Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Background: Thrombocytopenia is a condition where platelet counts are below the normal range (< 150 ×103 /µL), resulting in a higher risk of bleeding and affecting the results of hip arthroplasty. We assessed the impact of preoperative platelet counts on the clinical results of patients who underwent hip arthroplasty. Methods: Between April 2003 and March 2023, 437 patients (451 hips), who had preoperative thrombocytopenia of less than 150 ×103 /µL platelets, underwent hip arthroplasty. Preoperative platelet levels were categorized into severe thrombocytopenia (< 50 ×103 /µL) and non-severe thrombocytopenia (50–149 ×103 /µL). Total blood loss, operation time, requirement of transfusion, amount of transfusion, duration of surgical wound oozing, length of hospital stay, mortality rate at 1 year after surgery, and any complication were compared between the 2 groups. Results: No notable differences were observed in the surgery time or the total amount of blood loss between the groups. The requirement of transfusion and the amount of transfused blood were higher in the severe thrombocytopenia group. Prolonged oozing was found in around 18% in both groups, while periprosthetic joint infections occurred in 3 of the non-severe thrombocytopenia group. No significant difference was noted in the duration of hospital stay (25.6 ± 18.3 days vs. 19.4 ± 16.6 days, p = 0.067) and 1-year mortality (22.2% vs. 11.8%, p = 0.110). Conclusions Hip arthroplasties are safe for patients with low platelet counts and do not lead to prolonged hospital stays. On the other hand, patients with severe thrombocytopenia tend to need blood transfusions more frequently than those with less severe thrombocytopenia.

Background: The Arbeitsgemeinschaft für Osteosynthesefragen (AO) and the Orthopaedic Trauma Association (OTA) classification system for diaphyseal fracture has been recently revised to refine and enhance the accuracy of fracture categorization. This study aimed to investigate the interobserver reliability of the new AO/OTA classification and to compare it with the older version in femoral shaft fractures. Methods: We retrospectively analyzed 139 patients (mean age, 43.8 ± 19.5 years; 92 men and 47 women) with femoral shaft fractures who were treated from 2003 to 2017. Four well-trained observers independently classified each fracture following the previous and revised AO/OTA classification system. We calculated the Fleiss kappa for the interobserver reliability. Results: The previous classification showed the kappa value of 0.580 (95% confidence interval [CI], 0.547–0.613), and the revised version showed 0.528 (95% CI, 0.504–0.552). Both the old and the revised versions showed moderate reliability. Conclusions Our study highlights the moderate interobserver reliability of both the previous and new AO/OTA classification systems for diaphyseal femur fractures. These findings emphasize the importance of standardized systems in clinical decision-making and underscore the need for ongoing education and collaboration to enhance fracture classification.

Purpose: Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. Methods: This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). Results: Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). Conclusion Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.

Background: Implant-based immediate breast reconstruction surgery with nipple-sparing mastectomy has recently been favored by patients. However, in patients who do not wish to undergo balancing procedures, it is difficult to select the appropriate implant size, making it challenging to achieve a symmetrical breast shape. Therefore, this study investigated the differences in breast asymmetry and other complications in patients who underwent a two-stage procedure or direct-to-implant (DTI) breast reconstruction to determine whether the two-stage procedure can produce more favorable outcomes. Methods: The participants of this study were patients who underwent immediate two-stage breast reconstruction or DTI breast reconstruction from May 2018 to April 2022, did not receive postoperative radiotherapy, and did not wish to undergo any balancing procedures. An acellular dermal matrix was used for breast reconstruction in all patients, and a single reconstructive surgeon performed all the operations. Statistical significance was set at P<0.05. Results: No significant differences in complications were found between the patients who underwent DTI breast reconstruction and those who underwent two-stage breast reconstruction. In the two-stage breast reconstruction group, breast volume asymmetry was observed in 18.4% (seven patients), which was significantly lower than the percentage of 44.7% (17 patients) observed in the DTI group. Conclusions Breast asymmetry was observed in a significant proportion of the patients in both groups. However, because breast volume asymmetry was more common in the DTI group than in the two-stage breast reconstruction group, two-stage breast reconstruction may be a favorable method for patients who do not wish to undergo balancing procedures.

Background: Increasing longevity has caused the very old population to become the fastest-growing segment. The number of centenarians (over 100 years old) is increasing rapidly. Fractures in the elderly lead to excessive medical costs and decreased quality of life with socioeconomic burdens. However, little research has thoroughly examined the functional outcomes and mortality of hip fractures in centenarians. Methods: This is a retrospective observational study. Sixty-eight centenarian hip fracture patients were admitted to the 10 institutions from February 2004 to December 2019. Fifty-six patients with 1-year follow-up were finally included. The following data were obtained: sex, age, body mass index, Charlson comorbidity index value on the operation day, Koval’s classification for ambulatory ability, type of fracture, the time interval from trauma to surgery, American Society of Anesthesiologists grade, surgery-related complications, and duration of hospital stay. Postoperative Koval’s classification (at 1 year after surgery) and information about death were also collected. Multivariate analysis was performed to analyze the risk factors affecting mortality 1 year after surgery. Results: Mortality rates were 26.8% at 6 months and 39.3% at 1 year. The 90-day mortality was 19.6%, and one of them (2.1%) died in the hospital. The 1-year mortality rates for the community ambulatory and non-community ambulatory groups were 29% and 52%, respectively. Only 9 (16.1%) were able to walk outdoors 1 year after surgery. The remaining 47 patients (83.9%) had to stay indoors after surgery. Multivariate analysis demonstrated that the pre-injury ambulatory level (adjusted hazard ratio, 2.884; p = 0.034) was associated with the risk of mortality. Conclusions We report a 1-year mortality rate of 39.3% in centenarian patients with hip fractures. The risk factor for mortality was the pre-injury ambulatory status. This could be an important consideration in the planning of treatment for centenarian hip fracture patients.