Gamma-glutamyl transferase and cardiovascular events in patients with congenital heart disease.

INTRODUCTION: Serum gamma-glutamyl transferase activity (GGT) seems to predict cardiovascular events in different populations. However, no data exist on patients with congenital heart disease (CHD). METHODS: Observational, analytic, prospective cohort study design involving CHD patients and a control population to determine the effect of GGT levels on survival. RESULTS: A total of 589 CHD patients (58% males, 29 ± 14 years old) and 2745 matched control patients were followed up. A total of 69 (12%) CHD patients had a major acute cardiovascular event (MACE) during the follow-up time (6.1 [0.7-10.4] years). Patients with CHD and a GGT >60 U/L were significantly older, more hypertensive and dyslipidemic, had a worse NYHA functional class and a greater anatomical complexity than CHD patients with a GGT ≤60 U/L. The binary logistic regression analysis showed that age, a great CHD anatomical complexity, and having atrial fibrillation/flutter were the predictive factors of higher GGT levels (>60 U/L). The Kaplan-Meier analysis showed that patients with CHD and a GGT concentration above 60 UL showed the lowest probability of survival compared to that of CHD with GGT ≤60 U/L and controls irrespective of their GGT concentrations (p < .001). Similarly, the multivariable Cox regression analysis found an independent association between higher GGT levels (>60 U/L) and a worse prognosis (HR 2.44 [1.34-4.44], p = .003) among patients with CHD. CONCLUSION: Patients with CHD showed significant higher GGT levels than patients in the control group having those with higher GGT concentrations (>60 U/L) the worst survival.

The incidence of skin melanoma in Gran Canaria (Canary Islands, Spain) is lower than expected in Southern Europe despite high-risk environmental conditions: an island-wide cross-sectional study.

BACKGROUND: The Canary Islands are a leading European touristic destination. The ultraviolet index (UVI) in the region is the highest in Spain, and similar to indexes registered in Australia and New Zealand, which hold the highest incidence of skin melanoma worldwide. Yet according to cancer registry data, the incidence in the Canary Islands in the late 1990s was the lowest in Spain (among the lowest in Europe) and about six times lower than in New Zealand. PURPOSE: To analyze the incidence rates of skin melanoma in Gran Canaria island between 2007 and 2018. METHODS: The study was based in the two centres of the Canary Islands' Healthcare Service centralizing melanoma care in Gran Canaria. We analyzed crude and age-standardized (ASR) incidence rates of invasive cutaneous melanoma for the period 2007-2018 following the inclusion criteria of the International Agency for Research on Cancer (IARC). Clinical and histological characteristics of melanoma patients were assessed. RESULTS: A total of 1058 patients were included. The incidence rates obtained matched the latest available Canary Islands' cancer registry data, confirming its reliability (ASR, Segi-Doll world standard population: 6.4 cases per 100,000 habitants for 2008-2012). The incidence was also below the latest IARC predictions for Southern Europe (GLOBOCAN 2018). Histological characteristics of patients were similar to other Southern European series. CONCLUSIONS: The incidence of skin melanoma in Gran Canaria is unexpectedly low for a Southern European population exposed to such a high UVI. Further research in the Canary Islands could provide insight into a better understanding of melanoma pathogenesis.

The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: A multicentre collaborative study.

OBJECTIVES: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52-bp deletion or type 2, 5-bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. METHODS: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. RESULTS: With 7.5 years of median follow-up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5-year thrombosis-free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (P = .002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (P = .046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR-type 2 groups but not JAK2V617F vs CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P = .04) adjusted by age. CONCLUSIONS: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.

Malnutrition is independently associated with an increased risk of major cardiovascular events in adult patients with congenital heart disease.

