Purpose: To report on the local control and toxicity of 5-fraction, high-conformal ultrafractionated radiation therapy (RT) for primary tumors in patients with metastatic breast cancer (MBC) who did not undergo planned surgical intervention. Methods: We retrospectively reviewed 27 patients with MBC who underwent 5-fraction high-dose ultrafractionated intensity-modulated RT for their primary tumors between 2017 and 2022 at our institution. A median dose of 66.8 Gy (range, 51.8–83.6 Gy) was prescribed to the gross tumor, calculated in 2-Gy equivalents using an α/β ratio of 3.5, along with a simultaneous integrated boost of 81.5%. The primary endpoint of this study was local control. Results: The median tumor size and volume were 5.1 cm and 112.4 cm3 , respectively. Treatment was generally well tolerated, with only 15% of the patients experiencing mild acute skin toxicity, which resolved spontaneously. The best infield response rate was 82%, with the objective response observed at a median time of 10.8 months post-RT (range, 1.4–29.2), until local progression or the last follow-up. At a median follow-up of 18.3 months, the 2-year local control rate was 77%. A higher number of prior lines of systemic therapy was significantly associated with poorer 2-year local control (one–two lines, 94% vs three or more lines, 34%; p = 0.004). Post-RT, 67% of the patients transitioned to the next line of systemic therapy, and the median duration of maintaining the same systemic therapy post-RT was 16.3 months (range, 1.9–40.3). Conclusion In our small dataset, 5-fraction, high-conformal ultrahypofractionated breast RT offered promising 2-year local control with minimal toxicity. Further studies are warranted to investigate the optimal dose and role in this setting.

Purpose: Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT. Materials and Methods: Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2. Results: Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680). Conclusion Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning.

PURPOSE: The COVID-19 pandemic has caused 1.4 million deaths globally and is associated with a 3-4 times increase in 30-day mortality after a fragility hip fracture with concurrent COVID-19 infection. Typically, death from COVID-19 infection occurs between 15 and 22 days after the onset of symptoms, but this period can extend up to 8 weeks. This study aimed to assess the impact of concurrent COVID-19 infection on 120-day mortality after a fragility hip fracture. METHODS: A multi-centre prospective study across 10 hospitals treating 8% of the annual burden of hip fractures in England between 1st March and 30th April, 2020 was performed. Patients whose surgical treatment was payable through the National Health Service Best Practice Tariff mechanism for "fragility hip fractures" were included in the study. Patients' 120-day mortality was assessed relative to their peri-operative COVID-19 status. Statistical analysis was performed using SPSS version 27. RESULTS: A total of 746 patients were included in this study, of which 87 (11.7%) were COVID-19 positive. Mortality rates at 30- and 120-day were significantly higher for COVID-19 positive patients relative to COVID-19 negative patients (p < 0.001). However, mortality rates between 31 and 120-day were not significantly different (p = 0.107), 16.1% and 9.4% respectively for COVID-19 positive and negative patients, odds ratio 1.855 (95% CI 0.865-3.978). CONCLUSION Hip fracture patients with concurrent COVID-19 infection, provided that they are alive at day-31 after injury, have no significant difference in 120-day mortality. Despite the growing awareness and concern of "long-COVID" and its widespread prevalence, this does not appear to increase medium-term mortality rates after a hip fracture.
COVID-19 ; Hip Fractures/surgery* ; Humans ; Pandemics ; Prospective Studies ; Retrospective Studies ; State Medicine ; United Kingdom/epidemiology*

