A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Robotic abdominoperineal resection for T4b rectal cancer using the da Vinci SP platform.

PURPOSE: The aim of the present report wasto describe a novel technique of robotic abdominoperineal resection (APR) for the treatment of T4b low rectal cancer using the da Vinci® Single-Port (SP) system (Intuitive Surgical, Sunnyvale, CA, USA). METHODS: A 3-cm transverse incision was made in the left lower quadrant of the abdomen, in the area designated for permanent colostomy. A Uniport® (Dalim Medical, Seoul, Korea) was introduced and a 25 mm multichannel SP trocar was inserted into the Uniport. A 5-mm laparoscopic assistant port was introduced on the upper midline. A video showing each step of the technique is attached. RESULTS: Two consecutive female patients (70 and 74 years old) underwent SP robotic APR with partial resection of the vagina 8 weeks after preoperative chemoradiotherapy. In both cases, rectal cancer was located 1 cm above the anal verge and invaded the vagina (initial stage and ymrT stage T4b). Operative time was 150 and 180 min, respectively. Estimated blood loss was 10 and 25 ml, respectively. No postoperative complications occurred. The length of postoperative hospital stay was 5 days in both cases. The final pathological stage was ypT4bN0 and ypT3N0 respectively. CONCLUSIONS: In this first experience, SP robotic APR appears to be a safe and feasible procedure for locally advanced low rectal cancer. In addition, the invasiveness of the procedure is reduced by means of the SP system, which only requires a single incision in the area designated for colostomy. Prospective studies on a larger number of patients are necessary to confirm the outcomes of this technique compared to other minimally invasive approaches.

Long Term Vortex Flow Evolution around a Magnetic Island in Tokamaks.

We present a gyrokinetic analysis of the vortex flow evolution in a magnetic island in collisionless tokamak plasmas. In a short term ω[over ¯]_{D}t<1, where ω[over ¯]_{D} is the secular magnetic drift of the orbit center, initial monopolar vortex flow approaches to its residual level determined by the neoclassical enhancement of polarization shielding after collisionless relaxation. The residual level depends on the location inside an island and is higher than the Rosenbluth-Hinton level [M.N. Rosenbluth and F.L. Hinton, Phys. Rev. Lett. 80, 724 (1998)PRLTAO0031-900710.1103/PhysRevLett.80.724] due to finite island width. In a long term ω[over ¯]_{D}t>1, the residual vortex flow evolves to a dipolar zonal-vortex flow mixture due to toroidicity-induced breaking of a helical symmetry. The mixture forms localized flow shear layers near the island separatrix away from X points. The deviation of the streamlines of the mixture flows from magnetic surfaces allows turbulence advection across the island. We expect a small island w≲qρ_{Ti}/s[over ^] provides a favorable condition for this mixture flow formation, while the monopolar vortex flow persists for a larger island.

Regulation of Alfvén Eigenmodes by Microturbulence in Fusion Plasmas.

Global gyrokinetic simulations of mesoscale reversed shear Alfven eigenmodes (RSAE) excited by energetic particles (EP) in fusion plasmas find that RSAE amplitude and EP transport are much higher than experimental levels at nonlinear saturation, but quickly diminish to very low levels after the saturation if background microturbulence is artificially suppressed. In contrast, in simulations coupling micro-meso scales, the RSAE amplitude and EP transport decrease drastically at the initial saturation but later increases to the experimental levels in the quasisteady state with bursty dynamics due to regulation by thermal ion temperature gradient (ITG) microturbulence. The quasisteady state EP transport is larger for a stronger microturbulence. The RSAE amplitude in the quasisteady state ITG-RSAE turbulence from gyrokinetic simulations, for the first time, agrees very well with experimental measurements.

Analysis of predisposing factors in unilateral maxillary sinus fungal ball: the predictive role of odontogenic and anatomical factors.

