Protocol for the ASTRO study (SSOP-01): a multicentre prospective cohort study investigating adverse events based on electronic patient-reported outcomes in patients with breast cancer after adjuvant chemotherapy.

INTRODUCTION: Symptom-related adverse events associated with perioperative chemotherapy in patients with breast cancer include short-term adverse events such as nausea and vomiting. However, changes in the severity and duration of prolonged symptom-related adverse events have not been fully investigated. We present a protocol of a study that aims to clarify the prevalence of symptom-related adverse events in patients with breast cancer 1 year after neoadjuvant or adjuvant chemotherapy using an electronic patient-reported outcomes (ePRO) system. METHODS AND ANALYSIS: This multicentre prospective observational cohort study will include patients with breast cancer who have received preoperative or postoperative adjuvant chemotherapy. The final injection date of the cytotoxic agent will be the study initiation date. Patients will report every 2 weeks from the initiation date to 12 weeks and every 4 weeks from 12 weeks to 1 year, and they can enter this information into the ePRO system from anywhere. The primary outcome will be the prevalence of symptom-related adverse events according to the ePRO system 1 year after the date of the last injection of the cytotoxic drug used in neoadjuvant or adjuvant chemotherapy for breast cancer. To increase multi-institutional enrolment, two cohorts will be included. Cohort 1 will comprise patients with acquisition of baseline patient information regarding preoperative chemotherapy and presurgery characteristics. Cohort 2 will comprise patients without acquisition of baseline patient information. The target sample size is ≥250 per year. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee at each participating institution. The results will be presented at major national and international conferences and submitted to peer-reviewed journals. TRIAL STATUS: Registration was started in October 2021. By August 2022, a total of 132 participants were enrolled. Follow-up will be continued through December 2024. TRIAL REGISTRATION NUMBER: UMIN000045422.

Pediatric internal auditory canal cavernous hemangioma with rapid progression of sensorineural hearing loss: illustrative case.

BACKGROUND: Cavernous hemangioma of the internal auditory canal is extremely rare and is characterized by symptoms such as vertigo, sensorineural hearing loss, and facial nerve dysfunction. OBSERVATIONS: A health examination on an 11-year-old female in the fifth grade revealed hearing loss in the left ear. She also had dizziness that had persisted for approximately 1 year. Pure-tone audiometry revealed sensorineural hearing loss in her left ear. Rightward horizontal and rotatory nystagmus was detected. Facial paralysis was not present. Magnetic resonance imaging showed a lesion that was suspected to be hemangioma. The authors selected a left suboccipital retrosigmoid approach. The tumor showed a berry-tufted appearance throughout the cerebellopontine angle. The seventh cranial nerve penetrated the tumor and partly circulated outside the tumor with marked adhesion. The authors partially resected the tumor to avoid damaging the facial nerve. A histological examination identified cavernous hemangioma. LESSONS: The fundamental treatment for cavernous hemangioma of the internal auditory canal is complete surgical removal; however, any surgical intervention may result in hearing loss and facial paralysis. The extent of surgery needs to be decided intraoperatively based on the balance between preoperative symptoms and postoperative complications.

Spinal Epidural Hematoma Due to Venous Congestion Caused by Nutcracker Syndrome.

The causes of spinal epidural hematoma (SEH) have been attributed to coagulopathy, trauma, vascular anomalies, and so forth. The incidence of vascular anomalies shown by digital subtraction angiography has been reported to be 15%, and most cases have been reported to be spinal epidural arteriovenous fistulae. SEH has rarely been caused by venous congestion. We report a case of SEH in a 78-year-old male who presented to our emergency department with sudden-onset back pain, followed by complete paraplegia with bladder and rectal disturbance. Magnetic resonance imaging revealed a dorsally placed extradural hematoma extending from T10 to L1. An urgent laminectomy from T11 to L2 was performed. Computed tomography angiography (CTA) performed 1 week after the operation showed compression of the left renal vein between the aorta and superior mesenteric artery with dilation of the surrounding veins, including the spinal epidural venous plexus, at the same level as the hematoma. This was diagnosed as Nutcracker syndrome (NCS), which was consistent as a cause of SEH. The patient's symptoms gradually improved, and after 6 months, he regained normal strength in his lower extremities, but bladder and rectal disturbance remained and required intermittent self-catheterization. We chose conservative treatment for NCS, and SEH did not recur until the patient died of a cause unrelated to SEH or NCS. SEH could occur secondary to venous congestion including NCS. We emphasize the importance of investigating venous return to evaluate the etiology of SEH, which can be clearly visualized using CTA.

