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Background: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. The infection is associated with a high mortality rate and risk of recurrence. We assessed risk factors for death or recurrent CDI (CDI) in patients with diabetes mellitus (DM)., Methods: This retrospective cohort study was conducted at a single institution from 2019 to 2020. CDI was defined as a positive toxin assay for C. difficile. CDI was defined as a repeat positive toxin assay within ≤ 60 days of stopping CDI treatment. Logistic regression models were used to identify risk factors for CDI-related mortality, recurrence, and the combined outcome of mortality and recurrence., Results: Of the 252 enrolled patients with CDI, 19% had DM. Only 49% of patients with DM fully recovered after the first CDI occurrence, whereas 69% of patients without diabetes fully recovered ( p = 0.021); 23% of patients with DM vs. 17% of patients without DM had recurrences ( p  = 0.200); and 23% of patients with DM vs. 15% of patients without DM died ( p  = 0.169). DM was associated with mortality (OR 2.75, 95% CI 0.94-8.06) and the combined outcome (OR 2.10, 95% CI 1.05-4.18). Nosocomial transmission, immunosuppression, CKD, and age were associated with mortality., Conclusions: Diabetes is associated with a worse prognosis in patients with CDI. Prevention efforts should be optimized in patients with diabetes by reducing CDI transmission and avoiding nonessential medications, such as PPIs or antibiotics when they are not necessary. [Figure: see text].

Assessment of side effects associated with COVID-19 vaccination is required to monitor safety issues and acceptance of vaccines in the long term. We found a significant knowledge gap in the safety profile of COVID-19 vaccines in Bangladesh. We enrolled 1805 vaccine recipients from May 5, 2021, to April 4, 2023. Kruskal-Wallis test and χ2 test were performed. Multivariable logistic regression was also performed. First, second and third doses were administered among 1805, 1341, and 923 participants, respectively. Oxford-AstraZeneca (2946 doses) was the highest administered followed by Sinopharm BIBP (551 doses), Sinovac (214 doses), Pfizer-BioNTech (198 doses), and Moderna (160 doses), respectively. Pain at the injection site (80-90%, 3200-3600), swelling (85%, 3458), redness (78%, 3168), and heaviness in hand (65%, 2645) were the most common local effects, and fever (85%, 3458), headache (82%, 3336), myalgia (70%, 2848), chills (67%, 2726), muscle pain (60%, 2441) were the most prevalent systemic side effects reported within 48 h of vaccination. Thrombosis was only reported among the Oxford-AstraZeneca recipients (3.5-5.7%). Both local and systemic effects were significantly associated with the Oxford-AstraZeneca (p-value < 0.05), Pfizer-BioNTech (p-value < 0.05), and Moderna (p-value < 0.05) vaccination. Chronic urticaria and psoriasis were reported by 55-60% of the recipients after six months or later. The highest percentage of local and systemic effects after 2nd and 3rd dose were found among recipients of Moderna followed by Pfizer-BioNTech and Oxford-AstraZeneca. Homogenous doses of Oxford-AstraZeneca and heterogenous doses of Moderna and Pfizer-BioNTech were significantly associated with elevated adverse effects. Females, aged above 60 years with preexisting health conditions had higher risks. Vaccination with Pfizer-BioNTech (OR 4.34, 95% CI 3.95-4.58) had the highest odds of severe and long-term effects followed by Moderna (OR 4.15, 95% CI 3.92-4.69) and Oxford-AstraZeneca (OR 3.89, 95% CI 3.45-4.06), respectively. This study will provide an integrated insight into the safety profile of COVID-19 vaccines., (© 2024. The Author(s).)

Background/Objectives : Early identification of complications in chronic and infectious diseases can reduce clinical deterioration, lead to early therapeutic interventions and lower morbidity and mortality rates. Here, we aimed to assess the feasibility of a novel clinical decision support system (CDSS) based on the automatic generation of alerts through remote patient monitoring and to identify the patient profile associated with the likelihood of severe medical alerts. Methods : A prospective, multicenter, open-label, randomized controlled trial was conducted. Patients with COVID-19 in home isolation were randomly assigned in a 1:1 ratio to receive either conventional primary care telephone follow-up plus access to a mobile app for self-reporting of symptoms (control group) or conventional primary care telephone follow-up plus access to the mobile app for self-reporting of symptoms and wearable devices for real-time telemonitoring of vital signs (case group). Results : A total of 342 patients were randomized, of whom 247 were included in the per-protocol analysis (103 cases and 144 controls). The case group received a more exhaustive follow-up, with a higher number of alerts (61,827 vs. 1825; p < 0.05) but without overloading healthcare professionals thanks to automatic alert management through artificial intelligence. Baseline factors independently associated with the likelihood of a severe alert were having asthma (OR: 1.74, 95% CI: 1.22-2.48, p = 0.002) and taking corticosteroids (OR: 2.28, 95% CI: 1.24-4.2, p = 0.008). Conclusions : The CDSS could be successfully implemented and enabled real-time telemonitoring of patients' clinical status, providing valuable information to physicians and public health agencies.

