Human leukocyte antigen association with azathioprine-induced drug hypersensitivity reactions in patients with anti-neutrophil cytoplasmic antibody associated vasculitis

Azathioprine (AZA) drug hypersensitivity reaction (DHR) is an uncommon yet potentially lethal condition that often goes unrecognised in patients with anti-Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV). We conducted a retrospective review of AAV patients on AZA maintenance therapy (N = 35). Participants were categorised into those who had experienced AZA-DHR (N = 15) and those who were AZA-tolerant (N = 20). Human leukocyte antigen (HLA) typing was performed in both groups. The primary endpoint was identification of a HLA gene association with AZA-DHR in the context of AAV. HLA-C*06:02, was solely expressed in AZA-DHR patients (33.3 %), whilst no patient who tolerated AZA carried this allele (0.0 %). This yielded a positive predictive value of 100 % for HLA-C*06:02 in predicting AZA-DHR in AAV patients, negative predictive value of 66.7 %, sensitivity of 33.3 % and specificity of 100 %. HLA-C*06:02 may predict the development of AZA-DHR in patients with AAV and inform safer therapeutic choice.     

Subchondroplasty in the treatment of bone Marrow lesion in early Knee Osteoarthritis: A systematic review of clinical and radiological outcomes

BackgroundKnee osteoarthritis (KOA) is increasingly prevalent in North American society. The significant societal burden it represents makes it essential to promote and target new treatments in earlier phases of the disease. Among others, subchondroplasty is a newly documented technique using calcium phosphate injection targeting the osteochondral lesions preceding KOA, also known as Bone Marrow Lesions (BMLs). This article aimed to review the existing literature on clinical and radiological outcomes of subchondroplasty in the treatment of BMLs in KOA.MethodA systematic review was performed using PubMed, Embase, Medline and Cochrane Database of Systematic Reviews. Studies on calcium phosphate injections into BMLs for KOA and its clinical and radiological outcomes were screened and reviewed by independent evaluators.ResultsAfter screening, ten articles were included, totaling 540 patients. Follow-up ranged from 6 months to 7 years. Overall, the procedure showed significant functional and quality of life improvement, as well as pain relief, as shown by Patients-Reported Outcomes Measures (PROMs). There were very few complications reported, the most important being leakage of calcium phosphate outside the targeted site. Conversion rate to total knee arthroplasty (TKA) ranged from 14 % to 30 % at 2 years post-procedure. Long term radiological outcomes have been poorly documented.ConclusionsSubchondroplasty is a promising avenue for the treatment of KOA. However, quality evidence is still required before any real conclusions and practical management guidelines can be drawn. Prospective, randomized studies with a control group and a rigorous assessment of long-term clinical and radiological outcomes are recommended.     

Ghrelin level as a biomarker for knee osteoarthritis severity and appearance in HIV + patients

BackgroundKnee Osteoarthritis (KOA) is a multifactorial disease with several mechanisms to promote articular cartilage damage. New molecules, such as ghrelin, have been recently reported to participate in the pathogenesis and progression of KOA. In HIV + patients, arthralgias are the most frequent musculoskeletal manifestations, mainly affecting joints such as the knee. Also, it has been reported that HIV + patients have a reduction of ghrelin even with treatment compared to HIV- patients. However, there is no report in the literature evaluating ghrelin and KOA in the HIV + population. We aimed to evaluate whether serum ghrelin levels can function as a biomarker for OA in HIV + patients.MethodsWe recruited 40 patients, 20 HIV+, and 20 HIV- controls, and grouped as follows: HIV+/KOA+; HIV+/KOA-; HIV-/KOA+; HIV-/KOA-. Clinical features were obtained during clinical visits. Peripheral blood samples were acquired to measure serum ghrelin levels.ResultsThe HIV+/KOA + group significantly reduced serum ghrelin levels when compared with the other groups. Comparing the ghrelin levels with the patients’ nadir of CD4⁺ T-cells count, we identified a statistically significant negative correlation in the KOA- group (r = −0.80, P < 0.007). An ROC curve analysis, for the accuracy of ghrelin levels to identified HIV+/KOA + from HIV+/KOA- patients, found an area under the curve of 0.83 (95 % CI 0.65–0.10; P = 0.017), with a cut-off < 4026 pg/mL serum ghrelin levels, with a sensitivity of 0.62 (95 % CI 0.32–0.86), and a specificity of 0.10 (95 % CI 0.59–0.10).ConclusionThis study shows the potential use of ghrelin levels as a biomarker for KOA in the high-risk HIV population that should be further analyzed.     

Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD

BackgroundThe clinical significance of rare mutations in LDL metabolism genes on nonalcoholic fatty liver disease (NAFLD) severity is not well understood.ObjectiveTo examine the significance of mutations in LDL metabolism genes including apolipoprotein B (APOB), proprotein convertase subtilisin kexin 9 (PCSK9) and LDL receptor (LDLR) in patients with NAFLD.MethodsPatients with biopsy-confirmed NAFLD from the NASH Clinical Research Network studies were stratified into 3 groups of LDL-C (≤50 mg/dL, 130–150 mg/dL, ≥ 190 mg/dL) and then 120 (40 per group) were randomly selected from the strata. We examined the presence of mutations on LDL genes and analyzed its association with selected NAFLD-related features. Multivariable analyses were adjusted for age, race, gender and use of statins.ResultsAmong 40 patients with LDL-C ≤ 50 mg/dL, 7 (18%) patients had heterozygous variants in APOB and 2 had heterozygous variants in PCSK9 (5%). We also found heterozygous mutations in 3 (8%) patients with LDL-C ≥ 190 mg/dL; 2 and 1 located in LDLR and APOE genes, respectively. Compared to wild-type controls with LDL-C ≤ 50, APOB carriers displayed higher levels of alanine aminotransferase (85.86 ± 35.14 U/L vs 45.61 ± 20.84 U/L, Adj. P = 0.002) and steatosis >66% (57% vs 24%, Adj. P = 0.050). These associations remained statistically significant after excluding statin users. Other histological features of NAFLD severity were not different between wild-type controls and APOB mutation carriers.ConclusionMutations in the APOB gene are common among NAFLD patients with very low LDL-C and may be associated with increased aminotransferase levels and steatosis severity.     

Fluorescence in situ hybridization for detecting Coxiella burnetii in tissue samples from chronic Q fever patients

ObjectiveDetection of the intracellular bacterium Coxiella burnetii, causative agent of chronic Q fever, is notoriously difficult. Diagnosis of and duration of antibiotic treatment for chronic Q fever is partly determined by detection of the bacterium with polymerase chain reaction (PCR). Fluorescence in situ hybridization (FISH) might be a promising technique for detecting C. burnetii in tissue samples from chronic Q fever patients, but its value in comparison with PCR is uncertain. We aim to assess the value of FISH for detecting C. burnetii in tissue of chronic Q fever patients.MethodsFISH and PCR were performed on tissue samples from Dutch chronic Q fever patients collected during surgery or autopsy. Sensitivity, specificity, and overall diagnostic accuracy were calculated. Additionally, data on patient and disease characteristics were collected from electronic medical records.ResultsIn total, 49 tissue samples from mainly vascular walls, heart valves, or placentas, obtained from 39 chronic Q fever patients, were examined by FISH and PCR. The sensitivity and specificity of FISH compared to PCR for detecting C. burnetii in tissue samples from chronic Q fever patients was 45.2% (95% confidence interval (CI), 27.3% – 64.0%) and 84.6% (95% CI, 54.6% – 98.1%), respectively. The overall diagnostic accuracy was 56.8% (95% CI, 42.2% - 72.3%). Two C. burnetii PCR negative placentas were FISH positive. Four FISH results (8.2%) were deemed inconclusive because of autofluorescence.ConclusionWith an overall diagnostic accuracy of 57.8%, we conclude that FISH has limited value in the routine diagnostics of chronic Q fever.     