BACKGROUND: The pathogenesis of maxillary sinus fungal ball (MSFB) is explained by aerogenic and odontogenic factors. We evaluated the predisposing factors, including intranasal anatomical and dental factors for increased diagnostic accuracy. METHODOLOGY: In this study, 117 patients who underwent endoscopic sinus surgery for unilateral MSFB were included. Preoperative computed tomography (CT) scans were used to analyze the presence of anatomical variations (anterior and posterior nasal septal deviation (NSD), concha bullosa (CB), infraorbital cell (haller cell), paradoxical middle turbinate, everted uncinate process and MS size). Dental factors including history of dental procedures and findings on CT scans were reviewed. RESULTS: Anterior and posterior NSD toward non-affected side were significantly associated with the presence of FB. The presence of CB and infraorbital cell was higher in the non-affected side rather than in the lesion side. Compared to non-affected MS, FB-presence MS was shallower and had a larger height to depth ratio. The presence of dental history was significantly higher on FB-presence MS than non-affected MS. In multivariable analysis, posterior NSD toward non-affected side, dental history increased the aOR of MSFB, while the presence of CB and infraorbital cell decreased the aOR of MSFB. CONCLUSIONS: The occurrence of MSFB seems to be associated with ipsilateral odontogenic factors, followed by anatomic variations including posterior NSD toward non-affected side and absence of CB and infraorbital cell.

Controlled synthesis of dicalcium phosphate dihydrate (DCPD) from metastable solutions: insights into pathogenic calcification.

Calcium phosphate (CaP) compounds may occur in the body as abnormal pathogenic phases in addition to their normal occurrence as bones and teeth. Dicalcium phosphate dihydrate (DCPD; CaPO4·2H2O), along with other significant CaP phases, have been observed in pathogenic calcifications such as dental calculi, kidney stones and urinary stones. While other studies have shown that polar amino acids can inhibit the growth of CaPs, these studies have mainly focused on hydroxyapatite (HAp; Ca10(PO4)6(OH)2) formation from highly supersaturated solutions, while their effects on DCPD nucleation and growth from metastable solutions have been less thoroughly explored. By further elucidating the mechanisms of DCPD formation and the influence of amino acids on those mechanisms, insights may be gained into ways that amino acids could be used in treatment and prevention of unwanted calcifications. The current study involved seeded growth of DCPD from metastable solutions at constant pH in the presence of neutral, acidic and phosphorylated amino acid side chains. As a comparison, solutions were also seeded with calcium pyrophosphate (CPP; Ca2P2O7), a known calcium phosphate inhibitor. The results show that polar amino acids inhibit DCPD growth; this likely occurs due to electrostatic interactions between amino acid side groups and charged DCPD surfaces. Phosphoserine had the greatest inhibitory ability of the amino acids tested, with an effect equal to that of CPP. Clustering of DCPD crystals giving rise to a "chrysanthemum-like" morphology was noted with glutamic acid. This study concludes that molecules containing an increased number of polar side groups will enhance the inhibition of DCPD seeded growth from metastable solutions.

Initial experience with a suprapubic single-port robotic right hemicolectomy in patients with colon cancer.

BACKGROUND: We developed a novel suprapubic single-port robotic right hemicolectomy (spRHC) procedure for patients with right colon cancer using a da Vinci SP Surgical System. The aim of this study was to determine the safety and feasibility of this technique. METHODS: We performed the spRHC procedure on five patients with right colon cancers between July and September 2020. All procedures including colon mobilization, D3 lymphadenectomy, and intracorporeal anastomosis were completed using the single-port robotic platform through a mini-transverse suprapubic incision and an additional assistant port. Data regarding patient characteristics, perioperative outcomes and pathologic results were analyzed. RESULTS: Four of the five patients were males. The median age was 69 years (range, 58-77 years).Two patients received preoperative chemotherapy for advanced colon cancer. The median total operative time was 160 min (range, 150-240 min). The median docking time was 4 min 40 s (range, 2 min 10 s-5 min 10 s). The median console time was 105 min (range, 100-120 min). There were no conversions to multiport or open surgeries. The median hospital stay was 7 days (range, 5-12 days). One patient experienced a wound infection. The median number of harvested lymph nodes was 41 (range, 39-50 lymph nodes). CONCLUSIONS: SpRHC is safe and feasible. However, further comparative studies are needed to assess whether this procedure can provide patients with significant benefits compared with multiport robotic surgery.

An initial experience with a novel technique of single-port robotic resection for rectal cancer.

