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Heba Ahmed Osman,1 Hanaa Nafady-Hego,2 Khalid Ali Nasif,3,4 Heba A Ahmed,5 Ekram Abdel-Rahman Mahmoud,6 Noher Mohamad Abass,7 Amal Rayan,8 Marwa Ahmed Mahmoud,9 Asmaa Nafady10 1Department of Tropical Medicine and Gastroenterology, Qena Faculty of Medicine, South Valley University, Qena, Egypt; 2Department of Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia; 4Department of Biochemistry, Faculty of Medicine, Minia University, Minia, Egypt; 5Department of Clinical and Chemical Pathology Sohag Faculty of Medicine Sohag University, Sohag, Egypt; 6Department of Medical Microbiology & Immunology, Faculty of Medicine, Sohag University, Sohag, Egypt; 7Department of Internal Medicine, Faculty of Medicine, Sohag University, Sohag, Egypt; 8Department of Clinical Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt; 9Department of Medical Physiology, Faculty of Medicine, Sohag University, Sohag, Egypt; 10Department of Clinical and Chemical Pathology, Qena Faculty of Medicine, South Valley University, Qena, EgyptCorrespondence: Heba Ahmed Osman, Tropical Medicine and Gastroenterology, Qena Faculty of Medicine, South Valley University, Qena, Egypt, Email drheba.saleh@med.svu.edu.eg; hebaahmed198098@yahoo.comIntroduction: HCC is frequently diagnosed late, when only palliative treatment is available. So, we try to use different immunological markers to identify early HCC in patients with unremarkable raised AFP.Methods: This study was conducted on 112 participants divided into two equal groups: Group I, 56 patients with liver cirrhosis and different stages of HCC; Group II, 56 patients with liver cirrhosis. The diagnosis of HCC was based on AASLD guidelines. TNM and BCLC classification systems are used for staging of HCC.Results: A significant reduction in the median percentage of lymphocyte subset (CD3+, CD4+, CD8+, CD19+) and NK cell percentage (CD56+) has been detected in HCC patients (all P < 0.001). In the HCC group the median monocyte subpopulations CD14+ CD16− Classical, CD14++ CD16+ Intermediate, and CD14−+ CD16++ Non-Classical were 11.7, 4.0, and 3.5, respectively, with marked reduction compared with liver cirrhosis group (all P < 0.001). Patients with advanced stages (BCLC C and D) were more likely to have significantly higher median CD33+ than patients with early stages (BCLC A and B) (P = 0.05); also, the median levels of HLA DR+ lymphocytes % in the HCC case group were 21.8 in patients with advanced disease (BCLC C and D) and 13.1 in patients with early stages of the disease (P = 0.04). Patients with late stage (TNM III) were more likely to have significantly higher median CD14+ CD16− Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16− than patients with early stages (TNM I and II).Conclusion: Patients with HCC with unremarkable raised AFP showed marked reduction in lymphocytes, natural killer cells, and all monocyte subpopulations. In addition, patients with advanced HCC showed increased CD33+ and HLA DR+ lymphocytes %, CD14+ CD16− Classical monocyte subset, CD36+ HLA DR+, and CD36+ CD16− compared with patients with early stages of HCC.Keywords: monocyte subpopulation, lymphocyte subset, hepatocellular carcinoma, Barcelona clinic liver cancer, tumor (T), nodes (N), metastases (M)

Moza Alishaq,1 Hanaa Nafady-Hego,2 Andrew Jeremijenko,3 Jameela Ali Al Ajmi,4 Mohamed Elgendy,5 Naser Ali Asad Al Ansari,4 Hamed Elgendy,4,6 Abdul-Badi Abou-Samra,1,3 Adeel A Butt4,7,8 1Department of Quality and Clinical Transformation, Hamad Medical Corporation, Doha, Qatar; 2Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Medicine, Hamad Medical Corporation, Doha, Qatar; 4Hamad Medical Corporation, Doha, Qatar; 5Faculty of Medicine, Universiti Sains of Malaysia, Kelantan, Malaysia; 6Anesthesia Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 7Departments of Medicine and Population Health Sciences, Weill Cornell Medical College, New York, NY, USA; 8Departments of Medicine and Population Health Sciences, Weill Cornell Medical College, Doha, QatarCorrespondence: Adeel A Butt, Department of Medicine, Hamad Medical Corporation, PO Box 3050, Doha, Qatar, Email aabutt@hamad.qaObjective: 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.Keywords: SARS-CoV-2, COVID-19, work-place restrictions, women, infections, Qatar