Before starting a drug that suppresses immunity, it is of paramount importance to screen for hidden infections in patients with inflammatory diseases. Latent tuberculosis infection (LTBI) is a condition characterized by an immune response to M. tuberculosis antigens without clinical manifestations. The highest risk of progression to active disease occurs in individuals who are immunosuppressed or in children. Patients who are candidates for treatment with TNF-alpha inhibitors should be evaluated with interferon gamma release assays and a chest radiograph. We present a case of a 42 year old woman with a history of Crohn disease treated with infliximab and fever with adenopatys.

Background and Purpose: Chronic kidney disease (CKD) is associated with high morbidity, burden, and resource utilization, and represents a major challenge for healthcare systems. The purpose of this study was to analyse the care patterns for these patients and to reach a consensus on the key factors that should be implemented for an optimal care model in CKD, through a multidisciplinary and integrative vision., Materials and Methods: A multidisciplinary panel of professionals with experience in the field of CKD was formed, composed of an advisory committee of 15 experts and an additional panel of 44 experts. Challenges and areas for improvement across the continuum of care were identified through review of scientific evidence and individual interviews with the advisory committee. Key factors for an optimal model of care in CKD were agreed and assessed using the Rand/UCLA consensus methodology (adapted Delphi), evaluating their appropriateness and necessity., Results: 38 key factors were identified for an optimal CKD patient care model, organised into four challenges: (1) Development of CKD management models and increased visibility of the disease, (2) Prevention, optimisation of screening, early diagnosis and registration of CKD at all levels of care, (3) Comprehensive, multidisciplinary and coordinated monitoring, ensuring therapeutic optimisation and continuity of care, and (4) Reinforcement of CKD training for health care professionals and patients. 35 key factors were assessed by the panel as adequate and clearly necessary, and of these, 14 were considered highly imperative., Conclusions: There is consensus on the need to prioritise CKD care at both institutional and societal levels, moving towards optimal models of CKD care based on prevention and early detection of the disease, as well as comprehensive and coordinated patient monitoring and training and awareness-raising at all levels. The key factors identified constitute a roadmap that can be implemented in the different Autonomous Communities and contribute to a significant improvement in the patient's care., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones., Methods: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis., Findings: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p < 0.001). Candida spp. showed higher rate in non-COVID-19 (74.2 % vs. 66.8 %; p = 0.015), meanwhile Aspergillus spp. confirmed its predominance in COVID-19 hematological patients (35.4 % vs. 19.1 %; p < 0.001). IPA was diagnosed in 703 patients and 11.2 % (79 cases) were CAPA. The multivariate logistic regression analysis found that the diagnosis of COVID-19 disease at hospital admission increased more than two-fold IPA development [OR: 2.5, 95CI (1.9-3.1), p < 0.001]. B-cell malignancies - specifically B-cell non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia and acute lymphoblastic leukemia - showed between four- and six-fold higher CAPA development and 90-day mortality rates ranging between 50 % and 72 %. However, myeloid malignancies did not show higher CAPA rates compared to IPA in non-COVID-19 patients., Conclusion: COVID-19 constitutes an independent risk factor for developing aspergillosis in B-cell hematological malignancies and the use of antifungal prophylaxis during hospitalizations may be warranted., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-1854/coif). The authors have no conflicts of interest to declare.

Background: Non-small cell lung cancer (NSCLC) has undergone a major change in the last decade in terms of survival and prognosis due to the introduction of new drugs in the last 10 years. One of the drugs with the most promising preliminary results in NSCLC are PARP inhibitors (iPARPs), whose clinical trials have very heterogeneous results. The use of iPARPs in NSCLC may lead to increased survival in several selected patients, and their use may become a standard in the coming years. However, there is currently controversy about the efficacy and safety of these drugs in NSCLC. Therefore, future studies are needed to evaluate their role in these tumours. The aim of this review is to evaluate the efficacy and safety of iPARPs in the treatment of NSCLC., Methods: We performed a systematic review with meta-analysis using the different clinical trials (PubMed, COCHRANE, Science Direct, EMBASE and the clinical trial registry) that evaluated the efficacy and safety of iPARP in NSCLC by PRISMA criteria. The primary endpoint was to evaluate the efficacy of iPARPs in the treatment of NSCLC through overall and progression-free survival (OS and PFS). Two authors independently reviewed the articles and abstracts (A.O.H. and J.R.R.), with subsequent confirmation by a third independent reviewer (E.B.M.). The heterogeneity of the included studies in the meta-analysis was assessed by using the I2 statistic., Results: A total of 14 articles were included for analysis (2,651 patients). A total of 1,503 patients were randomised in iPARP arms and 1,148 patients were included in control arms. Three clinical trials were conducted in localised or locally advanced NSCLC and 11 in advanced or metastatic stages. The global OS of the meta-analysis showed a hazard ratio (HR) of 0.85 [95% confidence interval (CI): 0.74-0.97] with a heterogeneity (I2) of 0% (P=0.84). PFS showed a HR of 0.93 (95% CI: 0.74-1.17) with an I2=51% (P=0.07). The overall adverse event rate (grade 1-5) was similar in both iPARP and placebo arms., Conclusions: iPARPs are a future promising in the treatment of NSCLC in terms of efficacy and safety. Proper patient selection [homologous recombination deficiency (HRD) positive] is key for future clinical trials. The studies conducted to date open a new approach for a novel treatment modality in NSCLC.

