SARS-CoV-2 infection in 3,241 School working staffs: Impact of SARS CoV-2 variants of concern [Wild, B.1.1.7 and Omicron].

BACKGROUND: There is debate over whether physical attendance at school affects the spread of the SARS-CoV-2 pandemic. METHODS: A cohort of personnel from several schools in Qatar provided nasopharyngeal swabs (NPS) for SARS-CoV-2 RT-PCR and rapid antigen testing. Each of them was monitored for infection until February 2022. RESULTS: In total, 3,241 employees gave samples for analysis. Prior to the start of the 2020-2021 academic year (Group I), 3.49% of samples tested positive for SARS-CoV-2. Most of the positive PCR results were from male, senior, non-teaching staff members. Only 110 (3.39%) employees who had enrolled in face-to-face instruction before the B.1.1.7 variant's emergence (Group II), 238 (7.34%) after the B.1.1.7 variant's emergence (Group III), and 410 (12.65%) after the introduction of the Omicron variant (Group IV) had reported infection by PCR test. Most people who tested positive by PCR after enrolling in school were young, female teachers. In the Cox Proportional-Hazards Model, exposure to a confirmed case, the presence of symptoms in the two weeks prior to exposure in all groups-young age in Groups II and III, male gender in Groups I and IV, shared housing in Group III, and the presence of comorbidities in Groups II and III independently predicted SARS-CoV-2 infection in school staff. CONCLUSION: Critical information about the risk of SARS-CoV-2 infection in school workers during the whole pandemic is provided by our study. School operations in Qatar were made safer through initial and ongoing screenings, as well as widespread vaccination of school personnel.

Genetic Factors Associated with Morphine Consumption in Women Undergoing Laparoscopic Cholecystectomy: A Prospective Cohort Study.

Introduction: Morphine has been a crucial analgesic agent used perioperatively in various surgical procedures. Genetic factors can lead to morphine dose requirement interpatient variability. Our objective was to determine the contribution of genetic polymorphisms in human µ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 to the variation of the perioperative morphine consumption in women undergoing laparoscopic cholecystectomy. Methods: This is a prospective cohort study that included 102 adult Arab females undergoing laparoscopic cholecystectomy. The exposures were carrying the genetic variants of OPRM1, ABCB1 and rs2952768. Our primary outcome was total morphine or morphine equivalent dose required perioperatively. The secondary outcomes were pain score during the first 24 hours and adverse drug reactions. A standardized, general anaesthesia was used for all subjects. In addition to the genetic factors, we also investigated non-genetic factors influencing post-operative pain sensitivity and morphine consumption. Results: Both (rs1799971, A>G) in OPRM1 and (rs2952768, T>C) showed statistically significant association with intra-operative total morphine dose requirements. Patients carrying the "G" allele in OPRM1 had a significantly higher total morphine mean rank dose compared to the AA genotype [62.9 vs 47.1, p=0.008]. Furthermore, patients homozygous for the rs2952768 (T>C) minor allele "CC" had a higher mean rank compared to the other genotypes [72.7 vs 50.1, p=0.046]. Conclusion: OPRM1 (rs1799971) and rs2952768 are associated with variation of intra-operative morphine consumption in laparoscopic cholecystectomy. Clinical Trial Identifier: This study was registered at ClinicalTrials.gov, NCT04621864. https://clinicaltrials.gov/ct2/show/NCT04621864.

Optimizing risk factors influence Intensive Care stay after Hyperthermic Intraperitoneal Chemotherapy? An observational cohort study.

