1.Controlling tumor progression and recurrence in mice through combined treatment with a PD-L1 inhibitor and a designer Salmonella strain that delivers GM-CSF.
Heung Jin JEON ; Daejin LIM ; EunA SO ; Solbi KIM ; Jae-Ho JEONG ; Miryoung SONG ; Hyo-Jin LEE
Acta Pharmaceutica Sinica B 2024;14(12):5479-5492
Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered Salmonella to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor. The engineered Salmonella enabled delivery of recombinant GM-CSF into mouse tumors, activating recruitment of immune cells, such as M1-polarized macrophages, dendritic cells, and CD8+ T cells. Combination treatment with the PD-L1 inhibitor and engineered Salmonella increased the survival rate of tumor-bearing mice by 25%. New tumor growth was strongly suppressed, and visible tumors disappeared at 120 days post-infection (dpi) in mice rechallenged with additional tumor implantation at 100 dpi. The number of memory T cells increased >2-fold in tumor-rechallenged mice. Our findings demonstrate superiority of the engineered Salmonella as a cancer therapeutic agent with precise targeting ability, immune-boosting activity, and ease of combination with other therapeutics.
2.Antimicrobial effect of infrared diode laser utilizing indocyanine green against Staphylococcus aureus biofilm on titanium surface
Seung Gi KIM ; Si-Young LEE ; Jong-Bin LEE ; Heung-Sik UM ; Jae-Kwan LEE
Journal of Dental Rehabilitation and Applied Science 2024;40(2):55-63
Purpose:
This study aimed to assess the antimicrobial efficacy of an 810-nm infrared diode laser with indocyanine green (ICG) against Staphylococcus aureus on sandblasted, large grit, and acid-etched (SLA) titanium surfaces, comparing its effectiveness with alternative chemical decontamination modalities.
Materials and Methods:
Biofilms of S. aureus ATCC 25923 were culturedon SLA titanium disks for 48 hours. The biofilms were divided into five treatment groups: control, chlorhexidine gluconate (CHX), tetracycline (TC), ICG, and 810-nm infrared diode laser with ICG (ICG-PDT). After treatment, colony-forming units were quantified to assess surviving bacteria, and viability was confirmed through confocal laser-scanning microscope (CLSM) imaging.
Results:
All treated groups exhibited a statistically significant reduction in S. aureus (P < 0.05), with notable efficacy in the CHX, TC, and ICG-PDT groups (P < 0.01). While no statistical difference was observed between TC and CHX, the ICG-PDT group demonstrated superior bacterial reduction. CLSM images revealed a higher proportion of dead bacteria stained in red within the ICG-PDT groups.
Conclusion
Within the limitations, ICG-PDT effectively reduced S. aureus biofilms on SLA titanium surfaces. Further investigations into alternative decontamination methods and the clinical impact of ICG-PDT on peri-implant diseases are warranted.
3.Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea
Byung-Joon KIM ; Jun-Seop SHIN ; Byoung-Hoon MIN ; Jong-Min KIM ; Chung-Gyu PARK ; Hee-Jung KANG ; Eung Soo HWANG ; Won-Woo LEE ; Jung-Sik KIM ; Hyun Je KIM ; Iov KWON ; Jae Sung KIM ; Geun Soo KIM ; Joonho MOON ; Du Yeon SHIN ; Bumrae CHO ; Heung-Mo YANG ; Sung Joo KIM ; Kwang-Won KIM
Diabetes & Metabolism Journal 2024;48(6):1160-1168
Background:
Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans.
Methods:
A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness.
Conclusion
A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.
4.Perioperative nutritional practice of surgeons in Korea: a survey study
Ji-Hyeon PARK ; Mi Ran JUNG ; Sang Hyun KIM ; Hongbeom KIM ; Gyeongsil LEE ; Jae-Seok MIN ; Heung-Kwon OH ; Jung Hoon BAE ; Yoona CHUNG ; Dong-Seok HAN ; Seung Wan RYU ;
Annals of Clinical Nutrition and Metabolism 2024;16(3):134-148
Purpose:
Enhanced recovery after surgery (ERAS) protocols advocate reduced fasting and early nutrition to improve recovery in surgical patients. However, data on ERAS implementation among Korean surgeons performing major abdominal surgeries remain sparse.
