Impact of SARS-CoV-2 infection and COVID-19 pandemic on the morbidity and mortality of amyotrophic lateral sclerosis patients in Valencia, Spain.

BACKGROUND AND PURPOSE: The purpose was to describe the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization for coronavirus disease 2019 (COVID-19) and related death and to assess the impact of the pandemic in the survival of amyotrophic lateral sclerosis (ALS) patients. METHODS: The risk of SARS-CoV-2 infection, hospitalization for COVID-19 and related death was assessed in ALS patients alive between March 2020 and July 2022. To evaluate its impact in the overall survival of ALS patients, the survival of patients who died before and during the pandemic was compared. RESULTS: Amongst 263 ALS patients alive during the pandemic, 62 got infected during the study period (infection rate 14.34 per 100 person-years). Most infections (68%) occurred during the sixth wave (November 2021 to January 2022) and most patients (67%) were vaccinated at the time of infection. The hospitalization rate due to COVID-19 was 4.16 per 100 person-years. The multivariable model confirmed non-invasive ventilation (NIV) use prior to infection as a risk factor for hospitalization (odds ratio [OR] = 7.96, p = 0.003) and COVID-19 vaccination as a protective factor (OR = 0.093, p = 0.025) independent of age, sex and gastrostomy. Within 30 days after infection, 7% of non-ventilated patients started NIV and five patients (8.06%) died, of whom four were previously ventilated. The median survival of ALS patients was similar before and during the pandemic and no effect was found in the Cox regression model (hazard ratio 1.02, p = 0.89). CONCLUSIONS: This study shows a high risk of severe COVID-19 amongst ALS patients requiring NIV. Nevertheless, the pandemic showed no impact in the overall survival of ALS patients, probably due to a high vaccination rate and an adequate access to healthcare resources.

Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population.

Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, ≥27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with ≥27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028) and a family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of ≥27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.

Altered Lipid Moieties and Carbonyls in a Wistar Rat Dietary Model of Subclinical Fatty Liver: Potential Sex-Specific Biomarkers of Early Fatty Liver Disease?

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver. To date, there is a lack of knowledge about the subtype of lipid structures affected in the early stages of NAFLD. The aim of this study was to analyze serum and liver lipid moieties, specifically unsaturations and carbonyls, by nuclear magnetic resonance (NMR) in a subclinical Wistar rat model of NAFLD for detecting early alterations and potential sex dimorphisms. Twelve weeks of a high-fat diet (HFD) induced fat accumulation in the liver to a similar extent in male and female Wistar rats. In addition to total liver fat accumulation, Wistar rats showed a shift in lipid subtype composition. HFD rats displayed increased lipid carbonyls in both liver and serum, and decreased in unsaturated fatty acids (UFAs) and polyunsaturated fatty acids (PUFAs), with a much stronger effect in male than female animals. Our results revealed that the change in fat was not only quantitative but also qualitative, with dramatic shifts in relevant lipid structures. Finally, we compared the results found in Wistar rats with an analysis in a human patient cohort of extreme obesity. For the first time to our knowledge, lipid carbonyl levels and lipoproteins profiles were analyzed in the context of subclinical NAFLD. The association found between lipid carbonyls and alanine aminotransferase (ALT) in a human cohort of extremely obese individuals further supports the potential role of lipid moieties as biomarkers of early NAFLD.

Role of selenium in type 2 diabetes, insulin resistance and insulin secretion.

Selenium is a trace mineral essential for life that acts physiologically through selenoproteins. Among other actions, the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood, selenoprotein P, seem to play an important role in type 2 diabetes mellitus and insulin resistance by weakening the insulin signaling cascade through different mechanisms. Recent findings also suggest that selenoproteins also affect insulin biosynthesis and insulin secretion. This review discussed the role of selenium in type 2 diabetes and the complex interplay between selenoproteins and insulin pathways.

Femtosecond Laser-Assisted LASIK With and Without the Adjuvant Use of Mitomycin C to Correct Hyperopia.