BACKGROUND: It may be necessary to admit patients receiving Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to the intensive care unit (ICU). They were required to evaluate the length of ICU stay (LOS) following HIPEC, as well as their survival rates and risk factors that influence LOS. METHODS: 74 HIPEC patients were observed after being admitted to the ICU. Their assignments were made based on their LOS at the ICU. Short stay group, patients who stayed in the ICU for three days or less (S-group) and patients who stayed for three days or longer (L-group). RESULTS: Survival rates for both groups were comparable. After HIPEC, they exhibited intraoperative hypotension (P = 0.015), hyopthermia (P = 0.014), and hyperglycemia (P = 0.010). Additionally, patients in group L underwent longer surgeries (P = 0.013), lost more blood (P = 0.043), and required more transfusions (P = 0.001). Subjects in group-L had higher SOFA, fentanyl, and vasopressor requirements (all P 0.001), higher ALT and AST levels, disrupted K, lower Na, and higher INR levels (all P 0.001), as well as a higher APACHE II score (P = 0.007). Preoperative BUN had an independent risk factor for LOS of 0.861; (95% CI), (0.742- 0.999); P = 0.048; and crystalloid transfusion had an independent risk factor of 1.000; (95% CI), (0.999- 1.000); P = 0.003. CONCLUSIONS: Transfusions of crystalloids and BUN were independent risk factors for extended LOS. ICU LOS had no impact on survival. All measures should be taken to control hemostasis in vulnerable HIPEC participants.

Seroprevalence of SARS-CoV-2 Infection Among Working Women and Impact of Workplace Restrictions.

Objective: To determine the prevalence of SARS-CoV-2 virus infection among female workers who were restricted to working from home compared with those who continued to attend in-person work. Methods: As part of national surveillance program, serum samples for SARS-CoV-2 antibody testing and nasopharyngeal swabs for SARS-CoV-2 PCR were obtained on 1636 female school staff and salon/spa workers who were restricted to work remotely (restricted group) and 1190 female health-care workers who continued in-person work (unrestricted group). Results: Seropositivity rate was 5.1% among the restricted and 22.7% among the unrestricted group (P < 0.0001). Presence of symptoms at baseline (adjusted odds ratio [aOR], 2.88; 95% CI 2.09-3.97), contact with a confirmed case (aOR 2.34; 95% CI 1.37-3.98), and unrestricted work type (aOR 4.71; 95% CI 3.24-6.86) were associated with a higher risk of infection, while increasing age was associated with a lower risk of infection. Conclusion: Prevalence of SARS-CoV-2 infection as determined by seropositivity was higher among women who were not subject to workplace restrictions.

SARS-CoV-2 PCR and antibody positivity among school staff at the beginning and end of the first school term.

BACKGROUND: There is controversy regarding the role of in-person attendance in schools and transmission of the SARS-CoV-2 pandemic. Several studies have demonstrated no increase in transmission, while some have reported large outbreaks with in-person attendance. We determined the incidence and risk factors for SARS-CoV-2 infection among school staff after one school term. METHODS: Nasopharyngeal swabs (NPS) for SARS-CoV-2 RT-PCR and blood for SARS-CoV-2 antibody testing were obtained from staff at a large international school in Qatar at the beginning of the 2020-2021 school year and repeated at the end of the first term. RESULTS: A total of 376 staff provided samples for testing. At the beginning of the 2020-2021 school year, the PCR positivity for SARS-CoV-2 was 13%, while seropositivity was 30.1%. A majority of those who tested positive either by PCR or serologically, were non-teaching staff. At the end of the first school term four months later, only 3.5% of the initially antibody-negative staff had seroconverted. In multivariable logistic regression analysis, male gender (OR 11.48, 95%CI 4.77-27.64), non-teaching job category (OR 3.09, 95%CI 1.10-8.64), contact with a confirmed case (OR 20.81, 95%CI 2.90-149.18), and presence of symptoms in the preceding 2 weeks [1-2 symptoms OR 4.82, 95%CI 1.79-12.94); ≥3 symptoms OR 42.30, 95%CI 3.76-476.43) independently predicted SARS-CoV-2 infection in school staff before school starting. CONCLUSION: Male gender, non-teaching job, presence of symptoms, and exposure to a confirmed case were associated with higher risk of infection. These data can help policymakers in determining the optimal strategy for school reopening.

Risk factors for breakthrough SARS-CoV-2 infection in vaccinated healthcare workers.

