Extensive Assessment of Underlying Etiological Factors in Primary Infertile Men Reduces the Proportion of Men With Idiopathic Infertility

ObjectiveUp to 40% of infertile men remain without a recognized cause (i.e., idiopathic infertility). We aimed to identify, categorize, and report the supposed causes of male infertility in a cohort of white-European men presenting for primary couple’s infertility, by using a thorough and extensive baseline diagnostic work-up.Material and MethodsCross-sectional study of 1,174 primary infertile men who underwent a thorough diagnostic work-up including: detailed medical history, physical examination, hormonal assessment, genetic testing, semen analyses; semen and urine cultures; testis color Duplex US. Men without any identified causal factor were considered as idiopathic. Six different etiological categories were established, and their prevalence was estimated. Logistic regression models estimated the risk of missing causal identification.ResultsA possible causal factor was identified in 928 (81%) men. Hypogonadism was the most frequent identified cause (37%), followed by varicocele (27%). Genetic abnormalities were found in 5% of patients. A causal factor was more easily identifiable for the more severe infertility cases, and azoospermic men were those less likely to be defined as idiopathic (OR and 95% CIs: 0.09; 0.04-0.20). Relative proportion of identified causes remained constant during the 10-year study period (p>0.43).ConclusionsDue to a more comprehensive and extensive diagnostic work-up, at least one underlying cause of male infertility factor in 4 out of 5 infertile men can be identified. Men with a less severe phenotype remain a clinical challenge in terms of establishing a possible etiologic factor. Further studies are needed to assess which subset of infertile men deserves a more extensive work-up.

Prevalence of Cyclomodulin-Positive E. coli and Klebsiella spp. Strains in Mexican Patients with Colon Diseases and Antimicrobial Resistance

Colon diseases, such as colorectal cancer (CRC), are multifactor diseases that affect more than one million people per year; recently, the microbiota has been associated with an etiologic factor, specifically bacterial cyclomodulin positivity (CM+). Unfortunately, there are no studies from Mexico that detail the presence of bacterial CM+ in patients with colon diseases. We therefore performed a comprehensive study to investigate the associations and prevalence of cyclomodulin-positive Diarrheagenic E. coli (DEC), non-DEC, and Klebsiella spp. strains isolated from Mexican subjects with colon diseases. In this work, we analyzed 43 biopsies, 87 different bacteria were isolated, and E. coli was the most frequently noted, followed by Klebsiella spp., and Enterococcus spp. E. coli, non-DEC, and EPEC belonging to phylogroup B2 were the most prevalent. More than 80% of E. coli and Klebsiella were CM+. pks, cdt, cnf, and cif were identified. cdt was associated with non-DEC, cif and its combinations with EPEC, as well as cdt and psk with Klebsiella. Lastly, all the CM+ bacteria were resistant to at least one antibiotic (34% were MDR, and 48% XDR). In conclusion, the high prevalence of bacterial CM+ in colon disease patients suggests that these bacteria play an important role in the genesis of these diseases.

Seroconversion following the first, second, and third dose of SARS-CoV-2 vaccines in immunocompromised population; A systematic review and meta-analysis

Background: Immunocompromised (IC) patients are at higher risk of more severe COVID-19 infections than the general population. Special considerations should be dedicated to such patients. We aimed to investigate the efficacy of COVID-19 vaccines based on the vaccine type and etiology as well as necessity of booster dose in this high-risk population.Materials and methods: We searched PubMed, Web of Science, and Scopus databases for observational studies published between June 1st, 2020, and September 1st, 2021, which investigated the seroconversion after COVID-19 vaccine administration in adult patients with IC conditions. For investigation of sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. Statistical analysis was performed using R software.Results: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 81 articles in the meta-analysis. The overall crude prevalence of seroconversion after the first (n: 7,460), second (n: 13,181), and third (n: 909, all population were transplant patients with mRNA vaccine administration) dose administration was 26.17% (95% CI: 19.01%, 33.99%, I2= 97.1%), 57.11% (95% CI: 49.22%, 64.83%, I2= 98.4%), and 48.65% (95% CI: 34.63%, 62.79%, I2= 94.4%). Despite the relatively same immunogenicity of mRNA and vector-based vaccines after the first dose, the mRNA vaccines induced higher immunity after the second dose. Regarding the etiologic factor, transplant patients were less likely to develop immunity after both first and second dose rather than patients with malignancy (17.0% vs 37.0% after first dose, P=0.02; 38.3% vs 72.1% after second dose, P<0.001) or autoimmune disease (17.0% vs 36.4%, P=0.04; 38.3% vs 80.2%, P<0.001). To evaluate the efficacy of the third dose, we observed an increasing trend in transplant patients after the first (17.0%), second (38.3%), and third (48.6%) dose.Conclusion: The rising pattern of seroconversion after boosting tends to be promising. In this case, more attention should be devoted to transplant patients who possess the lowest response rate.

