Prolongation of the Time Window From Traumatic Limb Amputation to Replantation From 6 to 33 Hours Using Ex Vivo Limb Perfusion.

INTRODUCTION: Continuous extracorporeal perfusion (ECP), or machine perfusion, holds promise for prolonged skeletal muscle preservation in limb ischemia-reperfusion injury. This study aimed to extend the amputation-to-replantation time window from currently 6 hours to 33 hours using a 24-hour ECP approach. MATERIALS AND METHODS: Six large white pigs underwent surgical forelimb amputation under general anesthesia. After amputation, limbs were kept for 9 hours at room temperature and then perfused by 24-hour ECP with a modified histidine-tryptophan-ketoglutarate (HTK) solution. After ECP, limbs were orthotopically replanted and perfused in vivo for 12 hours. Clinical data, blood, and tissue samples were collected and analyzed. RESULTS: All 6 forelimbs could be successfully replanted and in vivo reperfused for 12 hours after 9 hours of room temperature ischemia followed by 24 hours ECP. Adequate limb perfusion was observed after replantation as shown by thermography and laser Doppler imaging. All pigs survived without severe organ failure, and no significant increase in inflammatory cytokines was found. Macroscopy and histology showed marked interstitial muscular edema of the limbs, whereas myofiber necrosis was not evident, implying the preservation of muscular integrity. CONCLUSIONS: The use of a 24-hour ECP has successfully extended limb preservation to 33 hours. The modified histidine-tryptophan-ketoglutarate perfusate demonstrated its ability for muscle protection. This innovative approach not only facilitates limb replantation after combat injuries, surmounting geographical barriers, but also broadens the prospects for well-matched limb allotransplants across countries and continents.

Chloroprocaine 3% for anesthesia during cesarean section in a patient with dopa-responsive dystonia: A case report.

RATIONALE: Dopa-responsive dystonia (DRD) is a rare autosomal dominant hereditary disorder with a prevalence of 0.5 per million population. The disease is characterized by onset of dystonia in childhood, progressive aggravation of the dystonia with diurnal fluctuation, and complete or near complete alleviation of symptoms with low-dose oral levodopa. The incidence of DRD is low, and only a few publications have described this disorder connected with anesthesia. PATIENT CONCERNS: We present a case involving a pregnant woman with DRD who continued levodopa/benserazide throughout the pregnancy. The perioperative anesthesia management was described. We used chloroprocaine 3% for epidural anesthesia during cesarean section. DIAGNOSES: Dopa-responsive dystonia. INTERVENTIONS: Levodopa/benserazide. OUTCOMES: In summary, levodopa/benserazide was continued throughout our patient's pregnancy with a good obstetric outcome, and chloroprocaine was safely used in epidural anesthesia without deterioration of her dystonic symptoms. LESSONS: Chloroprocaine was safely used in epidural anesthesia without deterioration of her dystonic symptoms.

The Potential Neurological Impact of Intraoperative Hyponatremia Using Histidine-Tryptophan-Ketoglutarate Cardioplegia Infusion in Adult Cardiac Surgery.

Background and Objectives: The relationship between histidine-tryptophan-ketoglutarate (HTK)-induced hyponatremia and brain injury in adult cardiac surgery patients is unclear. This study analyzed postoperative neurological outcomes after intraoperative HTK cardioplegia infusion. Materials and Methods: A prospective cohort study was conducted on 60 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Of these patients, 13 and 47 received HTK infusion and conventional hyperkalemic cardioplegia, respectively. The patients' baseline characteristics, intraoperative data, brain injury markers, Mini-Mental State Examination (MMSE) scores, and quantitative electroencephalography (qEEG) data were collected. Electrolyte changes during cardiopulmonary bypass, the degree of hyponatremia, and any associated brain insults were evaluated. Results: The HTK group presented with acute hyponatremia during cardiopulmonary bypass, which was intraoperatively corrected through ultrafiltration and normal saline administration. Postoperative sodium levels were higher in the HTK group than in the conventional cardioplegia group. The change in neuron-specific enolase levels after cardiopulmonary bypass was significantly higher in the HTK group (p = 0.043). The changes showed no significant differences using case-control matching. qEEG analysis revealed a significant increase in relative delta power in the HTK group on postoperative day (POD) 7 (p = 0.018); however, no significant changes were noted on POD 60. The MMSE scores were not significantly different between the two groups on POD 7 and POD 60. Conclusions: HTK-induced acute hyponatremia and rapid correction with normal saline during adult cardiac surgeries were associated with a potential short-term but not long-term neurological impact. Further studies are required to determine the necessity of correction for HTK-induced hyponatremia.