BACKGROUND AND AIMS: Malnutrition is found frequently during chronic diseases, and its prevalence and relation to disease outcome in adult patients with congenital heart disease (CHD) remains unknown. METHODS AND RESULTS: A cohort of 393 consecutive stable congenital heart disease (CHD) patients was followed up in a single dedicated clinical unit. Demographic, clinical and laboratory parameters, along with a nutritional risk index (NRI), were studied, as well as major acute cardiovascular events (MACE), defined as arterial thrombotic events, heart failure requiring hospitalization or cardiovascular and non-cardiovascular mortality. The median age of the patients was 23 years (17-35) and 225 (57%) were males. Median plasma albumin concentration was 4.5 (4.2-4.7) g/dL, the body mass index was 23 (21-27) kg/m2, the NRI was 112 (106-118), and 33 (8%) patients showed malnutrition (NIR<100). A worse NYHA functional class (II and III), total cholesterol and serum glucose levels were significant risk factors associated with malnutrition (NRI<100) in CHD patients. During a median follow-up of 8 (5-10) years, 39 (10%) CHD patients suffered a MACE. Multivariable Cox regression analysis showed that older patients (years) [HR 1.06 (1.04-1.09), p < 0.001], CHD patients with great anatomical complexity [HR 4.24 (2.17-8.27), p < 0.001] and those with a lower NRI [HR 0.95 (0.93-0.98), p = 0.001] had a significant worse MACE-free survival, being the NRI a better predictor of MACE than albumin concentration. CONCLUSIONS: A low NRI is independently associated with a significant increased risk of MACE in CHD patients.

Rotational forceps: a retrospective study evaluating anatomical and functional consequences for the pelvic floor.

INTRODUCTION AND HYPOTHESIS: The use of Kielland's rotational forceps is considered to involve greater technical difficulty and may be associated with a higher rate of pelvic floor trauma. Our main objective was to evaluate the association between avulsion of the levator muscle and rotational and non-rotational forceps. METHODS: This was an observational study carried out at a tertiary hospital that recruited singleton cephalic vaginally primiparous women with previous Kielland's forceps delivery between March 2012 and May 2017. Patients were retrieved from a local database, contacted consecutively and blinded to all clinical data. Power calculations determined a sample of n = 160 patients. All women underwent a urogynecological interview, clinical examination and 4D translabial ultrasound (TLUS). The 4D TLUS volumes were stored and analyzed offline by an experienced ultrasound examiner who was blinded to all clinical data. RESULTS: A total of 165 patients were available for analysis. Rotational forceps accounted for 27.3% (45 out of 165) of the study sample. Avulsion was present in 41.8% (69 out of 165) of all forceps deliveries. On multivariate analysis, rotational forceps was associated with avulsion, with an adjusted odds ratio (OR) of 2.57 (CI 95% 1.20-5.62, p = 0.016). Body mass index at the beginning of gestation was found to be a protective factor, with an adjusted OR of 0.918 (CI 95% 0.847-0.986, p = 0.025). CONCLUSION: Rotational forceps is associated with a higher avulsion rate than non-rotational forceps, with an adjusted OR of over 2.5. Obstetricians need to consider the potential long-term consequences of performing a rotational forceps for mothers.

Survival and Lung Function Changes in Hypersensitivity Pneumonitis According to Radiological Phenotypes Compared With Idiopathic Pulmonary Fibrosis.

INTRODUCTION: The main objective of this study was to estimate survival and changes in lung function in patients with chronic hypersensitivity pneumonitis (HP), both fibrotic (f-HP) and nonfibrotic (nf-HP), and to compare them with those in patients with idiopathic pulmonary fibrosis (IPF). METHODS: HP was diagnosed based on antigen exposure, HRCT (high-resolution CT scan), BAL (bronchoalveolar lavage), and histology. According to HRCT, HP was classified into fibrotic and non-fibrotic phenotypes. In most cases, IPF was diagnosed based on HRCT findings. RESULTS: We identified 84 patients: 46 with IPF, 18 with f-HP, and 20 with nf-HP. Five-year survival was 23.9% in IPF, 72% in f-HP, and 100% in nf-HP (p <0.0001). Honeycombing was associated with decreased survival in IPF (p <0.001) and in f-HP (p <0.0001). The mean loss of FVC (forced vital capacity) % pred. (percent predicted) was -18.3% in IPF (p =0.001), -4.8% in f-HP, and -6.0% in nf-HP. The mean change in DLCO (diffusion capacity for carbon monoxide) % pred. was -10.2% in IPF (p <0.002), -0.5% in f-HP, and +1.9% in nf-HP. The agreement between radiological phenotypes and histology in HP was 89.6%. CONCLUSIONS: We found shorter survival in IPF, followed by f-HP, and nf-HP. Over time, we did not find significant changes in FVC% pred. or DLCO% pred. in HP, while a significant decline in IPF was noted. In HP, we found strong agreement between radiological phenotypes and histology. Radiological signs suggestive of lung fibrosis in HP were reliable for the diagnosis of f-HP and seem to have intrinsic prognostic value.