BACKGROUND AND OBJECTIVE: The risk factors for breakthrough infections among healthcare workers (HCW) after completion of a full course of vaccination are poorly understood. Our objective was to determine the risk factors for breakthrough SARS-CoV-2 infection among HCWs at a national healthcare system in Qatar. METHODS: We identified all HCWs at Hamad Medical Corporation in Qatar between December 20, 2020 and May 18, 2021 with confirmed SARS-CoV-2 RT-PCR infection >14 days after the second vaccine dose. For each case thus identified, we identified one control with a negative test after December 20, 2020, matched on age, sex, nationality, job family and date of SARS-CoV-2 testing. We excluded those with a prior positive test and temporary workers. We used Cox regression analysis to determine factors associated with breakthrough infection. RESULTS: Among 22,247 fully vaccinated HCW, we identified 164 HCW who had breakthrough infection and matched them to 164 controls to determine the factors associated with SARS-CoV-2 breakthrough infection. In the breakthrough infection group the nursing and midwifery job family constituted the largest group, spouse was identified as the most common positive contact followed by a patient. Exposure to a confirmed case, presence of symptoms and all other job families except Allied Health Professionals when compared with nursing and Midwifery staff independently predicted infection. CONCLUSION: Presence of symptoms and contact with a confirmed case are major risk factors for breakthrough SARS-CoV-2 infection after vaccination, and these groups should be prioritized for screening even after full vaccination.

Short term survival of critically ill COVID-19 Egyptian patients on assisted ventilation treated by either Dexamethasone or Tocilizumab.

Tocilizumab (TCZ) and Dexamethasone are used for the treatment of critically ill COVID-19 patients. We compared the short-term survival of critically ill COVID-19 patients treated with either TCZ or Dexamethasone. 109 critically ill COVID-19 patients randomly assigned to either TCZ therapy (46 patients) or pulse Dexamethasone therapy (63 patients). Age, sex, neutrophil/ lymphocyte ratio, D-dimer, ferritin level, and CT chest pattern were comparable between groups. Kaplan-Meier survival analysis showed better survival in Dexamethasone group compared with TCZ (P = 0.002), patients didn't need vasopressor at admission (P < 0.0001), patients on non-invasive ventilation compared to patients on mechanical ventilation (P<0.0001 ), and in patients with ground glass pattern in CT chest (P<0.0001 ) compared with those who have consolidation. Cox regression analysis showed that, TCZ therapy (HR = 2.162, 95% CI, 1.144-4.087, P <0.0001) compared with Dexamethasone group, higher neutrophil/Lymphocyte ratio (HR = 2.40, CI, 1.351-4.185, P = 0.003), lower PaO2/FiO2, 2 days after treatment, (HR = 1.147, 95% CI, 1.002-1.624, P < 0.0001) independently predicted higher probability of mortality. Dexamethasone showed better survival in severe COVID-19 compared to TCZ. Considering the risk factors mentioned here is crucial when dealing with severe COVID-19 cases.Clinical trial registration No clinicalTrials.gov: Nal protocol approved by Hospital Authorities, for data collection and for participation in CT04519385 (19/08/2020).

SARS-CoV-2 infection in mortuary and cemetery workers.

BACKGROUND: Mortuary and cemetery workers may be exposed to the bodies of people with SARS-CoV-2 infection; however, prevalence of infection among these groups is unknown. METHODS: Nasopharyngeal swabs (NPS) for RT-PCR and serologic testing for SARS-CoV-2 were performed on mortuary and cemetery workers in Qatar. Data on specific job duties, living conditions, contact history, and clinical course were gathered. Environmental sampling was carried out to explore any association with infection. Logistic regression analysis was used to determine the factors associated with infection. RESULTS: Forty-seven mortuary workers provided an NPS and seven (14.9%) were PCR positive; 32 provided a blood sample and eight (25%) were antibody positive, six (75%) who were seropositive were also PCR positive. Among the 81 cemetery workers, 76 provided an NPS and five (6.6%) were PCR positive; 64 provided a blood sample and 22 (34.4%) were antibody positive, three (13.6%) who were seropositive were also PCR positive. Three (22.2%) and 20 (83.3%) of the infected mortuary and cemetery workers were asymptomatic, respectively. Age <30 years (OR 4.9, 95% CI 1.7-14.6), community exposure with a known case (OR 4.7, 95% CI 1.7-13.3), and presence of symptoms in the preceding 2 weeks (OR 9.0, 95% CI 1.9-42.0) were independently associated with an increased risk of infection (PCR or antibody positive). Of the 46 environmental and surface samples, all were negative or had a Ct value of >35. CONCLUSION: A substantial proportion of mortuary and cemetery workers had evidence of SARS-CoV-2 infection, which was incidentally detected upon serologic testing. These data are most consistent with community acquisition rather than occupational acquisition.

