遗传性球形红细胞增多症并存β地中海贫血双重溶血性贫血的鉴别诊断

目的:对3例溶血性贫血疑难病例进行鉴别诊断。方法:柱层析法定量测定血红蛋白A2(HbA2),国际血液学标准化委员会(ISCH)推荐速率法测定红细胞葡萄糖6磷酸脱氢酶(G6PD)和丙酮酸激酶(PK),梯度凝胶电泳分析红细胞膜血影蛋白,其他溶血试验按常规方法操作。同期进行家系调查。结果:3例患者外周血并存浅染靶形红细胞和浓染球形红细胞,红细胞渗透脆性试验(OFT)初始溶血Nacl浓度和酸化甘油溶血试验(AGLT50)均为阴性,3例患者的HbA2和2例患者的抗碱血红蛋白(HbF)增高。3例患者的双亲一方为遗传性球形红细胞增多症(HS)指标异常,另一方为β地中海贫血(βTh)。结论:3例患者均并存HS和βTh。HS和βTh并存时会明显干扰溶血试验特别是红细胞膜病的实验指标,这种情况必须特别注意血象提示和形态学提示,并进行溶血系统分析和家系调查。     

Atypical pharmacokinetics of atazanavir in an HIV-1-infected patient

An HIV-infected patient with very low atazanavir (ATV) plasma trough concentrations despite clinical signs of poor drug tolerability was described. By therapeutic drug monitoring (TDM), the authors found that the patient had an atypical ATV pharmacokinetics characterized by rapid drug absorption followed by very fast drug clearance probably attributable to his genetic background. This case underlines the importance of traditional and pharmacogenetic-based TDM for the individualization of ATV therapy in HIV-1 patients.     

Effect of epoetin zeta for correction of renal anemia in hemodialysis patients with thalassemia minor

Two patients with thalassemia minor and end-stage renal failure on hemodialysis were treated with epoetin zeta (Silapo®, Retacrit®; STADA, Germany), a medicinal product that was developed and registered as biosimilar to epoetin alfa. Dosing was titrated individually for two patients to achieve a stable hemoglobin (Hb) concentration of 10.5–12.0 g/dL. One patient was treated intravenously with epoetin zeta; the other patient was treated subcutaneously. After 12 weeks of therapy both patients achieved Hb levels within the target range, confirming the effi cacy of epoetin zeta in patients with thalassemia minor.     

Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.     

A case of non-cirrhotic portal hypertension associated with anti-retroviral therapy in a Japanese patient with human immunodeficiency virus infection

The diagnosis of non-cirrhotic portal hypertension (NCPH), a rare but potentially life-threatening complication in human immunodeficiency virus (HIV)-positive individuals, often occurs only after the emergence of fatal manifestations such as bleeding of esophageal varices. We herein report a female Japanese HIV patient who developed NCPH approximately 4 years after discontinuation of 65 months of didanosine (ddI) administration. The patient presented with severe ascites, bloody bowel discharge, extreme abdominal swelling, and symptoms of portal hypertension but no sign of liver cirrhosis. Examination revealed esophageal varices, oozing-like bleeding from a wide part of the colon, significant atrophy of the right lobe of the liver, and arterio-portal shunting and recanalization from the left medial segment branch of the portal vein to a paraumbilical vein, but no visible obstruction of the main trunk of the portal vein. Treatment for esophageal varices consisted of coagulation therapy with argon plasma after enforcement by endoscopic sclerotherapy and oral administration of β-blockers for elevated portal blood pressure. The patient has not experienced gastrointestinal bleeding in the approximately 5 years since the diagnosis of NCPH. Reviewing this case suggests the importance of suspecting NCPH in HIV patients with liver dysfunction of unknown etiology with a history of ddI and other purine analogs use, as well as the importance of controlling portal hypertension and esophageal varices in the treatment of NCPH.     