Stellate ganglion block with procaine in breast cancer survivors with hot flashes and sleep disturbances undergoing Endocrine Therapy.

Breast cancer survivors under endocrine therapy (ET) suffer from side effects such as hot flashes and sleep disturbance accompanied by poor quality of life. Many quit ET early and reduce their survival rate. Guidelines recommend gabapentin next to yoga or acupuncture. The role of side effects related to compliance with ET over years require new and effective therapies. Stellate ganglion block (SGB) has shown evidence of safety and efficacy and was found to be more effective than pregabalin without side effects. However, practical guidelines for the long-term use of SGB are still missing. We primarily used procaine instead of bupivacaine presuming effectiveness paired with lower toxic risks. Twenty-nine breast cancer survivors with severe hot flashes and sleep disturbance under ET received SGB with Procaine. Diaries recorded hot flashes and sleep quality scores up to week 24. All patients took part and none refused SGB. Each Patient received one SGB every 4 weeks without any side effects observed. Weekly scores were reduced from baseline by -33.6% (P < .01) (hot flashes) and -22.3% (P < .01) (sleep disturbances) after 4, and by -58.8% (P < .01) (hot flashes) and -50.8% (P < .01) (sleep disturbances) after twenty-for weeks. A wavelike reduction indicated a limited effect of a single SGB during continuous ET. We showed, that procaine in SGB is as effective as bupivacaine with lower risks and costs. High significant reductions in hot flashes and sleep disturbances after 1 and 6 months were found. We conclude that breast cancer survivors need individual treatment with SGB due to her personal impact. Hence, SGB should find its way to guidelines and daily routines as a valuable method for treating side effects in breast cancer survivors undergoing ET.

Effect of Femoral Nerve Block with Different Concentrations of Chloroprocaine on Early Postoperative Rehabilitation Training After Total Knee Arthroplasty.

BACKGROUND Patients experience severe pain in early postoperative rehabilitation after total knee arthroplasty (TKA). This study aimed to compare the effect of femoral nerve block with different concentrations of chloroprocaine on postoperative rehabilitation in patients with TKA. MATERIAL AND METHODS Ninety patients who only received unilateral TKA were randomly and equally divided into C1 (1% chloroprocaine 0.2 ml/kg), C2 (2% chloroprocaine 0.2 ml/kg), or NS (0.9% sodium chloride solution 0.2 ml/kg) groups. The patients received rehabilitation 3 times a day on days 3-6 after surgery, and femoral nerve block was performed with corresponding solution 10 min before each training session. We recorded the maximum knee flexion angles (MKFA) and maximum knee extension angles (MKEA) during active exercise on day 7 after surgery, as well as the incidence of MKFA ³100°, American knee society (AKS) scores, and postoperative rehabilitation satisfaction. Adverse effects after administration in each group were also recorded. RESULTS Compared with group NS, patients in group C1 and C2 had larger MKFA during active exercise on day 7 after TKA, and had better rehabilitation satisfaction (P<0.05). MKEA, the incidence of MKFA ≥100°, and AKS scores showed no significant differences in the 3 groups. There were more patients with decline of muscle strength in group C2 (P<0.05), and no other adverse reactions were recorded. CONCLUSIONS Chloroprocaine for femoral nerve block can be safely used in rehabilitation after TKA and to improve the knee flexion angle in the early postoperative period. Because they may have fewer adverse effects, 1% chloroprocaine 0.2 ml/kg may be preferred.

Local anesthetics as a therapeutic tool for post COVID-19 patients: A case report.

