How can we establish animal models of HIV-associated lymphoma?

Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

Against all odds:The road to success in the development of human immune reconstitution mice

The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.

Pulmonary alveolar proteinosis induced by X-linked agammaglobulinemia:A case report

BACKGROUND Pulmonary alveolar proteinosis(PAP)and X-linked agammaglobulinemia(XLA)are rare diseases in children.Many theories infer that immunodeficiency can induce PAP,but these reports are almost all review articles,and there is little clinical evidence.We report the case of a child with both PAP and XLA.CASE SUMMARY A 4-month-old boy sought medical treatment due to coughing and difficulty in breathing for>2 wk.He had been hospitalized multiple times due to respiratory infections and diarrhea.Chest computed tomography and alveolar lavage fluid showed typical PAP-related manifestations.Genetic testing confirmed that the boy also had XLA.Following total lung alveolar lavage and intravenous immunoglobulin replacement therapy,the boy recovered and was discharged.During the follow-up period,the number of respiratory infections was significantly reduced,and PAP did not recur.CONCLUSION XLA can induce PAP and improving immune function contributes to the prognosis of children with this type of PAP.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide,with a 5-year relative survival rate of approximately 18%.The similarity between incidence and mortality(830000 deaths per year)underscores the bleak prognosis associated with the disease.HCC is the fourth most common malignancy and the second leading cause of cancer death in China.Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus(HBV)or hepatitis C virus(HCV)infection,alcoholism or alcoholic steatohepatitis,nonalcoholic fatty liver disease,or nonalcoholic steatohepatitis.Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC.Although the total number of human immunodeficiency virus(HIV)-infected patients is declining globally the incidence of HCC is increasing in HIVinfected patients,especially those who are coinfected with HBV or HCV.As a result,people infected with HIV still face unique challenges in terms of their risk of developing HCC.AIM To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection.METHODS The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed.Among these,27 patients underwent hepatectomy(operation group)and 29 patients received conservative treatment(nonoperation group).All patients signed informed consents in line with the provisions of medical ethics.The general data,clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified.RESULTS The median disease-free survival(DFS)and overall survival(OS)of HIV-HCC patients in the surgical group were 13 months and 17 months,respectively,and the median OS of patients in the nonsurgical group was 12 months.The OS of the surgical group was significantly longer than that of the control group(17 months vs 12 months,respectively;P<0.05).The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis,postoperative microvascular invasion(MVI),a CD4+T-cell count<200/μL,Barcelona stage C-D,and men who have sex with men(MSM;P<0.05).CONCLUSION Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination,late tumor detection,late BCLC stage,CD4+T<200/μL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy.In addition,there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV,Child-Pugh score,alpha-fetoprotein measurement value,and HART-efficient antiretroviral therapy after the diagnosis of HIV(P<0.05).Therefore,these factors may also affect the survival and prognosis of patients.

Primary extrapulmonary tuberculosis diagnosis warrants extraprecautious pulmonary tuberculosis exclusion workup

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis(an uncommon extrapulmonary tuberculosis condition)utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction.The diagnosis chiefly relied on high-end examinations,like computed tomography scans and histopathological evaluation of postoperatively resected bowel tissue,which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition.Given the geographic locations where the patient had been(and/or treated),pivotal consideration of tuberculosis-associated endemicities in those regions,like human immunodeficiency virus(HIV)infection,might have improved the case description.The obtainment of HIV-relevant histories,like intravenous drug use and sexual practice,are good places to start.The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radiohistopathological resemblance with pulmonary Mycobacterium tuberculosis.Altogether,this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative,comprehensive,systematic,and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

Clinical approach for pulmonary alveolar proteinosis in children

In this editorial,we discuss the clinical implications of the article by Zhang et al.Pulmonary alveolar proteinosis(PAP)is a rare lung disease characterized by excessive surfactant accumulation in the alveoli.It is classified into four categories:Primary,secondary,congenital,and unclassified forms.Primary PAP is caused by the disruption of granulocyte-macrophage colony-stimulating factor(GM-CSF)receptor signaling,which is necessary for the clearance of surfactant by alveolar macrophages.It is further divided into autoimmune PAP,caused by anti-GM-CSF antibodies blocking alveolar macrophage activation,and hereditary PAP,resulting from mutations in genes encoding GM-CSF receptors.Secondary PAP develops due to conditions affecting the number or function of alveolar macrophages,such as infections,immunodeficiency,hematological disorders,or exposure to inhaled toxins.Congenital PAP is linked to mutations in genes involved in surfactant protein production.Notably,the causes of PAP differ between children and adults.Diagnostic features include a characteristic"crazypaving"pattern on high-resolution computed tomography,accompanied by diffuse ground-glass opacities and interlobular septal thickening.The presence of PAP can be identified by the milky appearance of bronchoalveolar lavage fluid and histological evaluation.However,these methods cannot definitively determine the cause of PAP.Whole lung lavage remains the standard treatment,often combined with specific therapies based on the underlying cause.