Objectives: Mass gathering events may facilitate the transmission of foodborne diseases. We determined the presentations and causative organisms of gastrointestinal illness among the attendees of the Fédération Internationale de Football Association Football World Cup 2022 (FIFA 2022)., Methods: The study was conducted at Hamad Medical Corporation in Qatar, which served as the national reference laboratory for all microbiology testing. We retrieved all stool testing data from the attendees of FIFA 2022 from October 1 to December 31, 2022. Stool microscopy for ova and parasite and cultures were performed on all samples. Polymerase chain reaction testing was performed for cases of suspected foodborne outbreaks or when a rapid result was required for public health response., Results: Among 2179 samples tested, one or more organisms were identified in 424 cases. The most common reasons for testing were acute diarrhea/gastroenteritis (51.4%), abdominal pain (11.5%), screening/surveillance of contacts (10.6%), and fever (7.6%). Bacteria were identified in 92.5% (Salmonella spp. 40%, Escherichia coli 25.7%, and Shigella spp. 8.8%), viruses in 7.8%, and parasites in 2.8% of the samples., Conclusions: The number of individuals who underwent stool testing during the FIFA 2022 was low. The yield of stool testing was higher for those with acute diarrhea/gastroenteritis and fever but not for those with abdominal pain or for surveillance/screening., Competing Interests: Dr. Butt has received investigator-initiated grant funding from Gilead Sciences and Merck and Company (to the institution), which is unrelated to the work presented here. The remaining authors declare no financial conflict of interest regarding the content of this article., (© 2024 The Author(s).)

Health care workers (HCWs) may be at a variable risk of SARS-CoV2 infection. Regardless of their involvement in providing direct clinical treatment, most of the prior research had included all HCWs. Understanding infection rates, risk factors and outcomes among different subgroups of HCWs is crucial. From February 28, 2020 to January 1, 2022, we conducted a retrospective analysis encompassing all full-time non-clinical staff (NCS) subcontracted with Hamad Medical Corporation (HMC) facilities. To determine current or previous SARS-CoV2 infection, all personnel underwent RT-PCR and/or serology testing. To identify the demographic factors linked to the risk of infection, we utilized Cox-Hazard regression analysis. Herein 3158/6231 (50.7%) subcontracted NCS tested positive for SARS-CoV-2 by RT-PCR or serology during the research period. The median age was 30 years (IQR 25,35), 69.8% of the population were males, 82.4% were from South Asia, 86.6% did not have any concomitant conditions. 6032 (96.8%) of the population lived in shared housing, while 4749 (76.2%) had low to median levels of education. While infection (PCR positive with or without seropositive results) was independently predicted by male gender, working in the catering, laundry, and security sectors and being intermediate (7-12 years of education), lower (0-6 years of education), higher (exposure to confirmed case), and having symptoms. Male gender, working in the security sectors and being intermediate (7-12 years of education) were independently associated with accidently detected cases (PCR negative and seropositive). 299 (4.8%) required hospitalization, of them 3 cases were severe pneumonia and one required ICU admission without mechanical ventilation, with no deaths reported. In conclusion Infection rates among NCS are high. The majority are asymptomatic and may contribute to ongoing illness spread in the public or in healthcare facilities. During a pandemic, routine screening of this population is crucial and may aid in containing the spread of infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Inc.)