BACKGROUND: The da Vinci single-port (SP) system is designed to facilitate single-incision robotic surgery in a narrow space. We developed a new procedure of rectal resection using this system. The aim of the present study was to evaluate the technical feasibility and safety of SP robotic rectal resection for rectal cancer patients based on our initial experience. METHODS: A study was conducted on consecutive patients with mid or low rectal cancer who had SP robotic resection at our institution between July and September 2020. The demographic characteristics, perioperative data, and pathology results of the patients were retrospectively analyzed. RESULTS: There were 5 patients (3 males, 2 females, median age 57 years (range 36-73 years). The median tumor height from the anal verge was 4 cm (range 3-5 cm). Two patients received preoperative chemoradiotherapy for advanced rectal cancer. A single docking was conducted, and the median docking time was 4 min 20 s (range 3 min 30 s to 5 min). The median total operation time was 195 min (range 155-240 min), and the median time of pelvic dissection was 45 min (range 36-62 min). All patients had circumferential and distal tumor-free resection margins. One patient experienced an anastomosis-related complication. The median duration of hospital stay was 7 days (range 7-8 days). CONCLUSIONS: Our initial experience suggests that SP robotic rectal resection is safe and feasible. Further clinical trials comparing SP and multiport robotic rectal resection should be conducted to verify the superior aspects of this new system.

Long-term clinical outcomes of total mesorectal excision and selective lateral pelvic lymph node dissection for advanced low rectal cancer: a comparative study of a robotic versus laparoscopic approach.

BACKGROUND: The long-term outcomes of minimally invasive lateral pelvic lymph node dissection (LPND) are not completely known. The aim of this study was to compare long-term outcomes between robotic and laparoscopic LPND in low rectal cancer patients with suspected lymph node metastasis in the pelvic sidewall. METHODS: We retrospectively reviewed the records of all rectal cancer patients who had laparoscopic or robotic total mesorectal excision (TME) with LPND between March 2006 and June 2016. Stage IV patients were excluded. The outcomes of patients who had laparoscopic and robotic TME with LPND were compared. RESULTS: Twenty-nine patients had laparoscopic LPND and 70 had robotic LPND. No significant differences in patient characteristics were observed between the two groups. The urinary retention rate was lower in the robotic group than in the laparoscopic group (7.1% vs. 24.1%; p = 0.043). During a median follow-up of 44.3 months, the overall recurrence rates were 48.3% and 31.4% in the laparoscopic and robotic groups, respectively (p = 0.175). The 5-year disease-free survival rates were 50.4% and 67.0% in the laparoscopic and robotic groups, respectively (p = 0.227). The 5-year overall survival rates were 65.0% and 92.2% in the laparoscopic and robotic groups, respectively (p = 0.017). CONCLUSIONS: Robotic TME with LPND is safe and feasible. In particular, it is associated with lower urinary retention. Robotic TME with LPND might yield a similar local recurrence rate and 5-year disease-free survival, but favorable long-term overall survival as compared to the laparoscopic approach. However, considering the retrospective nature and both major variables of TME and LPND involved together, this should be cautiously interpreted.

Learning curve of laparoscopic living donor right hepatectomy.

BACKGROUND: The feasibility and learning curve of laparoscopic living donor right hepatectomy was assessed. METHODS: Donors who underwent right hepatectomy performed by a single surgeon were reviewed. Comparisons between open and laparoscopy regarding operative outcomes, including number of bile duct openings in the graft, were performed using propensity score matching. RESULTS: From 2014 to 2018, 103 and 96 donors underwent laparoscopic and open living donor right hepatectomy respectively, of whom 64 donors from each group were matched. Mean(s.d.) duration of operation (252·2(41·9) versus 304·4(66·5) min; P < 0·001) and median duration of hospital stay (8 versus 10 days; P = 0·002) were shorter in the laparoscopy group. There was no difference in complication rates of donors (P = 0·298) or recipients (P = 0·394) between the two groups. Total time for laparoscopy decreased linearly (R2 = 0·407, ß = -0·914, P = 0·001), with the decrease starting after approximately 50 procedures when cases were divided into four quartiles (2nd versus 3rd quartile, P = 0·001; 3rd versus 4th quartile, P = 0·023). Although grafts with bile duct openings were more abundant in the laparoscopy group (P = 0·022), no difference was found in the last two quartiles (P = 0·207). CONCLUSION: Laparoscopic living donor right hepatectomy is feasible and an experience of approximately 50 cases may surpass the learning curve.