Effect of early nutritional initiation on post-cerebral infarction discharge destination: A propensity-matched analysis using machine learning.

AIM: Malnutrition is associated with poor outcomes in cerebral infarction patients, with research indicating that early nutritional initiation may improve the short-term prognosis of patients. However, evidence supported by big data is lacking. Here, to determine the effect of nutritional initiation during the first 3 days after hospital admission on home discharge rates, propensity score matching was conducted in patients with acute cerebral infarction. METHODS: This retrospective observational study, using the Diagnosis Procedure Combination anonymised database in Japan, included 41 477 ischaemic cerebral infarction patients hospitalised between 2016 and 2019. The patients were divided into two groups: those who received oral or enteral nutrition during the first 3 days of hospital admission (early nutrition group, n = 37 318) and those who did not (control group, n = 4159). One-to-one pair-matching was performed using propensity scores calculated via extreme gradient boosting to limit the confounding variables of the two groups. RESULTS: After propensity score matching, 3541 pairs of patients were selected. The dependence of home discharge rates on early nutrition was significant (p < 0.05), and the effectiveness of early nutrition for home discharge showed an odds ratio of 1.79 (95% confidence interval of 1.59-2.03 in Fisher's exact test). CONCLUSIONS: Our findings revealed that early nutritional initiation during the first 3 days of admission resulted in higher home discharge rates.

Treatment Outcomes of Stent-Assisted Coil Embolization for Ruptured Vertebral Artery Dissecting Aneurysms: The Preservation of Branches May Improve the Prognosis.

Objective: Subarachnoid hemorrhage due to ruptured vertebral artery dissecting aneurysm (rVADA) is associated with a high frequency of acute rebleeding and requires early treatment following onset. Parent artery occlusion (PAO) or stent-assisted coiling (SAC) embolization is selected as a treatment option according to the individual patient condition. This report is a retrospective examination evaluating the treatment outcomes for rVADA. Methods: The subjects were 20 rVADA patients (16 men and 4 women) who underwent endovascular treatment at our institution. The mean patient age was 52.9 years. Ten patients each were allocated to the PAO group and SAC group. We evaluated and compared the following parameters: presence of hemorrhagic complications, presence of ischemic complications, requirement of retreatment, and Glasgow Outcome Scale (GOS) after 90 days. Results: The reasons for selecting SAC were contralateral occlusion or a small diameter in three patients, the posterior inferior cerebellar artery (PICA) involvement in three patients, perforating artery from dissected lesion in five patients, and anterior spinal artery in one patient. There was no rebleeding in any patient. Symptomatic ischemic complications were observed in four patients in the PAO group and in one in the SAC group. Hyper-intense lesions in the brainstem on MRI DWI were noted in five patients in PAO group and in one in the SAC group. Retreatment was required for three patients in the PAO group and for four in the SAC group. Favorable outcomes (GOS 4, 5) after 90 days were observed for three patients in the PAO group and for eight patients in the SAC group (p = 0.0257). Conclusion: SAC that can preserve branches is a useful treatment option for rVADA. Further studies on a greater number of subjects are required to establish the optimal dose of antiplatelet agents and anticoagulants, and for stent selection.

Influence of Muscle Fiber Direction on Migration of Salmonella Enteritidis, Staphylococcus aureus, and Escherichia coli into Raw Chicken Breast.