Background: We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar., Methods: We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality., Results: Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had ≥ 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P = 0.002), and longer hospital length of stay (63 vs. 43 days; P = 0.003), and higher 30-day mortality (38% vs. 14%; P<0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09-10.17)., Conclusion: Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation should be especially monitored for development of ICAD., Competing Interests: Dr. Butt has received investigator-initiated grant funding from Gilead Sciences and Merck and Company (to the institution, Veterans Health Foundation of Pittsburgh) which are unrelated to the work presented here. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Al Ajmi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alishaq et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Coronavirus infectious disease 2019 (COVID-19) confirmed cases are characterized by T lymphopenia. Total apoptotic and cytotoxic T-lymphocyte antigen-4 (CTLA-4) expressing cells among CD4+/CD8+ cells were analyzed in 24 COVID-19 patients (16 out-patients and 8 in-patients) and 18 healthy volunteers using flow cytometry to detect their possible role in T lymphopenia. Hospitalized patients did not show significant difference compared to non-hospitalized patients. While the percentage and absolute count of CD4+/CD8+ cells were significantly reduced in COVID-19 cases compared to healthy control (P < .05), the proportion of apoptotic and CTLA-4 expressing CD4+/CD8+ cells were significantly up-regulated in COVID-19 patients (P < .05). In addition, apoptotic and CTLA-4+/CD4+ cells were directly related to dyspnea duration, chest CT score, ferritin, and C-reactive protein and inversely correlated with platelet count in COVID-19 patients. While apoptotic and CTLA-4+/CD8+ cells were directly related to lymphocyte count in COVID-19 patients. The apoptotic and CTLA-4+ cells were directly related to each other in CD4+/CD8+ cells (P < .05). White blood cells (WBCs) (×103/L), eosinophils (ratio and count), lymphocyte ratio, neutrophil ratio, neutrophil/lymphocyte ratio, neutrophil/CD4 ratio, neutrophil/CD8 ratio, CD4+ cells ratio, and CTLA-4+ cells percentage), and CD8+ cells (ratio, count, total apoptotic cell, and CD152 + cells) were all found to be significantly altered in association with COVID-19. Total lymphopenia and depletion of CD4+/CD8+ cells are characterizing COVID-19 patients. Increased apoptosis and CTLA-4 expression in CD4+/CD8+ cells in COVID-19 and their correlations with reduced cell count and severity indicators as CRP and ferritin can be used for diagnosis and follow up of the clinical severity. Our current study proposes promising future diagnostic and therapeutic targets., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pulmonary embolism (PE) a consequence of hypercoagulability status associated with chronic obstructive pulmonary disease (COPD) and worsens its course. Recently, microRNAs (miRNAs) have been linked to PE in COPD settings. We aimed to measure expression levels of miRNAs145 and 126 in COPD patients with and without PE., Methods: Herein, miRNA (145 and 126) expression levels were measured in 250 COPD patients with PE by quan-titative real-time PCR, and their data were compared with 300 COPD patients without PE., Results: Our results showed that miRNA-145 expression was downregulated in COPD patients with PE compared to those without PE. The reverse was observed in miRNA-126 expression that was higher in COPD patients with PE than in those without PE. miRNA-145 correlated positively with FEV1/FVC and correlated negatively with D-dimer in all patients regardless of the presence of PE. In addition, miRNA-126 positively correlated with D-dimer and negatively correlated with FEV1/FVC in all studied COPD patients., Conclusions: Lower levels of miRNA-145 and higher levels of miRNA-126 associated with worse diagnosis PE in patients with COPD. Extensive studies are mandated to bring a better understanding of the role of these miRNAs in the mechanism of thrombosis in COPD patients.

Background: The role of lymphocyte subsets in the diagnosis and follow up of COVID-19 is still unclear. So, we aim to study the changes in lymphocyte subsets and HLA-DR expression in the peripheral blood of hospitalized COVID-19 patients., Methods: Lymphocyte subsets and HLA-DR expression were detected in the peripheral blood of 36 hospitalized patients of COVID-19; their data were compared to that of 36 healthy controls of comparable age and gender., Results: Total lymphocytes, the percentage of CD3 T, CD4 T and CD8 T cells significantly decreased, while that of CD 56 cells significantly increased in SARS-CoV-2 infected patients. The expression of HLA-DR is down regulated in these cells. Neutrophil/lymphocyte ratio, neutrophil/CD3 ratio, neutrophil/CD4 ratio, and neutrophil/CD8 ratio are significantly increased in patients compared with controls. The absolute count of CD3, CD4, CD8 and CD19 cells, significantly decreased in SARS-CoV-2 infected patients., Conclusions: A marked reduction in CD8+T and CD4+T count together with HLA-DR cell expression with obvious impairment in cellular immunity has been detected in patients with more severe impairment and progressive course for the disease.