Effectiveness of onsite and online education in enhancing knowledge and use of human immunodeficiency virus pre-and postexposure prophylaxis

BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group.AIM To investigate the effects of both onsite and online health education on the knowledge of,and willingness to use,PrEP and PEP among individuals receiving PEP services.METHODS Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing,conducted from January 1 to June 30,2022.Health education was provided both onsite and online during follow-up.Surveys assessing knowledge of,and willingness to use,PrEP/PEP were administered at baseline and again at 24 wk post-intervention.RESULTS A total of 112 participants were enrolled in the study;105 completed the follow-up at week 24.The percentage of participants with adequate knowledge of,and willingness to use,PrEP significantly increased from 65.2%and 69.6%at baseline to 83.8%and 82.9%at the end of the intervention(both P<0.05).Similarly,those with adequate knowledge of,and willingness to use,PEP increased from 74.1%and 77.7%at baseline to 92.4%and 89.5%at week 24(P<0.05).Being between 31 years and 40 years of age,having a postgraduate degree or higher,and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP(both P<0.05).CONCLUSION The findings show that both onsite and online health education significantly improved the knowledge of,and increased willingness to use,PrEP and PEP in individuals utilizing PEP services.

HPV/HBV or HPV/HCV Co-Infections in Women Treated for Chronic Hepatitis at Hôpital Saint Camille in Ouagadougou, Burkina Faso

Introduction: Cervical cancer is a public health concern and is mainly caused by Human papillomaviruses (HPV). In many parts of the world, studies are being carried out to understand the different genotypes to better tackle this issue. We conducted a study to determine the prevalence of HPV genotypes in women with chronic hepatitis B or C infection, co-infected or not with HIV, treated at the Hôpital Saint Camille in Ouagadougou (Burkina Faso). Methods: This study was conducted from April to July 2023, including 100 women in gastroenterology at Hôpital Saint Camille. A questionnaire on their socio-demographic and life style was administrated;and endocervical samples were collected using sterile swabs and then sent to Centre of Biomolecular Research Pietro Annigoni (CERBA). HPV molecular detection and genotyping were performed by PCR and hybridization using the HPV Direct Flow Chips kit. Data were analysis using chi square test or Fischer’s exact test with a significance threshold for p Results: The prevalence of HPV infection was 28% (28/100) on the sample of women tested. The most frequent genotypes were HPV 52 (8.33%), followed by HPV 18 and 68 (6.25% each) for high-risk HPVs, and HPV 6, 44/55 and 62/81 (8.33% each) for low-risk HPVs. Conclusion: This study, the first of its kind in Burkina Faso on this group of the population, reveals that the most frequent genotypes found in this study are not included in the vaccine available in Burkina Faso (Gardasil®4).

Oncological features and prognosis of colorectal cancer in human immunodeficiency virus-positive patients: A retrospective study

BACKGROUND Due to the prolonged life expectancy and increased risk of colorectal cancer(CRC)among patients with human immunodeficiency virus(HIV)infection,the prognosis and pathological features of CRC in HIV-positive patients require examination.AIM To compare the differences in oncological features,surgical safety,and prognosis between patients with and without HIV infection who have CRC at the same tumor stage and site.METHODS In this retrospective study,we collected data from HIV-positive and-negative patients who underwent radical resection for CRC.Using random stratified sampling,24 HIV-positive and 363 HIV-negative patients with colorectal adenocarcinoma after radical resection were selected.Using propensity score matching,we selected 72 patients,matched 1:2(HIV-positive:negative=24:48).Differences in basic characteristics,HIV acquisition,perioperative serological indicators,surgical safety,oncological features,and long-term prognosis were compared between the two groups.RESULTS Fewer patients with HIV infection underwent chemotherapy compared to patients without.HIV-positive patients had fewer preoperative and postoperative leukocytes,fewer preoperative lymphocytes,lower carcinoembryonic antigen levels,more intraoperative blood loss,more metastatic lymph nodes,higher node stage,higher tumor node metastasis stage,shorter overall survival,and shorter progression-free survival compared to patients who were HIV-negative.CONCLUSION Compared with CRC patients who are HIV-negative,patients with HIV infection have more metastatic lymph nodes and worse long-term survival after surgery.Standard treatment options for HIV-positive patients with CRC should be explored.