Oral Spirulina Platensis Attenuates Hyperglycemia and Exhibits Antinociceptive Effect in Streptozotocin-Induced Diabetic Neuropathy Rat Model.

INTRODUCTION: Diabetic neuropathy is a common consequence of diabetes. Hyperalgesia is one of the main symptoms of diabetic neuropathy. In response to noxious stimuli, streptozotocin (STZ)-induced diabetic rats show exaggerated hyperalgesic behavior, while Spirulina platensis has anti-inflammatory, antioxidant, and insulin-like effects. To assess the antinociceptive effect of oral Spirulina platensis (SP) powder on formalin-induced nociceptive responses in STZ-induced diabetic rats. METHODS: Sixty mature male albino rats were randomly allocated into six equal groups (10 in each group). Group 1 (control non-diabetic group) received 0.9% saline; group 2 was given oral pure SP powder-treated as a non-diabetic control group, group 3 was sodium salicylate-treated rats and used as a positive non-diabetic control group, group 4 managed as vehicle-treated diabetic rats, group 5 considered as SP-treated-diabetic group, and sodium salicylate-treated-diabetic rats used as a diabetic positive control group (group 6). STZ-diabetic rats were orally given SP in a dose of 500 mg kg/day for 1 month. The formalin test was implemented in two phases: the early phase in the first 10-min post-formalin injection, and the late phase was considered in the 15-60 min post-formalin injection time interval. RESULTS: Pain scores were increased in the diabetic groups during both phases of the experiment. Blood glucose was significantly reduced in diabetic rats that received oral SP, P < 0.01. Besides, SP-treated rats had lower pain scores during both phases of the experiment than untreated diabetic ones. However, in the sodium salicylate group, the pain score was reduced only during the second phase. An exaggerated nociceptive response occurred in diabetic rats after the formalin test. A significant antinociceptive effect appeared in SP-treated control and diabetic rats. DISCUSSION: The findings suggest that oral Spirulina platensis could have a potential therapeutic role for managing induced painful diabetic neuropathy in rats.

Decreased Analgesic Requirements in Super Morbidly Versus Morbidly Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Scarce data exists about analgesic requirements in super morbidly obese (SMO) patients who underwent sleeve gastrectomy. We attempted to investigate analgesic requirements for SMO, when compared with morbidly obese (MO) individuals who underwent sleeve gastrectomy and its impact on postoperative outcome. METHODS: We studied 279 consecutive patients (183 MO, 96 SMO) who underwent bariatric surgery. Data analysis included perioperative anaesthetic management, analgesic consumptions, opioids side effects, and ICU admission. RESULTS: The SMO group showed higher patients with asthma, epilepsy, obstructive sleep apnoea (OSA), and ASA III percentages (P = 0.014, P = 0.016, P Ë‚ 0.001, and P Ë‚ 0.001, respectively). There were no significant differences in the total morphine consumption intraoperatively, or after 24 h. However, reduced consumption of intraoperative fentanyl and morphine in SMO when calculated per total body weight (TBW) (P = 0.004 and P = 0.001, respectively). At PACU, tramadol consumption per TBW and lean body mass (LBM) were significantly reduced in SMO (P = 0.001 and P = 0.025, respectively). Paracetamol consumption was significantly reduced in the SMO group (P = 0.04). They showed higher comorbidities (P Ë‚ 0.001), longer anaesthesia time (P = 0.033), and greater ICU admissions (P Ë‚ 0.001). Vomiting was higher in the MO group (P = 0.004). Both groups showed comparable pain scores (P = 0.558) and PACU stay time (P = 0.060). CONCLUSIONS: Super morbidly obese patients required fewer opioids and analgesics perioperatively. They exhibited higher comorbidities with greater anaesthesia time and ICU admissions. PACU stay time and pain scores were comparable.

