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.     

The effects of initial graft tension on femorotibial relationship following anatomical rectangular tunnel anterior cruciate ligament reconstruction using bone–patellar tendon–bone graft

BackgroundThe purpose of this study was to elucidate the effects of the difference of initial graft tension on the femorotibial relationship on an axial plane and its chronological change following anatomical anterior cruciate ligament (ACL) reconstruction.MethodsA total of 63 patients who underwent anatomical ACL reconstruction were included in this study. The graft was fixed at full knee extension with manual maximum (higher graft tension; group H) and 80 N (lower graft tension; group L) pulls in 31 and 32 patients, respectively. The femorotibial positional relationship in axial computed tomography at 1 week and 1 year postoperatively were retrospectively evaluated. The side-to-side differences (SSDs) and the amount of changes of SSDs over 1 year were compared between groups.ResultsThe SSDs of the external rotational angle of the tibia in group H were significantly larger than those in group L at postoperative 1 week (2.7 ± 3.9° vs. 0.3 ± 3.3°; P < 0.01). The amount of internal rotational changes of SSDs of the internal–external rotational angles over 1 year in group H was significantly larger than that in group L (−3.6 ± 3.9° vs. − 0.3 ± 2.7°; P < 0.01). No significant differences were observed on the anterior–posterior translation distance and medial–lateral shift distance.ConclusionThe application of higher initial graft tension resulted in excessive external rotation of the tibia to the femur at 1 week postoperatively in anatomical ACL reconstruction, and the excessive early external tibial rotation had resolved over 1 year.     

First successful pregnancy outcome after twelve abortions in a Tunisian-woman with the rare p phenotype

IntroductionAnti-PP1P k alloantibody, is produced in the serum of individuals with the rare p phenotype. It is associated with severe haemolytic transfusion reactions, recurrent spontaneous early abortions as well as haemolytic disease of the foetus and newborn. Anti-PP1P k alloimmunization in pregnancy differ from others in their physiopathology. It seems that the placenta would be the main target of anti-PP1P k antibody.Case reportThis report concerns a 35 year old female, with a history of a high incidence (12) of early and recurrent miscarriages. She was found to have the extremely rare p phenotype and anti-PP1P k antibody in her serum. Her 13th pregnancy was successfully managed by plasmapheresis. No substitution fluid was added. Oral hydration was recommended before and after the apheresis sessions. 12 plasmapheresis cycles were performed before a healthy term female infant weighing 3 kg600 g, was delivered by caesarean section at 38 weeks of gestation.ConclusionPlasmapheresis seems to be the treatment of choice in the management of anti-PP1P k fetomaternal incompatibilities. However in this case, we opted for an original and less expensive protocol. We did resort, neither to substitution fluid nor to intravenous immunoglobulin.     

ATP7B variant spectrum in a French pediatric Wilson disease cohort

Background/aimThe spectrum of ATP7B variants varies significantly according to geographic distribution, and there is insufficient data on the variants observed in the French population.MethodsClinical data of 113 children included in the French WD national registry were gathered from March 01, 1995 to July 01, 2020. Data included epidemiological, clinical, laboratory, genetics.ResultsDiagnosis was made at a mean age of 11.0 ± 4.1 years (range 1–18 years). At diagnosis, 91 patients (79.8 %) had hepatic manifestations, 18 (15.8 %) presented neurological manifestations, and 4 patients (3.5 %) were asymptomatic. Only 29 patients (25 %) were homozygous for a variant. We have found a total of 102 different variants including 14 novel variants. Recurrent variant p.His1069Gln was the most prevalent, n = 31 alleles (14,2%), with only seven homozygous; in contrast 55% of variants are identified in only one family. 45% were truncating variants. In respect of mutated exon, the three most prevalent were exon 14 (16.5%), exon 8 (13.8%), and exon 3 (11.5%). When considering patients with two Nonsense / Frameshift variants as a group and those with two Missense variants, we found significantly lower ceruloplasmin for the former: 2.8 ± 0.7 mg/dl vs 8.4 ± 5mg/dl (p<0.05).Conclusionp.His1069Gln is the most frequent variant (14,2%) and exons 14, 8, and 2 of the ATP7B gene account for 41.7% of total variants. However, there is significant heterogeneity in the French population concerning the other ATP7B variants. Nonsense / Frameshift variants were associated with lower ceruloplasmin levels.     

