Ultrasound features of congenital cytomegalovirus infection in the first trimester:A case report

BACKGROUND Congenital cytomegalovirus(CMV)infection represents a significant public health concern as the most prevalent viral infection in newborns,potentially leading to severe neurological and developmental complications.The majority of cases are asymptomatic and remain undetected during pregnancy due to the absence of effective screening methods.CASE SUMMARY A 27-year-old primigravida presented for early pregnancy ultrasound,which revealed an atypical finding:A normal anechoic thalamus appearing hyperechoic on the mid-sagittal view of the fetal head.Subsequent ultrasound examinations during mid and late gestation demonstrated classic intracranial features sug-gestive of congenital CMV infection.Chromosomal karyotyping and microarray analysis of the fetus yielded no significant abnormalities.Following compre-hensive prenatal counseling regarding potential adverse fetal outcomes,the patient elected to continue her pregnancy.She ultimately underwent cesarean delivery at 42 weeks gestation at another facility,resulting in the birth of a female neonate.At five months of age,the infant presented with epilepsy and significant growth and developmental delays.CONCLUSION Congenital CMV infection occurs during the first trimester may manifest as hyperechoic thalamus which can be revealed by ultrasound in the mid-saggital view of the fetal head.Future research should investigate the correlation between echogenic thalamus and developmental outcomes,as well as explore early sc-reening techniques for suspected congenital CMV infection cases.

Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients:A systematic review of clinical trials

BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.

Septic shock due to cytomegalovirus colitis associated with rituximab use:A case report

BACKGROUND Cytomegalovirus(CMV)infections can cause significant morbidity and mortality in immunocompromised individuals.CMV targets dysfunctional lymphocytes.Chronic rituximab(RTX)therapy can cause B-lymphocyte dysfunction,increasing CMV risk.Rarely,CMV infections present with critical illness such as septic shock.CASE SUMMARY A 64-year-old African American woman presented with generalized weakness and non-bloody watery diarrhea of 4-6 weeks duration.She did not have nausea,vomiting or,abdominal pain.She had been on monthly RTX infusions for neuromyelitis optica.She was admitted for septic shock due to pancolitis.Blood investigations suggested pancytopenia and serology detected significantly elevated CMV DNA.Valganciclovir treatment led to disease resolution.CONCLUSION This case illustrates an extremely rare case of CMV colitis associated with RTX use presenting with septic shock.High suspicion for rare opportunistic infections is imperative in individuals with long-term RTX use.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Management of cytomegalovirus infection after liver transplantation

Cytomegalovirus(CMV)infection is one of the primary causes of morbidity and mortality following liver transplantation(LT).Based on current worldwide guidelines,the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment.CMV-IgG serology is the established technique for pretransplant screening of both donors and recipients.The clinical presentation of CMV infection and disease exhibits variability,prompting clinicians to consistently consider this possibility,partic-ularly within the first year post-transplantation or subsequent to heightened immunosuppression.At annual symposia to discuss CMV prevention and how treatment outcomes can be improved,evidence on the incorporation of immune functional tests into clinical practice is presented,and the results of studies with new antiviral treatments are evaluated.Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation,a consensus reflected in the guidelines has not been formed.Determining the most appro-priate strategy at the individual level appears to be the key to enhancing out-comes.Although prevention strategies reduce the risk of CMV disease,the disease can still occur in up to 50%of high-risk patients.A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients.The objective of this study was to establish a compre-hensive framework for the management of CMV in patients who have had LT.

Cytomegalovirus infection in non-immunocompromised critically ill patients:A management perspective

Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.

Role of viruses in periodontitis:An extensive review of herpesviruses,human immunodeficiency virus,coronavirus-19,papillomavirus and hepatitis viruses

Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.