Perioperative management and postoperative outcome of patients undergoing cytoreduction surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND AIMS: The existence of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a multidisciplinary approach for peritoneal cancer gains acceptance in many countries including Saudi Arabia. The aim of our study is to describe the perioperative management of patients who received CRS/HIPEC and to report their outcomes and complications at our tertiary centre. METHODS: The preoperative characteristics, surgical variables, perioperative management, postoperative course and outcomes of 38 CRS/HIPEC patients were prospectively collected and analysed. RESULTS: The mean age of our patients was 52 years, and 23 (60.5%) of them were females. The overall postoperative mortality was 42.1%. Univariate analyses of risk factors for deaths after HIPEC demonstrated that low preoperative (haemoglobin, potassium, calcium and albumin), high (tumour marker (CA19.9), intraoperative transfusion of human plasma protein (HPP), colloids, postoperative activated partial thromboplastin time and bacterial infections were potential risk factors for patient's mortality. Multivariate analysis of those variables demonstrated that low preoperative calcium [hazard ratio (HR) = 0.116; 95% confidence interval (CI) = 0.033-0.407; P = 0.001], high intraoperative HPP transfusion (HR = 1.004; 95% CI = 1.001-1.003; P = 0.012) and presence of postoperative bacterial infection (HR = 5.987; 95% CI = 1.009-35.54; P = 0.049) were independent predictors of patient's death. Seventy morbidities happened after HIPEC; only bacterial infection independently predicted postoperative mortality. CONCLUSION: To improve postoperative outcome of CRS/HIPEC, optimisation of transfusion, temperature, electrolytes and using broader-spectrum prophylaxis to manage postoperative infections should be warranted.

Analysis of Bacterial and Fungal Infections after Cytoreduction Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Observational Single-Centre Study.

INTRODUCTION: While hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreduction surgery (CRS) has been shown to improve patient survival and disease-free progression in peritoneal carcinoma (PC) patients, the procedure relates to a high postoperative infection rate. Herein, we report the bacterial and fungal infections after CRS and HIPEC from a single institution in Saudi Arabia. PATIENTS AND METHODS: A prospective observational study was conducted on 38 patients with PC selected for CRS/HIPEC procedure between 2012 and 2015 in our centre. RESULTS: Postoperative bacterial and fungal infection within 100 days was 42.2%, bacterial infection was reported always, and fungal infection was reported in 5 (13.2%) cases. Infections from the surgical site were considered the most common infection site. Multidrug-resistant extended-spectrum beta-lactamase (ESBL) Escherichia coli was the most frequent isolate, followed by multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Lower preoperative albumin and a prolonged preoperative activated partial thromboplastin time (APTT) are associated with postoperative infections, while a prolonged preoperative hospital stay (hazard ratio (HR) = 1.064; confidence interval (CI) = 1.002-1.112; P=0.042) and more intraoperative blood loss (>10%) (HR = 3.919; 95% CI = 1.024-14.995; P=0.046) were independent risk factors for postoperative infections. Three cases died during the follow-up period; all were due to infection. DISCUSSION: The infection rate in our centre compared to previous studies of comparable patients was matching. Effective management of postoperative infections should be considered, and identified risk factors in this study can help to focus on effective prevention and treatment strategies.

Dexmedetomidine and propofol sedation requirements in an autistic rat model.

BACKGROUND: Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms. METHODS: Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABAA) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed. RESULTS: Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABAA receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats. CONCLUSIONS: This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using GABAA and glutamate receptor gene expression highlight possible underlying mechanisms.

