective data. METHODS: We retrospectively analyzed the data of 162 patients admitted to Kansai Medical University Hospital between January 2018 and December 2020, who received ST for PCP prophylaxis. We compared clinical characteristics, laboratory data, and incidence of AEs between ST non-discontinuation and ST discontinuation groups. Additionally, we divided the patients into non-developing and developing thrombocytopenia (≥ Grade 1) groups based on the investigation results. RESULTS: No patients developed PCP while receiving ST. The most common causes of ST discontinuation were thrombocytopenia (37%), liver dysfunction (20%), and rash (18%). Multivariate analysis revealed thrombocytopenia (≥ Grade 1) as a factor significantly associated with ST discontinuation. Furthermore, we identified three factors correlated with thrombocytopenia (≥ Grade 1): age ≥50 years, lymphocyte count <1000/µL, and platelet count <180,000/µL. CONCLUSIONS: Patients with the aforementioned factors are at higher risk of developing thrombocytopenia (≥ Grade 1) during ST administration for PCP prophylaxis. Therefore, platelet count monitoring is essential to enhance safety and efficacy of ST treatment. Nonetheless, further research is warranted to explore additional implications and interventions.

RNA fluorescence in situ hybridization hybridisation using photo-cross-linkable beacon probes containing pyranocarbazole in living E. coli.

Understanding intracellular nucleic acids is very important for analysing RNA function and for the diagnosis of genetic diseases. In this study, we demonstrated RNA fluorescence in situ hybridisation in living cells. The described method does not a washing procedure, which affects the detection sensitivity for RNAs with secondary structures and, therefore, is a major limitation of conventional approaches. Ultrafast RNA photo-crosslinking using pyranocarbazole accelerated the invasion of FISH probes, enabling them to target RNAs with secondary structures. Thus, the newly developed method successfully increased the detection sensitivity by 5.4-fold following photo-irradiation at 400 nm for 120 s. In addition, we optimised the beacon probe for detecting target nucleic acids under physiological conditions at 37 °C.

HyperArc VMAT planning for single and multiple brain metastases stereotactic radiosurgery: a new treatment planning approach.

PURPOSE: The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT plan with those of the conventional VMAT (C-VMAT). MATERIAL AND METHODS: For 23 patients (1-4 brain metastases), C-VMAT and HA-VMAT plans with a prescription dose of 20-24 Gy were retrospectively generated, and dosimetric parameters for PTV (homogeneity index, HI; conformity index, CI; gradient index, GI) and brain tissue (V2Gy-V16Gy) were evaluated. Subsequently, the physical characteristics (modulation complexity score for VMAT, MCSV; Monitor unit, MU) of both treatment approaches were compared. RESULTS: HA-VMAT provided higher HI (1.41 ± 0.07 vs. 1.24 ± 0.07, p < 0.01), CI (0.93 ± 0.02 vs. 0.90 ± 0.05, p = 0.01) and lower GI (3.06 ± 0.42 vs. 3.91 ± 0.55, p < 0.01) values. Moderate-to-low dose spreads (V4Gy-V16Gy) were significantly reduced (p < 0.01) in the HA-VMAT plan over that of C-VMAT. HA-VMAT plans resulted in more complex MLC patterns (lower MCSV, p < 0.01) and higher MU (p < 0.01). CONCLUSIONS: HA-VMAT plans provided significantly higher conformity and rapid dose falloff with respect to the C-VMAT plans.

Can clinically relevant dose errors in patient anatomy be detected by gamma passing rate or modulation complexity score in volumetric-modulated arc therapy for intracranial tumors?

We investigated whether methods conventionally used to evaluate patient-specific QA in volumetric-modulated arc therapy (VMAT) for intracranial tumors detect clinically relevant dosimetric errors. VMAT plans with coplanar arcs were designed for 37 intracranial tumors. Dosimetric accuracy was validated by using a 3D array detector. Dose deviations between the measured and planned doses were evaluated by gamma analysis. In addition, modulation complexity score for VMAT (MCSv) for each plan was calculated. Three-dimensional dose distributions in patient anatomy were reconstructed using 3DVH software, and clinical deviations in dosimetric parameters between the 3DVH doses and planned doses were calculated. The gamma passing rate (GPR)/MCSv and the clinical dose deviation were evaluated using Pearson's correlation coefficient. Significant correlation (P < 0.05) between the clinical dose deviation and GPR was observed with both the 3%/3 mm and 2%/2 mm criteria in clinical target volume (D99), brain (D2), brainstem (D2) and chiasm (D2), albeit that the correlations were not 'strong' (0.38 < |r| < 0.54). The maximum dose deviations of brainstem were up to 4.9 Gy and 2.9 Gy for Dmax and D%, respectively in the case of high GPR (98.2% with 3%/3 mm criteria). Regarding MCSv, none of the evaluated organs showed a significant correlation with clinical dose deviation, and correlations were 'weak' or absent (0.01 < |r| < 0.21). The use of high GPR and MCSv values does not always detect dosimetric errors in a patient. Therefore, in-depth analysis with the DVH for patient-specific QA is considered to be preferable for guaranteeing safe dose delivery.

VMAT-SBRT planning based on an average intensity projection for lung tumors located in close proximity to the diaphragm: a phantom and clinical validity study.

The aim of the this study was to validate the use of an average intensity projection (AIP) for volumetric-modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT) planning for a moving lung tumor located near the diaphragm. VMAT-SBRT plans were created using AIPs reconstructed from 10 phases of 4DCT images that were acquired with a target phantom moving with amplitudes of 5, 10, 20 and 30 mm. To generate a 4D dose distribution, the static dose for each phase was recalculated and the doses were accumulated by using the phantom position known for each phase. For 10 patients with lung tumors, a deformable registration was used to generate 4D dose distributions. Doses to the target volume obtained from the AIP plan and the 4D plan were compared, as were the doses obtained from each plan to the organs at risk (OARs). In both phantom and clinical study, dose discrepancies for all parameters of the dose volume (D(min), D(99), D(max), D(1) and D(mean)) to the target were <3%. The discrepancies of D(max) for spinal cord, esophagus and heart were <1 Gy, and the discrepancy of V20 for lung tissue was <1%. However, for OARs with large respiratory motion, the discrepancy of the D(max) was as much as 9.6 Gy for liver and 5.7 Gy for stomach. Thus, AIP is clinically acceptable as a planning CT image for predicting 4D dose, but doses to the OARs with large respiratory motion were underestimated with the AIP approach.