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., (© 2021. The Author(s).)

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., Competing Interests: All authors declare no competing interest and have no financial disclosures relevant to this paper.

Methods: We recruited 40 cases of advanced NSCLC, stages III and IV, aged > 18-<70 years old, and eligible to receive chemotherapy with or without radiotherapy, along with 20 healthy controls of comparable age and sex; after diagnosis and staging of patients, blood samples were collected for flow cytometric detection of Mo-MDSCs., Results: Significant accumulation of Mo-MDSCs in patients compared to their controls ( p < 0.0001). Furthermore, these cells accumulated significantly in stage IV compared to stage III ( p = 0.006) and correlated negatively with overall survival ( r = -0.471, p = 0.002), lymphocyte to monocyte ratio ( r = -0.446, p = 0.004), and mean platelet volume to platelet count ratio (MPV/PC) ( r = -0.464, p = 0.003), patients with Mo-MDSCs < 13% had significantly better survival than those with Mo-MDSCs ≥ 13% ( p = 0.041)., Conclusion: Mo-MDSCs represent one of the key mechanisms in the immunosuppressive tumor microenvironment (TME) to play major roles not only in the carcinogenesis of lung cancer but also in disease progression and prognosis and, in addition, predict the efficacy of immune checkpoint inhibitors; our results provided some support to target Mo-MDSCs and needed to be augmented by further studies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Asmaa M. Zahran et al.)

Background: While many studies have reported the rate and risk of SARS-CoV-2 infection among healthcare workers (HCWs), there are scant data regarding the impact of employment type and job grades upon such risk., Methods: We determined the rate of SARS-CoV-2 infection based on a positive nasopharyngeal swab (NPS) PCR among employees of a large national healthcare system. Antibody testing was performed on those who agreed to provide a blood sample. Using logistic regression analysis, we determined the risk of infection (PCR+) associated with demographic characteristics, job family and job grade., Results: We identified 35,075 staff (30,849 full-time, 4,226 outsourced) between March 1-October 31, 2020. Among full-time employees, 78.0% had a NPS (11.8% positive). Among outsourced staff, 94.4% had a NPS (31.1% positive). Antibody testing was performed on 33.9% full-time employees (13.0% reactive), and on 39.1% of the outsourced staff (47.0% reactive). PCR-positivity was higher among outsourced staff (31.0% vs. 18.3% in non-clinical and 9.0% in clinical full-time employees) and those in the low-grade vs. mid-grade and high-grade job categories. Male sex (OR 1.88), non-clinical job family (OR 1.21), low-grade job category (OR 3.71) and being an outsourced staff (OR 2.09) were associated with a higher risk of infection., Conclusion: HCWs are a diverse population with varying risk of infection. Clinical staff are at a lower risk likely due to increased awareness and infection prevention measures. Risk is higher for those in the lower socioeconomic strata. Infection is more likely to occur in non-healthcare setting than within the healthcare facilities., Competing Interests: Dr. Butt has received an investigator initiated research grant (to the institution, Veterans Health Foundation of Pittsburgh) form Gilead Sciences which is unrelated to this work. All other authors declare no competing interest and have no financial disclosures relevant to this paper.