Intrathecal Morphine Improves Hemodynamic Parameters and Analgesia in Patients Undergoing Aortic Valve Replacement Surgery: A Prospective, Double-Blind, Randomized Trial.

BACKGROUND: Intrathecal morphine (ITM) has been used in hopes of providing good postoperative analgesia in cardiac surgery. Little is known about its use in isolated aortic valve replacement surgery. OBJECTIVES: To evaluate the effects of 7 µ/kg ITM administration in aortic valve replacement in regards to hemodynamics, pain score, and postoperative complications when compared to general anesthesia alone. STUDY DESIGN: A randomized, double-blind trial. SETTING: Academic medical center. METHODS: Forty-four patients, who underwent aortic valve replacement, were randomly assigned to receive ITM, before the induction of general anesthesia (ITM group, n = 22) or no intrathecal injection i.e., general anesthesia alone (control group, n = 22). Induction of anesthesia was done with fentanyl, propofol, and isoflurane. Pain scores, determined by visual analog scale (VAS), were recorded immediately after extubation, at the first, sixth, twelfth, eighteenth, and twenty-fourth hour after extubation. Hemodynamics, heart rate, mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, and cardiac index were recorded intra-operatively and up to 24 hours post-operatively. RESULTS: VAS scores were lower in the ITM group at each measured time than control group (P < 0.01). The cumulative fentanyl consumption during the first 24 hours after extubation was significantly reduced by 35% in the ITM group (951 µg /first 24 hours) as compared to the control group (1463.6 µg /first 24 hours), (P < 0.001). The mean time to first request for rescue analgesia was significantly prolonged in the ITM group (20.11 ± 4.24 hours, P < 0.001) compared with the control group (0.60 ± 0.44 hours). The mean tramadol consumption dose was significantly reduced in the ITM group (279.33 ± 61.35 mg), compared with the control group (895 ± 106.42 mg), (P < 0.001). Hemodynamic parameters exhibited a significant decrease in HR and MAP in the ITM group, but no significant difference was found in regards to CVP, PCWP, and CI. Glyceryl trinitrate consumption in the first 24 hours was significantly reduced by 43% in the ITM group (28.3 mg /first 24 hours) when compared to the control group (145.5 mg /first 24 hours), (P < 0.001). Extubation time (4.5 ± 7.5 vs. 5.3 ± 1.0 hours, P < 0.05) and intensive care unit length of stay (3.7 ± 1.0 vs. 5.6 ± 1.6 days, P < 0.01) were shorter in the ITM group. LIMITATIONS: Small sample size. CONCLUSIONS: In valvular heart disease patients undergoing aortic replacement surgery, ITM is a good adjunct to general anesthesia as a safe and effective analgesic alternative. It provides better hemodynamic control, earlier tracheal extubation, and shorter ICU stay. KEY WORDS: Intrathecal, morphine, fentanyl, analgesia, aortic, cardiac, surgery.

Utility of CD127 combined with FOXP3 for identification of operational tolerance after liver transplantation.