Background: The introduction of immunotherapy in the treatment of non-small cell lung cancer (NSCLC) has resulted in a radical change in patients' treatment responses and survival rates. The increased percentage of long survivors, improved toxicity profiles compared to chemotherapy, and the possible applications for different NSCLC scenarios, have led to immune checkpoint inhibitors (ICIs) becoming the cornerstone of NSCLC treatment. Therefore, the objective of this review is to describe the current and future perspectives of NSCLC treatment., Methods: A systematic review according to the PRISMA criteria has been performed based on clinical trials with immunotherapy in NSCLC from the start of these treatments until June 2022., Results: The use of ICIs is widespread across both first- and second-line treatments with anti-PD-1, anti-PD-L1, and anti-CTLA-4 drugs. New indications for immunotherapy in NSCLC have focused on adjuvant (atezolizumab) and neoadjuvant (nivolumab), with ICIs now present in all stages of NSCLC treatment. Given the promising results seen in clinical trials, new ICIs [anti- lymphocyte activation gene-3 (LAG-3) or IDO1] currently under development, will soon be used as standard treatment for NSCLC., Conclusions: Immunotherapy is the mainstay of NSCLC treatment in all stages, including adjuvant, neoadjuvant and advanced tumors. The development of new molecules will revolutionize the treatment of NSCLC in the coming years., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4218/coif). JPMG serves as an unpaid editorial board member of Annals of Translational Medicine from June 2022 to May 2024. The other authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Introduction: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data., Methods: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria., Results: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70-93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14-96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients., Conclusions: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity.

Background: The aim of this study is to investigate the use of once-weekly semaglutide in a real population of patients with type 2 diabetes mellitus (T2DM) over 70 years in two Spanish hospitals., Methods: An observational, retrospective, and multicenter clinical study was designed. It included 60 patients with T2DM, with a mean age of 76.5 years, 63.3% women, and a mean of 15.5 years of evolution of T2DM, all managed in the outpatient clinical setting. The primary endpoint was the change in HbA1c from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of patients achieving HbA1c <7.0% and body weight loss >5%., Results: After 12 months of follow-up, the reductions in HbA1c were -0.61±0.9% (P<0.0001) in the total cohort. Body weight reductions were -8.2±5.3 kg (P<0.0001). Overall, 67% reached the objective of an HbA1c level of <7%, and 73% achieved a weight loss of ≥5%., Conclusions: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA1c and body weight in adults aged over 70 years with T2DM, without notable adverse effects, which supports real-world use.

COVID-19 has had a negative impact on the health care of patients with cardiovascular disease and patients at high risk of cardiovascular disease. The restrictions affecting access to the health care system have conditioned the care received, resulting in poorer control and a higher risk of events. Taking action to improve the care provided during health emergencies is mandatory. It is important to promote the development of telemedicine and patient empowerment by fostering health literacy and a higher degree of self-care. In addition, primary care and coordination between health care levels should be improved. Moreover, the simplification and optimization of treatment, for example, using the cardiovascular polypill, have led to an improvement in adherence, better control of vascular risk factors, and a reduced risk of events. The present document provides specific recommendations for improving the care provided to patients under a health emergency.

MALS, also called celiac artery compression syndrome, celiac axis syndrome, or Dunbar syndrome, is a rare entity caused by progressive stenosis of the celiac trunk secondary to extrinsic compression of the fibers of the median arcuate ligament. The prevalence is unknown, but it is estimated that it is a casual finding in up to a third of autopsies2,3, being more prevalent in women between 30 and 50 years of age4. Symptoms and signs include postprandial abdominal pain, exercise-induced pain, nausea, vomiting, and weight loss3. However, most cases are asymptomatic. The case that we present was a 56-year-old man, with a history of dyslipidemia, type 2 diabetes mellitus, and chronic ischemic heart disease. He was a former smoker. He reported a history of recurrent abdominal pain, especially postprandial.