BACKGROUND: Post COVID-19 syndrome (PC-19S) appears to be independent of acute illness severity and humoral response. The involvement of the autonomic nervous system (ANS), expressed by dysautonomia, has been hypothesized as a contributor. Several studies have associated the therapeutic effects of local anesthetics (LA) to their action on the ANS. To the best of our knowledge, this is the first report of therapeutic injections with LA linked to clinical improvement in a patient with PC-19S. PATIENT CONCERNS AND DIAGNOSES: This was a 54-year-old-man with postCOVID-19 symptoms lasting 14 weeks, including fatigue, breathlessness, diarrhea, muscle pain, and emotional lability. INTERVENTIONS AND OUTCOME: Injections of 0.5% procaine in the stellate ganglion (SG) and sphenopalatine ganglion (SPG), and in clinically relevant points in the scalp, thorax, and abdomen were performed 3 times over 3 months. The patient reported progressive improvement and was asymptomatic upon completing the treatment. Prescribed medications were discontinued. The 36-Item Short Form Health Survey (SF-36) score showed significant improvement across all SF-36-domains. CONCLUSION: Subanesthetic doses of LA injected in clinically relevant points led to rapid and complete symptom resolution in this patient with PC-19S. Targeted LA injections may have therapeutic benefits in PC-19S and in other chronic diseases linked to stress and inflammation.

PAX9 reactivation by inhibiting DNA methyltransferase triggers antitumor effect in oral squamous cell carcinoma.

Aberrant DNA hypermethylation is associated with oral carcinogenesis. Procaine, a local anesthetic, is a DNA methyltransferase (DNMT) inhibitor that activates anticancer mechanisms. However, its effect on silenced tumor suppressor gene (TSG) activation and its biological role in oral squamous cell carcinoma (OSCC) remain unknown. Here, we report procaine inhibited DNA methylation by suppressing DNMT activity and increased the expression of PAX9, a differentiation gene in OSCC cells. Interestingly, the reactivation of PAX9 by procaine found to inhibit cell growth and trigger apoptosis in OSCC in vitro and in vivo. Likely, the enhanced PAX9 expression after exposure to procaine controls stemness and differentiation through the autophagy-dependent pathway in OSCC cells. PAX9 inhibition abrogated procaine-induced apoptosis, autophagy, and inhibition of stemness. In OSCC cells, procaine improved anticancer drug sensitivity through PAX9, and its deficiency significantly blunted the anticancer drug sensitivity mediated by procaine. Additionally, NRF2 activation by procaine facilitated the antitumor response of PAX9, and pharmacological inhibition of NRF2 by ML385 reduced death and prevented the decrease in the orosphere-forming potential of OSCC cells. Furthermore, procaine promoted antitumor activity in FaDu xenografts in athymic nude mice, and immunohistochemistry data showed that PAX9 expression was significantly enhanced in the procaine group compared to the vehicle control. In conclusion, PAX9 reactivation in response to DNMT inhibition could trigger a potent antitumor mechanism to provide a new therapeutic strategy for OSCC.

Custodiol® Supplemented with Synthetic Human Relaxin Decreases Ischemia-Reperfusion Injury after Porcine Kidney Transplantation.

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% (p = 0.042) and 125% (p = 0.019), respectively, while RIPK1 expression was downregulated to 82% (p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI.

Effect of different cardioprotective methods on extracorporeal circulation in fetal sheep: a randomized controlled trial.

BACKGROUND: Congenital heart disease is a leading cause of death in newborns and infants. The feasibility of fetal cardiac surgery is linked to extracorporeal circulation (ECC); therefore, cardioplegic solutions need to be effective and long-lasting. METHODS: Eighteen pregnant sheep were divided into an ECC-only group, St. Thomas' Hospital cardioplegic solution (STH1) group (STH group), and HTK preservation solution (Custodiol®) group (HTK group). Markers of myocardial injury including troponin I (cTnI), troponin T (cTnT) and creatine kinase myocardial band (CKMB) were measured at specific time points (T1: pre-ECC, T2: 30 min of ECC, T3: 60 min of ECC, T4: 60 min post-ECC, T5: 120 min post-ECC). Myocardial tissue was removed from the fetal sheep at T5, and apoptosis was detected by TUNEL staining. RESULTS: Changes in the serum cTnI, cTnT and CKMB concentrations were not significantly different among the three groups before and during the ECC(T1,T2,T3). At 60 min after ECC shutdown(T4), cTnI and cTnT concentrations were significantly higher in the STH group than before the start of ECC. The concentration of cTnI was higher in the STH group than in the HTK and ECC-only groups. The concentration of cTnT was higher in the STH group than in the ECC-only group. At 120 min after ECC shutdown(T5), cTnI and cTnT concentrations were significantly higher in the ECC and HTK groups than before the start of ECC, and CKMB concentration was significantly higher in STH and HTK groups. The concentrations of cTnT, cTnI and CKMB was higher in the STH group than in the HTK and ECC-only groups. The number of TUNEL-positive cells in the HTK and STH groups was higher than in the ECC-only group. The number of TUNEL-positive cells in the STH group was higher than in the HTK group. There was no statistically significant difference among the groups in the heart rate and mean arterial pressure after ECC. CONCLUSION: The HTK preservation solution was significantly better than STH1 in reducing the release of cardiomyocyte injury markers and the number of apoptotic cells in fetal sheep ECC. Fetal sheep receiving ECC-only had an advantage in all indicators, which suggests ECC-only fetal heart surgery is feasible.

