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From February 21 through April 1, 2019, a total of 229 cases of out-of-hospital cardiac arrest were reported in four provinces of Lombardy, Italy. During the same period in 2020 (the first 40 days of the Covid-19 epidemic), 362 cases were reported — a 58% increase. Of the additional 133 cases in 2020, a total of 103 involved suspected or diagnosed Covid-19.

The relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients with severe COVID-19, some of whom succumbed. A control population of healthy subjects was included. Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes, with an increased proportion of mature natural killer (NK) cells and low T-cell numbers. NK cells and CD8+ T cells overexpressed T-cell immunoglobulin and mucin domain-3 (TIM-3) and CD69. NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1 (PD-1) positive cells and reduced frequencies of natural killer group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- and sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing NK cells, associated with a reduced ability to secrete interferon (IFN)γ. Patients with poor outcome showed a contraction of immature CD56bright and an expansion of mature CD57+ FcεRIγneg adaptive NK cells compared to survivors. Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors. Of note, monocytes secreted abundant quantities of IL-6, IL-8, and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69, PD-1 and TIM-3 expression and restoration of CD8+ T cell numbers. A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection, probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes. These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.

INTRODUCTION:The natural history of autoimmune gastritis (AIG) has been poorly described. In this study, we report the long-term natural history and clinical clustering of the full spectrum of AIG, from the potential to the complicated stage.METHODS:Prospective single-center study conducted in a tertiary referral center. Patients with AIG at any stage (0 = potential; 1 = early; 2 = florid; 3 = severe; and 4 = complicated) were enrolled (January 2000-December 2022). The histopathological evolution, the clinical presentation, and the correlates of evolution of potential AIG were assessed.RESULTS:Four hundred ninety-eight patients with AIG (mean age 56.7 ± 15.2 years, F:M ratio 2.5:1) were included, of whom 93 experienced potential AIG. The maximum disease duration was 27 years (median 18, interquartile range 14-23), while the overall median follow-up was 52 months (interquartile range 12-95). Age was significantly lower in stage 0 compared with that in the other stages. Accidental histologic evidence and hematologic findings were the most common clusters of diagnosis. The overall median rate of progression was 7.29 per 100 persons/yr (95% confidence interval [CI] 6.19-8.59), while the stage-specific rates of progression were 10.85 (stage 0; 95% CI 7.75-15.18), 14.83 (stages 1-2; 95% CI 11.89-18.49), and 2.68 (stage 3; 95% CI 1.88-3.84). Newly onset neoplastic complications at follow-up occurred in 41/483 patients (8.5%; 23 neuroendocrine tumors and 18 epithelial dysplasia). No cases of adenocarcinoma were noticed. Male sex was associated with a greater likelihood of evolving from potential AIG to overt AIG.DISCUSSION:AIG is a progressive disorder, with a virtually absent risk of gastric adenocarcinoma. Patients with potential AIG should be monitored because they carry a high risk of evolving into overt AIG.

Congenital infection with cytomegalovirus is a major cause of morbidity in neonates. In this phase 2, placebo-controlled trial, hyperimmune globulin given to mothers with primary CMV infection at 5 to 26 weeks of gestation did not significantly alter the course of infection. Every year, approximately 0.6% of all newborns in the United States and the European Union are congenitally infected with human cytomegalovirus (CMV). 1 , 2 Approximately 20% of these infected newborns are symptomatic at birth or will have sequelae such as sensorineural hearing loss, cognitive defects, and motor defects. 3 Primary CMV infection that develops in a woman during pregnancy confers the highest risk of congenital infection and disease. 4 Identification of pregnant women with primary CMV infection is feasible by means of detection of virus-specific IgM and low IgG avidity. However, the unavailability of a therapeutic intervention of proven efficacy in the case . . .

Many management strategies exist for neuroendocrine liver metastases. These strategies range from surgery to ablation with various interventional radiology procedures, and include both regional and systemic therapy with diverse biological, cytotoxic, or targeted agents. A paucity of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of many publications detailing management. This Review represents the views from an international conference, for which 15 expert working groups prepared evidence-based assessments addressing specific questions, and from which an independent jury derived final recommendations. The aim of the conference was to review the existing approaches to neuroendocrine liver metastases, assess the evidence on which management decisions were based, develop internationally acceptable recommendations for clinical practice (when evidence was available), and make recommendations for clinical and research endeavours. This report represents the final clinical statements and proposals for future research.

