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  • 1
    In: Pharmacology, S. Karger AG, Vol. 106, No. 11-12 ( 2021), p. 588-596
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We identified genetic variants on 〈 i 〉 SLC47A1, SLC28A1, ABCG2, TBC1D4, 〈 /i 〉 and 〈 i 〉 ARID5B 〈 /i 〉 that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on 〈 i 〉 SLC47A1 〈 /i 〉 , 〈 i 〉 SLC28A1 〈 /i 〉 , and 〈 i 〉 ABCG2 〈 /i 〉 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.
    Type of Medium: Online Resource
    ISSN: 0031-7012 , 1423-0313
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1483550-2
    SSG: 15,3
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  • 2
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 48, No. 1 ( 2023), p. 357-366
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Urea is a toxin present in acute kidney injury (AKI). We hypothesize that reduction in serum urea levels might improve clinical outcomes. We examined the association between the reduction in urea and mortality. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Patients with AKI admitted to the Hospital Civil de Guadalajara were enrolled in this retrospective cohort study. We create 4 groups of urea reduction ratio (UXR) stratified by their decrease in urea from the highest index value in comparison to the value on day 10 (0%, 1–25%, 26–50%, and & gt;50%), or at the time of death or discharge if prior to 10 days. Our primary endpoint was to observe the association between UXR and mortality. Secondary observations included determination of which types of patients achieved a UXR & gt;50%, whether the modality of kidney replacement therapy (KRT) effected changes in UXR, and if serum creatinine (sCr) value changes were similarly associated with patient mortality. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A total of 651 AKI patients were enrolled. The mean age was 54.1 years, and 58.6% were male. AKI 3 was present in 58.5%; the mean admission urea was 154 mg/dL. KRT was started in 32.4%, and 18.9% died. A trend toward decreased risk of death was observed in association with the magnitude of UXR. The best survival (94.3%) was observed in patients with a UXR & gt;50%, and the highest mortality (72.1%) was observed in patients achieving a UXR of 0%. After adjusting for age, sex, diabetes mellitus, CKD, antibiotics, sepsis, hypovolemia, cardio-renal syndrome, shock, and AKI stage, the 10-day mortality was higher in groups that did not achieve a UXR of at least 25% (OR: 1.20). Patients achieving a UXR & gt;50% were most likely initiated on dialysis due to a diagnosis of the uremic syndrome or had a diagnosis of obstructive nephropathy. Percentage change in sCr was also associated with increased mortality risk. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 In our retrospective cohort of AKI patients, the percent decrease in UXR from admission was associated with a stratified risk of death. Patients with a UXR & gt;25% had the best associated outcomes. Overall, a greater magnitude in UXR was associated with improved patient survival.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1482922-8
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  • 3
    In: Fetal Diagnosis and Therapy, S. Karger AG, Vol. 48, No. 3 ( 2021), p. 163-173
    Abstract: 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 The aim of the study was to describe the feasibility of open fetal microneurosurgery for intrauterine spina bifida (SB) repair and to compare perinatal outcomes with cases managed using the classic open fetal surgery technique. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 In this study, we selected a cohort of consecutive fetuses with isolated open SB referred to our fetal surgery center in Queretaro, Mexico, during a 3.5-year period (2016–2020). SB repair was performed by either classic open surgery (6- to 8-cm hysterotomy with leakage of amniotic fluid, which was replaced before uterine closure) or open microneurosurgery, which is a novel technique characterized by a 15- to 20-mm hysterotomy diameter, reduced fetal manipulation by fixing the fetal back, and maintenance of normal amniotic fluid and uterine volume during the whole surgery. Perinatal outcomes of cases operated with the classic open fetal surgery technique and open microneurosurgery were compared. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Intrauterine SB repair with a complete 3-layer correction was successfully performed in 60 cases either by classic open fetal surgery ( 〈 i 〉 n 〈 /i 〉 = 13) or open microneurosurgery ( 〈 i 〉 n 〈 /i 〉 = 47). No significant differences were observed in gestational age (GA) at fetal intervention (25.4 vs. 25.1 weeks, 〈 i 〉 p 〈 /i 〉 = 0.38) or surgical times (107 vs. 120 min, 〈 i 〉 p 〈 /i 〉 = 0.15) between both groups. The group with open microneurosurgery showed a significantly lower rate of oligohydramnios (0 vs. 15.4%, 〈 i 〉 p 〈 /i 〉 = 0.01), preterm rupture of the membranes (19.0 vs. 53.8%, 〈 i 〉 p 〈 /i 〉 = 0.01), higher GA at birth (35.1 vs. 32.7 weeks, 〈 i 〉 p 〈 /i 〉 = 0.03), lower rate of preterm delivery & #x3c;34 weeks (21.4 vs. 61.5%, 〈 i 〉 p 〈 /i 〉 = 0.01), and lower rate of perinatal death (4.8 vs. 23.1%, 〈 i 〉 p 〈 /i 〉 = 0.04) than the group with classic open surgery. During infant follow-up, the rate of hydrocephalus requiring ventriculoperitoneal shunting was similar between both groups (7.5 vs. 20%, 〈 i 〉 p 〈 /i 〉 = 0.24). All patients showed an intact hysterotomy site at delivery. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Intrauterine spina repair by open fetal microneurosurgery is feasible and was associated with better perinatal outcomes than classic open fetal surgery.
    Type of Medium: Online Resource
    ISSN: 1015-3837 , 1421-9964
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1482292-1
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  • 4
    In: Case Reports in Neurology, S. Karger AG, Vol. 13, No. 2 ( 2021-8-19), p. 541-548
    Abstract: The spectrum of autoimmune encephalitis (AE) encompasses several entities characterized by a variable frequency of psychiatric symptoms, cognitive dysfunction, focal deficits, and seizures. Although patients with AE can be categorized in specific syndromes, overlapping manifestations are also common. Furthermore, atypical correlations between clinical phenotypes and autoantibody profiles could occur in rare cases. Here, we report the rare case of a young adult man attending due to new-onset seizures and a history of memory loss, autonomic disturbances, headache, behavioral changes, and visual and olfactory hallucinations. The patient was subjected to a complete diagnostic approach that included a comprehensive laboratory workup, neuropsychological testing, electroencephalogram, cerebrospinal fluid (CSF) analysis, brain MRI, and positron emission tomography/computed tomography scan that revealed a functional and structural compromise of the bilateral medial temporal lobes. Together with the clinical manifestations of the patient, these findings were compatible with the diagnosis of autoimmune limbic encephalitis (ALE). Strikingly, further analysis of the CSF showed autoantibodies against the N-methyl-D-aspartate (NMDA) receptor. We found very few cases of the co-occurrence of anti-NMDA receptor antibodies and nonparaneoplastic ALE in the literature, especially in male patients. Our report exemplifies the complicated differential diagnosis of ALE and adds clinical information of the association with anti-NMDA receptor antibodies.
    Type of Medium: Online Resource
    ISSN: 1662-680X
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2505302-4
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  • 5
    In: Case Reports in Oncology, S. Karger AG, Vol. 14, No. 1 ( 2021-2-23), p. 47-55
    Abstract: We herein report the challenging evaluation and planning process involved in performing the first successful surgical resection of a renal tumor with extensive inferior vena cava tumor thrombosis reaching the right atrium in a pediatric patient within the Central American region. In November 2018, the Oncology Department of the National Children’s Hospital in Costa Rica consulted our Center for Liver Transplantation and Hepatobiliary Surgery for the evaluation of a clinical case involving a 6-year-old female patient with progressive Budd-Chiari syndrome caused by a Wilms’ tumor of the right kidney with tumor thrombosis of the inferior vena cava reaching the right atrium. A multistage surgical safety strategy combining liver transplant techniques and cardiac surgery was thereafter designed and implemented, achieving complete excision of the tumor thrombus from the inferior vena cava with right nephrectomy. Postoperatively, the patient exhibited complete clinical resolution of Budd-Chiari syndrome and has remained tumor free with excellent quality of life while pursuing her second grade of primary school education 22 months after the successful implementation of this multistage surgical safety strategy. The combination of liver transplantation techniques and cardiac surgery based on a multistage surgical safety strategy minimized the occurrence of unexpected intraoperative events and allowed for complete renal tumor resection and level IV thrombectomy for the first time in a pediatric patient of a public health system in a developing country within the Central American region.