Background: Breakthrough infections after SARS-CoV-2 vaccination have been reported. Clinical outcomes in these persons are not widely known., Methods: We evaluated all vaccinated persons with breakthrough infection ≥14 days after the second vaccine dose and unvaccinated controls matched on age, sex, nationality, and reason for testing between December 23, 2020 and March 28, 2021 in Qatar. Our primary outcome was severe disease defined as hospitalization, mechanical ventilation, or death., Results: Among 456 persons cases of breakthrough infection and 456 unvaccinated matched controls with confirmed infection, median age was 45 years, 60.7% were males, and ≥1 comorbid condition was present in 61.2% of the vaccinated and 47.8% of the unvaccinated persons (P=0.009). Severe disease was recorded in 48 (10.5%) of the vaccinated and 121 (26.5%) of the unvaccinated group (P<0.001). Factors associated with severe disease included increasing age (HR vs. <40 years old: >40-60 years, HR 2.32; >60-70 years, HR 4.34; >70 years, HR 5.43); presence of symptoms at baseline (HR 2.42, 95%CI 1.44-4.07); and being unvaccinated (HR 2.84, 95%CI 1.80-4.47)., Conclusions: In persons with breakthrough SARS-CoV-2 infection, increasing age is associated with a higher risk of severe disease or death, while vaccination is associated with a lower risk. Presence of comorbidities was not associated with severe disease or death among persons with breakthrough infection., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Interaction between multiple myeloma (MM) cells and proximal monocytes is expected during plasma cell proliferation. However, the role of monocyte subsets in the disease progression is unknown., Objective: This study evaluated circulating monocyte populations in MM patients and their correlation with disease severity., Methods: Peripheral monocytes from 20 patients with MM attending Assiut University Hospital in Assiut, Egypt, between October 2018 and August 2019 were processed using a flow cytometry procedure and stratified using the intensity of expression of CD14 and CD16 into classical (CD16 - CD14 ++ ), intermediate (CD16 + CD14 ++ ), and non-classical (CD16 ++ CD14 + ) subsets. The data were compared with data from 20 healthy control participants with comparable age and sex., Results: In patients with MM, the percentage of classical monocytes was significantly lower (mean ± standard error: 77.24 ± 0.66 vs 83.75 ± 0.5), while those of non-classical (12.44 ± 0.5 vs 8.9 ± 0.34) and intermediate (10.3 ± 0.24 vs 7.4 ± 0.29) monocytes were significantly higher when compared with those of controls (all p < 0.0001). Proportions of non-classical and intermediate monocytes correlated positively with serum levels of plasma cells, M-protein, calcium, creatinine and lactate dehydrogenase, and correlated negatively with the serum albumin level. Proportions of classical monocytes correlated positively with albumin level and negatively correlated with serum levels of M-protein, plasma cells, calcium, creatinine, and lactate dehydrogenase., Conclusion: Circulating monocyte subpopulations are skewed towards non-classical and intermediate monocytes in MM patients, and the intensity of this skewness increases with disease severity., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2021. The Authors.)

Evidence on the efficacy of adding macrolides (azithromycin or clarithromycin) to the treatment regimen for COVID-19 is limited. We testify whether adding azithromycin or clarithromycin to a standard of care regimen was superior to standard of supportive care alone in patients with mild COVID-19.This randomized trial included three groups of patients with COVID-19. The azithromycin group included, 107 patients who received azithromycin 500 mg/24 h for 7 days, the clarithromycin group included 99 patients who received clarithromycin 500 /12 h for 7 days, and the control group included 99 patients who received standard care only. All three groups received only symptomatic treatment for control of fever and cough .Clinical and biochemical evaluations of the study participants including assessment of the symptoms duration, real-time reverse transcription-polymerase chain reaction (rRT-PCR), C-reactive protein (CRP), serum ferritin, D-dimer, complete blood count (CBC), in addition to non-contrast chest computed tomography (CT), were performed. The overall results revealed significant early improvement of symptoms (fever, dyspnea and cough) in patients treated with either azithromycin or clarithromycin compared to control group, also there was significant early conversion of SARS-CoV-2 PCR to negative in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).There was no significant difference in time to improvement of fever, cough, dyspnea, anosmia, gastrointestinal tract "GIT" symptoms and time to PCR negative conversion between patients treated with azithromycin compared to patients treated with clarithromycin (p > 0.05 for all). Follow up chest CT done after 2 weeks of start of treatment showed significant improvement in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).Adding Clarithromycin or azithromycin to the therapeutic protocols for COVID-19 could be beneficial for early control of fever and early PCR negative conversion in Mild COVID-19.Trial registration: (NCT04622891) www.ClinicalTrials.gov retrospectively registered (November 10, 2020)., (© 2021. The Author(s).)

We investigated what proportion of the population acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whether the herd immunity threshold has been reached in 10 communities in Qatar. The study included 4,970 participants during June 21-September 9, 2020. Antibodies against SARS-CoV-2 were detected by using an electrochemiluminescence immunoassay. Seropositivity ranged from 54.9% (95% CI 50.2%-59.4%) to 83.8% (95% CI 79.1%-87.7%) across communities and showed a pooled mean of 66.1% (95% CI 61.5%-70.6%). A range of other epidemiologic measures indicated that active infection is rare, with limited if any sustainable infection transmission for clusters to occur. Only 5 infections were ever severe and 1 was critical in these young communities; infection severity rate of 0.2% (95% CI 0.1%-0.4%). Specific communities in Qatar have or nearly reached herd immunity for SARS-CoV-2 infection: 65%-70% of the population has been infected.