ANTECEDENTES: Se evaluó la viabilidad y la curva de aprendizaje de la hepatectomía derecha de donante vivo MÉTODOS: Se llevó a cabo una revisión de los donantes sometidos a hepatectomía derecha por un único cirujano. Las comparaciones entre el abordaje abierto y laparoscópico con respecto a los resultados operatorios, incluyendo el número of aberturas de los conductos biliares en el injerto se realizó utilizando un análisis de emparejamiento por puntaje de propensión. RESULTADOS: Desde 2014 a 2018, 96 y 103 donantes fueron sometidos a hepatectomía derecho de donante vivo por cirugía abierta y laparoscópica, respectivamente, de los cuales 64 donantes fueron emparejados para ambos grupos. La media del tiempo operatorio (304,3 ± 66,5 versus 252,2 ± 41,9 minutos, P < 0,001) y la mediana de la estancia hospitalaria fueron más cortas en el grupo de cirugía laparoscópica (10 versus 8 días, P = 0,002). No hubo diferencias entre ambos grupos en las tasas de complicaciones de los donantes (P = 0,298) o receptores (P = 0,394). El tiempo total de la laparoscopia disminuyó linealmente (R2= 0,407, ß = -0,914, P = 0,001) y esta disminución comenzó a partir aproximadamente de los 50 casos realizados cuando los casos fueron divididos en cuatro cuartiles (segundo a tercero y tercero a cuarto, P = 0,001 y P = 0,023, respectivamente). Aunque los injertos con aperturas de los conductos biliares fueron más numerosos en el grupo laparoscópico (P = 0,022), no se hallaron diferencias en los dos últimos cuartiles (P = 0,207). CONCLUSIÓN: La hepatectomía derecha de donante vivo por vía laparoscópica es viable, y una experiencia de aproximadamente 50 casos, puede superar la curva de aprendizaje.

Vaginal compared with intramuscular progestogen for preventing preterm birth in high-risk pregnant women (VICTORIA study): a multicentre, open-label randomised trial and meta-analysis.

OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

Efficacy and safety of PAC-14028 cream - a novel, topical, nonsteroidal, selective TRPV1 antagonist in patients with mild-to-moderate atopic dermatitis: a phase IIb randomized trial.

BACKGROUND: Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown. OBJECTIVES: To assess the clinical efficacy and safety of PAC-14028, a TRPV1 antagonist, via topical application in patients with AD. METHODS: In this 8-week, phase IIb, randomized, double-blind, multicentre, vehicle-controlled study, patients with mild-to-moderate AD were randomized to receive PAC-14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90. RESULTS: A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC-14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC-14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC-14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two-grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported. CONCLUSIONS: PAC-14028 cream may be an effective and safe treatment modality for the treatment of patients with mild-to-moderate AD.

Factors affecting quality of life in patients with vitiligo: a nationwide study.

BACKGROUND: Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. OBJECTIVES: To explore the QoL of patients with vitiligo and to identify factors affecting QoL. METHODS: A nationwide questionnaire-based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex-29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex-29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. RESULTS: Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20-84). The median duration of disease was 3·0 years (range 0-60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex-29. Additionally, the QoL of patients aged 20-59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. CONCLUSIONS: A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.

Functional characterization of O-methyltransferases used to catalyse site-specific methylation in the post-tailoring steps of pradimicin biosynthesis.

AIMS: To identify the roles of the two O-methyltransferase homologous genes pdmF and pdmT in the pradimicin biosynthetic gene cluster of Actinomadura hibisca P157-2. METHODS AND RESULTS: Pradimicins are pentangular polyphenol antibiotics synthesized by bacterial type II polyketide synthases (PKSs) and tailoring enzymes. Pradimicins are naturally derivatized by combinatorial O-methylation at two positions (i.e., 7-OH and 11-OH) of the benzo[α]naphthacenequinone structure. PdmF and PdmT null mutants (PFKO and PTKO) were generated. PFKO produced the 11-O-demethyl shunt metabolites 11-O-demethylpradimicinone II (1), 11-O-demethyl-7-methoxypradimicinone II (2), 11-O-demethylpradimicinone I (3) and 11-O-demethylpradimicin A (4), while PTKO generated the 7-O-demethyl derivatives pradimicinone II (5) and 7-hydroxypradimicin A (6). Pradimicinones 1, 2, 3, and 5 were fed to a heterologous host Escherichia coli harbouring expression plasmid pET-22b::pdmF or pET-28a::pdmT. PdmF catalysed 11-O-methylation of pradimicinones 1, 2, and 3 regardless of O-methylation at the C-7 position, while PdmT was unable to catalyse 7-O-methylation when the C-11 hydroxyl group was methylated (5). CONCLUSIONS: PdmF and PdmT were involved in 11-O- and 7-O-methylations of the benzo[α]naphthacenequinone moiety of pradimicin, respectively. Methylation of the C-7 hydroxyl group precedes methylation of the C-11 hydroxyl group in pradimicin biosynthesis. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first reported demonstration of the functions of PdmF and PdmT for regiospecific O-methylation, which contributes to better understanding of the post-PKS modifications in pradimicin biosynthesis as well as to rational engineering of the pradimicin biosynthetic machinery.