Bilateral internal thoracic artery versus single internal thoracic artery plus radial artery: A double meta-analytic approach.

OBJECTIVES: We explored the current evidence on the best second conduit in coronary surgery carrying out a double meta-analysis of propensity score matched or adjusted studies comparing bilateral internal thoracic artery (BITA) versus single internal thoracic artery plus radial artery. METHODS: PubMed, Embase, and Google Scholar were searched for propensity score matched or adjusted studies comparing BITA versus single internal thoracic artery plus radial artery. The end point was long-term mortality. Two statistical approaches were used: the generic inverse variance method and the pooled meta-analysis of Kaplan-Meier-derived individual patient data. RESULTS: Twelve matched populations comparing 6450 patients with BITA versus 9428 patients with single internal thoracic artery plus radial artery were included in our meta-analysis. The generic inverse variance method showed a statistically significant survival benefit of the BITA group (hazard ratio, 0.84; 95% CI, 0.74-0.95; P = .04). The Kaplan-Meier estimates of survival at 1, 5, 10, and 15 years of the BITA group were 97.0%, 91.3%, 80.0%, and 68.0%, respectively. The Kaplan-Meier estimates of survival at 1, 5, 10, and 15 years of the single internal thoracic artery plus radial artery group were 97.3%, 91.5%, 79.9%, and 63.9%, respectively. The Kaplan-Meier-derived individual patient data meta-analysis applied to very long follow-up time data, showed that BITA provided a survival benefit after 10 years from surgery (hazard ratio, 0.77; 95% CI, 0.63-0.94; P = .01). No differences in terms of survival between the 2 groups were detected when the analysis was focused on the first 10 years of follow-up (hazard ratio, 0.99; 95% CI, 0.91-1.09; P = .93). CONCLUSIONS: The present meta-analysis suggests that double internal thoracic artery may provide, compared with single internal thoracic artery plus radial artery, a statistically significant survival advantage after 10 years of follow-up, but not before. VIDEO ABSTRACT.

Analysis of a novel protocol of pulsed intravenous cyclophosphamide for recalcitrant or severe ocular inflammatory disease.