Clinical outcomes of single-dose cardioplegia in high-risk coronary bypass.

BACKGROUND: Despite the increasing popularity of single-dose cardioplegia techniques in coronary artery bypass grafting, the time window for successful reperfusion remains unclear. This study aimed to compare different cardioplegic techniques based on early and 30-day clinical outcomes via thorough monitoring. METHODS: This prospective cohort study included high-risk patients undergoing coronary artery bypass grafting and receiving 3 different types of cardioplegia between January 2017 and June 2019. Group 1 (n = 101) had a single dose of del Nido cardioplegia, group 2 (n = 92) had a single dose of histidine-tryptophane-ketoglutarate, and group 3 (n = 119) had cold blood cardioplegia. Patients were examined perioperatively by memory loop recording and auto-triggered memory loop recording for 30 days, with documentation of predefined events. RESULTS: Interleukin-6 and cardiac troponin levels in group 1 were significantly higher than those in groups 2 and 3. The incidence of predefined events as markers of inadequate myocardial protection was significantly higher group 1, with more frequent atrial fibrillation attacks and more hospital readmissions. The readmission rate was 17.6% in group 1, 9% in group 2, and 8% in group 3. CONCLUSIONS: Our data demonstrate the long-term efficacy of cardioplegic techniques, which may become more crucial in high-risk patients who genuinely have a chance to benefit from adjunct myocardial protection. Patients given del Nido cardioplegia had a significantly more prominent inflammatory response and higher troponin levels after cardiopulmonary bypass. This group had issues in the longer term with significantly more cardiac events and a higher rehospitalization rate.

Comparison of Chloroprocaine Versus Lidocaine With Epinephrine, Sodium Bicarbonate, and Fentanyl for Epidural Extension Anesthesia in Elective Cesarean Delivery: A Randomized, Triple-Blind, Noninferiority Study.

BACKGROUND: For emergent intrapartum cesarean delivery (CD), the literature does not support the use of any particular local anesthetic solution to extend epidural analgesia to cesarean anesthesia. We hypothesized that 3% chloroprocaine (CP) would be noninferior to a mixture of 2% lidocaine, 150 µg of epinephrine, 2 mL of 8.4% bicarbonate, and 100 µg of fentanyl (LEBF) in terms of onset time to surgical anesthesia. METHODS: In this single-center randomized noninferiority trial, adult healthy women undergoing CD were randomly assigned to epidural anesthesia with either CP or LEBF. Sensory blockade (pinprick) to T10 was established before operating room (OR) entry for elective CD. On arrival to the OR, participants received the epidural study medications in a standardized manner to simulate the conversion of "epidural labor analgesia to surgical anesthesia." The primary outcome was the time to loss of touch sensation at the T7 level. A noninferiority margin was set at 3 minutes. The secondary outcome was the need for intraoperative analgesia supplementation. RESULTS: In total, 70 women were enrolled in the study. The mean onset time to achieve a bilateral sensory block to touch at the T7 dermatome level was 655 (standard deviation [SD] = 258) seconds for group CP and 558 (269) seconds for group LEBF, a difference in means of 97 seconds (90% confidence interval [CI], SD = -10.6 to 204; P = .10 for noninferiority). The upper limit of the 90% CI for the mean difference exceeded the prespecified 3-minute noninferiority margin. There was no meaningful difference in the requirement for intraoperative analgesia between the 2 groups. CONCLUSION: Both anesthetic solutions have a rapid onset of anesthesia when used to extend low-dose epidural sensory block to surgical anesthesia. Data from the current study provide insufficient evidence to confirm that CP is noninferior to LEBF for rapid epidural extension anesthesia for CD, and further research is required to determine noninferiority.