PURPOSE: To compare the visual and refractive results of femtosecond laser-assisted LASIK (FS-LASIK) with and without the adjuvant use of mitomycin C (MMC) to correct hyperopia. METHODS: A total of 152 consecutive hyperopic eyes were included in this retrospective, observational cohort study, comparing 76 eyes treated with FS-LASIK + MMC with 76 age- and refraction-matched eyes treated with FS-LASIK without MMC. Visual and refractive results were evaluated 1 day, 1 week, and 1, 3, 6, and 15 months postoperatively. RESULTS: Preoperative mean spherical equivalent was +3.27 diopters (D) versus +3.50 D in the MMC and no MMC groups, respectively (P > .05). Three months postoperatively, uncorrected distance visual acuity was significantly better in the MMC group (0.93 ± 0.2) than in the no MMC group (0.87 ± 0.2) (P = .01). The residual spherical equivalent was significantly lower in the MMC group (+0.18 ± 0.40 D) than in the no MMC group (+0.42 ± 0.50 D) (P = .01). Fifteen months postoperatively, including re-treated eyes, no significant differences were found in uncorrected distance visual acuity, corrected distance visual acuity, and residual refraction. Slightly better outcomes were found in the MMC group in terms of efficacy, safety, and predictability; however, these small differences were not statistically significant. The incidence of re-treatments during the 15-month follow-up was significantly lower in the MMC group than in the no MMC group (6.6% vs 10.5%, respectively) (P = .01). CONCLUSIONS: FS-LASIK with or without the intraoperative use of MMC is safe and effective to correct hyperopia. However, slightly better refractive outcomes and a lower incidence of re-treatments were observed when intraoperative MMC was used, at least in a 15-month follow-up. [J Refract Surg. 2018;34(1):23-28.].

Long-term Follow-up of LASEK With Mitomycin C Performed to Correct Myopia in Thin Corneas.

PURPOSE: To evaluate the long-term outcomes of laser-assisted subepithelial keratomileusis (LASEK) with intraoperative use of mitomycin C (MMC) performed on thin corneas for the correction of myopia. METHODS: This retrospective cohort study included 100 eyes with a preoperative central corneal thickness (CCT) thinner than 500 µm that underwent LASEK + MMC with at least 6 years of follow-up. Stability of visual acuity and refraction and the efficacy, safety, and predictability at the examinations 3 months and the last annual postoperative visit were analyzed. RESULTS: Preoperative CCT was 482.9 ± 14.7 µm (range: 433 to 499 µm). Mean preoperative spherical equivalent was -4.09 ± 2.3 diopters (D). At the 3-month postoperative visit, mean CCT was 419.79 ± 32.6 µm. The residual spherical equivalent showed a statistically significant regression (P = .001) in the comparison between the 3-month and the last annual postoperative visit. The efficacy index showed a significant decrease (P = .01) and the safety index remained stable around 0.96. Six or more years after the surgery, 85 eyes (85%) were within ±0.50 D and 94 eyes (94%) eyes were within ±1.00 D of emmetropia. The topography did not show signs of secondary corneal ectasia in any eye. CONCLUSIONS: LASEK with intraoperative use of MMC seems to be safe, effective, and predictable to correct myopia in corneas thinner than 500 µm and with normal preoperative topography, providing good visual and refractive outcomes with no topographic signs of corneal ectasia in a mean 6.5-year follow-up. [J Refract Surg. 2017;33(12):813-819.].

Direct identification of microorganisms from thioglycolate broth by MALDI-TOF MS.

We developed an easy MALDI-TOF MS-based assay to identify microorganisms directly from thioglycolate broth. A total of 101 positive thioglycolate broths inoculated with 15 different kinds of samples were evaluated. In 91 samples (90.1%), direct MALDI-TOF MS identifications were the same as those obtained after conventional laboratory procedures including subcultures. In 10 samples misidentified by direct processing, yeasts or mixed cultures grew in the thioglycolate subcultures, or high cellular debris hampered a correct analysis. This rapid method can provide a fast, clinically- relevant species-level identification without disturbing the daily workflow in clinical microbiology laboratories.

First Report of Acute Postoperative Endophthalmitis Caused by Rothia Mucilaginosa after Phacoemulsification.