Aim: This work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments., Methods: This study analyzed patients in an ongoing, multicenter, prospective, pre-post, uncontrolled cohort registry that enrolls unique, consecutive patients with type 2 diabetes treated with weekly subcutaneous semaglutide. Steatosis/fibrosis were determined by HSI (<30 ruled out, >36 steatosis) and FIB-4 (<1.3 ruled out, >2.67 fibrosis), respectively., Results: The sample included 213 patients (46.9% women) with a median age of 64 (19) years. The median baseline body mass index and weight were 36.1 (8.4) kg/m 2 and 98 (26.9) kg, respectively. A total of 99.9% had HSI values indicating steatosis, with a mean HSI of 47.9 (8.2). Additionally, 10.8% had fibrosis (FIB-4 > 2.67) and 42.72% had values in intermediate ranges (FIB-4 1.3-2.67). At 24 weeks, there was a significant reduction in HSI (-2.36 (95%CI 1.83-2.9) p < 0.00001) and FIB-4 (-0.075 (95%CI 0.015-0.14) p < 0.016), mainly related to declines in body weight, triglyceride levels, insulin resistance (estimated by the triglyceride-glucose index), and liver enzymes., Conclusion: These results show that weekly subcutaneous semaglutide had a beneficial effect on liver steatosis that went beyond glucose control. Its effects were mainly related to weight loss, a decline in biomarkers, and improvements in insulin sensitivity. For many patients, early detection is essential for improving MAFLD outcomes and may allow for selecting the most efficient treatment options., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Background: Nowadays the poly-ADP ribose polymerase inhibitors (iPARPs) are the mainly treatment for the ovarian cancer and other solid tumours. However, given its recent use, long-term toxicity is still under study. The occurrence of acute leukaemias and myelodysplastic syndromes (MDS) secondarily to iPARPs is known (0.5-1%)., Case Description: We present the case of a 78-year-old patient with a serous carcinoma of ovary in maintenance treatment with Niraparib after response to platinum. Along with the ovarian carcinoma the patient developed a diffuse large cell B lymphoma (DLBCL) five years ago, treated with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) with complete response. The patient was evaluated in the emergency due to constitutional syndrome, objectifying a bicytopenia (platelets 28,000/mcL, haemoglobin 9.6 g/dL). In the study of bicytopenia, a bone marrow infiltration by high-grade B lymphoma was diagnosed., Conclusions: The action of iPARPs on the selection of acquired mutations in clonal haematopoiesis maybe have been able to accelerate the process of relapse and leukemisation of the previous lymphoma. The association of treatment with iPARPs and the development of lymphomas is key for increasing knowledge of the safety profiles these drugs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-22-91/coif). The authors have no conflicts of interest to declare., (2023 AME Case Reports. All rights reserved.)

Background: A high cobalamin level has been related to non-malignant diseases (mainly liver diseases, alcoholism, and renal diseases) and cancer (hematological malignancies and solid cancers such as liver and stomach cancer). However, a previous high level of cobalamin and the implications in the possible development of cancer is still unclear. The main aim of this study was to describe if a previous high cobalamin level is a determinant in the future development of cancer in five years of follow-up. The secondary objective was to determine any differences between cancer groups., Methods: A retrospective study was performed. Two databases were employed. The first one included all patients who had a determination of cobalamin in a routine blood test during the year 2010 (a total of 44,166 patients). The second one showed every patient who was admitted to the reference hospital, Hospital Clinico Universitario de Valladolid, during the following five years. Finally, a number of 6710 patients was included. Both databases belong to the medical records of the Hospital Data Surveillance System and are completely validated. Multivariate logistic regression analyses were employed to evaluate the association between cobalamin levels and the appearance of cancer (total and in each subgroup). All analyses were performed using IBM SPSS 24 software (IBM Corp., Armonk, NY, USA)., Results: The sample studied showed a clear association between the risk of hematological cancer and a previous high Cbl level. This relationship was higher among patients with the highest levels (over 779 pmol/L), showing almost two times more risk for development of hematological malignance within 5 years in the multivariate analysis (OR: 1.975, 95% CI: 1.056-3.697, P=0.033). Hematological malignancies were mostly diagnosed within the first three years (86.6%), showing a similar percentage in those three years. There was no association between this previous level and the development of any other type of cancer., Conclusions: Our study shows that a high cobalamin plasma level (hypervitaminosis) is associated with the development of hematologic cancer within five years after the measurement. The clinical implication of these findings, together with the clinical suspicion, reinforces the necessity of carrying out specific screening hematological tests in patients with not justified elevated plasma cobalamin levels. New prospective and multicenter studies are necessary to validate these results.

DRESS syndrome is a multisystem disorder that appears in the context of an adverse drug reaction, characterized by fever, rash and peripheral eosinophilia with involvement of other organs such as the liver. The typical liver involvement is acute toxic hepatitis (DILI), showing improvement and a tendency to resolution when corticotherapy is started. We must not forget this manifestation in the clinical context of a DRESS syndrome.