Assessment of popliteal neurovascular safety during all-inside suturing of the posterior horn of the lateral meniscus using Upright MRIs of the knee joint

BackgroundTo examine the risk of injury to the popliteal neurovascular bundle (pNVB) during all-inside repair of the posterior horn of the lateral meniscus (PHLM) using Upright-MRIs.MethodsUpright-MRIs of 61 knees in extension (ext) and 90°-flexion (flex) were included. Distance D from the PHLM to the pNVB was compared between extended and 90°-flexed position, subgroups with/without joint-effusion and evaluated according to demographics. Portal safety was assessed simulating suturing of the PHLM via four arthroscopy portals. Distance d (shortest space from the simulated suturing-device trajectory lines to the pNVB) was compared among portals in increasing distances from the posterior cruciate ligament (PCL).ResultsD is longer in flex (17.3 ± 6.0 mm) than in ext (11.3 ± 4.2 mm, p < 0.0001). MRIs with joint-effusion displayed longer values of D than scans without joint-effusion (flex: 20.4 ± 7.1 mm vs. 16.1 ± 5.2 mm, p = 0.012). Shorter distances are associated with female gender, lower body weight and lower BMI. At 0 mm from the PCL, the 1 cm-lateral portal was the safest (p < 0.0001) whereas at 3 mm/6mm/9mm/12 mm the 1 cm-medial portal showed the longest d values (p < 0.0001 each).ConclusionAll-inside suturing of the PHLM is safer in 90°-flexion, in presence of intraarticular fluid and in male patients with increasing weight/BMI. Sutures of the PHLM at 0 mm from the PCL are safer from a 1 cm-lateral portal whereas for tears located ≥ 3 mm from the PCL a 1 cm-medial portal involves a lower neurovascular risk. Upright-MRI proves excellent for preoperative planning to minimize neurovascular risks.     

Anatomical description and short-term follow up clinical results for ultrasound-guided injection of medial collateral ligament bursa: New conservative treatment option for symptomatic degenerative medial meniscus tear

BackgroundIn this study, we investigated newly developed ultrasound (US)-guided medial collateral ligament (MCL) bursa injection as a conservative therapy for symptomatic degenerative medial meniscal (MM) tears. We aimed to describe the anatomical target and precise technique of this injection, confirm its accuracy using fresh cadaveric knees, and then evaluate preliminary clinical outcomes.MethodsAnatomical studies were performed on three fresh cadavers. For the clinical study, 50 patients with medial knee joint pain without knee osteoarthritis were treated with US-guided MCL bursa injection. Severity of pain was assessed pre-injection, and 1 week and 4 weeks post-injection using a 0–10 numerical rating scale (NRS). Clinical success was defined as a full return to daily activities. All patients underwent magnetic resonance imaging (MRI) within 1 week of the first injection. Patients who underwent surgery within 12 months of the first injection were investigated as clinically unsuccessful cases, and MRI and arthroscopic findings were examined.ResultsCompared with pre-injection (6.8 ± 1.2), the average NRS score was significantly lower at 1 week (1.8 ± 2.0) and at 4 weeks (1.5 ± 1.7) post-injection (both P < 0.01). The primary clinical success rate was 76.0%, and injection-related adverse events were not observed. Nine patients underwent surgery (arthroscopic surgery for degenerative flap tear (n = 7) and high tibial osteotomy for medial meniscus posterior root tear and proximal tibial malalignment (n = 2)).ConclusionsUS-guided MCL bursa injection is safe, reproducible, and effective for symptomatic MM degenerative tears. However, US-guided injections of the MCL bursa may be ineffective for flap tears and posterior root tears.     