Methods:
A survey conducted by the External Relation Committee of the Korean Society of Surgical Metabolism and Nutrition assessed perioperative nutritional practices among 389 Korean general surgeons from February to September 2023. The survey covered preoperative fasting, carbohydrate drinks, nasogastric tube use, postoperative dietary progression, parenteral nutrition (PN), and oral supplements, yielding 551 responses stratified by specialty.
Results:
More than 80% of respondents practiced “midnight NPO (Nil Per Os)” fasting, often at the anesthesiology department’s request, while 70%–80% reported no use of preoperative carbohydrate drinks. Most surgeons began dietary progression with water on postoperative day one, advancing to a liquid or soft diet by day two. PN was routinely prescribed by 49% of respondents, with a common dosage of 1,000–1,500 kcal/d. Oral supplements were selectively provided, with 21% of surgeons prescribing them universally.
Conclusion
The results reveal significant variability in perioperative nutrition practices across Korean surgical specialties, with many adhering to traditional practices despite ERAS guidelines. These findings highlight a need for standardized guidelines in Korea to optimize perioperative nutritional support and improve patient recovery outcomes following major abdominal surgeries.
5.Perioperative nutritional practice of surgeons in Korea: a survey study
Ji-Hyeon PARK ; Mi Ran JUNG ; Sang Hyun KIM ; Hongbeom KIM ; Gyeongsil LEE ; Jae-Seok MIN ; Heung-Kwon OH ; Jung Hoon BAE ; Yoona CHUNG ; Dong-Seok HAN ; Seung Wan RYU ;
Annals of Clinical Nutrition and Metabolism 2024;16(3):134-148
Purpose:
Enhanced recovery after surgery (ERAS) protocols advocate reduced fasting and early nutrition to improve recovery in surgical patients. However, data on ERAS implementation among Korean surgeons performing major abdominal surgeries remain sparse.
Methods:
A survey conducted by the External Relation Committee of the Korean Society of Surgical Metabolism and Nutrition assessed perioperative nutritional practices among 389 Korean general surgeons from February to September 2023. The survey covered preoperative fasting, carbohydrate drinks, nasogastric tube use, postoperative dietary progression, parenteral nutrition (PN), and oral supplements, yielding 551 responses stratified by specialty.
Results:
More than 80% of respondents practiced “midnight NPO (Nil Per Os)” fasting, often at the anesthesiology department’s request, while 70%–80% reported no use of preoperative carbohydrate drinks. Most surgeons began dietary progression with water on postoperative day one, advancing to a liquid or soft diet by day two. PN was routinely prescribed by 49% of respondents, with a common dosage of 1,000–1,500 kcal/d. Oral supplements were selectively provided, with 21% of surgeons prescribing them universally.
Conclusion
The results reveal significant variability in perioperative nutrition practices across Korean surgical specialties, with many adhering to traditional practices despite ERAS guidelines. These findings highlight a need for standardized guidelines in Korea to optimize perioperative nutritional support and improve patient recovery outcomes following major abdominal surgeries.
6.Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea
Byung-Joon KIM ; Jun-Seop SHIN ; Byoung-Hoon MIN ; Jong-Min KIM ; Chung-Gyu PARK ; Hee-Jung KANG ; Eung Soo HWANG ; Won-Woo LEE ; Jung-Sik KIM ; Hyun Je KIM ; Iov KWON ; Jae Sung KIM ; Geun Soo KIM ; Joonho MOON ; Du Yeon SHIN ; Bumrae CHO ; Heung-Mo YANG ; Sung Joo KIM ; Kwang-Won KIM
Diabetes & Metabolism Journal 2024;48(6):1160-1168
Background:
Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans.
Methods:
A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness.
Conclusion
A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.
7.Antimicrobial effect of infrared diode laser utilizing indocyanine green against Staphylococcus aureus biofilm on titanium surface
Seung Gi KIM ; Si-Young LEE ; Jong-Bin LEE ; Heung-Sik UM ; Jae-Kwan LEE
Journal of Dental Rehabilitation and Applied Science 2024;40(2):55-63
Purpose:
This study aimed to assess the antimicrobial efficacy of an 810-nm infrared diode laser with indocyanine green (ICG) against Staphylococcus aureus on sandblasted, large grit, and acid-etched (SLA) titanium surfaces, comparing its effectiveness with alternative chemical decontamination modalities.