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 PaO 2 /FiO 2 , 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).

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., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background : Dysfunction of the peripheral blood monocytes in the form of changes in their proportion, cytokines or pattern-recognition receptors (PRR) expressions may be involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Our aim is to analyze the three monocyte subsets; classical, non-classical and intermediate monocytes and their expression of Toll-like receptors 2 (TLR-2) and 4 (TLR-4) in T1DM patients. Methods : The peripheral blood monocytes of 20 T1DM patients were analyzed by Flow cytometry to measure their count and TLR-2 and TLR-4 expression. Results : T1DM patients had more non-classical and intermediate monocytes, whereas classical monocytes were comparable between patients and control (20 healthy volunteers). Classical, non-classical and intermediate monocytes had no significant correlations with hemoglobin (Hb) A1C in controls, while all subsets showed positive correlations with HbA1C in T1DM. TLR-2 and TLR-4 expression were significantly increased in classical monocytes in patients, especially those with diabetic ketoacidosis (DKA), and both of them showed positive correlations with the duration of T1DM. The expression of TLR-2 inside non-classical monocytes showed a negative correlation with LDL cholesterol and TLR-4/TLR-2 ratio showed positive correlations with the duration of T1DM and negative correlations with total cholesterol. The expression of TLR-2 inside intermediate monocytes showed positive correlations with the duration of T1DM and TLR-4/TLR-2 ratio showed negative correlations with the duration of T1DM Conclusions: The observed changes in both proportions and TLR-2 and TLR-4 expression of monocyte subsets can raise the possible role in the pathogenesis of early stages of T1DM and DKA. Abbreviations APC: allophycocyanin; CBC: complete blood picture; DKA: diabetic acidosis; DM: diabetes mellitus; FITC: fluorescein isothiocyanate; FSC: forward scatter; Hb: haemoglobin; MFI: mean channel fluorescence intensity; PE: phycoerythrin; PRR: pattern-recognition receptors; SPSS: statistical package for the social sciences; SSC: side scatter; T1DM: Type1DM; TLRs: toll-like receptors.

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., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Anaesthesia.)

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., Competing Interests: The authors declare that they have no conflicts of interest.

The mechanism of action of CD8 + CD25 High+ FOXP3 + T cells in hepatocellular carcinoma (HCC) has not been fully understood. Herein, the role of CD8 + CD25 High+ FOXP3 + T cells in HCC was compared with that of CD4 + CD25 High+ FOXP3 + regulatory T cells (conventional Tregs). Thirty-five patients with HCC and twenty age and sex-matched healthy adults (controls) were enrolled. The percentage of CD8 + CD25 High+ FOXP3 + T cells and conventional Tregs in peripheral blood was measured by flow cytometry. Our results revealed that the percentage of peripheral CD8 + CD25 High+ FOXP3 + T cells in HCC patients was significantly higher than controls (P = 0.005). The conventional Tregs showed the same trend with a higher level in HCC than controls (P < 0.0001). FOXP3 expression of CD8 + CD25 High+ T cells is higher than that of CD8 + CD25 low+ and CD8 + CD25 Negative T cells. The percentage of CD8 + CD25 High+ FOXP3 + T cells positively correlated with that of conventional Tregs in HCC patients but not in controls. The higher alpha-fetoprotein positively correlated with the higher CD8 + CD25 High+ FOXP3 + T cells and conventional Tregs (R2 = 0.481, P < 0.0001 and R2 = 0.249, P = 0.001, respectively). The frequency of both CD8 + CD25 High+ FOXP3 + T cells and conventional Tregs was significantly increased in HCC with multiple lesions compared with those with one or two lesions. In conclusion: CD8 + CD25 High+ FOXP3 + T cells similar to conventional Tregs might be used as biomarkers of HCC progression. Therapy targeting the peripherally expanded CD8 + CD25 High+ FOXP3 + T cells may provide a novel perspective for HCC treatment., (Copyright © 2019 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus (HCV)-specific immune response is believed to play a crucial role in viral clearance. There is, nevertheless, no reliable parameter to monitor this immune response or predict chronic HCV infection development., Method: An observational case-control study was performed to identify such parameters, peripheral blood mononuclear cells from 57 children with chronic HCV were systemically phenotyped, and the serum level of Interferon gamma and interleukin (IL) -17 was measured. The data were compared with 37 age-matched healthy volunteers (controls)., Results: Children with chronic HCV infection had a lower frequency of natural killer cells (NK) cells, CD56Dim NK cells and expansion of CD56Bright NK cells compared with controls (P = 0.001, P < 0.0001 and P < 0.0001 respectively). Increased CD56Dim NK cells were negatively correlated with the higher viral load, R 2  = 0.29, P = 0.05, while, increased NK T cells were positively correlated with high viral load, R 2  = 0.17, P = 0.011. T helper cells, naive T cells, CD127 negative T cells, and HLA-DR-positive T cells significantly increased in patients than in controls. The frequency of CD4+CD25high+ T regulatory (Treg) cells increased in HCV-infected patients, compared with those in control, and FOXP3 was upregulated within them. Treg cells' increase was positively correlated with high viral load, R 2  = 0.45, P = 0.004. The level of IL-17 was higher in HCV patients than that in control, P < 0.0001., Conclusion: Although the contribution of those markers to the chronic HCV establishment in children remains elusive, the results may provide important clues for reliable indicators of HCV infection., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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.