The management and outcome of cryptococcosis in patients with different immune statuses and treatment protocols: A multicenter real-world study in Jiangsu Province - China

ObjectiveThe incidence of cryptococcosis is increasing in non-immunocompromised patients. However, the evidence on proper management is inadequate in this population. We conducted this multi-center real-world study in pulmonary cryptococcosis patients with different immune statuses, so as to provide practical evidence for optimized clinical management of cryptococcosis, especially for mild-to-moderate immunodeficient diseases patients.MethodsThis is a prospective observational study. The clinical data of patients with proven cryptococcosis were collected and analyzed from 7 tertiary teaching hospitals in Jiangsu Province, China from January, 2013 to December, 2018. Proven cases include pulmonary cryptococcosis, cryptococcal meningitis, cryptococcemia and cutaneous cryptococcosis. Patients were followed up over 24 months. According to their immune status, patients with cryptococcosis were divided into three groups, namely immunocompetent group (IC), mild-to-moderate immunodeficient diseases group (MID), severe immunodeficient diseases group (SID). Meanwhile, pulmonary crypotococcosis (PC) and extrapulmonary crypotococcosis (EPC) were also classified and analyzed.Results255 proven cases of cryptococcosis were enrolled. Finally, 220 cases completed the follow-up. 143 proven cases (65.0%) were immunocompetent (IC), 41 cases (18.6%) were MID, and 36 cases (16.4%) were SID. 174 cases (79.1%) were PC and 46 cases (20.9%) were EPC. The mortality was significantly higher in SID and MID patients [47.2% (SID) vs. 12.2% (MID) vs. 0.0% (IC), p<0.001]. The mortality was also significantly higher in EPC patients [45.7% vs. 0.6% (PC), p<0.001]. Patients with alternative initial antifungal treatment had higher mortality than patients with guideline recommended initial treatment [23.1% vs. 9.5%, p=0.041]. In MID group, the mortality of receiving alternative initial antifungal treatment was significantly higher than recommended initial treatment [2/3 vs. 3/34(8.8%), p=0.043]. In pulmonary cryptococcosis patients with MID, the mortality was very similar to IC group [0.0% vs. 0.0% (IC)], lower than SID group [0.0% vs. 11.1% (SID), p=0.555]. However, in extrapulmonary cryptococcosis patients with MID, the mortality was significantly higher than that in IC [62.5% vs. 0.0% (IC)], and similar to SID patients [62.5% vs. 59.3% (SID)].ConclusionThe immune status exert a significant influence on the management and prognosis of cryptococcosis patients. The mortality of cryptococcosis patients with MID is higher than that of immunocompetent patients. For MID patients with pure pulmonary cryptococcosis, it is acceptable to take the treatment recommended as IC patients. For the MID patients with extrapulmonary cryptococcosis, the mortality is high and the initial treatment should follow the regimen for SID patients. Following the recommended treatment regimen in the IDSA guideline can reduce mortality in patients with cryptococcosis. Starting on alternative initial antifungal treatment may bring worse outcomes.     

Loss of anti-AT1R reactivity in ELISA post-adsorption – False reactivity or interference in the assay?

Autoantibodies to Angiotensin II type 1 receptor (AT1R) are associated with detrimental outcomes in organ transplants. However, reports showed that adsorption with latex beads reduced positive anti-AT1R antibodies, suggesting possible false reactivity. To investigate this conundrum, we studied 11 samples positive for AT1R antibodies with an ELISA kit before and after adsorption. Adsorption significantly reduced the measurable level of AT1R antibodies (28.3 ± 9.8 vs. 6.3 ± 3.0 U/ml, p < 0.001). AT1R antibodies were lower when post-adsorption serum was added back at 1:1 ratio to the neat serum compared to the diluent control (8.6 ± 4.2 vs. 18.1 ± 10.3 U/ml, p = 0.02). Sham adsorption with the buffer from Adsorb Out™ kit without beads also suppressed the detection of anti-AT1R antibodies (32.7 ± 9.1 vs. 8.1 ± 3.9 U/ml, p < 0.001). Thus, rather than actively removing nonspecific antibodies by the beads, the adsorption process introduces soluble factors that interfere with the detection of anti-AT1R antibodies with the ELISA kit.     