ABSTRACT: The influence of muscle fiber direction (parallel or perpendicular) in relation to the inoculation surface on migration of Salmonella Enteritidis, Staphylococcus aureus, and Escherichia coli into raw chicken breasts was examined. Chicken breast samples with two types of surface fibers (running parallel or perpendicular to the surface) were inoculated with cultures of each bacterium. Inoculated samples were stored for 5 min, 1 h, or 24 h at 4°C. After storage, the samples were divided into segments, and bacterial counts were determined in different regions (inoculation surface, inoculation surface to 1 cm, 1 to 2 cm, 2 to 4 cm, and 4 to 6 cm). The migration of bacteria did not change at 5 min or 1 h regardless of fiber direction. However, after 24 h each bacterium was detected at 4 to 6 cm in the pieces of sample with a perpendicular muscle fiber surface cut. Although these bacteria were detected at 4 to 6 cm in samples with muscle fibers perpendicular to the inoculated surface, these results do not clearly indicate that bacteria migrated into the chicken breast. To monitor actual migration of bacteria into the chicken breast, the tops of the perpendicular muscle fibers of the breast sample were inoculated with bioluminescent E. coli Xen-14. Various regions of the breast sample (inoculation surface and cut surfaces at 1, 2, 4, and 6 cm) were stamped directly on growth medium. Culture revealed that the bacteria migrated directly under the contaminated site and dispersed along the surface of the chicken breast segments. More bacteria distributed laterally than migrated directly below the contamination site. These results suggest that the direction of the muscle fibers is a major factor influencing migration of pathogenic bacteria into chicken breast.

The clinical impact of the left atrial posterior wall lesion formation by the cryoballoon application for persistent atrial fibrillation: Feasibility and clinical implications.

INTRODUCTION: The left atrial (LA) posterior wall (LAPW) has been targeted to improve the clinical outcomes in patients with persistent atrial fibrillation (PersAF). This study aimed to investigate the feasibility, safety, and clinical implications of cryoballoon (CB) applications on the LAPW to accomplish electrical isolation (EI) of the LAPW with CB. METHODS: A total of 100 patients (males, 84; mean age, 64 ± 10 years) with PersAF were enrolled. The first 50 patients underwent only pulmonary vein isolation (PVI) (PVI-only group) and the remaining 50 patients underwent PVI and EI of the LAPW with CB (EI-LAPW group). RESULTS: One-year sinus rhythm maintenance probability was significantly higher in the EI-LAPW group than in PVI-only group (80.0% vs 55.1%, P = 0.01). The success rate of constructing an LA roof block line (LA-RB), bottom block line, and EI of the LAPW was 92%, 60%, and 58%, respectively. The nadir CB temperature (-45°C ± 4°C vs -39°C ± 5°C, P = 0.005) and anatomical angle of the left atrial roof (106°C ± 30°C vs 144°C ± 17°C, P < 0.001) significantly predicted the successful LA-RB construction. The left ventricular ejection fraction was significantly higher in unsuccessful cases than in successful cases of an EI of the LAPW (64% ± 8% vs 58% ± 11%, P = 0.041). Even though the EI of the LAPW was unsuccessful, CB freezing in LAPW significantly debulked the nonscar area (≥0.1 mV) in LAPW (18.1 ± 5.6 vs 2.2 ± 3.1 cm 2 , P < 0.001) and provided the equivalent 1-year outcome of successful cases (79.3% vs 81.0%, P = 0.90). CONCLUSION: The combination of PVI and EI of the LAPW with CB provided better clinical outcomes than conventional PVI procedure for patients with PersAF.

Clinical investigation of esophageal injury from cryoballoon ablation of persistent atrial fibrillation.