用1升全血中平均血红蛋白密度鉴别诊断缺铁性贫血和地中海贫血特征

目的探讨1升全血中平均血红蛋白密度(MDHLWB)鉴别诊断缺铁性贫血(IDA)和地中海贫血特征(TT)的临床价值。方法根据物理学"密度"的概念建立了一个新的红细胞参数MDHLWB[MDHLWB=(MCH/MCV×10-3)×RBC计数]。随机选取经血液表型分析诊断的150例IDA和166例TT成年病例,用ROC曲线分析确定MDHLWB鉴别诊断TT和IDA的cutoff值。以分子诊断并结合铁代谢指标分析作为金标准,将MDHLWB和文献报道的IDA和TT鉴别诊断指标用于296例临床小细胞低色素贫血个体的鉴别诊断以评估MDHLWB的临床应用价值。结果 MDHLWB鉴别成年男、女IDA与TT的最佳cutoff值分别为男1.736和女1.493。MDHLWB诊断TT的敏感性(SE)、特异性(SP)、阳性预测值(PPV)、阴性预测值(NPV)、诊断效率(EDF)和约登指数(Youden’s index,YI)分别为96.32%、90.98%、92.90%、95.28%、93.92%和0.873,优于其他鉴别诊断指数。结论 MDHLWB可快速、有效地鉴别诊断单纯性的IDA和TT。     

Immune reconstitution to parvovirus B19 and resolution of anemia in a patient treated with highly active antiretroviral therapy

Immune reconstitution inflammatory syndrome (IRIS) is an unsolved problem in the treatment of human immunodeficiency virus (HIV)-1 infection. Despite the high seroprevalence of parvovirus B19 (PVB19) among HIV-1-positive patients, reports on PVB19-induced anemia, especially that associated with PVB19-related IRIS, in these patients are limited. We present the case of a man with acquired immunodeficiency syndrome who developed severe transfusion-dependent anemia and was seropositive and borderline positive for immunoglobulin-M and IgG antibodies against PVB19, respectively. PVB19-DNA was also detected in his serum. The patient was diagnosed with pure red cell anemia (PRCA) caused by a primary PVB19 infection and was treated with periodical blood transfusions. However, he subsequently tested negative for IgG antibodies and developed chronic severe anemia with high levels of PVB19 viremia. This indicated a transition from primary to persistent infection. After initiation of highly active antiretroviral therapy, the patient showed an inflammatory reaction with rapid deterioration of anemia and seroconversion of the IgG antibody to PVB19. Subsequently, PRCA was completely resolved, but the patient’s serum still contained low levels of PVB19-DNA. Thus, this was a case of IRIS associated with PVB19 infection. Our report highlights the significance of seroconversion to PVB19 in the diagnosis of IRIS and re-emphasizes the finding that persistently high levels of PVB19 viremia after primary infection are probably because of the lack of protective antibodies.     

Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy.

The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed alpha1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that alpha1 circle numbers in blood remain high for the first 10-15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, alpha1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal alpha1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on alpha1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in alpha1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as alpha1 circle numbers are normal in a substantial subset of HIV-1-infected individuals.     

Impact of IFN‐β1a in treatment of a COVID‐19 patient with beta thalassemia and diabetes mellitus: A case report

Patients with chronic diseases are severely affected by acute coronavirus syndrome. In this regard, patients with beta thalassemia intermedia and diabetes mellitus (DM) are also at high risk for coronavirus‐induced respiratory failure. The present study aimed to report a case with COVID‐19 with a history of chronic diseases, beta thalassemia intermedia, and DM. A 25‐year‐old man visited with complaints of severe shortness of breath, fever, cough without sputum, and tachypnea and admitted to the Intensive Care Unit. The patient had a history of DM, beta thalassemia intermedia, and pervious history of the splenectomy. In peripheral complete blood count (CBC diff), the number of white blood cell count was 41,100 of which 38.6% were lymphocytes. We measured the normal platelet count, hemoglobin level (9.4), and red blood cell count (3.56). ESR was 97, CRP = pos+++ and PCR was positive. The high‐resolution lung CT indicated ground glass opacities in peripheral areas. The patient underwent 13 days of oxygen therapy with reservoir bag‐mask, non‐invasive ventilation, nasal oxygen, and pharmacological treatment with IFN‐β1a and meropenem, and finally discharged with an improvement of the clinical condition. Timely initiation of treatment is very important and significant for patients with beta thalassemia intermedia with COVID‐19, especially despite the underlying disease of DM. According to the present report, the use of IFN‐β1a was effective as a treatment option for COVID‐19.     

Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia

BackgroundStroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha‐thalassemia and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha‐thalassemia and G6PD(A⁻) variant with abnormal TCD velocities among Nigerian children with SCA.MethodsOne hundred and forty‐one children with SCA were recruited: 72 children presented with normal TCD (defined as the time‐averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha‐thalassemia (the α‐3.7 globin gene deletion) was determined by multiplex gap‐PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism—polymerase chain reaction.ResultsThe frequency of α‐thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α‐/ α α: 41.7%, α ‐/ α ‐: 11.1%] versus 21/69 (30.4%) [α‐/ α α: 27.5%, α ‐/ α ‐: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α‐thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20–0.78, p = 0.007]. However, the frequencies of G6PDA⁻ variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).ConclusionOur study reveals the protective role of α‐thalassemia against the risk of abnormal TCD in Nigerian children with SCA.     

Tumour necrosis factor alpha in fat redistribution syndromes associated with combination antiretroviral therapy in HIV-1-infected patients: potential role in subcutaneous adipocyte apoptosis

BACKGROUND: The pathogenesis of fat redistribution syndromes (FRS) observed in the setting of highly active antiretroviral therapy (HAART) for the treatment of HIV-1-infection remains elusive. A dysregulation of the tumour necrosis factor alpha (TNF-alpha) system occurs in HIV-infected patients with FRS. MATERIALS AND METHODS: The study looked at both the in vivo and in vitro relationship between TNF-alpha and the degree of subcutaneous adipocyte apoptosis in 60 HIV-1-infected patients on HAART with FRS, another 60 HIV-1-infected patients on HAART without FRS and 60 uninfected control patients. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP (deoxyuridine 5'-triphosphate)-digoxigenin Nick End Labelling (TUNEL) method. Soluble receptors of TNF-alpha were determined by the sandwich enzyme immunoassay technique. The in vitro viability was assessed by staining with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and apoptosis by TUNEL. RESULTS: HIV-1-infected patients with FRS had significantly higher degrees of subcutaneous adipocyte apoptosis than those without FRS (P = 0.0001) and uninfected controls (P < 0.0001). There was a statistically significant association between serum levels of soluble TNF-alpha receptors #1 and #2 and the degree of subcutaneous adipocyte apoptosis in patients with and without FRS (P < 0.0001 for both receptors). In vitro, the addition of TNF-alpha (10 ng mL(-1)) to an adipocyte culture embedded with indinavir, either alone or in clinically relevant combinations with stavudine (d4T) and lamivudine (3TC), significantly decreased adipocyte viability (P = 0.0001) and increased adipocyte apoptosis (P < 0.0001) with respect to that observed with the addition of antiretrovirals alone. CONCLUSIONS: TNF-alpha plays a significant role in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infected patients on highly active antiretroviral therapy.     

Mutations to the probe of Cobas TaqMan HIV-1 ver. 1.0 assay causing undetectable viral load in a patient with acute HIV-1 infection

We encountered a human immunodeficiency virus (HIV)-1 in which the viral load was undetectable with the Cobas TaqMan HIV-1 ver. 1.0 (CTM v.1.0) in a patient with acute HIV-1 infection. The CTM v.1.0 assay showed more than 1,000-fold underestimation compared with the subsequent Cobas Amplicor Monitor v.1.5 assay. Because five mismatches to the CTM v.1.0 assay probe in the HIV-1 virus in the patient were disclosed by the manufacturer, partial gag regions of the HIV genome were directly sequenced from the patient’s plasma viral RNA. The detected single nucleotide point mutations were located near the 5′-end of the Cobas Amplicor Monitor probe. Clinicians should be very careful in making interpretations when indeterminate Western blot analysis results and a low or even undetectable HIV-1 viral load are encountered with the CTM HIV-1 ver. 1.0 assay in patients with suspected acute HIV infection. Repeating Western blot analysis is essential before considering a low HIV-1 viral load to be a false-positive result.     