COVID-19 infection and vaccination rarely impact HLA antibody profile in waitlisted renal transplant candidates- a multicenter cohort

Although rare, infection and vaccination can result in antibodies to human leukocyte antigens (HLA). We analyzed the effect of SARS-CoV-2 infection or vaccination on HLA antibodies in waitlisted renal transplant candidates. Specificities were collected and adjudicated if the calculated panel reactive antibodies (cPRA) changed after exposure. Of 409 patients, 285 (69.7 %) had an initial cPRA of 0 %, and 56 (13.7 %) had an initial cPRA > 80 %. The cPRA changed in 26 patients (6.4 %), 16 (3.9 %) increased, and 10 (2.4 %) decreased. Based on cPRA adjudication, cPRA differences generally resulted from a small number of specificities with subtle fluctuations around the borderline of the participating centers’ cutoff for unacceptable antigen listing. All five COVID recovered patients with an increased cPRA were female (p = 0.02). In summary, exposure to this virus or vaccine does not increase HLA antibody specificities and their MFI in approximately 99 % of cases and 97 % of sensitized patients. These results have implications for virtual crossmatching at the time of organ offer after SARS-CoV-2 infection or vaccination, and these events of unclear clinical significance should not influence vaccination programs.     

Association between SARS-CoV-2 infection and de novo HLA donor specific antibody production in lung transplant recipients: Single-center study

The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients. Respiratory viral infections may be associated with de-novo HLA donor-specific antibody production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in lung transplant recipients include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo HLA donor specific antibody production in lung transplant recipients. We performed a retrospective chart review of 24 consecutive lung transplant recipients diagnosed with COVID-19 to investigate this concern. We observed no significant differences in the CPRA or MFI levels of HLA class I and II antibodies pre- COVID-19 compared to 1 and 6 months post-COVID-19 diagnosis in 11/24 (45.8 %) LTR (p = 0.98 and p = 0.63 respectively). HLA class I and II DSA were detected in 5/24 LTR pre-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.89). De-novo HLA class I and II DSA were detected in 1/24 (4.2 %) LTR at one month post-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.54). Our results suggest that there was no significant association between SARS-CoV-2 infection and immunomodulation on pre-existing or de novo HLA donor specific antibodies.     

Clostridioides difficile colonization among very young children in resource-limited settings

ObjectivesTo describe the epidemiology and risk factors for Clostridioides difficile (C. difficile) colonization among young children in eight low-resource settings.MethodsWe tested 41 354 monthly non-diarrhoeal and diarrhoeal stools for C. difficile toxin genes (TcdA and TcdB) using quantitative PCR (qPCR) in 1715 children from birth to age two years in a multisite birth cohort study. We estimated the prevalence, cumulative incidence, and seasonality of C. difficile colonization and investigated the associations of C. difficile detection with risk factors of infection, markers of enteropathy, and growth.ResultsThe prevalence of C. difficile detection was lower in diarrhoeal (2.2%; n = 151/6731) compared to non-diarrhoeal stools (6.1%; n = 2106/34 623). By 24 months of age, the cumulative incidence of C. difficile varied widely by site, with 17.9% (n = 44; Pakistan) to 76.3% (n = 148; Peru) of children having at least one positive stool. Only Bangladesh and Pakistan had seasonal differences in C. difficile detection. Female sex (adjusted risk ratio (aRR): 1.18; 95% CI: 1.02–1.35), cephalosporin use in the past 15 days (aRR: 1.73; 95% CI: 1.39–2.16), and treated water (aRR: 1.24; 95% CI: 1.02–1.50) were risk factors for C. difficile positivity. The presence of C. difficile was significantly associated with elevated faecal myeloperoxidase, neopterin, and α-1-antitrypsin, but no associations were found between C. difficile and child growth at 24 months of age.DiscussionC. difficile colonization among children ages 0–2 years was variable across low-resource settings. Significant elevation of intestinal inflammation and barrier disruption markers associated with C. difficile detection suggests a subclinical impact of colonization.     