BACKGROUND: The cryoballoon (CB) can be utilized for extra pulmonary vein (PV) ablation such as for a left atrial (LA) posterior wall (LAPW) isolation. However, scrutiny of the esophageal injuries during the LAPW isolation has never been performed. We sought to thoroughly investigate the esophageal lesions (ELs) and gastric hypomotility (GH) caused by an LAPW isolation using a CB. METHODS: A total of 101 persistent atrial fibrillation patients who underwent an LAPW isolation using a CB were enrolled. The CB was applied on the roof and bottom area of the LAPW after a PV isolation. The luminal esophageal temperature (LET) was monitored by a thermistor probe during the CB applications. When the LET reached 15°C, the freezing application was prematurely interrupted. Esophagogastroscopy was performed on the next day following the ablation. RESULTS: All PVs were successfully isolated in all patients. A successful LAPW isolation solely with CB ablation was performed in 72 (71.3%) patients. Cryofreezing applications were prematurely interrupted due to low LETs in 49 (48.5%) patients predominantly during the LA bottom line ablation. ELs and GH were observed in 11 (10.9%) and 16 patients (15.8%), respectively. The nadir LET tended to be lower in patients with ELs and GH than in those without (ELs: 14.8 ± 4.5°C vs 17.4 ± 6.0°C, P = 0.17; GH: 15.5 ± 4.5°C vs 17.5 ± 6.1°C, P = 0.23, respectively). CONCLUSIONS: Esophageal complications such as ELs and GH occur during the LAPW isolation with a CB. There was no reliable predictor of those adverse events.

"Clinical Impact of the Cryoballoon Temperature and Occlusion Status on the Success of Pulmonary Vein Isolation".

BACKGROUND: Complete occlusion of the pulmonary veins (PVs) with the cryoballoon (CB) is considered to be the crucial factor for a successful PV isolation (PVI). We investigated whether a complete occlusion was indispensable for a successful CB based PVI of every PV. METHODS AND RESULTS: Atrial fibrillation patients (n=123, 97; paroxysmal) undergoing a de novo PVI were enrolled. A total of 477 PVs were analyzed. The occlusion grade (OG) was scored as follows: OG3 (complete occlusion), OG2 (incomplete occlusion with slight leakage), OG1 (poor occlusion with massive leakage). There was no significant difference in the CB temperature (CBT) at all measured time points (from 30 to 120sec after freezing) and nadir CBT between OG2 and OG3 in all PVs except for the right inferior PV (RIPV). The RIPV isolation success rate was significantly lower for the OG2 status than OG3 (97.5 vs. 57.6%; p<0.0001). In contrast, there was not significant difference in the isolation success rate of the other three PVs between OG2 and OG3. In particular, the success rate of the right superior PV (RSPV) isolation was >95% for both OG2 and OG3. Phrenic nerve paralysis (PNP) was provoked during the RSPV isolation in two patients in whom the RSPVs were frozen during OG3. CONCLUSION: An OG3 may not always be required for a successful PVI of all PVs except the RIPV. OG2 could have comparable effects as OG3 in terms of a successful RSPV isolation. Not aiming for OG3 for the RSPV may reduce the risk of PNP.

Efficient identification of compounds suppressing protein precipitation via solvent screening using serial deletion mutants of the target protein.

The control of protein solubility is a subject of broad interest. Although several solvent screening methods are available to search for compounds that enhance protein solubilization, their performance is influenced by the intrinsic solubility of the tested protein. We now present a method for screening solubilizing compounds, using an array of N- or C-terminal deletion mutants of the protein. A key behind this approach is that such terminal deletions of the protein affect its aggregation propensity. The solubilization activities of trial solvents are individually assessed, based on the number of solubilized mutants. The solubilizing compounds are then identified from the screened solvents. In this study, the C-terminal chemokine receptor-binding region of the cytoplasmic protein, FROUNT (FNT-C), which mediates intracellular signals leading to leukocyte migration, was subjected to the multicomponent screening. In total, 192 solution conditions were tested, using eight terminal deletion mutants of FNT-C. We identified five solvent conditions that solubilized four or five mutants of FNT-C, and the compounds in the screened solvents were then, respectively, assessed in terms of their solubilization ability. The best compound for solubilizing FNT-C was 1,6-hexanediol. Indeed, 1,6-hexanediol bound to FNT-C and suppressed its precipitation, as showed by NMR and dynamic light scattering analyses.

Clinical assessment of cryoballoon ablation in cases with atrial fibrillation and a left common pulmonary vein.