The impact of robotic surgery on quality of life, urinary and sexual function following total mesorectal excision for rectal cancer: a propensity score-matched analysis with laparoscopic surgery.

AIM: Quality of life (QoL) and functional outcomes are at risk of being impaired after rectal surgery, but there has been no large prospective study to thoroughly assess QoL according to surgical approach. We have investigated the impact of laparoscopic and robotic total mesorectal excision (TME) on QoL and functional outcomes. METHOD: Patients undergoing laparoscopic or robotic TME for rectal cancer between 2009 and 2013 were prospectively included in this questionnaire-based survey of QoL together with variations in urinary and sexual function. A propensity score analysis was retrospectively conducted to compare outcomes between groups in a cohort matched 1:1 for age, sex, body mass index, preoperative chemoradiation status and tumour height. The survey was performed preoperatively and 3, 6 and 12 months after surgery. RESULTS: Global health status/QoL was similar between the two groups for 130 matched pairs, but the robotic group showed better role, emotional and social functioning and experienced less fatigue and financial difficulty. International Prostatic Symptom Scores in men increased postoperatively, with significantly less impairment in the robotic group at 6 months. These scores were comparable to preoperative scores at 6 months in the robotic group and at 12 months in the laparoscopic group. Of 48 sexually active men in each group, International Index of Erectile Function-5 scores decreased postoperatively, returning to preoperative levels at 6 months in the robotic group and at 12 months in the laparoscopic groups. CONCLUSION: The robotic approach for TME was associated with less impairment of urinary and sexual function; QoL was comparable to the laparoscopic approach.

Association of support from family and friends with self-leadership for making long-term lifestyle changes in patients with colorectal cancer.

The purpose of this study was to examine the association of support from family and friends for adoption of healthy eating habits and performing exercise with improvements of self-leadership in patients with colorectal cancer (CRC). This cross-sectional study examined 251 patients with CRC who received primary curative surgery in South Korea. Demographic and clinical information, receipt of social support for adoption of healthy eating habits and performing exercise and self-leadership were collected. Greater participation by family and the use of rewards for performance of exercise were associated with greater behavioural awareness and volition, greater task motivation and constructive cognition of self-leadership in patients. Patients exercising with friends had greater task motivation in self-leadership. The use of rewards by family was associated with performing and maintaining exercise programme for more than 6 months, and family encouragement to adopt healthy eating habits was associated with excellent quality of diet. Family support for exercising and adopting healthy eating habits had more wide-ranging benefits in self-leadership than support from friends; however, support from each group improved self-leadership. Support from family was valuable for increasing the actual performance of exercise and for helping patients with cancer to adopt healthy diets.

Impact of Mixed Xenogeneic Porcine Hematopoietic Chimerism on Human NK Cell Recognition in a Humanized Mouse Model.

Mixed chimerism is a promising approach to inducing allograft and xenograft tolerance. Mixed allogeneic and xenogeneic chimerism in mouse models induced specific tolerance and global hyporesponsiveness, respectively, of host mouse natural killer (NK) cells. In this study, we investigated whether pig/human mixed chimerism could tolerize human NK cells in a humanized mouse model. Our results showed no impact of induced human NK cell reconstitution on porcine chimerism. NK cells from most pig/human mixed chimeric mice showed either specifically decreased cytotoxicity to pig cells or global hyporesponsiveness in an in vitro cytotoxicity assay. Mixed xenogeneic chimerism did not hamper the maturation of human NK cells but was associated with an alteration in NK cell subset distribution and interferon gamma (IFN-γ) production in the bone marrow. In summary, we demonstrate that mixed xenogeneic chimerism induces human NK cell hyporesponsiveness to pig cells. Our results support the use of this approach to inducing xenogeneic tolerance in the clinical setting. However, additional approaches are required to improve the efficacy of tolerance induction while ensuring adequate NK cell functions.

Use of supplemental anti-HBc testing of donors showing non-discriminating reactive results in multiplex nucleic acid testing.