Objectives: To investigate the use of once-weekly semaglutide in a real population of people with type 2 diabetes mellitus (T2DM) in three Spanish hospitals., Method: An observational, retrospective and multicenter clinical study was designed that included 166 participants with T2DM, distinguishing between a group naïve to GLP-1RA (n=72) and another switching from another GLP-1RA (n=94), all managed in the outpatient clinical setting. The primary endpoint was the change in HbA1c from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of people with T2DM, achieving HbA1c <7.0% and body weight loss >5%., Results: After 24 months of follow-up, the reductions in HbA1c were -0.91 ± 0.7% (p<0.001) in the total cohort, -1.13 ± 1.38% (p<0.019) for GLP-1RA-naïve participants, and -0.74 ± 0.9% (p<0.023) for GLP-1RA-experienced participants. Body weight reductions were -12.42 ± 9.1% in GLP-1RA-naïve participants vs. -7.65 ± 9.7% in GLP-1RA-experienced participants (p<0.001). In the total cohort, 77.1% reached the objective of an HbA1c level <7%, and 12.7% reached between 7.1% and 7.5%. Additionally, 66.9% achieved a weight reduction ≥5%. Of all cohort, 90% received 1 mg of semaglutide once a week. The reported adverse events were consistent with the known safety profile of semaglutide., Conclusions: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA1c and body weight in a wide range of adults with T2DM, without notable adverse effects, which supports real-world use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garcia de Lucas, Miramontes-González, Avilés-Bueno, Jiménez-Millán, Rivas-Ruiz and Pérez-Belmonte.)

Background and Objectives: In the pandemic caused by SARS-CoV-2, identifying which risk factors are associated with the most serious forms of the disease is important. Blood group A has been presented in various studies as a poor prognostic factor. The objective of this study was to evaluate whether patients with blood group A were associated with more important comorbidities, measured by the Charlson Index, which may explain their worse clinical evolution., Patients and Methods: A prospective and consecutive study examined 100 patients diagnosed with COVID-19 and admitted in March 2020. A multivariate linear regression model was used to evaluate the association of blood group A with the Charlson Index., Results: Patients in group A had a higher Charlson Index ( P  = .037), rate of lymphopenia ( P  = .039) and thrombopenia ( P  = .014), and hospital mortality ( P  = .044). Blood group A was an independent factor associated with the Charlson Index (B 0.582, 95% CI 0.02-1.14, P  = .041)., Conclusions: Group A was independently associated with greater comorbidity, associated with an increase of 0.582 points in the Charlson Index compared to other blood groups. It was also associated with lower hospital mortality., (© 2021 Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: In the pandemic caused by SARS-CoV-2, identifying which risk factors are associated with the most serious forms of the disease is important. Blood group A has been presented in various studies as a poor prognostic factor. The objective of this study was to evaluate whether patients with blood group A were associated with more important comorbidities, measured by the Charlson Index, which may explain their worse clinical evolution., Patients and Methods: A prospective and consecutive study examined 100 patients diagnosed with COVID-19 and admitted in March 2020. A multivariate linear regression model was used to evaluate the association of blood group A with the Charlson Index., Results: Patients in group A had a higher Charlson Index (P=.037), rate of lymphopenia (P=.039) and thrombopenia (P=.014), and hospital mortality (P=.044). Blood group A was an independent factor associated with the Charlson Index (B 0.582, 95% CI 0.02-1.14, P=0.041)., Conclusions: Group A was independently associated with greater comorbidity, associated with an increase of 0.582 points in the Charlson Index compared to other blood groups. It was also associated with lower hospital mortality., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Background: Old age is one of the most important risk factors for severe COVID-19. Few studies have analyzed changes in the clinical characteristics and prognosis of COVID-19 among older adults before the availability of vaccines. This work analyzes differences in clinical features and mortality in unvaccinated very old adults during the first and successive COVID-19 waves in Spain., Methods: This nationwide, multicenter, retrospective cohort study analyzes unvaccinated patients ≥ 80 years hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). Patients were classified according to whether they were admitted in the first wave (March 1-June 30, 2020) or successive waves (July 1-December 31, 2020). The endpoint was all-cause in-hospital mortality, expressed as the case fatality rate (CFR)., Results: Of the 21,461 patients hospitalized with COVID-19, 5,953 (27.7%) were ≥ 80 years (mean age [IQR]: 85.6 [82.3-89.2] years). Of them, 4,545 (76.3%) were admitted during the first wave and 1,408 (23.7%) during successive waves. Patients hospitalized in successive waves were older, had a greater Charlson Comorbidity Index and dependency, less cough and fever, and met fewer severity criteria at admission (qSOFA index, PO2/FiO2 ratio, inflammatory parameters). Significant differences were observed in treatments used in the first (greater use of antimalarials, lopinavir, and macrolides) and successive waves (greater use of corticosteroids, tocilizumab and remdesivir). In-hospital complications, especially acute respiratory distress syndrome and pneumonia, were less frequent in patients hospitalized in successive waves, except for heart failure. The CFR was significantly higher in the first wave (44.1% vs. 33.3%; -10.8%; p < 0.001) and was higher among patients ≥ 95 years (54.4% vs. 38.5%; -15.9%; p < 0.001). After adjustments to the model, the probability of death was 33% lower in successive waves (OR: 0.67; 95% CI: 0.57-0.79)., Conclusions: Mortality declined significantly between the first and successive waves in very old unvaccinated patients hospitalized with COVID-19 in Spain. This decline could be explained by a greater availability of hospital resources and more effective treatments as the pandemic progressed, although other factors such as changes in SARS-CoV-2 virulence cannot be ruled out., (© 2022. The Author(s).)