Prevalence of lymphedema among Anderson-Fabry disease patients: A report from the Fabry registry

BackgroundAnderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities. Very limited data exist on lymphedema in AFD patients.MethodsUsing data from the Fabry Registry (NCT00196742) with 7671 patients included (44% males and 56% females), we analyzed the prevalence of lymphedema among AFD patients who were ever assessed for lymphedema and studied the age of first reported lymphedema. Additionally, we assessed whether patients received AFD-specific treatment at some point during their clinical course. The data was stratified by gender and phenotype.ResultsOur study showed that lymphedema occurred in 16.5% of the Fabry Registry patients who were ever assessed for lymphedema (n = 5487). Male patients when compared to female patient have higher prevalence (21.7% vs 12.7%) and experienced lymphedema at a younger age (median age at first reported lymphedema of 43.7 vs 51.7 years). When compared to other phenotypes, classic phenotype has the highest prevalence of lymphedema with the earliest reported lymphedema. Among those who reported lymphedema, 84.5% received AFD-specific treatment during their clinical course.ConclusionsLymphedema is a common manifestation of AFD in both genders, with a tendency to present later in female patients. Recognition of lymphedema can offer an important opportunity for intervention and potential impact on associated morbidity. Additional future studies are needed to characterize the clinical implications of lymphedema in AFD patients and identify additional treatment options for this growing population.     

Genetic diversity of HLA system in two populations from Sinaloa,Mexico: Culiacán and rural Sinaloa

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 286 Mexicans from the state of Sinaloa living in Culiacán (N = 103) and rural communities (N = 183) to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes for the state of Sinaloa include ten Native American most probable ancestry and five European most probable ancestry haplotypes. The admixture estimates revealed that the main genetic components in the state of Sinaloa are European (62.39 ± 3.47%) and Native American (37.61 ± 2.85%), while the African genetic component was estimated as virtually absent (0.00 ± 1.86%).     

Cardiomyopathy prevalence exceeds 30% in individuals with TTN variants and early atrial fibrillation

PurposeTTN truncating variants (TTNtvs) represent the largest known genetic cause of dilated cardiomyopathies (DCMs), however their penetrance for DCM in general populations is low. More broadly, patients with cardiomyopathies (CMs) often exhibit other cardiac conditions, such as atrial fibrillation (Afib), which has also been linked to TTNtvs. This retrospective analysis aims to characterize the relationship between different cardiac conditions in those with TTNtvs and identify individuals with the highest risk of DCM.MethodsIn this work we leverage longitudinal electronic health record and exome sequencing data from approximately 450,000 individuals in 2 health systems to statistically confirm and pinpoint the genetic footprint of TTNtv-related diagnoses aside from CM, such as Afib, and determine whether vetting additional significantly associated phenotypes better stratifies CM risk across those with TTNtvs. We focused on TTNtvs in exons with a percentage spliced in >90% (hiPSI TTNtvs), a representation of constitutive cardiac expression.ResultsWhen controlling for CM and Afib, other cardiac conditions retained only nominal association with TTNtvs. A sliding window analysis of TTNtvs across the locus confirms that the association is specific to hiPSI exons for both CM and Afib, with no meaningful associations in percent spliced in ≤90% exons (loPSI TTNtvs). The combination of hiPSI TTNtv status and early Afib diagnosis (before age 60) found a subset of TTNtv individuals at high risk for CM. The prevalence of CM in this subset was 33%, a rate that was 3.5 fold higher than that in individuals with hiPSI TTNtvs (9% prevalence), 5-fold higher than that in individuals without TTNtvs with early Afib (6% prevalence), and 80-fold higher than that in the general population.ConclusionOur retrospective analyses revealed that those with hiPSI TTNtvs and early Afib (～1/2900) have a high prevalence of CM (33%), far exceeding that in other individuals with TTNtvs and in those without TTNtvs with an early Afib diagnosis. These results show that combining phenotypic information along with genomic population screening can identify patients at higher risk for progressing to symptomatic heart failure.     