Scavenging right atrial Bretschneider histidine-tryptophan-ketoglutarate cardioplegia: Impact on hyponatremia and seizures in pediatric cardiac surgery patients.

OBJECTIVE: Custodiol-HTK cardioplegia (Custodiol-HTK Koheler Chemie, GmbH, Bensheim, Germany) causes fluctuations in serum sodium levels, hyponatremia, and is associated with postoperative seizures. We investigated the influence of scavenging right atrial effluent during delivery on intraoperative serum sodium levels and postoperative seizure incidence in pediatric cardiac surgery patients. METHODS: A total of 204 patients younger than age 18 years undergoing congenital heart surgery between January 2016 and March 2018 were analyzed retrospectively. Serum sodium levels after administration of Custodiol-HTK cardioplegia were compared between the scavenge and nonscavenge groups and then in the propensity score-matched cohort (n = 96). Postoperative seizures were documented clinically and with electroencephalogram findings. Logistic regression models were used to identify the independent predictors of serum sodium level after aortic crossclamp. RESULTS: Of 204 patients, 156 (76.5%) were in the nonscavenge, and 48 (23.5%) in the scavenge groups. A serum sodium level <130 mEq/L after crossclamp and administration of Custodiol-HTK cardioplegia in the nonscavenge group were 70% versus 21% in the scavenge group (odds ratio, 8.8; 95% confidence interval, 4.1-18.3; P < .0001) in the entire cohort, and 77% versus 21% (odds ratio, 12.8; 95% confidence interval, 4.8-33.1; P < .0001) in the propensity score-matched cohort. Of 16 patients experiencing a postoperative seizure, 14 (87.5%) had a sodium level <130 mEq/L and 2 (12.5%) had a sodium level ≥130 mEq/L (odds ratio, 5.1; 95% confidence interval, 1.3-22.8; P = .021) after crossclamp. Postoperative seizures occurred in the nonscavenge group but not the scavenge group in the entire cohort (P = .02) and in the propensity score-matched patients (P = .041). Multivariable analysis of the entire cohort showed that scavenge intervention was an independent factor associated with significantly decreased risk of sodium level <130 mEq/L (odds ratio, 0.17; 95% confidence interval, 0.08-0.36; P = .000). CONCLUSIONS: Right atrial effluent scavenging was protective against fluctuations in serum sodium levels after crossclamp and Custodiol-HTK cardioplegia administration independently in both entire and matched cohort, and was also associated with decreased incidence of postoperative seizures.

Histidine-tryptophan-ketoglutarate solution versus University of Wisconsin solution in adult-to-adult living donor liver transplantation: A propensity score matching analysis from mainland China.

ABSTRACT: To compare the difference between University of Wisconsin (UW) solution and histidine-tryptophan-ketoglutarate (HTK) solution in adult living donor liver transplantation (LDLT).This study included LDLT patients at the Liver Transplantation Center of West China Hospital of Sichuan University from November 2001 to June 2018. These patients were classified into 2 groups depending on the use of the different preservation solutions, and the confounding factors between the 2 groups were eliminated by propensity score matching. Finally, the incidence of complications; serum examination at postoperative days 1, 3, 5, 7, 14, 21, and 30; and the overall survival rate of the 2 groups were compared to observe whether there were any differences between the 2 preservation solutions.Of the 298 patients we screened, 170 were treated with UW solution and 128 with HTK solution. After propensity score matching, 106 pairs of patients were selected. In the comparison of the 2 groups, the length of intensive care unit stay in the UW group was significantly longer than that in the HTK group (P = .022), but there was no difference in the total length of hospital stay between the 2 groups (P = .277). No statistically significant difference was observed in the 2 groups in terms of the incidence of complications or postoperative examinations. However, the incidence of early allograft dysfunction in the HTK group was slightly lower than that in the UW group (HTK: UW = 14.1%: 20.7%), although the difference was not statistically significant. In terms of the overall survival rate, the 1, 3, and 5-year survival rates of the HTK group were 85.5%, 70.2%, and 65.1%, respectively, while the 1, 3, and 5-year survival rates of the UW group were 83.1%, 67.2%, and 59.8%, respectively, and there was no significant difference between the 2 groups.In conclusion, our study shows that UW solution and HTK solution are equivalent in perioperative safety, the recovery of transplanted liver function, the occurrence of postoperative complications and overall survival and can be safely and effectively applied in adult LDLT. If economic factors are taken into account, HTK can save costs to a certain extent.