Background: The impact of glucagon-like peptide-1 receptor agonists on patients with heart failure has not been fully described. Our main objective was to evaluate the safety and clinical and glycemic efficacy of once-weekly semaglutide in obese patients with type 2 diabetes and heart failure., Methods: In this observational, retrospective, real-world study, we enrolled outpatients with type 2 diabetes, obesity, and heart failure who started semaglutide and were followed-up on at 3, 6, and 12 months., Results: A total of 136 patients were included. From baseline to 12 months, there was a significant improvement on the Kansas City Cardiomyopathy Questionnaire total symptom score (59.0 ± 24.1 vs 79.9 ± 28.4 points, p<0.01), a reduction in the proportion of patients with New York Heart Association functional class III (40.4% to 16.2%, p<0.01), and a reduction in N-terminal pro-brain natriuretic peptide levels (969.5 ± 653.5 vs 577.4 ± 322.1 pg/mL, p<0.01). Emergency department visits due to heart failure, hospitalizations due to heart failure, and all-cause hospitalizations also declined. Additionally, significant reductions in glycated hemoglobin (-1.4%) and body weight (-12.7 kilograms) were observed as well as a de-intensification of antidiabetic therapy. Moreover, semaglutide was safe and well-tolerated., Conclusion: In obese patients with type 2 diabetes and heart failure, the use of once-weekly semaglutide was safe and clinically efficacious, improving health and functional status. Nevertheless, more strong evidence on glucagon-like peptide-1 receptor agonists in heart failure is required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pérez-Belmonte, Sanz-Cánovas, Garcia de Lucas, Ricci, Avilés-Bueno, Cobos-Palacios, Pérez-Velasco, López-Sampalo, Bernal-López, Jansen-Chaparro, Miramontes-González and Gómez-Huelgas.)

The presence of a procoagulant state, COVID-19-related coagulopathy, and an increased rate of thrombotic events (TEs) is widely known about. However, descriptive studies are scarce. Here, we conducted a large retrospective study including 2894 hospitalized COVID-19 patients followed up during the first 18 months of the pandemic to completely characterize any TE. Major TEs showed a 3.45% incidence rate. TEs were associated with increased intubation/90-day mortality risk [OR = 1.71, 95% CI (1.12−2.61), p < 0.013]. Venous thrombotic events (VTEs) were more frequent than arterial thrombotic events (ATEs) (72% vs. 28%), associated with enhanced levels of D-dimer (cross-linked fibrin derivatives formed during thrombolysis), which were related to mortality but more useful for early detection of thrombosis. In this regard, D-dimer plasma levels above 2014 µg/mL at hospital admission identify TEs with 91% accuracy (AUC = 0.91, p < 0.001), rising to almost 95% (AUC = 0.94, p < 0.001) with a cut-off value of 2666 µg/mL in VTEs. Moreover, 41% of TEs occurred in patients receiving LMWH thromboprophylactic treatments in hospital or domiciliary therapies. SARS-CoV-2 infection along with a sedentary lifestyle derived from the confinement in 2020 could be more determinant than a procoagulant state in patients with risk factors for TEs. Furthermore, the normal results obtained from the thrombophilia study after the acute process are linked to this independent procoagulant state and to SARS-CoV-2-derived coagulopathy.

Background: Determining predictive biomarkers for immune checkpoint inhibitors (ICIs) is a current challenge in oncology. Previous studies on non-small cell lung cancer (NSCLC) have shown how TP53 gene mutations are correlated with different responses to ICIs. Strong and diffuse immuno-expression of p53 by immunohistochemistry (IHC) is interpreted as a likely indicator of a TP53 gene mutation. We aimed to assess the p53 protein expression via IHC in NSCLC as a predictive biomarker of the response to ICIs., Methods: This was a retrospective hospital-based study of patients with NSCLC treated with Nivolumab in the University Hospital of Salamanca. All diagnostic biopsies were studied via IHC (measuring p53 protein expression, peroxidase anti-peroxidase immunohistochemistry technique using Leica BOND Polymer development kits). Survival analysis was performed by subgroups of expression of p53 and other factors using the Kaplan-Meier estimator and Cox proportional-hazards model., Results: Seventy-three patients were included (59 men and 14 women). The median age was 68 (44-84) years. Thirty-six biopsies were adenocarcinoma, 34 were squamous, and three were undifferentiated. In 41 biopsies (56.2%), the cellular expression of p53 was <5% (Group A), and in 32 biopsies (43.8%), the expression was ≥5% (Group B). In the general analysis, no differences were observed in overall survival (OS) (A: 12 months vs B: 20 months; p = 0.070) or progression-free survival (PFS) (A: 4 m vs B: 7 m; p = 0.064). Significant differences were observed in adenocarcinomas for both OS (A: 8 m vs B: median not reached; p = 0.002) and PFS (A: 3 m vs 8 m; p = 0.013). No differences in PFS and OS were observed in squamous cell carcinoma. Significant differences were observed in OS in the PD-L1 negative group (0% expression) (A: 13 m vs B: 39 m; p = 0.024), but not in PFS (A: 3 m vs B: 7 m; p = 0.70). No differences were observed in the PD-L1 positive group., Conclusions: A trend toward a greater response to ICIs was observed in the PFS and OS of patients with high expression of p53 by IHC ( TP53 mutation), especially in the PD-L1 negative adenocarcinoma subgroup. These results will make it possible to make future modifications to the clinical guidelines of NSCLC according to the expression of p53., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system's involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system ( p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group ( p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669-61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments.