Performance of Xpert Ultra nasopharyngeal swab for identification of tuberculosis deaths in northern Tanzania

ObjectiveNumerous tuberculosis (TB) deaths remain undetected in low-resource endemic settings. With autopsy-confirmed tuberculosis as our standard, we assessed the diagnostic performance of Xpert MTB/RIF Ultra (Ultra; Cepheid) on nasopharyngeal specimens collected postmortem.MethodsFrom October 2016 through May 2019, we enrolled pediatric and adult medical deaths to a prospective autopsy study at two referral hospitals in northern Tanzania with next-of-kin authorization. We swabbed the posterior nasopharynx prior to autopsy and tested the samples later by Ultra. At autopsy we collected lung, liver, and, when possible, cerebrospinal fluid for mycobacterial culture and histopathology. Confirmed tuberculosis was defined as Mycobacterium tuberculosis complex recovery by culture with consistent tissue histopathology findings; decedents with only histopathology findings, including acid-fast staining or immunohistochemistry, were defined as probable tuberculosis.ResultsOf 205 decedents, 78 (38.0%) were female and median (range) age was 45 (0,96) years. Twenty-seven (13.2%) were found to have tuberculosis at autopsy, 22 (81.5%) confirmed and 5 (18.5%) probable. Ultra detected M. tuberculosis complex from the nasopharynx in 21 (77.8%) of 27 TB cases (sensitivity 70.4% [95% confidence interval {CI} 49.8–86.2%], specificity 98.9% [95% CI 96.0–99.9%]). Among confirmed TB, the sensitivity increased to 81.8% (95% CI 59.7–94.8%). Tuberculosis was not included as a death certificate diagnosis in 14 (66.7%) of the 21 MTBc detections by Ultra.DiscussionNasopharyngeal Ultra was highly specific for identifying in-hospital tuberculosis deaths, including unsuspected tuberculosis deaths. This approach may improve tuberculosis death enumeration in high-burden countries.     

Under-correction of preoperative varus alignment does not lead to a difference in in-vivo bone loading in 3D-SPECT/CT compared to neutral alignment

BackgroundThe aim was to investigate the correlation of bone tracer uptake (BTU) in SPECT/CT and changes in coronal knee alignment after total knee arthroplasty (TKA). We questioned if undercorrection of preoperative varus alignment leads to a difference in BTU compared to neutral alignment.MethodsConsecutive 66 patients who received SPECT/CT before and after TKA were retrospectively included. Adjusted mechanical alignment was the alignment target. The alignment of the knee was measured on 3D-CT by selecting standardized landmarks. Maximum (mean ± SD) and relative BTU (ratio to the reference) were recorded using a previously validated localization scheme (p < 0.05).ResultsIn the native group, 20 knees were aligned (30.3%) in valgus (HKA > 181.5°), 12 (18.2%) in neutral (178.5°-181.5°) and 34 (51.5%) in varus (HKA < 178°). Overall TKA changed the alignment towards neutral. 48.5% remained in the same groups, whereas 50% of native valgus and 33% of varus knees changed to neutral after TKA. In native varus alignment mean BTU was significantly higher in some medial tibial and femoral regions (fem1ia (p = 0.010), fem1ip (p = 0.002), tib1a.mid (p = 0.005), tib1a.tray (p = 0.000), tib1p.tray (p = 0.000)); in native valgus alignment mean BTU was higher in the corresponding lateral tibial and femoral regions (fem2ip (p = 0.001), tib2a.tray (p = 0.011), tib2p.tray (p = 0.002)). After TKA, a significant decrease in femoral and tibial BTU (femoral preoperative BTU 1.64 +/-0.69; femoral postoperative BTU 0.95 +/-0.42; p = 0.000// tibial preoperative BTU 1.65 +/- 0.93; tibial postoperative BTU 1.16 +/- 0.48; p = 0.000) and an increase in patellar BTU was observed (p = 0.025). Native varus alignment correlated with a higher medial BTU decrease medially. Undercorrection of preoperative varus alignment showed no higher BTU after TKA.ConclusionPreoperative varus alignment correlated with a higher decrease in BTU in specific femoral and tibial medial regions. Preoperative valgus alignment correlated with a higher decrease in the corresponding lateral regions. Undercorrection of preoperative varus alignment did not lead to higher bone loading reflected by BTU after TKA.     