Identification of hub genes and discovery of promising compounds in gastric cancer based on bioinformatics analysis.

Aim: To explore the mechanism of gastric carcinogenesis by mining potential hub genes and to search for promising small-molecular compounds for gastric cancer (GC). Materials & methods: The microarray datasets were downloaded from Gene Expression Omnibus database and the genes and compounds were analyzed by bioinformatics-related tools and software. Results: Six hub genes (MKI67, PLK1, COL1A1, TPX2, COL1A2 and SPP1) related to the prognosis of GC were confirmed to be upregulated in GC and their high expression was correlated with poor overall survival rate in GC patients. In addition, eight candidate compounds with potential anti-GC activity were identified, among which resveratrol was closely correlated with six hub genes. Conclusion: Six hub genes identified in the present study may contribute to a more comprehensive understanding of the mechanism of gastric carcinogenesis and the predicted potential of resveratrol may provide valuable clues for the future development of targeted anti-GC inhibitors.

Effectiveness of Bokeria-Boldyrev ACH Solution in Surgerical Treatment of Adult Patients with Obstructive Hypertrophic Cardiomyopathy.

The study examined effectiveness of pharmaco-cold cardioplegia employing solutions of enhanced buffer capacity during surgery of obstructive hypertrophic cardiomyopathy in adult patients (N=51) operated during 2013-2018. In group 1 (N=28), the cardioplegia was performed with HTK (Custodiol) solution, whereas in group 2 (N=23), it was carried out with Bokeria-Boldyrev ACH solution. The mean, minimum, and maximum ages in group 1 were 46, 21, and 64 years, respectively; in group 2 - 42, 14, and 70 years, respectively. In both groups, the patients were subjected to myoectomy of exit pathway in the left ventricle according to Bokeria-Morrow operation and annuloplasty of tricuspid valve accompanied by reconstructive surgery (or replacement) of mitral valve. Atrial fibrillation (if any) was suppressed with cryoablation (-60°Ð¡) of the openings of the right and left pulmonary veins. The surgery was carried out in hypothermic mode at 28°C. The significant intergroup differences were observed in the asystole latent period after the onset of antegrade or retrograde injection of cardioplegic solution. In group 1, the asystole latent periods determined after antegrade or retrograde injection were 53±7 or 170±30 sec, respectively; in group 2 - 32±6 and 97±11 sec (p<0.0001), respectively. The mean times of aortic cross-clumping in groups 1 and 2 were 66±8 and 64±6 min, respectively; the electromechanical action of the heart restored after aortic unclamping in 35±7 and 30±6 sec, respectively. The biochemical and clinical data revealed no significant intergroup differences. Overall, novel Bokeria-Boldyrev ACH cardioplegic solution secured effective protection of the myocardium against intraoperative ischemia in adult patients with obstructive hypertrophic cardiomyopathy and significantly decreased the asystole latent period.

The Radioprotective Effect of Procaine and Procaine-Derived Product Gerovital H3 in Lymphocytes from Young and Aged Individuals.

Ionizing radiation induces genomic instability in living organisms, and several studies reported an ageing-dependent radiosensitivity. Chemical compounds, such as scavengers, radioprotectors, and modifiers, contribute to reducing the radiation-associated toxicity. These compounds are often antioxidants, and therefore, in order to be effective, they must be present before or during exposure to radiation. However, not all antioxidants provide radioprotection. In this study, we investigated the effects of procaine and of a procaine-based product Gerovital H3 (GH3) on the formation of endogenous and X-ray-induced DNA strand breaks in peripheral blood mononuclear cells (PBMCs) isolated from young and elderly individuals. Interestingly, GH3 showed the strongest radioprotective effects in PBMCs from young subjects, while procaine reduced the endogenous amount of DNA strand breaks more pronounced in aged individuals. Both procaine and GH3 inhibited lipid peroxidation, but procaine was more effective in inhibiting mitochondria free radicals' generation, while GH3 showed a higher antioxidant action on macrophage-induced low-density lipoprotein oxidation. Our findings provide new insights into the mechanisms underlying the distinct effects of procaine and GH3 on DNA damage.