Background: Diabetic kidney disease is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. ESKD has a high prevalence in patients with diabetes mellitus (DM). CKD increases the chances of hypoglycaemia by different mechanisms, causes insulin resistance and a decrease in insulin metabolism. Both the "Kidney Disease: Improving Global Outcomes" (KDIGO) and "American Diabetes Association" (ADA) guidelines recommend the use of insulin as part of treatment, but the type of basal insulin is not specified., Methods: We reviewed the literature to determine whether first- and second-generation basal insulins are effective and safe in CKD patients. We reviewed specific pivotal studies conducted by pharmaceutical laboratories, as well as independent studies., Conclusions: Basal insulins are safe and effective in patients with CKD and diabetes mellitus but we do not have specific studies. Given that CKD is one of the main complications of type 2 DM, and insulin specific treatment in the final stages, the absence of studies is striking. Real-life data are also important since trials such as pivotal studies do not fully represent actual patients. Treatment should be individualized until we have specific trials in this type of population., (© 2021 Diabetes UK.)

The relationship between viral infections and cancer is well known and has been established for decades. Multiple tumours are generated from alterations secondary to viral infections 2 resulting from a dysregulation of the immune system in many cases. Certain causal relationships, such as that between the Epstein-Barr virus (EBV) in nasopharyngeal cancer or hepatitis C and B viruses in hepatocarcinoma, have been clearly established, and their implications for the prognosis and treatment of solid tumours are currently unknown. Multiple studies have evaluated the role that these infections may have in the treatment of solid tumours using immunotherapy. A possible relationship between viral infections and an increased response to immune checkpoint inhibitors (ICIs) has been established at a theoretical level in solid neoplasms, such as EBV-positive cavum cancer and human papillomavirus (HPV)-positive and oropharyngeal cancer. These could yield a greater response associated with the activation of the immune system secondary to viral infection, the consequence of which is an increase in survival in these patients. That is why the objective of this review is to assess the different studies or clinical trials carried out in patients with solid tumours secondary to viral infections and their relationship to the response to ICIs.

Competing Interests: The authors declare no conflict of interest.

Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor outcomes in COVID-19 patients., Methods: A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0., Results: A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI-(1.28-42.4), p = 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results., Conclusions: A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery-validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines' quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933-0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127-80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846-0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover-validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.

Myeloid-derived suppressor cells (MDSCs) are a set of immature myeloid lineage cells that include macrophages, granulocytes, and dendritic cell precursors. This subpopulation has been described in relation to the tumour processes at different levels, including resistance to immunotherapy, such as immune checkpoint inhibitors (ICIs). Currently, multiple studies at the preclinical and clinical levels seek to use this cell population for the treatment of different haematological neoplasms, together with ICIs. This review addresses the different points in ongoing studies of MDSCs and ICIs in haematological malignancies and their future significance in routine clinical practice.

Background: Since the first cases of COVID-19 were reported in Wuhan, the nutritional status of individuals infected with the virus has not been included in the risk profiles prepared. However, nutritional status, along with other factors, is decisive in the evolution of patients with other infectious diseases. The nutritional status of individuals is considered an indicator of health status. Furthermore, optimal nutritional status transcends the individual, and poor diet in a population can be considered a group risk factor. Evidence exists on the influence that diet has on the immune system and susceptibility to disease., Objective: To evaluate the nutritional status of patients older than 65 years who were admitted due to COVID-19 and how this has influenced the evolution of patients., Design: This prospective and observational study was performed in patients with COVID-19 infection confirmed by real-time polymerase chain reaction. Data were collected from the first 24 h of admission. All patients admitted during one month to the wards assigned to COVID-19 infection were included., Results: A total of 83 patients were studied. The statistical study of mortality showed associations with age ( p  = .005), living in a nursing home ( p  = .022), a high Charlson Comorbidity Index ( p  = .039), hypertension ( p  = .032), comorbidities of dementia ( p  = .019) and cerebral vascular disease ( p  = .041), and Barthel Index ( p  = .010). The analysis of the influence of the nutritional state on mortality revealed a statistical association between malnutrition and mortality in the pooled data analysis ( p  = .005) and analysis by degrees of malnutrition ( p  = .27)., Conclusions: Malnutrition was a risk factor as powerful as others such as hypertension, age, and different comorbidities. We must evaluate and treat the nutritional status of elderly patients with COVID-19 infection since it directly affects their evolution.