Effectiveness of hepatitis A vaccination among people living with HIV in Taiwan: Is one dose enough?

BackgroundSingle dose hepatitis A virus (HAV) vaccine had been proven its efficacy in immunocompetent but not immunocompromised hosts. We aim to investigate the effectiveness of one dose versus 2 doses HAV vaccine among people living with HIV (PLHIV).MethodWe conducted a 1:1 single center retrospective case–control study for PLHIV in Northern Taiwan. Case patients were those who received single dose HAV vaccine and controls were those who completed standard 2 doses HAV vaccine. Nationwide campaign of single dose HAV vaccine had been practiced for high risk population including PLHIV and those who had newly diagnosed sexually transmitted diseases.ResultsDuring February 2016 and December 2017, 90 cases received single dose HAV vaccine provided while the other 90 age-matched controls received 2 doses vaccine were enrolled. We found more injection drug users (22.22% vs. 1.11%, p < 0.0001), more co-infection with viral hepatitis C (28.89% vs. 5.56%, p < 0.0001), and history of syphilis infection (56.67% VS 30%, p = 0.0003) in single dose group than 2 doses group. Seroconversion rate at one year was significantly higher in 2 doses group (97.78% vs 56.67%, p < 0.0001). Among single dose group, people with hepatitis B or C virus co-infection (HBV: p = 0.02, aOR: 0.03, 95% CI: 0.002–0.55; HCV: p = 0.002, aOR: 0.22, 95% CI: 0.08–0.58) were less likely to achieve seropositivity, while those who had higher CD4 count at baseline and one year, had better response to vaccine.ConclusionTwo doses HAV vaccine is necessary among PLHIV to achieve sustained seroresponse rather than single dose.     

Prevalence and risk factors for endogenous fungal endophthalmitis in adult patients with candidemia at a tertiary care hospital in the Republic of Korea over 13 years

BackgroundEndogenous fungal endophthalmitis (EFE) is a critical complication of candidemia. We conducted a study to investigate the prevalence and risk factors for EFE.MethodsAdult candidemia patients ≥ 19 years who underwent an ophthalmological examination at a tertiary care hospital in the Republic of Korea from 2006 to 2018 were enrolled.ResultsThere was a total of 152 adult candidemia patients analyzed. EFE was found in 29 patients (19.1%). Patients were categorized into two groups (Non-endophthalmitis [NE] and endophthalmitis [E]). Between the two groups, there was no significant difference in terms of age, sex, and underlying comorbidities. However, there were more Candida albicans candidemia, abnormal alanine aminotransferase (ALT) at the time of candidemia diagnosis, receipt of antifungal treatment ≥ 48 hours after onset of candidemia symptoms and blood culture sample (AOCS), and candidemia clearance ≥ 5 days after initiation of antifungal treatment (AIAT) in the E group. A predictive model for the E was created, which had an area of 0.811 under the receiver operating characteristics curve. In a multivariate logistic regression analysis, C. albicans candidemia, ALT at the time of candidemia diagnosis, receipt of antifungal treatment ≥ 48 hours AOCS, and candidemia clearance ≥ 5 days AIAT were significantly associated with EFE.ConclusionEFE occurred in 19% of adult patients with candidemia. Adult candidemia patients with C. albicans candidemia, abnormal ALT, receipt of antifungal treatment ≥ 48 hours AOCS, and candidemia clearance ≥ 5 days AIAT need to be closely monitored for the possibility of EFE.     