A prospective, randomized, single-blind, multicentre, phase III study on organ preservation with Custodiol-N solution compared with Custodiol® solution in organ transplantation (kidney, liver and pancreas).

BACKGROUND: Organ preservation before transplantation is still a challenge. Both the University of Wisconsin and Bretschneider's histidine-tryptophan-ketoglutarate (HTK; Custodiol®) solution are standard for liver, kidney and pancreas preservation. Organ preservation with both solutions is comparable; recently, however, Custodiol® solution has been modified to Custodiol-N according to the needs of today. Thus, our study was defined to study its effect in clinical transplantation. METHODS: Patients undergoing kidney transplantation (n = 412) (including approximately 30 combined kidney-pancreas) or liver transplantation (n = 202) receive grafts that have been cold stored in either Custodiol® or Custodiol-N to demonstrate noninferiority of Custodiol-N regarding both graft function and graft injury after transplantation. DISCUSSION: Preclinical data have clearly shown that Custodiol-N is superior to Custodiol® in cold static organ preservation via mechanisms including inhibition of hypoxic cell injury, cold-induced cell injury and avoidance of adverse effects during warm exposure to the solution. Further clinical safety data on Custodiol-N for cardioplegia are available. Thus, this study was designed to compare Custodiol® with Custodiol-N for the first time in a prospective, randomized, single-blinded, multicentre, phase III clinical transplantation trial. TRIAL REGISTRATION: Eudra-CT, 2017-002198-20. Registered on 28 November 2018.

Single-dose cardioplegia protects myocardium as well as traditional repetitive dosing: A noninferiority randomized study.

OBJECTIVE: The present prospective noninferiority randomized trial was designed to demonstrate the safety and efficacy of a single dose of Custodiol histidine-tryptophan-ketoglutarate compared with repetitive cold-blood cardioplegia. METHODS: From October 2012 to May 2014, 110 patients were randomly assigned to 1 of 2 groups: Group 1 (55 patients) received repetitive cold-blood cardioplegia, and group 2 (55 patients) received single-dose Custodiol histidine-tryptophan-ketoglutarate. Isolated aortic valve replacement, isolated mitral valve replacement, and multivalve procedures represented the most frequent operations, with 39 cases (71%) in group 1 and 49 cases (89%) in group 2. There was no difference in cardiopulmonary bypass time (102 ± 26 minutes vs 99 ± 19 minutes, P = .70) or aortic crossclamp time (77 ± 19 minutes vs 74 ± 17 minutes, P = .33). All patients underwent preoperative electrocardiogram and determination of creatine kinase-MB, troponin I, left ventricular ejection fraction, and regional wall motion. Postoperative cardiac biomarkers were checked at 7, 24, and 48 hours, and an echocardiogram was obtained to check for left ventricular function abnormalities. RESULTS: There was no difference in cardiac biomarkers release between the 2 groups at baseline and 7, 24, and 48 hours postoperatively (creatine kinase, P = .18, troponin P = .23). Left ventricular function was similar between groups preoperatively and at 24 hours after surgery. No death or myocardial infarction was observed in either group. There were no differences in intensive care unit length of stay, incidence of atrial fibrillation, use of inotropes or vasopressors support, time of intubation, or creatinine levels. CONCLUSIONS: A single dose of Custodiol histidine-tryptophan-ketoglutarate cardioplegia is not inferior to repeated cold-blood cardioplegia during elective cardiac surgery.

Impact of Chloroprocaine on the Eligibility for Hospital Discharge in Patients Requiring Ambulatory Surgery Under Spinal Anesthesia: An Observational Multicenter Prospective Study.