Approximately 80% of Japanese osteoarthritic patients fall out of the safety range in restricted kinematically-aligned total knee arthroplasty in an analysis of preoperative long-leg radiograms

BackgroundRestricted kinematically-aligned total knee arthroplasty (KA-TKA) is a reasonable modification to avoid the alignment outlier that may cause implant failure. However, despite a noted high incidence of constitutional varus in Japanese individuals, there has been no investigation into how many knees require the restriction in restricted KA-TKA (RKA-TKA) among Japanese patients. Therefore, we conducted a study using preoperative long-leg radiograms.MethodsWe studied long-leg radiographs of 228 knees in 114 consecutive patients. The numbers of knees within the safety range and their corrective osteotomy angle in the restriction algorithms advocated by Almaawi et al. (2017) and MacDessi et al. (2020) were evaluated.ResultsAccording to the algorithms used by Almaawi et al. and MacDessi et al., out of 228 knees, 46 (20%) and 39 (17%) fell within the safety range, respectively. The mean correction angles of the hip-knee-ankle angle, lateral distal femoral angle and medial proximal tibial angle were 2.8 ± 3.4°, 0.4 ± 1.4° and 2.4 ± 2.8° in the algorithm used by Almaawi et al., while they were −4.9 ± 4.7°, 1.1 ± 2.5° and −6.0 ± 3.4° in the algorithm used by MacDessi et al. Most of the knees needed to be restricted in order to perform RKA-TKA, regardless of the algorithm used.ConclusionsBased on a preoperative analysis of long-leg radiograms in a Japanese population, most knees fall out of the safety range in RKA-TKA. Surgeons must consider whether to allow component outlier or to perform corrective osteotomy that likely requires soft tissue release.     

Osteotomy around the knee: Assessment of quality,content and readability of online information

BackgroundAs knee osteotomy surgery becomes increasingly accessible, more patients may turn to the Internet for information. This study examined the source, quality, content and readability of online information regarding osteotomy around the knee.MethodsThe first 70 websites returned by the top four search engines were identified using the key words: “knee osteotomy” and “high tibial osteotomy.” The websites were categorised by type and assessed using the DISCERN score, Journal of the American Medical Association (JAMA) benchmark criteria and a novel Knee Osteotomy-Specific Score (KOSS). The presence of the Health On the Net (HON) code accreditation seal was noted. Readability of each website was assessed using eight readability formulae. The mean reading grade level (RGL) was compared to the 6th and 8th grade reading levels. The mean RGL of each category was also compared.ResultsOf the 45 unique websites analysed, the majority were Physician (33%) and Journal websites (31%). The mean DISCERN score was 36.7 (±8.9) which is classified as ‘poor.’ The mean JAMA benchmark criteria score was 2.04 (±1.5) and Physician websites were most likely to be scored zero. The mean KOSS was 15.4 (±5.7). The highest scoring website was a Commercial site but, overall, Journal category sites provided the best quality information. Websites that bore the HONcode seal obtained higher DISCERN, JAMA benchmark criteria and Knee Osteotomy - Specific Scores.The cumulative mean RGL was 13.2 (±2.2) which exceeded the 6th grade level by an average of 7.2 grade levels and the 8th grade level by an average of 5.2 grade levels. No website (0%) was written at or below either the 6th or the 8th grade reading levels. The mean Flesch Reading Ease Score of all websites was 41.13 (±14.7) which is classified as ‘difficult.’ Journal websites had the highest RGL.ConclusionThe information available online regarding osteotomy around the knee varies tremendously in quality and completeness. Physician sites predominate, but these were among the lowest scoring of all websites. Even where high quality information is available, it is set at too high a level to be easily understood.Level of evidenceSurvey of materials – Internet.     