Virtual crossmatch for deceased donor kidney transplantation in the United States: A survey of histocompatibility lab directors and transplant surgeons

Virtual crossmatch (VXM) is used as an alternative to or in conjunction with a cell-based physical crossmatch (PXM) for assessing HLA (human leukocyte antigen) compatibility prior to deceased donor kidney transplantation (DDKT). Data on practice patterns and perceptions regarding VXM use in the US are limited. We performed a survey of US HLA directors and transplant surgeons regarding HLA testing and crossmatch strategies. 53 (56 %) HLA directors and 68 surgeons (representing ～ 23 % of US transplant centers) completed the survey. Both groups agreed that VXM could reduce cold ischemia time (CIT), costs and improve allocation efficiency. VXM use increased following the 2021 kidney allocation change. Reducing CIT was the primary reason for favoring VXM over PXM. Preference for VXM reduced as candidates’ panel reactive antibodies increased. Regulations, program policies and limitations of HLA technology were cited as important reasons for preferring PXM over VXM. Surgeons reported similar perceptions, but findings are limited by the low response rate. Finally, half the labs reported lacking specific protocols for VXM use. In conclusion, improved HLA technology and protocols along with changes to institutional procedures and policy regulations are needed for safer expansion of VXM in DDKT.     

HLA-E*01:01 + HLA-E*01:01 genotype confers less susceptibility to COVID-19, while HLA-E*01:03 + HLA-E*01:03 genotype is associated with more severe disease

BackgroundHLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8⁺ T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have different levels of expression and affinity for MHC Ia-derived peptide raises the question of whether HLA-E polymorphisms affect susceptibility to COVID-19 or its severity.Methods104 COVID-19 convalescent plasma donors with/without history of hospitalization and 18 blood donors with asymptomatic COVID-19, all were positive for anti-SARS-CoV-2 IgG antibody as well as a group of healthy control including 68 blood donors with negative antibody were subjected to HLA-E genotyping. As a privilege, individuals hadn’t been vaccinated against COVID-19 and therefore naturally exposed to the SARS-CoV-2.ResultsThe absence of HLA-E*01:03 allele significantly decreases the odds of susceptibility to SARS-CoV-2 infection [p = 0.044; OR (95 %CI) = 0.530 (0.286 – 0.983)], suggesting that HLA-E*01:01 + HLA-E*01:01 genotype favors more protection against SARS-CoV-2 infection. HLA-E*01:03 + HLA-E*01:03 genotype was also significantly associated with more severe COVID-19 [p = 0.020; 2.606 (1.163 – 5.844)ConclusionHere, our observation about lower susceptibility of HLA-E*01:01 + HLA-E*01:01 genotype to COVID-19 could be clinical evidence in support of some previous studies suggesting that the lower affinity of HLA-E*01:01 to peptides derived from the leader sequence of MHC class Ia may instead shift its binding to virus-derived peptides, which then facilitates target recognition by restricted conventional CD8⁺ T cells and leads to efficient cytolysis. On the other hand, according to other studies, less reactivity of HLA-E*01:01 with NKG2A abrogates NK cells or T cells inhibition, which may also lead to a greater cytotoxicity against SARS-CoV-2 infected cells compared to HLA-E*01:03. Taken together given HLA-E polymorphisms, the data presented here may be useful in identifying more vulnerable individuals to COVID-19 for better care and management. Especially since along with other risk factors in patients, having HLA-E*01:03 + HLA-E*01:03 genotype may also be associated with the possibility of severe cases of the disease.     