PURPOSE: To analyze the success rate of pulsed intravenous (IV) cyclophosphamide (CyP) for noninfectious ocular inflammatory disease and to identify risk factors for failure of therapy. DESIGN: Retrospective, interventional, noncomparative cohort study. PARTICIPANTS: One hundred ten eyes of 65 patients. METHODS: Through a computer search of the Massachusetts Eye Research and Surgery Institution's database, we identified patients who were treated with IV CyP between May 2005 and April 2012. We obtained demographic and clinical information through review of the electronic health record of each patient. MAIN OUTCOMES MEASURES: Clinical response, corticosteroid-sparing effect, recurrence rate, calculated "risk factors" for failure, visual acuity, and adverse reactions. RESULTS: Pulsed IV CyP achieved complete remission of inflammation (for ≥ 2 visits) in 54 patients (84.4%). Sustained remission of inflammation occurred in 70% of patients within 3 months, 86.6% of patients within 6 months, and 91.7% within 9 months. The mean time to achieving quiescence was 3.5 months. The success rate in reducing corticosteroid to prednisone ≤ 10 mg/d within 6 months, while maintaining control of ocular inflammation, was 89.7% (95% confidence interval [CI], 81.1-93.5%). The mean duration of clinical remission for those patients who had a positive response to CyP was 32.67 months (95% CI, 25.91-39.43). Relapse of vasculitis was observed in 1 patient (1.5%) after completing the course of therapy. Early initiation of therapy during the course of the disease was correlated with a lesser rate of recurrence (P = 0.028). The most common adverse effects were nausea (29%) and transient lymphopenia (26%). The mean best-corrected visual acuity (BCVA) improved from 0.59 ± 0.66 at baseline to 0.30 ± 0.54 at 6 months of follow-up (P<0.001). The mean follow-up period was 31.61 ± 20.47 months. CONCLUSIONS: Pulsed IV CyP employing our protocol results in an extremely high rate of sustained complete remission in patients with recalcitrant and fulminant, vision-threatening ocular inflammatory disorders, with an excellent safety profile in the hands of physicians trained and skilled in the art of this therapy. It also allows tapering and discontinuing corticosteroids in most patients. Early initiation of therapy may decrease the risk of relapses. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Effect of Conventional Cataract Surgery and Femtosecond Laser-Assisted Cataract Surgery on Bruch's Membrane Opening-Minimum Rim Width, Retinal Nerve Fiber Layer, and Macular Thickness.

Purpose: To evaluate the effect of conventional cataract surgery (CCS) and femtosecond laser-assisted cataract surgery (FLACS) on Bruch's membrane opening-minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer thickness (RNFL), and macular thickness (MT) using spectral-domain optical coherence tomography (SD-OCT). Methods: BMO-MRW, RNFL, and MT were measured using SD-OCT preoperatively, 1 month and 6 months after surgery in both CCS and FLACS groups. Differences between preoperative and postoperative values were evaluated in both groups. The postoperative changes were evaluated in each group and compared between groups. Results: A total of 146 eyes of 146 patients were included in this study, 65 underwent CCS, and 81 underwent FLACS. One month after surgery, there was an increase (in microns) of 20.93 in BMO-MRW, 4.26 in RNFL, and 7.85 in MT in CCS group (P < 0.001), and 17.7, 3.73, and 5.65, respectively, in FLACS group (P < 0.001). Six months after surgery, there was an increase of 12.53 in BMO-MRW, 1.42 in RNFL, and 4.72 in MT in CCS group (P < 0.001), and 13.7, 1.88, and 4.14, respectively, in FLACS group (P < 0.001). The postoperative changes in CCS group were similar to those in FLACS group. Conclusion: CCS as well as FLACS result in a slight increase in BMO-MRW, RNFL, and MT values one month and six months after surgery. Neither CCS nor FLACS lead to a deterioration in the parameters that define the structure of the optic nerve head and the macula. These results suggest that FLACS is as safe as CCS regarding the optic nerve head and the macula in normal eyes.

The Healthy Lifestyle Habits Screening Questionnaire: A pilot study in the Canary Islands.

OBJECTIVE: This study aimed to assess the validity and reliability of a self-administered screening questionnaire to detect deficiencies in the health habits of the adult population of the Canary Islands (Spain). DESIGN: The questionnaire initially included 30 items based on previous questionnaires and following the recommendations of the World Health Organization about healthy and unhealthy diet, screen time, physical activity, and sleep habits. It also included a section related to hygiene due to the importance that hygienic habits have in people's health. SETTING: The questionnaire was self-administered online. PARTICIPANTS: Data was collected from 401 participants from the Canary Islands (age range: 18-73 years) who volunteered to fill in the questionnaire online. RESULTS: The questionnaire revealed adequate overall reliability indexes (Cronbach's α>.70, Mcdonald's ω>.70), and construct validity. Hierarchical linear regression analysis revealed age, sex, and income to be significantly (p<.05) related to adults' health lifestyle habits in our population, sex and age explaining the majority of the variance. However, education and incomes were found non-significant (p>.05) when education was introduced into the model. Those results pointed out that older people and women show healthier lifestyle habits. CONCLUSION: The questionnaire proved to be a brief, reliable, and valid tool to assess health lifestyle habits in adults in the Canary Islands. Furthermore, results pointed out that in future intervention studies with children, variables such as adults' sex, age, and, to a lesser extent, monthly income should be taken into consideration.