Background: Failure of unicompartmental knee arthroplasty (UKA) is a distressing and technically challenging complication. Conventional conversion techniques (CCT) with rods and jigs have produced varying results. A robotic-assisted conversion technique (RCT) is an unexplored, though possibly advantageous, alternative. We compare our reconstructive outcomes between conventional and robotic methods in the management of failed UKA. Methods: Thirty-four patients with a failed UKA were retrospectively reviewed. Patients underwent conversion total knee arthroplasty (TKA) with either a CCT or RCT. Seventeen patients were included in each group. All procedures were done by a single surgeon at a single institution, with a mean time to follow-up of 3.6 years (range, 1 to 12).The primary outcome measures were the need for augments and polyethylene thickness. Secondary outcome measures were complications, need for revision, estimated blood loss (EBL), length of stay, and operative time. Results: The mean polyethylene thickness was 12 mm (range, 9 to 15) in the CCT group and 10 mm (range, 9 to 14) in the RCT groups, with no statistical difference between the two groups (P = 0.07). A statistically significant difference, however, was present in the use of augments. In the CCT group, five out of 17 knees required augments, whereas none of the 17 knees in the RCT group required augments (P = 0.04). Procedurally, roboticassisted surgery progressed uneventfully, even with metal artifact noted on the preoperative computerized tomography (CT) scans. Computer mapping of the residual bone surface after implant removal was a helpful guide in minimizing resection depth. No further revisions or reoperations were performed in either group. Conclusions Robotic-assisted conversion TKA is technically feasible and potentially advantageous. In the absence of normal anatomic landmarks to guide conventional methods, the preoperative CT scans were unexpectedly helpful in establishing mechanical alignment and resection depth. In this limited series, RCT does not seem to be inferior to CCT. Further investigation of outcomes is warranted.

Objectives: This 52-week, double-blind, randomized, Phase 3 study evaluated the long-term safety of esmirtazapine 1.5 mg and 3.0 mg in elderly outpatients (aged ≥65 years) with insomnia. Methods: Participants were randomized to receive esmirtazapine 1.5 mg or 3.0 mg administered once nightly. Safety and tolerability (primary objectives) were assessed via adverse event (AE) reporting, routine clinical measurements [vital signs; electrocardiogram (ECG); laboratory parameters], and residual-effects assessments. Total sleep time (TST), wake time after sleep onset (WASO), and sleep latency (SL) were assessed (secondary objectives). Results: Of 259 randomized participants, 153 completed treatment. AEs and serious AEs were reported by 89.8% and 7.0%, respectively, of 1.5 mg recipients, and 88.5% and 3.8%, respectively, of 3.0 mg recipients. Discontinuations due to AEs were reported in 16.4% and 18.3% of participants receiving esmirtazapine 1.5 mg and 3.0 mg, respectively. The most frequent AEs (>10%) were nasopharyngitis, somnolence, dizziness, headache, dry mouth, weight increase, and fatigue. One participant died; the death was judged unrelated to treatment. Elevated eosinophil counts were noted, but not considered clinically significant. No remarkable or clinically relevant changes in laboratory parameters, vital signs, or ECG were observed. There was no evidence of residual effects; alertness at awakening increased by a median of 17 (1.5 mg) and 15 (3.0 mg) points from baseline, respectively, and ability to work/function by 12 points (both groups; all p<0.0001). Improvements from baseline in TST, WASO, and SL were observed. Conclusions Esmirtazapine was reasonably tolerated in elderly outpatients with insomnia. No significant safety signals were observed.

Haematological cellular structures may be elucidated using automated full blood count (FBC) analysers such as Unicel DxH 800 via cell population data (CPD) analysis. The CPD values are generated by calculating volume, conductivity, and five types of scatter angles of individual cells which would form clusters or populations. This study considered 126 CPD parameter values of 1077 healthy Malaysian adults to develop reference intervals for each CPD parameter. The utility of the CPD reference interval established may range from understanding the normal haematological cellular structures to analysis of distinct cellular features related to the development of haematological disorders and malignancies.