Outcomes of corticosteroid treatment in critical Ill adult patients with respiratory viruses-related community acquired pneumonia – a propensity-matched case control study

ObjectivesTo assess the outcomes of corticosteroid treatment in critically ill patients with respiratory virus–related community-acquired pneumonia (CAP).Materials/methodsAdult patients who were admitted to the intensive care unit and had a polymerase chain reaction–confirmed diagnosis of respiratory virus–related CAP were included. Patients with and without corticosteroid treatment during the hospital course were retrospectively compared using a propensity score–matched case–control analysis.ResultsFrom January 2018 to December 2020, 194 adult patients were enrolled with 1:1 matching. The 14-day and 28-day mortality rates did not differ significantly between patients treated with and without corticosteroids (14-day mortality: 7% versus 14%, P = 0.11; 28-day mortality: 15% versus 20%, P = 0.35). However, multivariate analysis by using a Cox regression model revealed that corticosteroid treatment was an independent factor predicting decreased mortality (adjusted odds ratio, 0.46; 95% confidence interval, 0.22–0.97, P = 0.04). Subgroup analysis revealed lower 14-day and 28-day mortality rates in patients younger than 70 years treated with corticosteroids than in those not treated with corticosteroids (14-day mortality: 6% versus 23%; P = 0.01 and 28-day mortality: 12% versus 27%; P = 0.04).ConclusionsNon-elderly patients with severe respiratory virus–related CAP are more likely to benefit from corticosteroid treatment than elderly patients.     

Seroepidemiology of measles in immune generation in Taiwan: Prevalence of neutralizing antibody and immune response to reimmunization

BackgroundSecondary vaccine failure was the principal mechanic of measles reemergence in countries with high measles vaccine coverage. The information on neutralizing antibody (nAb) prevalence, epidemiological factors of waned immunity and immune response after reimmunization was essential to measles control but largely lacking in Taiwan.MethodsThe nAb and factors of wanned immunity to measles were evaluated in a cohort of 333 subjects aged 11–30 years in 2010. The longitudinal immune response to reimmunization (n = 30) and potential virus exposure (n = 24) were assessed in young healthcare workers (HCWs) during a hospital outbreak. The nAb titer was used to define susceptibility to measles disease (<120 mIU/mL) and infection (120–900 mIU/mL).ResultsIn the 2010 cohort, the susceptibility to measles diseases and infections was respectively identified in 35 (10.5%) and 226 (67.9%) subjects. A generalized linear model identified earlier ages of first immunization in childhood (P = 0.0214) and subjects aged ≥18 years (versus <18 years, P = 0.0425) as significant factors associated with lower nAb titers. Reimmunization of 30 seronegative HCWs resulted in seroconversion for all, with nAb titers significantly rising on day 5, peaking on day 15 and declining in month 4 post-immunization. Similar measles-specific IgG levels were observed in 24 seropositive HCWs before and 4 months after measles contact (P = 0.2352).ConclusionA lack of protective immunity to measles diseases might be identified in 10% of the Taiwanese population aged 11–30 years and associated with a trend toward earlier ages of the first measles vaccination. The wanned immunity can be boosted promptly by reimmunization but with uncertain durability.     

Detection of influenza and non-influenza respiratory viruses in lower respiratory tract specimens among hospitalized adult patients and analysis of the clinical outcome

BackgroundLower respiratory tract infection (LRTI) is one of the most fatal diseases for adults. Influenza is a well-recognized cause of severe pneumonia; however, the outcomes of LRTI caused by non-influenza respiratory viruses (NIRVs) have not been sufficiently investigated. This study aimed to describe the characteristics and outcomes of LRTI associated with respiratory viruses (RVs) in adults.Materials/methodsA retrospective review was performed using medical records of adult patients whose lower respiratory tract (LRT) specimens (endotracheal aspirate and bronchoalveolar lavage fluid) tested positive for RVs using multiplex PCR. Underlying comorbidities, laboratory data, and clinical outcomes were analyzed.ResultsAmong the 808 LRT specimens collected from 666 adult patients, RV was identified in 115 specimens (14%) from 106 patients (16%). The underlying comorbidities and laboratory data did not differ between patients with influenza- and NIRV-related LRTI. The 14-day and 30-day mortality rates were higher in the influenza group than in the NIRV group (24% versus 7%, p = 0.03 and 33% versus 13%, p = 0.02, respectively), whereas the 90-day mortality rate did not. In a multivariate Cox model to predict 90-day mortality, shock and acute kidney injury independently predicted a higher mortality rate (hazard ratio (HR): 4.28, 95% CI: 1.46–12.58, p = 0.01 and HR: 2.80, 95% CI: 1.28–6.15, p = 0.01, respectively), whereas the detection of influenza did not.ConclusionsInfluenza and NIRVs were associated with increased mortality due to LRTI in adults. Therefore, NIRVs are among key pathogens causing LRTI and should not be neglected by clinicians.     