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.

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.

Background: T-cell receptor Vδ2 γδ T cells (Vδ2 cells) participate in host defense, whereas Vδ1 γδ T cells (Vδ1 cells) may regulate immune responses. Vδ1 cells appear to play a role in fetomaternal tolerance and our aim was to examine their role in liver transplant tolerance., Methods: To determine whether Vδ1 cells increase within accepted grafts after semiallogeneic pediatric liver transplantation, the Vδ1/Vδ2 ratio was assessed at the transcriptional level and the complementarity-determining region 3 loop of the δ chain of Vδ1 cells was sequenced in biopsies from immunosuppression-free (n=6) or almost free (n=3) liver transplant recipients, referred to as group tolerance (Gr-Tol; n=9). The results were compared with biopsies from grafts of recipients on maintenance immunosuppression due to concern of rejection (Gr-IS; n=11). Chronically rejected grafts (Gr-CR; n=6) and normal livers (Gr-NL; n=8) were also examined., Results: The Vδ1/Vδ2 ratio was the highest in Gr-Tol (0.07±0.06) compared with Gr-IS (0.03±0.02; P=0.04), Gr-CR (0.01±0.02; P=0.008), and Gr-NL (0.02±0.04; P=0.01). There was an identical complementarity-determining region 3 sequence (100% homologous) among all recipients in Gr-Tol, which was dominant in six of nine recipients. This sequence was not seen in Gr-IS or Gr-CR, although it was observed in five of six normal livers., Conclusions: A unique Vδ1-bearing T-cell clone accumulates within accepted human liver grafts. It might be useful as a biomarker of tolerance and the identification of its ligand might aid in the development of a novel strategy for tolerance induction.

Pediatric recipients of living-donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi-allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post-Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr-tol), but not in 50 intolerant patients (Gr-intol). The Gr-intol consisted of 24 patients with rejection (Gr-rej) and 26 with fibrosis of grafts (Gr-fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11-7.02, P = 0.03], was a positive independent predictor, whereas HLA-A mismatch (0.18, 0.03-0.91, P = 0.04) was a negative predictor. HLA-DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr-intol (4.9%) compared with Gr-tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr-Tol (P = 0.02). Although HLA-B mismatch (8.73, 1.09-70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA-A match and the later predominance of Tregs are factors associated with OT., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