Association of polymorphisms of innate immunity-related genes and tuberculosis susceptibility in Mongolian population

BackgroundsGenetic polymorphism of the toll-like receptor 2, 4 (TLR2, TLR4) and natural resistance-associated macrophage protein 1 (NRAMP1) genes may affect host immune response to Mycobacterium tuberculosis (Mtb) and lead to the variation of susceptibility to tuberculosis (TB) in humans. However, the association of single nucleotide polymorphisms (SNP) in these genes and the susceptibility to TB in Mongolian population has not been investigated.MethodsWe conducted a genetic association study including 197 Mongolian TB patients and 217 Mongolian healthy controls in Inner Mongolia, China. DNA of blood samples was extracted and genotyped for 5 SNPs in TLR4, 4 SNPs in TLR2 and 5 SNPs in NRAMP1 by next-generation sequencing. A logistic regression was performed and odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the risk at TB by each SNP.ResultsThe most significant locus associated with the susceptibility to TB was TLR4 rs11536889. The frequency for allele C of TLR4 rs11536889 was 16.0% in TB patients and 23.5% in healthy controls, respectively. Rs11536889 C/C genotype of TLR4 was significantly associated with the low susceptibility against TB compared to G/G genotype in the dominant model (OR 0.62, 95% CI 0.41–0.94).ConclusionsThe TLR4 rs11536889 polymorphisms might be an indicative of the low susceptibility to TB in Mongolian population, which provides valuable information for the generation of effective strategy or measurement against TB in Mongolian population.     

Impact in the quality of life of parents of children with chronic diseases using psychoeducational interventions – A systematic review with meta-analysis

ObjectiveThis study aimed to identify psychoeducational interventions applied to parents of children with chronic diseases and evaluate their impact on their quality of life (QoL).MethodsIt was conducted in six databases, complemented by references from the included studies and other reviews, manual search, and contact with experts. We included primary studies on parents of children with chronic diseases that studied psychoeducational interventions versus standard care.ResultsWe screened 6604 titles and abstracts, reviewed the full text of 60 records, and included 37 primary studies. Half of the studies were on Asthma. We found three intervention formats: one-to-one (43%), groups (49%), and combined approach with individual and group settings (8%). More than 60% of the included studies found statistically significant differences between the intervention and the control group (p < 0.05).ConclusionSeveral interventions have shown efficacy in improving parental QoL. Despite that, there is insufficient evidence of interventions' implementation.Practice implicationsA holistic approach encompassing the patient and the family's biopsychosocial dimensions is fundamental in successfully managing chronic disease in children. It is vital to design and implement interventions accommodating the common issues experienced by children, parents, and families that deal with chronic childhood conditions.Systematic review registration number PROSPERO 2018 CRD42018092135.     

Calprotectin as a novel diagnostic approach to screen male infertility risk: A pilot study