We aimed at reporting the first case of rapidly progressive acute postoperative endophthalmitis after phacoemulsification cataract surgery in an immunocompetent patient caused by Rothia mucilaginosa. An immunocompetent patient manifested endophthalmitis signs 48 hours after an uncomplicated cataract surgery by phacoemulsification. A bacteria of the family Micrococcaceae was cultured in the vitreous biopsy, namely R. mucilaginosa. The patient did not show a favorable clinical response after vitrectomy and systemic, intravitreal, and topical fortified antibiotics. The patient's eye was very painful, and consequently, it deemed necessary to perform an evisceration. R. mucilaginosa may be an aggressive etiologic agent for postoperative endophthalmitis. Although the isolated R. mucilaginosa was susceptible to empirical treatment, it was impossible to control the infection with standard treatment, probably due to its ability to create a biofilm around the intraocular lens.

Candida nivariensis as a New Emergent Agent of Vulvovaginal Candidiasis: Description of Cases and Review of Published Studies.

Candida nivariensis is a new emergent agent related to human infections in the vaginal tract and other localizations, but the phenotypic characteristics are very similar to Candida glabrata and can be misidentified and underdiagnosed. We described four cases of vulvovaginitis identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed the results with PCR amplification and sequencing of the entire ITS genomic region (ITS1, ITS2 and 5.8 rRNA). We reinforce the need for new diagnostic tools for the correct identification of yeast infections.

Diversity of bla genes and low incidence of CTX-M in plasmid-mediated AmpC-producing Escherichia coli clinical isolates.

The aim of this study was to characterize plasmid-mediated AmpC (pAmpC)-producing Escherichia coli clinical isolates. A total of 101 strains with AmpC-susceptibility pattern were prospectively included. All isolates were tested by multiplex PCR to detect different bla genes. Phylogenetic groups were determined by a multiplex PCR assay. Antimicrobial susceptibility was tested by a microdilution commercial method. Presence of blapAmpC was detected in 79 (78.2%) of the strains; in these pAmpC-producing isolates, blaTEM was detected in 41 (51.9%) strains, blaSHV in 5 (6.3%) strains, blaOXA in 3 (3.8%) strains, and blaCTX-M in 3 (3.8%) strains. blaVIM and blaKPC were detected in one strain. Sixteen strains belonged to phylogroup A, 27 to B1, 20 to B2, and 16 to D. As conclusion, the majority of the strains of E. coli with AmpC-susceptibility pattern are pAmpC positive, although the association of extended-spectrum beta-lactamases (ESBL) and pAmpC is unusual.

Evaluation of the Sensititre Yeast One microdilution method for susceptibility testing of Candida species to anidulafungin, caspofungin, and micafungin.

INTRODUCTION: Echinocandins represent a new antifungal group with potent activity against Candida species. The purpose of our study was to evaluate the utility of the Sensititre Yeast One method to determine the in vitro activity of anidulafungin, micafungin, and caspofungin against Candida species isolated from clinical specimens. METHODS: A total of 131 Candida strains were tested using Sensititre Yeast One colorimetric microdilution method. They belonged to the following species: 42 C. albicans, 36 C. glabrata, 21 C. parapsilosis, 12 C. tropicalis, 10 C. krusei, 3 C. guilliermondii, 2 C. famata, 3 C. kefyr, 1 C. lusitaniae, 1 C. zeylanoides, and 1 C. lipolytica. For being considered susceptible the strains had to be inhibited by concentrations ≤2 mg/L of anidulafungin, caspofungin or micafungin. RESULTS: The 80.1% of the strains tested were inhibited by concentrations ≤0.25 mg/L of anidulafungin and micafungin. The activity of caspofungin was slightly lower (78.6% of strains inhibited by concentrations ≤0.25 mg/L). The 96.9% of strains turned out susceptible to concentrations ≤2 mg/L against the three echinocandins. Two strains of C. parapsilosis (9.5%), one of C. guilliermondii, and two of C. famata showed non-susceptible to one or more echinocandins. CONCLUSIONS: In our series, anidulafungin, micafungin, and caspofungin were effective against C. albicans, C. glabrata, C. tropicalis, C. krusei, C. kefyr, C. lusitaniae and C. lipolytica. The 96.9% of strains were susceptible to all three echinocandins. Thus, echinocandins are proved to exhibit excellent activity to the Candida species most frequently involved in human infections, except Candida parapsilosis.