Hepatitis C virus eradication in people living with human immunodeficiency virus:Where are we now?

Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

临床HIV感染者血液样本的保藏与利用

当前,艾滋病——获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)仍是人类面临的世界性且极具威胁性的重大公共卫生问题之一,其病原体为人类免疫缺陷病毒(human immunodeficiency virus,HIV)。HIV感染会导致CD4+T淋巴细胞的数量发生进行性减少,机体免疫功能遭受严重破坏,从而并发各种机会性感染及肿瘤等疾病[1]。

Relation between dysbiosis and inborn errors of immunity

Inborn errors of immunity(IEI)disorders,formerly primary immune deficiency diseases,are a heterogeneous group of disorders with variable hereditary transitions,clinical manifestations,complications and varying disease severity.Many of the clinical symptoms,signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity(dysbiosis).For example,in common variable immunodeficiency patients,the diversity of bacteria,but not fungi,in the gut microbiota has been found to be reduced and significantly altered.Again,this was associated with a more severe disease phenotype.Compromise of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients,causing Candida albicans to switch from commensal to pathogenic.Modification of the microbiota can be used as a therapeutic approach in patients with IEI.Prebiotics,probiotics,postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI patients.Clinical trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.

Human immunodeficiency virus cascade–continuum of care stages and outcomes in a hospital in southern Brazil

BACKGROUND The human immunodeficiency virus(HIV)continuum of care cascade illustrates the 90-90-90 goals defined by the Joint United Nations Program on HIV/acquired immunodeficiency syndrome(UNAIDS).The care cascade includes the following five steps:Diagnosis,linkage to care,retention in care,adherence to antiretroviral therapy(ART),and viral suppression.AIM To elaborate the HIV cascade of patients diagnosed with HIV at the Nossa Senhora da Conceição Hospital(HNSC)and to determine possible local causes for the loss of patients between each step of the cascade.METHODS This retrospective cohort study included patients diagnosed with HIV infection from January 1,2015 to December 31,2016 and followed up until July 31,2019.The data were analyzed by IBM SPSS software version 25,and Poisson regression with simple robust variance was used to analyze variables in relation to each step of the cascade.Variables with P<0.20 were included in multivariable analysis,and P<0.05 was considered significant.Pearson’sχ^(2) test was used to compare the groups of patients followed up at the HNSC and those followed up at other sites.RESULTS The results were lower than those expected by the UNAIDS,with 94%of patients linked,91%retained,81%adhering to ART,and 84%in viral suppression.Age and site of follow-up were the variables with the highest statistical significance.A comparison showed that the cascade of patients from the HNSC had superior results than outpatients,with a significant difference in the last step of the cascade.CONCLUSION The specialized and continued care provided at the HNSC was associated with better results and was closer to the goals set by the UNAIDS.The development of the HIV cascade using local data allowed for the stratification and evaluation of risk factors associated with the losses occurring between each step of the cascade.

Factors Associated with Antiretroviral Therapy Defaulting among Adult Patients Receiving Care at Chikankata Mission Hospital, Chikankata District, Zambia

Background: Defaulting on antiretroviral therapy has been identified as the most important factor contributing to the antiretroviral therapy failure rate. This study aimed to investigate factors associated with defaulting on antiretroviral therapy among adult patients receiving care at Chikankata Mission Hospital antiretroviral therapy clinic. Method: Cross-sectional analytical study on 385 participants selected by a computer generated random numbers technique of simple random sampling from among the patients receiving antiretroviral therapy at Chikankata Mission Hospital. Data collected were processed and analysed using Statistical Package for Social Science version 27. Univariate and backward multivariable logistic regression analysis was performed to identify factors associated with antiretroviral therapy defaulting. The level of significance was set at 5% with a confidence level of 95%. Results: Over half (58.4%) of the study participants defaulted on antiretroviral therapy. About 65.8% of study participants indicated improved health as the reason they defaulted on antiretroviral therapy. Most participants indicated that it was important to always go for antiretroviral therapy services (Adjusted Odds Ratio 1.95;95% Confidence Interval: [1.14 - 3.33], p = 0.015). Very few participants indicated poor family support for antiretroviral therapy services (Adjusted Odds Ratio 4.08;95% Confidence Interval: [2.02 - 8.23], p Conclusion: Defaulting on antiretroviral therapy continues to be a significant problem and needs to be addressed as a matter of priority. More counselling and awareness-raising programmes are required to improve knowledge and understanding on the importance of attending scheduled antiretroviral therapy clinics and services as well as the consequences of defaulting on antiretroviral therapy.