Research QuestionDiagnosis of male infertility is essentially based on the evaluation of semen quality (sperm concentration, motility, viability, and morphology). However, there is a lack of knowledge about possible molecules used as candidates for the early identification of male infertility risk. Calprotectin is a biological marker for inflammation, measured prevalently in stool specimens, widely used to discriminate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and for the subsequent monitoring of gastrointestinal diseases’ development. Would it be possible to use calprotectin determination to identify also male infertility risk?DesignCross-sectional pilot study investigated calprotectin concentration in the seminal fluid of 45 men (range: 23–51 yrs) that were under evaluation for semen quality at our Center for Reproductive Medicine. Calprotectin concentration was determined with a commercially available immuno-chromatographic test and successfully detected in 37 of the 45 analyzed men (age: 37.38 ± 6.59). A correlation with semen quality (concentration, motility, morphology) was assessed.ResultsHigher calprotectin concentration seemed to indicate a better quality of the seminal fluid. Normozoospermic subjects (Group A) had on average a calprotectin value of 0.215 ± 0.162 µg/ml (mean ± SD), while subjects with at least one of the semen parameters below reference values (Group B) showed lower calprotectin concentration (mean ± SD: 0.126 ± 0.068, p-value < 0.05). A significant difference was clearly evident between calprotectin concentration measured in seminal fluids with physiological sperm morphology (≥4%) as compared with teratozoospermic samples (<4%) (p-value < 0.05). Indeed, the developed ROC curves showed a good diagnostic accuracy (around 67 %) using calprotectin concentration (threshold value: 0.121 μg/ml) as a preliminary test to discriminate subjects with and without abnormal semen parameters, especially morphology.ConclusionsCalprotectin determination in the seminal fluid may be proposed as a biological marker for preliminary screening in male subjects at risk of infertility due to one or more alterations of semen quality.     

Nitric oxide donors offer protection to RBC from storage lesion

BackgroundRed blood cell (RBC), which is the most commonly transfused blood component, due to its ability to save a life in absence of any other blood components, can be stored up to maximum 6 weeks by following standard preservation procedure. During storage, RBC undergoes various biophysical and biochemical changes (commonly known as storage lesion) for which blood transfusion with “old RBC” shows a lot of clinical problems especially relevant to critically ill patients. Recent research on S-nitrosylation of haemoglobin to improve oxygen delivery of banked blood revealed the important role of nitric oxide (NO) in protecting storage lesion.Materials and methodsIn the present study, we used various “NO donating” chemicals with different NO release dynamics and chemistries in RBC storage cocktails to test the effects of NO on storage lesion. Changes in different storage markers were evaluated after 7 days storage of pre-treated RBC.ResultsAll the NO donors have shown protection against hemolysis. However, S-nitroso glutathione (GSNO) ranks first in shielding RBCs from storage lesion and additionally, it helps in elevating the value of 2, 3-di phosphoglycerate (2, 3-DPG), improving the RBC membrane fluidity and decreasing the adhesion towards endothelial monolayer.DiscussionPresent study reveals that NO released from NO donors confers protection against storage lesions of the RBC. Further, the study confirms that pre-treatment with GSNO, a NO donor and a nitrosylating agent, ensures the best protection to RBC during low temperature storage, when compared to other NO donor treatments.     

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.     

Respiratory pathogens – Some altered antibiotic susceptibility after implementation of pneumococcus vaccine and antibiotic control strategies

Background/purposeAntimicrobial resistance in Taiwan has been on the rise for two decades. The implementation of pneumococcal conjugate vaccination (PCV13) and enhanced antimicrobial control (2013–2015) by the government may have changed the antibiotic resistance.MethodsFour respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Moraxella catarrhalis) isolated in a single medical center during 2008–2017 were studied. We defined three temporal stages: (a) the first era (2008–2012), prior to implementation of the national immunization program (PCV13 vaccination), (b) the second era (2013–2015), during which an enhanced antibiotic control strategy was implemented, and (c) the third era (2016–2017), after implementation. Antimicrobial drug sensitivities were collected from two other hospitals: one from east Taiwan, one from west-central Taiwan.ResultsS. pneumoniae was frequently isolated during the first era. It declined progressively during the second era of PCV13 vaccination. S. pyogenes and M. catarrhalis were not frequently isolated. The drug susceptibility of S. pneumoniae to ceftriaxone and vancomycin remained high. The antimicrobial susceptibility of H. influenzae to amoxillin/clavulante declined over the three temporal stages, from 91.9%-79.5%–58.5% (all p < 0.05).ConclusionAntimicrobial resistance of H. influenzae increased during the latter part of the study period. The PCV13 vaccination program reduced the invasive pneumococcal disease and reduced the stress on the emergent drug resistance. This enhanced antibiotic control strategy was effective in terms of nosocomial drug resistance but not for community-associated pathogens.