    Type of Medium: Online Resource
    ISSN: 1662-6575
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2458961-5
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  • 6
    In: Case Reports in Oncology, S. Karger AG, Vol. 14, No. 1 ( 2021-3-1), p. 112-122
    Abstract: Calcitonin-negative neuroendocrine tumor (CNNET) of the thyroid is an extremely rare entity. In some of the previously reported cases within the literature, the terms “atypical medullary thyroid carcinoma,” “calcitonin-free oat cell carcinoma,” and “a distinct clinical entity” were applied to NETs without definitive evidence of calcitonin production. In the English-language literature, not only are there only few reported cases of CNNET, but the criteria for diagnosis in these cases are also controversial. Most of the current published cases were also treated surgically for local disease. We describe a case of NET of the thyroid with calcitonin, chromogranin A and thyroglobulin negativity, synaptophysin and TTF-1 positivity, and a high Ki-67 proliferation index with metastases in the cervical region as well as mediastinal adenopathies. This case was considered an unresectable thyroid carcinoma, and chemotherapy including cisplatin and etoposide was started as neoadjuvant treatment at the department of medical oncology. Total thyroidectomy plus bilateral and central cervical dissection was performed, and the patient underwent 2 cycles of adjuvant radiotherapy. Currently, the patient’s 〈 sup 〉 18 〈 /sup 〉 F-FDG-PET/CT findings show a complete response 17 months after diagnosis. In conclusion, CNNET of the thyroid is very rare and there is limited evidence regarding treatment in patients with metastases. Chemotherapy including cisplatin and etoposide as well as early aggressive surgical resection appears to positively impact patients’ survival.
    Type of Medium: Online Resource
    ISSN: 1662-6575
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2458961-5
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  • 7
    In: Dermatology, S. Karger AG, Vol. 237, No. 6 ( 2021), p. 952-960
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Vitiligo has an unpredictable course and a variable response to treatment. Furthermore, the improvement of some vitiligo lesions cannot be considered a guarantee of a similar response to the other lesions. Instruments for patient-reported outcome measures (PROM) can be an alternative to measure complex constructions such as clinical evolution. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 The aim of this study was to validate a PROM that allows to measure the clinical evolution of patients with nonsegmental vitiligo in a simple but standardized way that serves to gather information for a better understanding of the disease. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The instrument was created through expert consensus and patient participation. For the validation study, a prospective cohort design was performed. The body surface area affected was measured with the Vitiligo Extension Score (VES), the extension, the stage, and the spread by the evaluation of the Vitiligo European Task Force assessment (VETFa). Reliability was determined with test-retest, construct validity through hypothesis testing, discriminative capacity with extreme groups, and response capacity by comparing initial and final measurements. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Eighteen semi-structured interviews and 7 cognitive interviews were conducted, and 4 dermatologists were consulted. The instrument Clinical Evolution-Vitiligo (CV-6) was answered by 119 patients with a minimum of primary schooling. A wide range was observed in the affected body surface; incident and prevalent cases were included. The average time to answer the CV-6 was 3.08 ± 0.58 min. In the test-retest ( 〈 i 〉 n 〈 /i 〉 = 53), an intraclass correlation coefficient was obtained: 0.896 (95% CI 0.82–0.94; 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001). In extreme groups, the mean score was 2 (2–3) and 5 (4–6); 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001. The initial CV-6 score was different from the final one and the change was verified with VES and VETFa ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05, 〈 i 〉 n 〈 /i 〉 = 92). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The CV-6 instrument allows patient collaboration, it is simple and brief, and it makes it easier for the doctor to focus attention on injuries that present changes at the time of medical consultation.