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.

Evolution of heart transplant donor characteristics in the 21st century: A United States single center’s experience

Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic dysfunction.Our center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”donors.We detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.

Human lymphohematopoietic reconstitution and immune function in immunodeficient mice receiving cotransplantation of human thymic tissue and CD34＋ cells

Small animal models with functional human lymphohematopoietic systems are highly valuable for the study of human immune function under physiological and pathological conditions. Over the last two decades, numerous efforts have been devoted towards the development of such humanized mouse models. This review is focused on human lymphohematopoietic reconstitution and immune function in humanized mice by cotransplantation of human fetal thymic tissue and CD34＋ cells. The potential use of these humanized mice in translational biomedical research is also discussed.

Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes

Background Interferon （IFN） can inhibit human immunodeficiency virus type 1 （HIV-1） replication in vitro and in clinic.However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-HIV efficacy of a novel synthesized superior interferon α （slFNα）.Methods We performed in vitro experiments with HIV-1 IIB infected MT4 cells, and evaluated in vivo anti-HIV efficacy of slFNα in severe combined immunodeficient （SClD） mice reconstituted with human peripheral blood leukocytes （hu-PBL-SClD mice）.Results We found that the 50% effective concentrations （EC5o） of slFNα against the replication of HIV-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-α in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed： with 0.45 μg and 1.35 μg slFNα daily treatments, parts of SCID mice were protected from HIV infection, whereas 2.25 μg sIFNα daily treatments resulted in a terminally complete protection.Conclusions slFNα shows good anti-HIV activity both in vitro and in SCID mice, may be a promising anti-HIV agent deserving clinical investigation, especially considering the potential of IFN-α to inhibit HIV replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus （HCV）.

A DiGeorge Syndrome Case Report—Challenges of Diagnosis and Management

Background: DiGeorge syndrome (also known as velo-cardio-facial syndrome) is a rare multisystem genetic disorder occurring in approximately 1 in 4000 to 1 in 6000 live births [1]. Although advances in genetic screening have improved diagnosis in developed countries, the condition remains underdiagnosed in developing nations such as the Republic of Moldova, where access to genetic testing and family planning services is limited. Routine prenatal screening usually includes regular ultrasounds, monitoring of blood pressure, complete blood counts, coagulation studies, glucose, urine protein, and urine culture. Current ultrasound techniques have limitations in detecting this syndrome due to variability in interpretation, and genetic testing is often performed based on clinical discretion. The ultrasound could potentially point towards a genetic problem, as in DiGeorge, if multiple cardiac malformations are spotted in utero, but most cases such as this one are diagnosed after birth while being described as totally normal on prenatal ultrasound. Purpose: This study aims to highlight the diagnostic challenges and the need for comprehensive evaluation in identifying DiGeorge syndrome, emphasizing the importance of considering the syndrome as a whole rather than focusing on isolated organ system issues. Method: We present a case report of a 6-month-old girl who, after an uneventful pregnancy and normal prenatal ultrasound, presented with cardiac insufficiency. Following extensive investigations and multiple surgical interventions, DiGeorge syndrome was diagnosed at 9 months of age. Results: The patient’s diagnosis was delayed due to the lack of prenatal markers and the reliance on separate investigations of affected organ systems. Despite several interventions aimed at managing her symptoms, the final diagnosis was made after observing the association of multiple clinical features and conducting comprehensive genetic testing. Conclusions: This case underscores the importance of a holistic approach to diagnosis, which involves a thorough patient history, integration of diverse diagnostic tests, and recognition of the syndrome’s multi-system nature. It highlights the necessity for improved diagnostic protocols and increased awareness in regions with limited access to advanced genetic testing to prevent delays in identifying DiGeorge syndrome and to facilitate timely and appropriate management.