PURPOSE: To explore the role of salvage radiotherapy (RT) for recurrent thymoma as an alternative to surgery. MATERIALS AND METHODS: Between 2007 and 2015, 47 patients who received salvage RT for recurrent thymoma at Yonsei Cancer Center were included in this study. Recurrent sites included initial tumor bed (n = 4), pleura (n = 19), lung parenchyma (n = 10), distant (n = 9), and multiple regions (n = 5). Three-dimensional conformal and intensity-modulated RT were used in 29 and 18 patients, respectively. Median prescribed dose to gross tumor was 52 Gy (range, 30 to 70 Gy), with equivalent doses in 2-Gy fractions (EQD₂). We investigated overall survival (OS), progression-free survival (PFS), and patterns of failure. Local failure after salvage RT was defined as recurrence at the target volume receiving >50% of the prescription dose. RESULTS: Median follow-up time was 83 months (range, 8 to 299 months). Five-year OS and PFS were 70% and 22%, respectively. The overall response rate was 97.9%; complete response, 34%; partial response, 44.7%; and stable disease, 19.1%. In multivariate analysis, histologic type and salvage RT dose (≥52 Gy, EQD₂) were significantly associated with OS. The high dose group (≥52 Gy, EQD₂) had significantly better outcomes than the low dose group (5-year OS: 80% vs. 59%, p = 0.046; 5-year PFS: 30% vs. 14%, p=0.002). Treatment failure occurred in 34 patients; out-of-field failure was dominant (intra-thoracic recurrence 35.3%; extrathoracic recurrence 11.8%), while local failure rate was 5.8%. CONCLUSION: Salvage RT for recurrent thymoma using high doses and advanced precision techniques produced favorable outcomes, providing evidence that recurrent thymoma is radiosensitive.
Disease-Free Survival ; Follow-Up Studies ; Humans ; Lung ; Multivariate Analysis ; Pleura ; Prescriptions ; Radiotherapy ; Recurrence ; Thymoma ; Treatment Failure

BACKGROUND/AIMS: Endoscopic resection is a standard treatment for stage T1a esophageal cancer, with esophagectomy or radical radiation therapy (RT) performed for stage T1b lesions. This study aimed to compare treatment outcomes of each modality for clinical stage T1 esophageal cancer. METHODS: In total, 179 patients with clinical T1N0M0-stage esophageal cancer treated from 2006 to 2016 were retrospectively evaluated. Sixty-two patients with clinical T1a-stage cancer underwent endoscopic resection. Among 117 patients with clinical T1b-stage cancer, 82 underwent esophagectomy, and 35 received chemoradiotherapy or RT. We compared overall survival (OS) and recurrence-free survival (RFS) rates for each treatment modality. RESULTS: The median follow-up time was 32 months (range, 1 to 120 months). The 5-year OS and RFS rates for patients with stage T1a cancer receiving endoscopic resection were 100% and 85%, respectively. For patients with stage T1b, the 5-year OS and RFS rates were 78% and 77%, respectively, for the esophagectomy group; 80% and 44%, respectively, for the RT alone group; and 96% and 80%, respectively, for the chemoradiation group. The esophagectomy group showed significantly higher RFS than the RT alone group (p=0.04). There was no significant difference in RFS between the esophagectomy and chemoradiation groups (p=0.922). Grade 4 or higher treatment-related complications occurred in four patients who underwent esophagectomy. CONCLUSIONS: Endoscopic resection appeared to be an adequate treatment for patients with T1a-stage esophageal cancer. The multidisciplinary approach involving chemoradiation was comparable to esophagectomy in terms of survival outcome without serious complications for T1b-stage esophageal cancer.
Chemoradiotherapy ; Esophageal Neoplasms ; Esophagectomy ; Follow-Up Studies ; Humans ; Radiotherapy ; Retrospective Studies

BACKGROUND/AIMS: There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus. METHODS: Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method. RESULTS: Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy. CONCLUSIONS: Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients.
Anti-Bacterial Agents ; Asia ; Asian Continental Ancestry Group ; Consensus ; Constipation ; Diagnosis ; Diarrhea ; Diet ; Epidemiology ; Gastrointestinal Diseases ; Humans ; Intestines ; Irritable Bowel Syndrome ; Life Style ; Methods ; Probiotics