Background Sarcopenia is a disease associated with aging and a negative prognosis. Consensus‐based treatment consists in targeting muscle mass and function through physical exercise, optimization of protein intake, and vitamin D supplementation, but evidence is lacking. We evaluated the safety and efficacy of a muscle‐targeted nutritional support on the outcome of a physical exercise rehabilitation programme. Methods In a single‐site, double‐blind, randomized, controlled trial (NCT03120026; May 2017 to December 2018), old (≥65 years) adults [N = 140 (63% female patients; age, 81 ± 6 years)] without severe cognitive impairment, who were found to have sarcopenia by European Working Group on Sarcopenia in Older People 2010 criteria and hospitalized for physical rehabilitation, were randomized to receive until discharge (for at least 4 weeks and up to 8 weeks) a whey protein‐based nutritional formula enriched with leucine and vitamin D or an iso‐caloric control formula twice daily in addition to a standard hospital diet. The primary endpoint was the change in 4 m gait speed per month. Key secondary endpoints addressed the change in physical performance: chair‐stand test, timed up and go test, and short physical performance battery. Other secondary outcomes were the change in functional status, muscle strength and mass, cognitive status, and quality of life. The proportion of patients who improved their rehabilitation intensity profile and overall economic benefits (using length of stay and duration of rehabilitation as surrogate measures) were also evaluated. Results A total of 161 patients were screened and 140 were randomized to study interventions. Thirteen patients (experimental, n = 6; placebo, n = 7) discontinued the intervention because they disliked the product and intention‐to‐treat analyses were based on patients reassessed at discharge [n = 127 (66% female patients; age, 81 ± 6 years)]. Supplementation with the experimental formula (n = 64) resulted in greater increase in mean gait speed 0.061 m/s/month [95% confidence interval (CI), 0.043 to 0.080] than placebo [n = 63; −0.001 m/s/month (95%CI, −0.008 to 0.006)]: mean difference, 0.063 m/s/month (95%CI, 0.043 to 0.082) (P < 0.001). A significant effect was also found for muscle mass (P < 0.03) and all key secondary outcomes, functional and cognitive endpoints (P < 0.001 for all). Supplementation resulted also in higher proportion of patients improving their rehabilitation intensity profile (P = 0.003) and being discharged home (P = 0.002); shorter rehabilitation (P < 0.001); and hospital stay (P < 0.001). Conclusions In old adults with sarcopenia admitted to hospital for rehabilitation the consumption of a whey protein‐based nutritional formula enriched with leucine and vitamin D improved physical performance and function, as well as muscle mass, and reduced the intensity and costs of care.

Interest in animal-assisted therapy has been fuelled by studies supporting the many health benefits. The purpose of this study was to better understand the impact of an animal-assisted therapy program on children response to stress and pain in the immediate post-surgical period. Forty children (3-17 years) were enrolled in the randomised open-label, controlled, pilot study. Patients were randomly assigned to the animal-assisted therapy-group (n = 20, who underwent a 20 min session with an animal-assisted therapy dog, after surgery) or the standard-group (n = 20, standard postoperative care). The study variables were determined in each patient, independently of the assigned group, by a researcher unblinded to the patient's group. The outcomes of the study were to define the neurological, cardiovascular and endocrinological impact of animal-assisted therapy in response to stress and pain. Electroencephalogram activity, heart rate, blood pressure, oxygen saturation, cerebral prefrontal oxygenation, salivary cortisol levels and the faces pain scale were considered as outcome measures. After entrance of the dog faster electroencephalogram diffuse beta-activity (> 14 Hz) was reported in all children of the animal-assisted therapy group; in the standard-group no beta-activity was recorded (100% vs 0%, p<0.001). During observation, some differences in the time profile between groups were observed for heart rate (test for interaction p = 0.018), oxygen saturation (test for interaction p = 0.06) and cerebral oxygenation (test for interaction p = 0.09). Systolic and diastolic blood pressure were influenced by animal-assisted therapy, though a higher variability in diastolic pressure was observed. Salivary cortisol levels did not show different behaviours over time between groups (p=0.70). Lower pain perception was noted in the animal-assisted group in comparison with the standard-group (p = 0.01). Animal-assisted therapy facilitated rapid recovery in vigilance and activity after anaesthesia, modified pain perception and induced emotional prefrontal responses. An adaptative cardiovascular response was also present. ClinicalTrials.gov NCT02284100.