Evaluation of the diagnostic performance of the rapid test VIKIA HIV1/2 in a highly complex HIV-1 epidemic

The rapid test VIKIA HIV1/2 was evaluated in 210 Angolan subjects infected with multiple HIV-1 subtypes and complex recombinant forms and 225 seronegative individuals. All infected subjects tested positive (100% sensitivity); all seronegative subjects tested negative (100% specificity). VIKIA HIV1/2 is highly specific and sensitive even in highly complex epidemics.     

Safety and durability in a cohort of HIV-1 positive patients treated with once and twice daily darunavir-based therapy (SCOLTA Project)

Objective

To evaluate safety and durability of once-daily and twice-daily darunavir/ritonavir (DRV/r)-based treatment in HIV patients in clinical practice.

Methods

The Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) project is a prospective, observational, multicenter cohort created to assess the incidence of adverse events in patients receiving new antiretroviral drugs. Twenty-five Italian infectious diseases centers enroll patients and collect their data through this on-line system. Periodical evaluations of these patients, including physical examination and laboratory tests, were performed at baseline and every 6 months.

Results

Four hundred and twenty-nine patients were enrolled since May 2006. Eighty-five patients (19.8%) were prescribed once-daily DRV/r; 31 of them were treatment-naïve (36.5%). Among 54 (63.5%) treatment-experienced patients, 21 (38.9%) had undetectable viral load and started once-daily DRV/r as a simplification regimen. Patients on twice-daily regimen were older, more frequently lipodystrophic, HCV-coinfected, and in CDC stage C. In the following 24 months of follow-up, the viral load steadily decreased as well as the CD4 cell count rose. The reason for discontinuation did not significantly differ between groups. Mean blood glucose (BG) change from baseline did not show significant difference between groups, as well as high density lipoprotein cholesterol (HDL-C), triglycerides (TGL) and alanine transaminase (ALT). The survival curve shows that patients in the once-daily regimen withdrew treatment more frequently than those on twice-daily regimen (Log Rank Chi²P = 0.009).

Conclusion

Our study showed that DRV/r administrated both once daily or twice daily was safe and well tolerated with few discontinuations due to adverse events.     

Effectiveness of an early switch from intravenous to oral antimicrobial therapy for lower respiratory tract infection in patients with severe motor intellectual disabilities

An early switch from intravenous to oral antimicrobial therapy is useful for reducing the duration of the hospitalization in adult patients with community acquired-pneumonia, whereas the efficacy of switch therapy for pediatric patients with community acquired (CA)-lower respiratory tract infection (LRTI) is uncertain. The aim of this study is to investigate the efficacy of switch therapy for LRTI in patients with severe motor intellectual disabilities (SMID). This retrospective study was performed on 92 patients with SMID who were admitted to the Department of Pediatrics at the Hospital of University of Occupational and Environmental Health, Japan from April 1, 2010 to March 31, 2017 for the suspicion of bacterial LRTI and were initially treated with an intravenous antimicrobial agent. Clinical outcomes were compared between patients with switch therapy (Switch therapy group) and conventional intravenous antimicrobial therapy (No switch therapy group). Thirteen and 79 in patients with SMID belonged to Switch thrapy group and No switch therapy group, respectively. Length of hospital stay in Switch therapy group was significantly shorter than that in No switch therapy group (P = 0.002). In the patients undergoing switch therapy, there was no patient who required re-treatment and/or re-hospitalization. Switch therapy for LRTI was useful for the reduction of length of hospital stay without increasing risk of re-treatment and re-hospitalization in patients with SMID.