INTRODUCTION: This observational study was designed to assess the use of spinal anesthesia with chloroprocaine in the context of ambulatory surgery. METHODS: A prospective, multicenter, observational study was carried out among 33 private or public centers between May 2014 and January 2015 and adult patients, scheduled for a short ambulatory surgery under spinal anesthesia with chloroprocaine. The primary outcomes were anesthetic effectiveness, defined as performance of the whole surgical procedure without any additional anesthetic agent, and the time to achieve eligibility for hospital discharge. Secondary outcomes were the effect of chloroprocaine on motor and sensory blocks, patients' satisfaction, and the use of analgesics in the first 24 h after surgery. RESULTS: Among the 615 enrolled patients, 56% were male, the mean age was 47.2 ± 15.2 years, and most patients had an ASA (American Society of Anesthesiologists) status of 1 (63.7%). Main surgical procedures performed were orthopedic (62.6%) and gynecologic (16.1%), and the mean duration of surgery was 26.7 ± 16.7 min. The overall anesthetic success rate was 93.8% (95% CI [91.5%; 95.6%]) for the 580 patients with available data for primary criteria. The failure rate was lower than 7% for all surgical procedures, except for gynecologic surgery (14.8%; 95% CI [8.1%; 23.9%]). The average times of eligibility for hospital discharge and effective discharge were 252.7 ± 82.7 min and 313.8 ± 109.9 min, respectively. The time of eligibility for hospital discharge is defined as the recovery of the patient's normal clinical parameters and the time of effective discharge is defined as the time for the patient to leave the hospital after surgery. Eligibility for patient's discharge was achieved more rapidly in private than public hospitals (236.3 ± 77.2 min vs. 280.9 ± 80.7 min, respectively, p < 0.001). CONCLUSIONS: This study showed positive results on the effectiveness of chloroprocaine as a short-duration anesthetic and could be used to reduce the time to achieve eligibility for hospital discharge. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02152293. Registered on May 6, 2014. Date of enrollment of the first participant in the trial May 7, 2014.

Factors Determining the Choice of Spinal Versus General Anesthesia in Patients Undergoing Ambulatory Surgery: Results of a Multicenter Observational Study.

INTRODUCTION: Available short-acting intrathecal anesthetic agents (chloroprocaine and prilocaine) offer an alternative to general anesthesia for short-duration surgical procedures, especially ambulatory surgeries. Factors determining the choice of anesthesia for short-duration procedures have not been previously identified. METHODS: This observational, prospective, multicenter, cohort study was conducted between July 2015 and July 2016, in 33 private or public hospitals performing ambulatory surgery. The primary objective was to determine the factors influencing the choice of anesthetic technique (spinal or general anesthesia). Secondary outcomes included efficacy of the anesthesia, time to hospital discharge, and patient satisfaction. RESULTS: Among 592 patients enrolled, 309 received spinal anesthesia and 283 underwent general anesthesia. In both study arms, the most frequently performed surgical procedures were orthopedic and urologic (43.3% and 30.7%, respectively); 66.1% of patients were free to choose their type of anesthesia, 21.8% chose one of the techniques because they were afraid of the other, 16.8% based their choice on the expected ease of recovery, 19.2% considered their degree of anxiety/stress, and 16.9% chose the technique on the basis of its efficacy. The median times to micturition and to unassisted ambulation were significantly shorter in the general anesthesia arm compared with the spinal anesthesia arm (225.5 [98; 560] min vs. 259.0 [109; 789] min; p = 0.0011 and 215.0 [30; 545] min vs. 240.0 [40; 1420]; p = 0.0115, respectively). The median time to hospital discharge was equivalent in both study arms. In the spinal anesthesia arm, patients who received chloroprocaine and prilocaine recovered faster than patients who received bupivacaine. The time to ambulation and the time to hospital discharge were shorter (p < 0.001). The overall success rate of spinal anesthesia was 91.6%, and no significant difference was observed between chloroprocaine, prilocaine, and bupivacaine. The patients' global satisfaction with anesthesia and surgery was over 90% in both study arms. CONCLUSIONS: Patient's choice, patient fear of the alternative technique, patient stress/anxiety, the expected ease of recovery, and the efficacy of the technique were identified as the main factors influencing patient choice of short-acting local anesthesia or general anesthesia. Spinal anesthesia with short-acting local anesthetics was preferred to general anesthesia in ambulatory surgeries and was associated with a high degree of patient satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02529501. Registered on June 23, 2015. Date of enrollment of the first participant July 21, 2015.