INTRODUCTION: Pulmonary vein isolation (PVI) using a cryoballoon (CB) is a useful tool for treating atrial fibrillation (AF); however, the clinical efficacy of the CB has never been fully investigated in patients with a left common pulmonary vein (LCPV). METHODS AND RESULTS: Three hundred twenty-four consecutive paroxysmal AF patients underwent PVI with a CB. Three-dimensional computed tomography was performed in all patients before the ablation. The clinical outcomes of the AF ablation between patients with (Group A) and without an LCPV (Group B) were compared. An LCPV was observed in 27 (8%) patients. There were no significant differences in the procedure time (149 ± 45 min vs. 143 ± 40 min, respectively; P = 0.42) and percentage needing touch up ablation between the 2 groups (26% vs. 20%, respectively; P = 0.45). At a mean follow-up of 454 ± 195 days, 282 of 324 (87%) patients were free from any atrial tachyarrhythmias (ATs) after a single procedure. Twenty out of 27 (74%) Group A patients and 262 of 297 (88%) Group B patients were free from ATs (15-month Kaplan-Meier event free rate estimates, 77% and 89%, respectively; P = 0.02). A multivariate analysis identified the presence of an LCPV and the left atrial diameter as reliable predictors of recurrent ATs. CONCLUSIONS: The long-term clinical outcomes of ablation of AF with the CB was worse in patients with an LCPV than in those without. The presence of an LCPV and the LA size seemed to be reliable predictors of a worse outcome.

The application of alkaline and acidic electrolyzed water in the sterilization of chicken breasts and beef liver.

The sterilization effect of a combination treatment with alkaline electrolyzed water (AlEW) and strong acidic electrolyzed water (StAEW) on fresh chicken breasts and beef liver was evaluated. Samples (1, 5, and 10 g) were inoculated with Salmonella Enteritidis NBRC3313, Escherichia coli ATCC 10798, Staphylococcus aureus FDA209P, and S. aureus C-29 [staphylococcal enterotoxin A (SEA) productive strain] and subjected to a dipping combination treatment (4°C and 25°C for 3 min) with AlEW and StAEW. Combination treatment with AlEW and StAEW significantly reduced the bacteria, and reduction of more than 1 log colony-forming units (CFU)/g was achieved. Furthermore, this combination treatment significantly decreased the SEA gene expression level in samples. Some quality variables of the meat samples such as pH, lipid oxidation, color, amino-acid content, texture, and sensory characteristics showed no significant differences between the combination treatment with AlEW and StAEW and the untreated control.

Preventive effect against post-cataract endophthalmitis: drug delivery intraocular lens versus intracameral antibiotics.

PURPOSE: To compare hydrophilic acrylic intraocular lenses (IOLs) as an antibiotic drug-delivery system with intracameral antibiotic administration in terms of the ability to prevent endophthalmitis. METHODS: Antibiotic solutions of 0.3% (3 mg/ml) and 0.5% (5 mg/ml) gatifloxacin (GFLX) and 0.5% (5 mg/ml) and 1.5% (15 mg/ml) levofloxacin (LVFX) were prepared. IOLs made of hydrophilic acrylic and silicone were used. Hydrophilic acrylic IOLs were allowed to adsorb the antibiotic solutions. A clinically isolated strain, KOS1, of Enterococcus faecalis was used to induce experimental endophthalmitis in vivo. Antibiotic concentrations were determined with high-performance liquid chromatography (HPLC). Twelve hydrophilic acrylic IOLs with antibiotics were used for the in vitro antibiotic concentration assay. In vivo experiments were conducted with 51 rabbits in total. Antibiotic concentrations in the aqueous humor and effects against bacterial proliferation were evaluated. RESULTS: Concentrations of released antibiotics in vitro were highest on the first day and had decreased by the second day. When a comparison was made between similar initial concentrations, GFLX was released to a significantly higher concentration than LVFX (p < 0.001). In the antibiotic-treated IOL group, GFLX concentrations in the aqueous humor reached a peak at four hours postoperatively and then decreased. The intracameral antibiotic group showed similar tendencies, with a remarkably higher peak concentration. Effects against bacterial proliferation were comparable between the antibiotic-treated IOLs and intracameral antibiotic administration. CONCLUSIONS: Preventive effects against endophthalmitis were similar between antibiotic-treated IOL implantation and intracameral antibiotic administration.