Coronary surgery provides better survival than drug-eluting stent: A pooled meta-analysis of Kaplan- Meier-derived individual patient data.

OBJECTIVES: We explored the current evidence on coronary disease treatment comparing the survival of 2 therapeutic strategies: coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stent (DES). METHODS: PubMed, Embase, and Google Scholar were searched for randomized clinical trials comparing CABG versus PCI with DES. The end point was overall mortality. Two statistical approaches were used: the generic inverse variance method, which was used to pool the incident rate ratios, and the pooled meta-analysis of Kaplan-Meier-derived individual patient data. RESULTS: Eight randomized clinical trials comparing 4975 patients undergoing CABG and 4992 patients undergoing PCI were included in our meta-analysis. Generic inverse variance method showed a statistically significant survival benefit of the CABG group (incident rate ratio, 1.21; 95% confidence interval, 1.09-1.35; P < .01). The Kaplan-Meier estimates of survival at 1, 5, and 10 years of the CABG group were 97.1%, 90.3%, and 80.3%, respectively. The Kaplan-Meier estimates of survival at 1, 5, and 10 years of the PCI group were 97.0%, 87.7%, and 76.4%, respectively. The log-rank analysis confirmed a statistically significant benefit in term of overall mortality of the CABG group (hazard ratio, 1.24; 95% confidence interval, 1.11-1.38; P = .0001). CONCLUSIONS: The present meta-analysis suggests that CABG provides a consistent survival benefit over PCI with DES.

An Artificial Intelligence Prediction Model of Insulin Sensitivity, Insulin Resistance, and Diabetes Using Genes Obtained through Differential Expression.

Insulin is a powerful pleiotropic hormone that affects processes such as cell growth, energy expenditure, and carbohydrate, lipid, and protein metabolism. The molecular mechanisms by which insulin regulates muscle metabolism and the underlying defects that cause insulin resistance have not been fully elucidated. This study aimed to perform a microarray data analysis to find differentially expressed genes. The analysis has been based on the data of a study deposited in Gene Expression Omnibus (GEO) with the identifier "GSE22309". The selected data contain samples from three types of patients after taking insulin treatment: patients with diabetes (DB), patients with insulin sensitivity (IS), and patients with insulin resistance (IR). Through an analysis of omics data, 20 genes were found to be differentially expressed (DEG) between the three possible comparisons obtained (DB vs. IS, DB vs. IR, and IS vs. IR); these data sets have been used to develop predictive models through machine learning (ML) techniques to classify patients with respect to the three categories mentioned previously. All the ML techniques present an accuracy superior to 80%, reaching almost 90% when unifying IR and DB categories.

25OHVitamin D Levels in a Canarian Pediatric Population with and without Type 1 Diabetes: The Role of Acidosis.

The role of Vitamin D in the development of type 1 diabetes (T1D) is controversial. The Canary Islands have the highest incidence of childhood-onset T1D in Spain and one of the highest in Europe. We aimed to evaluate 25OHVitamin D concentrations in a Canarian pediatric population, to assess the existence of seasonal variation, to study their association with T1D, and to evaluate the role of acidosis in its levels. In a retrospective, case-control study, we obtained data from 146 T1D patients (<15 years of age) and 346 control children; 25OHVitamin D concentrations were assessed in serum by automatic ChemiLuminescence ImmunoAssay technology. We found significantly higher 25OHVitamin D levels in the summer and autumn months and an inverse correlation between T1D and age; 25OHVitamin D sufficiency was similar in both groups (44.5% vs. 45.1%), with significant differences in the percentage of patients presenting vitamin D deficiency (11.6% (T1D) vs. 16.4% (controls)). When stratified according to the presence of ketoacidosis at sampling, only patients with acidosis showed lower 25OHVitamin D concentrations than controls. Despite its subtropical geographic location, Vitamin D deficiency is frequent in children in Gran Canaria, and 25OHVitamin D concentrations show seasonal variation. After adjusting for acidosis, no differences were found between children with and without T1D.