[Susceptibility to fluconazole of clinical interest yeasts: new breakpoints]. / Sensibilidad a fluconazol de levaduras de interés clínico: nuevos puntos de corte.

INTRODUCTION: Recently, Pfaller et al (Drug Resist Update 2010; 13:180-95), have proposed new breakpoints for determining the in vitro susceptibility to fluconazole of Candida albicans, C. parapsilosis and C. tropicalis. The aim of this study was to establish the variations in sensitivity of these species applying these breakpoints, in relation to those of the Clinical and Laboratory Standards Institute (CLSI). METHODS: We analyzed 112 strains of Candida: 49 C. albicans, 40 C. parapsilosis and 23 C. tropicalis. Susceptibility to fluconazole was performed by the method Sensititre YeastOne. The breakpoints used to determine the minimum inhibitory concentration (MIC) were identified by CLSI and the ones proposed by Pfaller et al. RESULTS: According to the CLSI criteria, all isolates were susceptible to fluconazole. MIC50 and MIC90 were 0.5 mg/L and 2 mg/L for C. albicans and C. parapsilosis, 0.5 mg/L and 1 mg/L for C. tropicalis. With the new criteria, 109 (97%) strains were susceptible. Variations were seen in C. albicans, with 3 strains (6%) susceptible dose-dependent. CONCLUSIONS: When applying the breakpoints recommended by Pfaller et al, and EUCAST, the number of fluconazole-susceptible strains decreased according to the CLSI criteria, especially C. albicans.

Otomycosis due to filamentous fungi.

Otomycosis is common throughout the world but barely studied in Spain. Our objective was to determine the microbiological and epidemiological characteristics of this pathology in Cadiz (Spain) between 2005 and 2010. Samples from patients with suspicion of otomycosis underwent a direct microscopic examination and culture on different media for fungi and bacteria. Mycological cultures were incubated at 30°C for at least seven days. Identification of fungi was based on colonial morphology and microscopic examination of fungal structure. From a total of 2,633 samples, microbial growth was present in 1,375 (52.2%) and fungal isolation in 390 (28.4%). We identified 228 yeasts and 184 filamentous fungi (13.4% of positive cultures and 47.2% of otomycosis), associated with yeasts in 22 cases (5.6%). The most frequent species were Aspergillus flavus (42.4%), A. niger (35.9%), A. fumigatus (12.5%), A. candidus (7.1%), A. terreus (1.6%), and Paecilomyces variotii (0.5%). Infection was predominant in men (54.9%) and patients beyond 55 years old (46.8%). The most common clinical symptoms were itching (98.9%), otalgia (59.3%), and hypoacusis (56.0%). Fall season reported the lowest number of cases (20.1%). Incidence of otomycosis and fungi producing otomycosis vary within the distinct geographical areas. In Cadiz, this infection is endemic due to warm temperatures, high humidity, sea bathing, and wind, which contributes to disseminate the conidia. Despite Aspergillus niger has been reported as the main causative agent, A. flavus is predominant in Cadiz. Although infection is usually detected in warm months, we observed a homogeneous occurrence of otomycosis in almost all the seasons.

Urethritis due to Corynebacterium glucuronolyticum.

We describe a case of urethritis in a young man caused by Corynebacterium glucuronolyticum. This bacterium is a synonym of Corynebacterium seminale, a known agent of non-gonococcal urethritis, that cannot be regarded as commensal flora in the urogenital region when is isolated in a symptomatic clinical context. Accuracy in diagnosis and correct treatment is important for avoiding probable complications, for example prostatitis. Bacterial isolation is convenient, and an antimicrobial susceptibility test should be conducted to discover antimicrobial resistance. In our case the patient was successfully treated with fluoroquinolones and was symptom-free in 2 weeks.

Emergence of CTX-M-15-producing Klebsiella pneumoniae of multilocus sequence types 1, 11, 14, 17, 20, 35 and 36 as pathogens and colonizers in newborns and adults.