Mid-term results of complex primary total knee arthroplasty using a rotating-hinge implant

BackgroundThe indications and outcomes of semi- or fully-constrained knee implants in primary total knee arthroplasty (TKA) are still controversially discussed. The present study aims to evaluate the mid-term results and complications of a modular/non-modular rotating-hinge implant in complex primary TKA.MethodsEighty-two patients (86 knees) following primary TKA were retrospectively evaluated with a mean follow-up of 63 months. The functional outcome was assessed using the American Knee Society Score (AKSS) and the Oxford Knee Score (OKS). A Visual Analog Scale (VAS) was used to determine pain levels. Implant survival and reoperation rates were estimated using competing risk analysis. Cox regression analysis was performed to evaluate the influence of modularity on implant survival.ResultsThe survival rate with the endpoint implant revision was 90% (95 %CI:83–98%) and the survival rate with the endpoint all reoperations was 84% (95 %CI:75–94%) at 7 years. The AKSS improved significantly from 24 (SD 14.9, range:0–69) preoperatively to 83 (SD 14.3, range:57–100) postoperatively (p < 0.001); functional AKSS improved significantly from 27 (SD 24.3, range:0–100) to 46 (SD: 32.9, range 0–100) (p = 0.003), and OKS from 19 (SD: 8.3, range:5–43) to 29 (SD: 10.7, range:6–48), respectively (p < 0.0001). VAS decreased significantly from 8 (SD: 2.6, range:0–10) preoperatively to 3 (SD: 2.9, range:0–9) postoperatively (p < 0.0001). There was no significant influence of modularity on revision rates comparing modular to non-modular implants (p = 0.072).ConclusionsThe present rotating-hinge implant provides substantial improvement in function and reduction of pain with good implant survival in the mid-term. Modularity was not associated with higher rates of revision.     

Expression analysis of immune-regulatory molecules HLA-G,HLA-E and IDO in endometrial cancer

HLA-G has been widely implicated in advanced cancers through different pathways of immunosuppression allowing tumor escape. Contrarily, HLA-E has a controversial role in the tumor escape from the immune system. IDO catabolic enzyme is known to be up-regulated in many tumors types allowing their immune escape. Based on these considerations, we investigated the expression of HLA-G, HLA-E and IDO molecules in endometrial cancer (EC) and their association with prognostic clinicopathologic parameters. Their expression were checked in tumoral and adjacent endometrial tissues. Both HLA-G and IDO immunostaining were significantly increased in EC tissues compared to normal residual endometrial glands (Mann Whitney U-test, p = 0.0001 and p = 0,020 respectively). However, HLA-E was highly expressed in tumoral tissues as well as in normal residual endometrial glands (respectively, 100% and 81.8%). Increased HLA-G expression levels were observed in high histological grade (grade 3), and in the non-endometrioid type 2 EC. Unexpectedly, patients with IDO Low expression had significantly impaired overall survival compared to patients with IDO High (log-rank p = 0.021). Conversely, HLA-E low expression was associated to an improved overall survival EC (log-rank p = 0.004). We concluded that, HLA-G and IDO are highly expressed in EC compared to adjacent normal endometrial tissues, that might be interesting for the EC outcome.