Choroidal Neovascularization in Pediatric Patients: Analysis of Etiologic Factors, Clinical Characteristics and Treatment Outcomes

Background and Objectives: Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy, but very limited published data have reported in pediatric patients. This study aimed to investigate the etiologic factors, clinical features, and treatment outcomes of choroidal neovascularization (CNV) in children.Methods: In this study, 33 eyes in 30 patients aged 18 years or younger with CNV were included. Comprehensive ophthalmic examination was performed in all the patients. The demographic profiles, laterality, visual acuity, optical coherence tomographic findings, fundus fluorescein angiographic findings, and the underlying pathology were analyzed. The types, locations, treatment outcomes, and recurrences of CNV were noted.Results: The average age was 11.2 ± 4.6 (range, 1–18) years. Most CNVs affecting children were classic and type 2. The most common etiologic factors of CNV in pediatric patients were congenital/developing abnormalities (9/30, 30.0%) and inflammatory retinochoroidopathy (9/30, 30.0%), followed by idiopathic CNV (8/30, 26.7%). Subtype analysis showed that the etiologic factor was inflammatory retinochoroidopathy in children 12 years or older, whereas congenital/developing abnormalities were present in children younger than 12 years. Eyes with active CNVs required a mean of 1.40 ± 0.58 injections. No recurrence was observed during follow-up.Conclusions: The etiologic factors of CNV in young Chinese patients were diverse, with congenital/developing abnormalities, inflammatory retinochoroidopathy and idiopathic CNV being the 3 most common ones. Eyes with active CNVs had good responses to antivascular endothelial growth factor treatment with low recurrence.

Depressive and Anxious Symptoms in Hepatitis C Virus Infected Patients Receiving DAA-Based Therapy

Hepatitis C virus (HCV) represents the most important etiologic factor for advanced fibrosis/cirrhosis and hepatocellular carcinoma associated with a psychological dimension. Our study aims to assess, on a sample comprising of 90 HCV-infected subjects (96.67% F3-F4 METAVIR), the relationship between Direct-Acting Antiviral (DAA) therapies and the psychological effects of the liver disease, focused on the anxious and depressive symptoms. The comprehensive evaluation was done before starting the DAA treatment (BSL), after 12 weeks (End of Treatment—EOT), respectively after another 12 weeks (Sustained Viral Response—SVR). Presumable depressive and/or anxious symptoms were evaluated by Hospital Anxiety and Depression Scale (HADS). The reported depressive symptoms decreased from 21.11% (BSL) to 1.11% (SVR) (p < 0.00001), while the anxious ones dropped from 43.34% (BSL) to 4.44% (SVR) (p < 0.00001), without a clear evolutionary pattern. We identified no statistically significant interaction between comorbidities (anemia, CKD, obesity) over HADS scores evolution (p > 0.05), while the DAAs side-effects (fatigue, headache, pruritus) significantly influenced the anxious and depressive symptoms (p < 0.05). During and after the DAA-based therapy, patients with HCV infection presented a significantly reduced rate of the associated depressive and anxious relevant symptoms.