    Type of Medium: Online Resource
    ISSN: 1018-8665 , 1421-9832
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1482189-8
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  • 8
    In: Gerontology, S. Karger AG, Vol. 69, No. 3 ( 2023), p. 239-248
    Abstract: Introduction: Centenarians are considered a model of successful aging. Cuba exhibits one of the oldest populations in Latin America with more than two thousand centenarians. Methods: This study aimed to evaluate the immune phenotype of forty-three Cuban centenarians, their clinical characteristics such as comorbidities, frailty, body mass index, and some hemochemical parameters. Results: Centenarians had normal body mass indexes, relatively good health status, and 21.95% of them had no comorbidities; 53.6% were classified as frail, and 7% were classified as robust. In addition, 17% of centenarians were independent, and 41.46% were moderately dependent. The seroprevalence against cytomegalovirus was 100%. Concerning pro-inflammatory markers, the majority of them had very low cytokine levels and serum C-reactive protein around the normal limit. We also found the predominance of memory subsets over naive compartments in CD4+ and CD8+ T cells. Terminally differentiated CD8+CD28− T cells were higher in frail centenarians than in pre-frail, while CD8+CD57+ and CD8+EMRA T cells were higher in moderately and severely dependent individuals than in independent individuals. Severely dependent centenarians had a lower CD4+/CD8+ ratio. Conclusion: This study describes for the first time the predominance of memory subsets over naive compartments in CD4+ and CD8+ T cells, as well as its relation to frailty and/or dependency in a group of Cuban centenarians. Further studies are needed to continue understanding the natural biological aging mechanism and the relationship between terminally differentiated lymphocytes and inflammaging in the context of extreme longevity.
    Type of Medium: Online Resource
    ISSN: 0304-324X , 1423-0003
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1482689-6
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  • 9
    In: Neonatology, S. Karger AG, Vol. 119, No. 6 ( 2022), p. 745-752
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Hyperglycemia in very preterm infants is associated with increased morbidity and mortality. We aimed to investigate potential associations between early hyperglycemia, neonatal cerebral magnetic resonance imaging (MRI), and neurodevelopment at 2.5 years. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The study population included 69 infants with gestational age (GA) 22.3–31.9 weeks ( 〈 i 〉 n 〈 /i 〉 = 29 with GA & #x3c;28 weeks), born 2011–2014. Plasma glucose concentrations during the first week were checked according to clinical routines. Hyperglycemia was defined as glucose concentrations above 8.3 mmol/L (150 mg/dL) and above 10 mmol/L (180 mg/dL), respectively, categorized as the highest glucose days 0–2, number of days above 8.3 and 10 mmol/L, and prolonged (yes/no) 2 days or more above 8.3 and 10 mmol/L. The MRI analysis included morphological assessment, regional brain volumes, and assessment of apparent diffusion coefficient (ADC). Neurodevelopmental impairment (NDI) developed in 13 of 67 infants with available outcomes, of which 57 were assessed with the Bayley-III. Univariate and multiple linear and logistic regressions were performed with adjustments for GA, birth weight z-scores, and illness severity expressed as days on mechanical ventilation. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Hyperglycemia above 8.3 mmol/L and 10 mmol/L was present in 47.8% and 31.9% of the infants. Hyperglycemia correlated independently with lower white matter volume, but not with other regional brain volumes, and was also associated with lower ADC values in white matter. Hyperglycemia also correlated with lower Bayley-III cognitive and motor scores in infants with GA & #x3c;28 weeks, but there was no significant effect on NDI. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Early hyperglycemia is associated with white matter injury and poorer neurodevelopment in very preterm infants.
    Type of Medium: Online Resource
    ISSN: 1661-7800 , 1661-7819
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 2403535-X
    SSG: 12
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