Loss of cell surface expression of CD127 on CD4(+)CD25(++) regulatory T-cells (Tregs) may be a useful marker to efficiently isolate Tregs. As FOXP3 was specifically used to identify Tregs, combining these two markers could give better identification for patient with operational tolerance (OT) after liver transplantation. To testify this mixed lymphocyte reaction (MLR), the function of circulating CD4(+)CD25(++)CD127(dim) cells (CD127(dim) cells) was examined in immunosuppression (IS)-free pediatric recipients after liver transplantation (LTx) (group operational tolerance: OT) (Gr-tol n=25) compared to recipients who could not stop IS due to clinically overt rejection (group intolerance) (Gr-intol n=18), recipients who were weaning IS (Gr-weaning n=11) and age-matched healthy volunteers (Gr-vol n=11). In addition, the frequencies of CD127(dim) cells vs CD4(+)CD25(++)CD127(dim)FOXP3(+) (CD127(dim)FOXP3(+)) cells were compared in these four groups by FACS analyses. Our results showed that The proliferation of CD4 cells to donor antigens was reduced compared to third-party antigens only in Gr-tol (P=0.022) but not in other groups (P=NS). Depletion of CD127(dim) cells resulted in a donor antigen-specific abrogation of this MLR hyporesponsiveness in Gr-tol (P<0.001) but not other groups (P=NS). This implied that CD127 efficiently isolated donor antigen-specific Tregs. The frequencies of CD127(dim) cells were significantly lower in Gr-intol (5.2%±1.9%) compared to those in Gr-tol (7.8%±1.8%) (P<0.001) as were the frequencies of CD127(dim) FOXP3(+) cells (Gr-tol: 5.4%±1.7% vs Gr-intol: 2.9%±1.0%, P<0.001). Of interest, there were fewer CD127(dim)FOXP3(+) cells in Gr-intol (2.9%±1%) than in Gr-weaning (5.1%±1.8%) (P=0.002), but no difference in CD127(dim) cells (Gr-intol: 5.2%±1.9% vs Gr-weaning: 6.7%±2.0%) (NS). Thus, combining FOXP3 with CD127 for phenotype analysis demonstrated an unequivocal difference between Gr-intol and Gr-weaning that was not detected by CD127 alone. In conclusion CD127 was a useful surface marker to isolate donor-antigen-specific-Tregs in OT after LTx. The additive effect of its combination with FOXP3 is important in phenotypical Treg analyses of OT patients.

Outcome of Hepatitis B Virus Infection After Living-Donor Liver Transplant: A Single-center Experience Over 20 Years.

OBJECTIVES: Despite living-donor liver transplant being a life-saving therapy for patients with hepatitis B virus with or without hepatocellular carcinoma, outcomes for patients with these diseases are worse. Hepatitis B virus recurrence or relapse of hepatocellular carcinoma can result in subsequent graft loss or patient death. In this study, we discuss the postoperative outcomes of patients with hepatitis B virus infection after living-donor liver transplant. MATERIALS AND METHODS: We retrospectively analyzed 125 patients with hepatitis B virus-related end-stage liver disease, comparing results with 1228 control patients who had other pathologies, including hepatitis C virus, combined hepatitis B virus and hepatitis C virus, and neither virus. RESULTS: Survival rates of patients with hepatitis B virus did not differ from the control groups (P > .05). Patients with concurrent hepatitis B virus and hepatocellular carcinoma were significantly older (P < .0001), had critical status (P < .0001), had chronic underlying pathology (P = .001), lower graft-to-recipient body weight ratio (P = .047), needed more intraoperative plasma transfusion, and experienced more rejection episodes than those without hepatocellular carcinoma. Of interest, in 5 patients who had hepatitis B virus recurrence after living-donor liver transplant, Model for End-Stage Liver Disease score was significantly higher than those who did not have recurrence (P = .015). In addition, 2 patients had hepatocellular carcinoma recurrence in the form of peritoneal metastasis, with both patients having high preoperative alpha-fetoprotein levels. CONCLUSIONS: Our study provides details on long-term outcomes of patients with hepatitis B virus infection who had undergone living-donor liver transplant. Based on our results, we suggest that prolonged antiviral prophylactic therapy in the form of hepatitis B immunoglobulin with either lamivudine or entecavir be considered for patients who associated with risk factors to prevent postoperative recurrence.

Contrast patterns of Cytomegalovirus and Epstein-Barr virus infection in pediatric living-donor liver transplant recipients.