Infection after pediatric living donor liver transplantation (LDLT) is a major cause of morbidity and mortality. Here, we sought to determine the incidence, timing, location, and risk factors for bacterial and fungal infections. We retrospectively investigated infection for 3 postoperative months in 345 consecutive pediatric patients (56.2% were females) who underwent primary LDLT at Kyoto University Hospital, Japan. A total of 179 patients (51.9%) developed at least 1 bacterial and/or fungal infection episode, with an infection rate of 2.5 per patient. The predominant infection site was the surgical site (52%). Most of the bacterial and fungal infection occurred within the first month. Enterococcus species followed by multidrug-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were the predominant bacterial pathogens. All fungal isolates were Candida species. Prolonged preoperative hospital stay more than 7 days (P = 0.025) and bile leak (P = 0.047) were independent predictors of bacterial infection. Preoperative ascites (P = 0.009) and prolonged insertion of intravascular catheters (P = 0.001) independently predicted fungal infections. Bacterial and fungal infections were responsible for 42.9% of the causes of death in our study. To avoid bacterial and fungal infections after LDLT, broader-spectrum prophylaxis to cover the range of organisms seen in these infections should be considered as a more favorable treatment regimen to prevent prophylaxis failure, especially for patients with a preoperative hospital stay more than 7 days or operative complications in the form of a bile leak. Early drain removal and prophylactic antifungal drugs should be considered for patients with preoperative ascites. Cooperation between attending physicians and infectious disease physicians can improve the outcome of patients after LDLT., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Islet damage attributed to impaired exocrine cells during pancreas preservation and isolation procedure remains elusive, although released exocrine enzymes could directly damage islets. The aim of this study is to investigate the cellular mechanisms associated with exocrine cells and their possible impact on the islet cell survival and function after isolation. Mouse pancreata were stored in cold University of Wisconsin preservation solution for 0, 24 and 48 h and incubated with or without collagenase at 37°C for 15 min. During preservation, the percentage of exocrine cells with necrosis, which means impaired cellular membrane that allows intracellular enzymes to be released, remains low (< 10%) regardless of preservation time; whereas the percentage of exocrine cells with apoptosis, which means impaired nucleus and possible intact cellular membrane, increases over time of preservation. After collagenase-free incubation, however, the percentage of exocrine cells with necrosis became higher in longer preservation time, and more than 60% of the necrotic exocrine cells contained apoptosis as well. Islet cells located in pancreata with intact structure are almost kept away either from necrotic or apoptotic changes even after 48 h preservation followed by collagenase-free incubation. However, when islets are isolated after collagenase-containing incubation, the percentage of islet cells with necrosis increases over time of preservation up to approximately 40%. This study suggests that exocrine cells with necrosis could cause damage of isolated islets when the pancreas is dissociated and that the necrosis in exocrine cells might be induced mainly as the conversion from apoptosis that has already existed during preservation.

Background: CD4+CD25++CD45RA+ cells (naïve regulatory T cells [naïve-Tregs]) have been identified as a functionally premature form of CD4+CD25+++CD45RA(-) cells (conventional-Tregs). However, their contribution to transplant tolerance remains to be elucidated., Method: We examined the frequency and the function of conventional and naive-Tregs in the peripheral blood derived from operationally tolerant patients after pediatric living-donor liver transplant (Gr-tol). The data were compared with those of patients who were unable to be weaned off immunosuppression due to rejection (group-intolerance [Gr-intol]), patients in the process of weaning immunosuppression (Gr-weaning) and healthy volunteers (group-healthy volunteers [Gr-vol])., Results: In Gr-tol, the frequency of conventional-Tregs was significantly higher than that in Gr-vol and tended to be higher than that in Gr-intol. The frequency of naive-Tregs was significantly decreased in Gr-intol versus those in Gr-tol, -weaning, and -vol. In mixed lymphocyte reactions, donor-specific hyporesponsiveness of CD4+ cells was observed only in Gr-tol but not in the other groups. Depletion of conventional or naive-Tregs from CD4+ cells demonstrated that the suppressive properties of donor antigen-reactive conventional and naïve-Tregs were upregulated compared with those of third-party antigen-reactive conventional and naïve-Tregs in Gr-tol only., Conclusions: This is the first report providing detailed evidence that donor-specific naïve-Tregs were generated and their suppressive properties were upregulated in the peripheral blood of tolerant patients, whereas their frequency was downregulated in intolerant patients. Therefore, we speculate that not only conventional-Tregs play a role in Tx tolerance but also the role of naïve-Tregs is critical.