Materials and Methods:
Biofilms of S. aureus ATCC 25923 were culturedon SLA titanium disks for 48 hours. The biofilms were divided into five treatment groups: control, chlorhexidine gluconate (CHX), tetracycline (TC), ICG, and 810-nm infrared diode laser with ICG (ICG-PDT). After treatment, colony-forming units were quantified to assess surviving bacteria, and viability was confirmed through confocal laser-scanning microscope (CLSM) imaging.
Results:
All treated groups exhibited a statistically significant reduction in S. aureus (P < 0.05), with notable efficacy in the CHX, TC, and ICG-PDT groups (P < 0.01). While no statistical difference was observed between TC and CHX, the ICG-PDT group demonstrated superior bacterial reduction. CLSM images revealed a higher proportion of dead bacteria stained in red within the ICG-PDT groups.
Conclusion
Within the limitations, ICG-PDT effectively reduced S. aureus biofilms on SLA titanium surfaces. Further investigations into alternative decontamination methods and the clinical impact of ICG-PDT on peri-implant diseases are warranted.
8.Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea
Byung-Joon KIM ; Jun-Seop SHIN ; Byoung-Hoon MIN ; Jong-Min KIM ; Chung-Gyu PARK ; Hee-Jung KANG ; Eung Soo HWANG ; Won-Woo LEE ; Jung-Sik KIM ; Hyun Je KIM ; Iov KWON ; Jae Sung KIM ; Geun Soo KIM ; Joonho MOON ; Du Yeon SHIN ; Bumrae CHO ; Heung-Mo YANG ; Sung Joo KIM ; Kwang-Won KIM
Diabetes & Metabolism Journal 2024;48(6):1160-1168
Background:
Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans.
Methods:
A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness.
Conclusion
A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.
9.Perioperative nutritional practice of surgeons in Korea: a survey study
Ji-Hyeon PARK ; Mi Ran JUNG ; Sang Hyun KIM ; Hongbeom KIM ; Gyeongsil LEE ; Jae-Seok MIN ; Heung-Kwon OH ; Jung Hoon BAE ; Yoona CHUNG ; Dong-Seok HAN ; Seung Wan RYU ;
Annals of Clinical Nutrition and Metabolism 2024;16(3):134-148
Purpose:
Enhanced recovery after surgery (ERAS) protocols advocate reduced fasting and early nutrition to improve recovery in surgical patients. However, data on ERAS implementation among Korean surgeons performing major abdominal surgeries remain sparse.
Methods:
A survey conducted by the External Relation Committee of the Korean Society of Surgical Metabolism and Nutrition assessed perioperative nutritional practices among 389 Korean general surgeons from February to September 2023. The survey covered preoperative fasting, carbohydrate drinks, nasogastric tube use, postoperative dietary progression, parenteral nutrition (PN), and oral supplements, yielding 551 responses stratified by specialty.
Results:
More than 80% of respondents practiced “midnight NPO (Nil Per Os)” fasting, often at the anesthesiology department’s request, while 70%–80% reported no use of preoperative carbohydrate drinks. Most surgeons began dietary progression with water on postoperative day one, advancing to a liquid or soft diet by day two. PN was routinely prescribed by 49% of respondents, with a common dosage of 1,000–1,500 kcal/d. Oral supplements were selectively provided, with 21% of surgeons prescribing them universally.
Conclusion
The results reveal significant variability in perioperative nutrition practices across Korean surgical specialties, with many adhering to traditional practices despite ERAS guidelines. These findings highlight a need for standardized guidelines in Korea to optimize perioperative nutritional support and improve patient recovery outcomes following major abdominal surgeries.
10.Clinical Outcomes of Surgery after Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma
Yoo Na LEE ; Min Kyu SUNG ; Dae Wook HWANG ; Yejong PARK ; Bong Jun KWAK ; Woohyung LEE ; Ki Byung SONG ; Jae Hoon LEE ; Changhoon YOO ; Kyu-Pyo KIM ; Heung-Moon CHANG ; Baek-Yeol RYOO ; Song Cheol KIM
Cancer Research and Treatment 2024;56(4):1240-1251
Purpose:
Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy.
Materials and Methods:
We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020.
Results:
Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates, and postoperative pancreatic fistula rates (grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC.
Conclusion
Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.

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