OBJECTIVES: Cytomegalovirus and Epstein-Barr virus remain leading causes of morbidity and mortality in the living-donor liver transplant population, particularly in pediatric patients. Herein we compare the incidence, timing, and risk factors for infection in this group. MATERIALS AND METHODS: We performed a retrospective study of 344 consecutive pediatric patients 193 women (56.1%) who received living-donor liver transplants at Kyoto University Hospital. Patients were followed-up for maximum 7.1 ± 3.6 years (range, 0.02-13.2 y) after surgery. RESULTS: The mean age at the time of transplant was 3.95 ± 4.75 years (median, 1.38 y; range, 0.07-17.87 y). A total of 156 patients (45.2%) developed viral infections. Of those patients, 91 (26.5%) developed cytomegalovirus infection, and 93 (27%) developed Epstein-Barr virus. Cytomegalovirus developed at 39.3 ± 34.6 days, while Epstein-Barr virus developed 3.99 ± 3.67 years after transplant. Frequent rejection attacks (hazard ratio [HR],1.58; 95% confidence interval [CI]: 0.14-2.18; P = .006) were an independent predictor for postoperative cytomegalovirus infection, while preoperative cytomegalovirus seropositive results (HR, 1.76; 95% CI: 1.03-2.18; P = .038), short cold ischemia time (HR, 1.0; 95% CI: 0.99-1.0; P = .02), larger graft (HR, 1.3; 95% CI: 1.00-1.73; P = .047), and new cases compared to old cases (HR, 2.27; 95% CI: 1.14-4.52; P = .019) were independent predictors for postoperative Epstein-Barr virus infection. CONCLUSIONS: Extended surveillance of cytomegalovirus and Epstein-Barr virus DNAemia is recommended for pediatric patients receiving living-donor liver transplants, particularly infants who are at high risk, and especially those exposed to frequent attacks of rejection and those that receive larger grafts.

Outcome of critically-ill children after living-donor liver transplant.

OBJECTIVES: The outcome of children who had living-donor liver transplant was analyzed according to their status before transplant, and we analyzed the outcome of critically ill patients. MATERIALS AND METHODS: This was a retrospective analysis of children who received primary living-donor liver transplant at Kyoto University Hospital. According to the criteria of the United Network for Organ Sharing, we divided patients into 3 groups: Group A patients had been admitted to the intensive care unit before living-donor liver transplant; Group B patients were hospitalized but did not require intensive care unit stay; and Group C patients were living at home and underwent elective transplant. RESULTS: A total 685 patients met inclusion criteria. Children in Group A were younger than Group B and received liver grafts from younger donors than Group B and C. Group A patients had marked impairment in liver and renal function and coagulation profile and needed higher volumes of fresh frozen plasma transfusions. Group A patients had significantly worse outcomes and early patient death than the other group; Group A patient survival was 68.3%, 63.2%, 60.1%, and 56.1% at 1, 5, 10, and 15 years after living-donor liver transplant (P < .0001). Group A had worse graft survival than other groups (P < .0001), and Group A graft survival was 68.3%, 65.9%, 54.1%, and 49.9% at 1, 5, 10, and 15 years. Low gamma-glutamyl transpeptidase was an independent risk factor for patient death in Group A (hazard ratio, 1.004; 95% confidence interval, 1.0-1.007) (P < .05). Group A patients had a higher rate of multidrug-resistant hospital-acquired infections. CONCLUSIONS: Children who were admitted to the intensive care unit prior to living-donor liver transplant had marked impairment of pretransplant laboratory parameters and worse outcome than other groups.

Successful anesthetic management in a child after traumatic rupture of left main bronchus by a single-lumen cuffed-endotracheal tube.

Tracheobronchial injury (TBI) may lead to catastrophe if remains undetected or managed improperly. The incidence of TBI is less in children as compared with adults due to their pliable chest wall. Its clinical manifestations include persistent pneumothorax, cervical subcutaneous emphysema, pneumomediastinum, cyanosis, and respiratory insufficiency. The recommended airway management is to intubate the healthy bronchus with a single-lumen or double-lumen endotracheal tube (ET) and bypassing the injured side. We report successful anesthetic management of traumatic rupture of the left main bronchus in a child by using a single-lumen cuffed-ET. Many factors affect the outcome of such injuries and include the extent of the lesion, the resulting pulmonary status, the adequacy of surgical reconstruction. More severe injury may require lobectomy or pneumonectomy. Early diagnosis and proper management result in good functional outcome.