Objectives The aim of this study was to describe the radiological features of chronic thromboembolic pulmonary disease (CTEPD), not yet systematically described in the literature. Furthermore, we compared vascular scores between CTEPD and chronic thromboembolic pulmonary hypertension (CTEPH) patients, trying to explain why pulmonary hypertension does not develop at rest in CTEPD patients. Methods Eighty-five patients (40 CTEPD, 45 CTEPH) referred to our centre for pulmonary endarterectomy underwent dual-energy computed tomography pulmonary angiography (DE-CTPA) with iodine perfusion maps; other 6 CTEPD patients underwent single-source CTPA. CT scans were reviewed independently by an experienced cardiothoracic radiologist and a radiology resident to evaluate scores of vascular obstruction, hypoperfusion and mosaic attenuation, signs of pulmonary hypertension and other CT features typical of CTEPH. Results Vascular obstruction burden was similar in the two groups ( p = 0.073), but CTEPD patients have a smaller extension of perfusion defects in the iodine map ( p = 0.009) and a smaller number of these patients had mosaic attenuation ( p < 0.001) than CTEPH patients, suggesting the absence of microvascular disease. Furthermore, as expected, the two groups were significantly different considering the indirect signs of pulmonary hypertension ( p < 0.001). Conclusions CTEPD and CTEPH patients have significantly different radiological characteristics, in terms of signs of pulmonary hypertension, mosaic attenuation and iodine map perfusion extension. Importantly, our results suggest that the absence of peripheral microvascular disease, even in presence of an important thrombotic burden, might be the reason for the absence of pulmonary hypertension in CTEPD. Key Points • CTEPD and CTEPH patients have significantly different radiological characteristics . • The absence of peripheral microvascular disease might be the reason for the absence of pulmonary hypertension in CTEPD .

Background Prevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis. Methods The study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated. Results The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04–1.44] to 3.20 [1.97–5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18–1.21] to 0.47 [0.46–0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed. Conclusions During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection. Trial registration Retrospectively registered. Not applicable.

Background Vaccination rates are still suboptimal in cancer patients. Oncologists play a central role in recommending vaccines to their patients. Our goal was to investigate vaccine acceptance among cancer patients and understand the factors shaping their choices, thereby aiding physicians in better supporting their patients’ vaccination decisions. Methods We designed a prospective cross-sectional survey exploring vaccination status, attitudes, and reasons for hesitancy towards vaccinations against the main vaccine preventable diseases (VPDs) among patients undergoing active cancer treatment. The primary endpoint was to evaluate the proportion of vaccinated subjects in our cohort of cancer patients. The secondary endpoints were to assess the proportion of vaccinated subjects against different types of VPDs: flu, COVID-19, pneumococcal disease, Herpes Zoster (HZ). Results Between 12 February and 01 March 2024, a total of three hundred and seventeen patients with cancer were invited to respond to the survey, 309 of whom (97%) agreed to do it. Two hundred seventy-three patients (0.88, 95% confidence interval [CI] 0.84–0.91) had received at least one vaccination. Two hundred thirty-one patients (74.76%) reported that at their first oncology visit their oncologist recommended vaccinations, primarily anti-flu (92.21%) and anti-SARS-CoV-2 (83.55%) vaccinations, while less frequently the anti-pneumococcal (42.42%) and anti-HZ (37%) vaccines were recommended. On the univariate analysis, age over 75 years ( p  = 0.041), marital status ( p  = 0.003) and the oncologist’s vaccine recommendation during the first visit ( p  < 0.001) were significantly associated to vaccine acceptance. At the multivariable analysis, these variables were independently associated with vaccine willingness. Overall in our cancer population, the two main reasons for vaccine hesitancy were the lack of recommendation by the oncologist (55.41%, n  = 128) and the lack of awareness of the importance of vaccination in the context of oncological care (49.35%, n  = 114). Conclusions This survey emphasizes the importance of vaccine counseling by the oncologist to their patients. Oncologists can motivate patients to receive the correct vaccine schedule by addressing doubts and concerns about the potential negative impact of the vaccine on cancer and cancer therapies.