猪巨细胞病毒病

猪巨细胞病毒(Porcine Cytomegalovirus,PC-MV)是由疱疹病毒科β疱疹病毒亚科巨细胞病毒属的一种[1]。该病毒遍布全球[2],猪感染该病也是普遍存在,在北美、欧洲和日本,90%以上的猪群曾受到感染。对成年猪只通常只呈现隐性感染,而对3周齡以下仔猪常常诱发致命性的全身感染[3]。

人巨细胞病毒先天性感染胎鼠大脑皮质钙调素基因mRNA表达的研究

目的研究先天性人巨细胞病毒(HCMV)感染致脑损害后钙调素(calmodulin,CaM)基因 mRNA 表达的改变,以探讨先天性 HCMV 感染所致脑损害的机制。方法选用10周龄Balb/c 小鼠,雌雄小鼠腹腔内分别注射1.0ml、0.5ml、0.25ml HCMV 后合笼交配以建立先天性HCMV 中枢神经系统(CNS)感染小鼠模型,对照鼠腹腔注射1.0ml RPMI 1640液。剖腹取21天胎龄小鼠大脑皮质,以自行设计的 CaM cDNA 编码区的一对引物与一条 CaM 特异性探针,分别用逆转录聚合酶链反应(RT-PCR)技术检测 CaM mRNA 相对含量、用原位杂交检测大脑皮质细胞内相应 mRNA 的表达及定位。结果母鼠腹腔内接种 HCMV 量为1.0ml 与0.5ml 的临产胎鼠大脑皮质分离出相应病毒,病理学检查等确认发现了侵袭性脑膜脑炎性病理改变,证实HCMV 可经小鼠宫内传播至胎鼠 CNS。1.0ml 组与0.5ml 组胎鼠 RT-PCR 产物浓度明显高于0.25ml 组及对照组,而1.0ml 组与0.5ml 组间亦有明显差异。电泳结果显示对照组与0.25ml 组胎鼠未见阳性条带,而1.0ml 组胎鼠特异性条带信号强于0.5ml 胎鼠,仅略低于同组母鼠。原位杂交显示 CaM mRNA 不但出现在1.0ml 组胎鼠大脑皮质大神经元胞核及胞浆内,在中小神经元及胶质细胞的胞核及胞浆亦有高密度表达,阳性细胞的突起中亦有弱信号存在。结论提示先天性感染 HCMV 胎鼠大脑皮质内 CaM mRNA 表达量明显增加,且神经元及胶质细胞均有表达,并与感染剂量有依赖关系。提示 CaM mRNA 表达增高可能直接参与了 HCMV 先天性感染脑损害的过程。

更昔洛韦治疗小儿巨细胞病毒肝炎疗效观察

目的：观察更昔洛韦治疗小儿巨细胞病毒肝炎(CMV肝炎)的疗效。方法：将巨细胞病毒肝炎患儿34例分为更昔洛韦治疗组19例及病毒唑对照组15例进行比较。结果：治疗组和对照组血CMV—IgM或尿CMV—DNA转阴率分别为89．47％和40％，P<0．005；总有效率分别为84．21％和26．67％，P<0．005；且治疗组血清胆红素(SB)及谷丙转氨酶(ALT)恢复正常时间均较对照组缩短。两组治疗过程中均未见明显毒副作用。结论：更昔洛韦治疗小儿CMV肝炎疗效肯定，值得临床推广。

Cytomegalovirus infection after liver transplantation: Current concepts and challenges

Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. Risk factors for CMV disease are often interrelated, and include CMV D+/R-serostatus, acute rejection, female gender, age, use of high-dose mycophenolate mofetil and prednisone, and the overall state of immunity. In addition to the role of CMV-specif ic CD4+ and CD8+ T lymphocytes, there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis. In one study, liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher levels of CMV replication and clinical disease. Because of the direct and indirect adverse effects of CMV disease, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component in improving the outcome of liver transplantation. In the majority of transplant centers, antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-). However, the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease. In several prospective and retrospective studies, the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention and novel drugs with unique modes of action are needed. Currently, a randomized controlled clinical trial is being performed comparing the effi cacy and safety of maribavir, a novel benzimidazole riboside, and oral ganciclovir as prophylaxis against primary CMV disease in liver transplant recipients. The treatment of CMV disease consists mainly of intravenous (IV) ganciclovir, and if feasible, a reduction in the degree of immunosuppression. A recent controlled clinical trial demonstrated that valganciclovir is as effective and safe as IV ganciclovir for the treatment of CMV disease in solid organ (including liver) transplant recipients. In this article, the author reviews the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.