The dopaminergic system can adapt to the different physiological or pathological situations to which the kidneys are subjected throughout life, maintaining homeostasis of natriuresis, extracellular volume, and blood pressure levels. The role of renal dopamine receptor dysfunction is clearly established in the pathogenesis of essential hypertension. Its associations with other pathological states such as insulin resistance and redox balance have also been associated with dysfunction of the dopaminergic system. The different dopamine receptors (D1-D5) show a protective effect against hypertension and kidney disorders. It is essential to take into account the various interactions of the dopaminergic system with other elements, such as adrenergic receptors. The approach to therapeutic strategies for essential hypertension must go through the blocking of those elements that lead to renal vasoconstriction or the restoration of the normal functioning of dopamine receptors. D1-like receptors are fundamental in this role, and new therapeutic efforts should be directed to the restoration of their functioning in many patients. More studies will be needed to allow the development of drugs that can be targeted to renal dopamine receptors in the treatment of hypertension.

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge., (© 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Infection with SARS-CoV-2 is becoming the leading cause of death in most countries during the 2020 pandemic. The objective of this study is to assess the association between COVID-19 and cause-specific death. The design is retrospective cohort study. We included data from inpatients diagnosed with COVID-19 between March 18 and April 21, 2020, who died during their hospital stay. Demographic, clinical and management data were collected. Causes of death were ascertained by review of medical records. The sample included 128 individuals. The median age was 84 (IQR 75-89), 57% were men. In 109 patients, the death was caused by SARS-CoV-2 infection, whereas in 19 (14.8%, 95 CI 10-22%), the infection acted only as a precipitating factor to decompensate other pathologies. This second group of patients was older (88y vs 82, p < 0.001). In age-adjusted analysis, they had a greater likelihood of heart failure (OR 3.61 95% CI 1.15-11.32), dependency in activities of daily living (OR 12.07 95% CI 1.40-103.86), frailty (OR 8.73 95% CI 1.37-55.46). The presence of X-ray infiltrates was uncommon (OR 0.07, 95% CI 0.02-0.25). A higher percentage of patient deaths from causes unrelated to COVID-19 complications occurred during the two first weeks of the pandemic. Fifteen percent of patients with COVID-19 infection died from decompensation of other pathologies and the cause of death was unrelated to COVID-19 severe complications. Most of these patients had more comorbidities and were frail and elderly. These findings can partially explain the excess mortality in older people.

SARS-CoV-2 infection is associated with a high risk of malnutrition, mainly due to increased nutritional requirements and the presence of a severe and universal inflammatory state. Associated symptoms contribute to hyporexia, which perpetuates the negative nutritional balance. Furthermore, dysphagia, especially post-intubation, worsens and makes intake unsafe. This risk is greater in elderly and multimorbid patients. Inflammation to varying degrees is the common link between COVID-19 and the onset of malnutrition, and it is more correct to refer to disease-related malnutrition (DRM). DRM worsens the poor prognosis of SARS-CoV-2 infection, especially in the most severe cases. Therefore, it is necessary to identify and treat people at risk early, avoiding overexposure and direct contact with the patient. We cannot forget the role that a healthy diet plays in both prevention and recovery after discharge., (© 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Introduction and Objectives: The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH., Methods: SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up., Results: We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively., Conclusions: This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event., Clinical Trial Registration: http://www.clinicaltrials.gov. Identifier: NCT02693548., (Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

The aetiology of essential hypertension is complex and involves both environmental and genetic factors. Approximately 30% of the inter-individual variability in blood pressure is genetically determined. It has been shown that numerous vasoconstrictors stimulate RhoA in local populations of vascular SMCs that, in turn, promote localised constriction of arterial blood vessels and elevations in blood pressure. The VAV3 gene encodes for VAV3 protein, a Rho GEF factor. VAV3-AS1 gene, a lncRNA, may regulate VAV3 expression. We performed an observational prospective case-control study, including patients attending in the Vascular Risk Unit from the University Hospital Salamanca for 6 months. A replication study was performed with data from The Kaiser Permanent database of the University of California. The results suggest that T allele of the VAV3 rs7528153 and G allele of the VAV3-AS1 rs11185222 polymorphisms are associated with an increased risk of developing hypertension. We hypothesise that these polymorphisms could modify blood pressure, likely through a modification in the Rho/Rac pathway. Our results suggest that those polymorphisms could be useful genetic markers of susceptibility to suffering hypertension., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest. In the same way the correspondence author, and responsible for the article, declares no conflicts of interest., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)