The Need for Psychological Support of Health Workers during the COVID-19 Pandemic and the Influence on Their Work.

The aim of this research was to analyze how the need for psychological support of health workers (HCWs) influenced the beliefs, perceptions and attitudes towards their work during the COVID-19 pandemic and to predict the need of psychological assistance. A descriptive transversal study was conducted based on a self-administered questionnaire distributed to health professionals working in the Canary Islands, Spain. The data were analyzed using Pearson's chi-squared test and the linear trend test. The correlation test between ordinal and frequency variables was applied using Kendall's Tau B. Multiple logistic regression was used to predict dichotomous variables. The sample included 783 health professionals: 17.8% (n = 139) of them needed psychological or psychiatric support. Being redeployed to other services influenced the predisposition to request psychological help, and HCWs who required psychological support had more negative attitudes and perceptions towards their work. After five waves of COVID-19, these HCWs reported to be physically, psychologically and emotionally exhausted or even "burned out"; they did not feel supported by their institutions. The commitment of health personnel to fight against the COVID-19 pandemic decreased after the five waves, especially among professionals who required psychological support.

Effect of Preoperative Anxiety on Postoperative Pain after Craniotomy.

Pain following craniotomy is challenging. Preoperative anxiety can be one of the controllable factors for prevention of post-craniotomy pain. The main objective of this prospective observational study is to determine this relationship in patients undergoing scheduled craniotomy from February to June 2021. After excluding patients with Mini-Mental State Examination (MMSE) ≤ 24 points, we administered a preoperative State Trait Anxiety Inventory (STAI) questionnaire. We recorded the patient's analgesic assessment using the Numerical Rating Score (NRS) at 1, 8, 24, and 48 h after surgery. A total of 73 patients were included in the study. Twelve others were excluded due to a MMSE ≤ 24 points. The main predictors for NRS postoperatively at 1, 8, 24, and 48 h were STAI A/E score, male gender, youth, and depression. We identified a cut-off point of 24.5 in STAI A/E for predicting a NRS > 3 (sensitivity 82% and specificity 65%) at 24 h postoperative and a cut-off of 31.5 in STAI A/R (sensitivity 64% and specificity 77%). In conclusion, preoperative STAI scores could be a useful tool for predicting which patient will experience at least moderate pain after craniotomy. The identification of these patients may allow us to highlight psychological preparation and adjuvant analgesia.

Differences between the first and the second wave of critically ill COVID-19 patients admitted to the intensive care units.

Background: To compare the demographic characteristics and prognosis of patients admitted to the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19) pneumonia during the first wave (March-July) versus those admitted during the second wave (August-December). Methods: Prospective, observational, descriptive cohort-study including patients admitted to the ICU for COVID-19 pneumonia during the first wave (March-July 2020) or the second wave (August-December). The demographic characteristics, comorbidities, treatments, complications, and mortality in both pandemic waves were studied. Results: A total of 72 patients were included: Twenty-six admitted during the first wave and 46 during the second wave. Men were predominant in both waves: 61.5% versus 73.9%. The most frequently associated comorbidities in both periods were: arterial hypertension 65.4% versus 65.2%, diabetes mellitus 46.2% versus 34.8% and overweight, measured as (body mass index), 29.13 ± 3.38 versus 28.98 ± 4.25. More patients received noninvasive mechanical ventilation prior to invasive ventilation during the second wave (P < 0.01); the incidence of atelectasis and bronchial obstruction were lower during the second wave (P < 0.01 and P = 0.055 respectively); no further differences were observed in the occurrence of other complications. Conclusions: No significant differences were observed between the first and the second wave in the demographic characteristics or comorbidities of admitted patients. Blood hypertension, diabetes and overweight were remarkable risk factors. Improving our knowledge of the complications, these patients tend to develop was essential to reduce some of them, such as endotracheal tube obstruction or atelectasis, and to promote the use of noninvasive ventilation therapies.