BACKGROUND AND OBJECTIVES: The Korean Red Cross began nucleic acid amplification testing (NAT) for HIV and HCV in February 2005, and added HBV NAT beginning in June 2012. The current NAT system utilizes a multiplex assay for simultaneous detection of HBV DNA, HCV RNA and HIV-1 RNA. For samples that are reactive in the multiplex assay, we do specific tests for each virus. However, there have been cases of non-discriminated reactive (NDR) results which appear to be the result of non-specific reactions or cross-contamination, although some cases are considered to arise from the presence of low levels of HBV DNA due to occult hepatitis B infection. MATERIALS AND METHODS: We examined the incidence of NDR results in previous donations of some NAT-reactive donors. Additionally, for those donors with NDR results, we performed an HBV core antibody (anti-HBc) assay. RESULTS: From November 2015 to March 2016, there were 408 NAT-reactive donors. Of these, nineteen HBV NAT-reactive donors showed a history of NDR results in the past donations. Seven donors showed NDR results more than once. Of 771 NDR donors, 362 (47·0%) were anti-HBc reactive. CONCLUSION: The NDR donors had a substantially higher rate of anti-HBc reactivity than other blood donors indicating that some with anti-HBc reactivity represent donors with occult HBV. Therefore, the incorporation of an anti-HBc testing for NDR donors could improve blood safety testing for the Korean Red Cross.

Predictive performance of the modified Marsh and Schnider models for propofol in underweight patients undergoing general anaesthesia using target-controlled infusion.

BACKGROUND: : In our preliminary study, the modified Marsh (M-Marsh) model caused an inadvertent underdosing of propofol in underweight patients. However, the predictive performance of the M-Marsh and Schnider models incorporated in commercially available target-controlled infusion (TCI) pumps was not evaluated in underweight patients. METHODS: : Thirty underweight patients undergoing elective surgery were randomly allocated to receive propofol via TCI using the M-Marsh or Schnider models. The target effect-site concentrations (Ces) of propofol were, in order, 2.5, 3, 4, 5, 6 and 2 µg ml -1 . Arterial blood samples were obtained at least 7 min after achieving each pseudo-steady-state. RESULTS: A total of 172 plasma samples were used to determine the predictive performance of both models. The pooled median (95% confidence interval) biases and inaccuracies at a target Ce ≤ 3 µg ml -1 were -22.6 (-28.8 to -12.6) and 31.9 (24.8-36.8) for the M-Marsh model and 9.0 (1.7-16.4) and 28.5 (21.7-32.8) for the Schnider model, respectively. These values at Ce ≥ 4 µg ml -1 were -9.6 (-16.0 to -6.0) and 24.7 (21.1-27.9) for the M-Marsh model and 19.8 (12.9-25.7) and 36.2 (31.4-39.7) for the Schnider model, respectively. CONCLUSIONS: The pooled biases and inaccuracies of both models were clinically acceptable. However, the M-Marsh and Schnider models consistently produced negatively and positively biased predictions, respectively, in underweight patients. In particular, the M-Marsh model showed greater inaccuracy at target Ce ≤ 3 µg ml -1 and the Schnider model showed greater inaccuracy at target Ce ≥ 4 µg ml -1 . Therefore, it is necessary to develop a new pharmacokinetic model for propofol in underweight patients. CLINICAL TRIAL REGISTRATION: KCT0001502.

Effects of sugammadex vs. pyridostigmine-glycopyrrolate on post-operative nausea and vomiting: propensity score matching.

BACKGROUND: Sugammadex is a new agent that reverses neuromuscular blockade by aminosteroid neuromuscular blocker. This retrospective study compared the effects of sugammadex on post-operative nausea and vomiting (PONV) with those of a pyridostigmine-glycopyrrolate mixture. METHODS: We reviewed the electronic medical records of 7179 patients who had received fentanyl-based, intravenous, patient-controlled analgesia (IV-PCA) at Chung-Ang University Hospital between January 1, 2010 and December 31, 2015. We categorized the patients into two groups on the basis of the type of reversal agent to neuromuscular blockade that was used: a traditional reversal agent (pyridostigmine-glycopyrrolate mixture; Group R; n = 7059) and sugammadex (Group S; n = 120). The propensity score matching method was then used to select 408 subjects in Group R and 115 subjects in Group S; on the basis of their covariates, these subjects were then matched with a counterpart in the other group. RESULTS: After propensity score matching, the two groups were well balanced with respect to all baseline covariates. In Group S, the numeric rating scale of nausea on day 0, as well as the number of patients who vomited on day 0, was lower than that in group R. Furthermore, Group S used fewer rescue antiemetics on day 0 and had a higher complete response on day 0. CONCLUSION: Sugammadex might be more beneficial for PONV compared to pyridostigmine-glycopyrrolate mixture for patients who have received opioid-based IV-PCA.