Natural history of cytomegalovirus infection in a series of patients diagnosed with moderate-severe ulcerative colitis

AIM： To evaluate the natural history of human cytomegalovirus （HCMV） infection in a series of 28 ulcerative colitis patients in whom the search for HCMV was positive. METHODS： A series of 85 patients with moderate-se- vere ulcerative colitis flare-up were evaluated for a HCMV search by performing a haematoxylin and eosin stain, immunohistochemical assay and nested polymerase chain reaction on rectal biopsies. Among 85 screened patients （19 of whom were steroid resistant/dependant）, 28 were positive for HCMV; after remission the patients were followed up clinically and histologically. RESULTS： Among the 22 patients with complete follow- up, in 8 （36%） patients HCMV-DNA persisted in the in- testinal specimens. Among the HCMV positive patients, 4 （50%） experienced at least one moderate-severeflare-up of colitis without evidence of peripheral HCMV. Among the 14 HCHV negative patients, 3 with pouches developed pouchiUs and 5 out of 11 （45%） experienced a colitis flare-up. CONCLUSION： Our preliminary results suggest that HCHV may remain in the colon afber an acute coltis flare- up despite remission; it seems that the virus is not responsible for the disease relapse.

Infections in liver transplant recipients

Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications.In this article,we review the contemporary state of infectious complications during the post-operative period,with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation.Bacteria,and less commonly Candida infections,remain the predominant pathogens during the immediate post-operative period,especially during the first month,and infections caused by drugresistant strains are emerging.Infections caused by cytomegalovirus and Aspergillus sp.present clinically during the'opportunistic'period characterized by intense immunosuppression.As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed,one potential adverse effect is an increase in certain infections.Hence,it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk,local antimicrobial resistance patterns,and surveillance.A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.

Cytomegalovirus and ulcerative colitis:Place of antiviraltherapy

The link between cytomegalovirus(CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis(UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools(numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flareups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.

Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

AIM： TO investigate active cytomegalovirus （CMV） infection following the cydosporine A （CyA） treatment of steroid-refractory ulcerative colitis （UC）. METHODS： Twenty-three patients with severe UC not responding to steroid therapy （male 14, and female 9） enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA （average 4 mg/kg per day） for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology （IgM antibody by ELISA）, quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin （HE）-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS： No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV （IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%）. There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection （83.3%） required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION： Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy.

Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection

AIM:To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cyto-megalovirus (CMV) infection.METHODS: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exudates) as well as five aspects of ulcerative change (wide mucosal defect, punched-out ulceration, longitudinal ulceration, irregular ulceration, and cobble-stone-like appearance). Sensitivity, specificity, positive predictive value, and negative predictive value of each finding for CMV positivity were determined.RESULTS: The sensitivity of irregular ulceration for positive CMV was 100%. The specificity of wide mucosal defect was 95%. Punched-out ulceration and lon-gitudinal ulceration exhibited relatively high sensitivity and specificity (more than 70% for each).CONCLUSION:Specific colonoscopic findings in patients with UC complicated by CMV infection were identified. These findings may facilitate the early diagnosis of CMV infection in UC patients.

Eosinophilic gastroenteritis with cytomegalovirus infection in an immunocompetent child

A 3-year-old boy developed transient protein-losing gastroenteropathy associated with cytomegalovirus (CMV) infection. Both IgG and IgM antibodies to CMV were positive in a serologic blood test. Upper gastrointestinal endoscopy showed multiple erosions throughout the body of the stomach, without enlarged gastric folds. Histological examination of the biopsy specimens indicated eosinophilic gastroenteritis and CMV infection. The patient had complete resolution without specific therapy for CMV in four weeks. An allergic reaction as well as CMV infection played important roles in the pathogenesis of this case.

Management of cytomegalovirus infection and disease in liver transplant recipients

Cytomegalovirus(CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferredstrategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/Rliver transplant recipients, and such occurrence of lateonset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach(antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ(including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.

Design,delivery and efficacy testing of therapeutic nucleic acids used to inhibit hepatitis C virus gene expression in vitro and in vivo

Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated effectively.Toimprove this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental treatment.Antisense oligodeoxynucleotides(ODN) are

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.