Characterization of Pathogenesis and Inflammatory Responses to Experimental Parechovirus Encephalitis

Human parechovirus type 3 (PeV-A3) infection has been recognized as an emerging etiologic factor causing severe nerve disease or sepsis in infants and young children. But the neuropathogenic mechanisms of PeV-A3 remain unknown. To understand the pathogenesis of PeV-A3 infection in the neuronal system, PeV-A3-mediated cytopathic effects were analyzed in human glioblastoma cells and neuroblastoma cells. PeV-A3 induced interferons and inflammatory cytokine expression in these neuronal cells. The pronounced cytopathic effects accompanied with activation of death signaling pathways of apoptosis, autophagy, and pyroptosis were detected. A new experimental disease model of parechovirus encephalitis was established. In the disease model, intracranial inoculation with PeV-A3 in C57BL/6 neonatal mice showed body weight loss, hindlimb paralysis, and approximately 20% mortality. PeV-A3 infection in the hippocampus and cortex regions of the neonatal mouse brain was revealed. Mechanistic assay supported the in vitro results, indicating detection of PeV-A3 replication, inflammatory cytokine expression, and death signaling transduction in mouse brain tissues. These in vitro and in vivo studies revealed that the activation of death signaling and inflammation responses is involved in PeV-A3-mediated neurological disorders. The present results might account for some of the PeV-A3-associated clinical manifestations.

The Effect of Anti-anxiety Medications on the Clinical Symptoms of Anal Fissure: A Randomized Clinical Trial

Background: Fissure is a common chronic anorectal disease that causes symptoms such as pain, burning, bleeding, and psychiatric problems. One of the psychiatric complications is anxiety, which might be an etiologic factor or secondary to the disease. Materials and Methods: A total of 160 patients with anal fissure were randomly divided into two groups (80 patients treated with anti-anxiety medications along with standard anal fissure treatment and 80 patients with standard anal fissure treatment alone) after obtaining patient consent and demographic data. Then, the symptoms have recorded after treatment. Results: The results of our study indicated that the administration of anti-anxiety medications in patients with anal fissures relieved pain and anxiety scores among all patients. The anti-anxiety medications were more effective on patients younger than 40 years, men with less than two weeks duration of illness, and baseline anxiety greater than 26. Conclusion: A high prevalence of anal fissures affects the quality of life of patients. Besides the lack of effective treatment that shortens the pain and recovers patients faster, anti-anxiety medications such as benzodiazepines can use along with standard anal fissure treatment to reduce pain and anxiety in patients with acute anal fissure.

Lack of Association between Chlamydophila psittaci and Ocular Adnexal MALT Lymphoma in Korean Patients—Is the Geographic or Genetic Difference Significant?

Clamydophila psittaci (C. psittaci) has been proposed to be an etiologic factor in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the ocular adnexa. However, the pathogenetical significance of the infection has not been fully elucidated. Many previous studies have shown controversial results regarding C. psittaci detection rates in said patients, ranging from 0 to 87%. We investigated the presence of C. psittaci in a single institutional cohort (n = 150) of ocular adnexal MALT lymphoma (OAML) patients in Korea. We tried to exclude the methodological biases derived from the different primer sets in polymerase chain reaction-based studies. For that reason, we applied five sets of primers, including four previously reported and one newly designed primer set. There was no case of C. psittaci-positive OAML in repeated trials validated with appropriate positive and negative controls. All 150 cases showed negative results with five primer sets. These results suggest that the pathogenetic role of C. psittaci in ocular adnexal MALT lymphoma might have been overestimated to date, at least in the Korean population. Therefore, the molecular diagnosis of C. psittaci is considered a very low priority.

Effects of E-Cigarette Refill Liquid Flavorings with and without Nicotine on Human Retinal Pigment Epithelial Cells: A Preliminary Study

Smoking is an etiologic factor for age-related macular degeneration (AMD). Although cigarette smoke has been extensively researched for retinal pigment epithelial (RPE) cell degeneration, the potential for adverse effects on the retinal epithelium following exposure to flavored e-cigarette refill liquid has never been explored. In this preliminary study, we have examined the effects of 20 e-liquids (10 different flavored nicotine-free and 10 nicotine-rich e-liquids) used in e-cigarettes on the metabolic activity, membrane integrity, and mitochondrial membrane potential of RPE cells. Our results showed that of the flavors studied over the concentration range: 0.5, 1, and 2% v/v for a duration of 48 h, cinnamon was the most toxic and menthol was the second most toxic, while other flavors showed lesser or no cytotoxicity. The presence of nicotine augmented cytotoxicity for cinnamon, menthol, strawberry, vanilla, and banana while for other flavors there was no synergism. Together, our results demonstrate that exposure of RPE to flavored e-cigarette refill liquids caused significant cytotoxicity and may be a risk factor for the development of retinal pathogenesis, although further in-depth studies are necessary.