OBJECTIVES: To characterize the population structure and resistance mechanisms of Klebsiella pneumoniae isolates that are highly resistant to third-generation cephalosporins, collected from five Spanish hospitals. METHODS: A total of 162 K. pneumoniae isolates from five hospitals located in three geographical areas of Spain were characterized. The number of isolates from each hospital ranged from 3 to 82. The genetic relationship between isolates was established by PFGE and multilocus sequence typing (MLST). bla(ESBL) types and other antibiotic resistance genes were analysed by PCR and sequencing. Plasmids were classified according to their incompatibility group by a PCR-based replicon-typing scheme. RESULTS: All 162 isolates carried the bla(CTX-15) gene. Fifty-eight isolates (35.8%) caused clinical infections and 104 (64.2%) were colonizers. Sixty-nine (42.6%) isolates were collected from newborns and 93 (57.4%) from adults. Using PGFE, the 162 isolates were grouped into seven clusters that were further identified as members of the MLST types 1, 11, 14, 17, 20, 35 and 36. Two hospitals each had two different clones and the remaining three hospitals had a single CTX-M-15-producing K. pneumoniae clone. All clones carried different antibiotic resistance genes, including bla(OXA-1), aac(3)-IIa, aac(6')-Ib-cr, qnrS1 and qnrB. In four of the seven (57.1%) clones the bla(CTX-M-15) gene was transferred by conjugation; in all cases plasmids of the incompatibility group IncF were identified by PCR. CONCLUSIONS: This study shows that multiresistant K. pneumoniae producing CTX-M-15 of MLST types 1, 11, 14, 17, 20, 35 and 36 are spreading as pathogens and colonizers among newborns and adult patients in Spain.

[Evaluation of an applied program for the prevention and control of tuberculosis]. / Valoración de la aplicación de un programa de prevención y control de tuberculosis.

BACKGROUND: To evaluate the efficacy of a tuberculosis prevention and control program applied in the health care area of Cadiz (Spain). MATERIALS AND METHODS: Tuberculosis cases diagnosed by microbiological criteria (Ziehl-Neelsen/auramine smear and/or culture in Löwenstein-Jensen medium) from 1996 to 2000 were analyzed in relation to epidemiologic characteristics of the patients. Susceptibility studies were performed from 1997 onwards using the proportion method described by Canetti, Rist and Grosset. RESULTS: The rate of tuberculous infections gradually dropped from 38.4 cases/100,000 inhabitants in 1996 to 16.0 cases/100,000 inhabitants in 2000. Along the study period, the percentage of men affected by the disease ranged from 81.2% in 1996 to 70.0% in 2000. In 1996, 26.0% of tuberculous patients were HIV-positive, and in 2000, 27.5%. The sensitivity of microbiologic diagnosis increased considerably from 60.4% in 1996 to 67.5% in 2000. Multi-drug resistance (9.2% en 1997) has virtually disappeared in our area since 1998 (1.6%).CONCLUSIONS. Implementation of a plan for the prevention and control of tuberculosis in our geographic area was effective, resulting in a decrease in the infection rate to less than 25 cases/100,000 inhabitants, and improvements in microbiologic diagnosis and compliance with treatment. Tuberculous disease has affected an increasingly higher proportion of women, regardless of HIV status. Antimicrobial resistance, particularly multi-drug resistance is now low in our area.

Sepsis procedente de la comunidad en cuidados intensivos: factores de riesgo / Sepsis from community in Intensive care: risk factors

Se realizó un estudio prospectivo y transversal en pacientes sépticos ingresados en la Unidad de Cuidados Intensivos del hospital "Dr. Ángel Arturo Aballí" con los criterios de sepsis procedente de la comunidad en un período de 18 meses, comprendido desde septiembre de 1996 hasta marzo de 1998, con el objetivo de analizar la frecuencia de factores de riesgo asociados con la infección. Se evaluaron 70 pacientes que cumplían los criterios antes mencionados. Se tomó en la comunidad un grupo control de niños sanos. En los resultados se encontró que los factores asociados con la sepsis fueron: el sexo masculino (p=0,002, RR=2,7), la no lactancia materna (p=0,01, RR=3,3), la malnutrición por defecto (p=0,04, RR=2,1), el hacinamiento (p=0,0008, RR=2,4), el hábito de fumar (p=0,02, RR=2,4) y la mala higiene (p=0,01, RR=1,5)