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Abstract Background The differential diagnosis of stupor is complex, especially in emergency settings. Idiopathic recurrent stupor, linked to the "endozepine-4" effect, must be considered, too. Stupor associated with endozepine has recently been questioned because more sophisticated toxicological tests have revealed that it is just an unreported exogenous exposure to benzodiazepines. Case presentation A four-year-old child in a stupor state was admitted to the Emergency Department. The EEG carried out during the state of stupor showed a typical pattern of acute drug abuse. Toxicological analyses revealed a high concentration of benzodiazepine, while second-level analyses identified both lorazepam and lormetazepam. Benzodiazepines chronic exposure was detected in unconventional matrices analysis, such as hair. It was an acute lorazepam and lormetazepam intoxication in a chronic tox history. Conclusions Should a patient in a stupor show up in an emergency, it becomes of primary importance to perform EEG and high-sensibility toxicological tests. Once the acute intoxication has been resolved, it is essential to analyze alternative matrices, such as hair, to reconstruct the patient's previous tox history. This suggestion is highly recommended in case of children. Chronic benzodiazepine intoxication may be a manifestation of chronic abuse, especially when directed towards children.

Immune-checkpoint inhibitors (ICIs) have shown unprecedented success in a subset of immunogenic tumors, however a host of patients with advanced solid tumors fail to respond well or at all to immunotherapy. Refractory tumors commonly display a tumor microenvironment (TME) rich in immunosuppressive macrophages (M2-like) that suppress adaptive immunity and promote tumor progression. The ability to reprogram macrophages in the TME into an immune-active state holds great promise for enhancing responses to ICIs. Lucicebtide (previously referred to as ST101) is a peptide antagonist of the transcription factor C/EBPβ, a key activator of the transcriptional program in immunosuppressive macrophages. Here we show that lucicebtide exposure reprograms human immunosuppressive M2-like macrophages to a pro-inflammatory M1-like phenotype, restores cytotoxic T cell activation in immunosuppressed co-culture assays in vitro, and further increases T-cell activity in M1-like/T cell co-cultures. In immunocompetent, macrophage-rich triple-negative breast and colorectal cancer models, lucicebtide induces repolarization of tumor-associated macrophages (TAMs) to a pro-inflammatory M1-like phenotype and suppresses tumor growth. Lucicebtide synergizes with anti-PD-1 therapy and overcomes resistance to checkpoint inhibition in anti-PD-1-refractory tumors, but in vivo responses are impaired by systemic macrophage depletion, indicating that macrophage reprogramming is integral to lucicebtide activity. These results identify lucicebtide as a novel immunomodulator that reprograms immunosuppressive macrophage populations to enhance anti-tumor activity and suggests its utility for combination strategies in cancers with poor response to ICIs.

Introduction: Cancer treatments have a detrimental impact on the quality of life (QoL) of young women with breast cancer (YWBC). Research exploring QoL trajectories has been mostly centered on postmenopausal women. Here we report longitudinal changes across all QoL domains and associated factors in YWBC. Methods: In this prospective longitudinal cohort study, women aged ≤40 with stage I-III BC completed the European Organization for the Research and Treatment of Cancer Core QoL questionnaire at diagnosis and during 4 follow-up visits over 5 years, alongside demographic and clinical data collection. Group-based multivariate trajectory modeling was used to identify patient groups based on their functional and symptom scores, finding 3 groups (best, good, and poor). Factors associated with each trajectory pattern were identified with multinomial logistic models. Results: A total of 477 women (median age: 36; IQR: 32–38) were clustered into the best (n = 259, 54 %), good (n = 79, 17 %), or poor trajectory groups (n = 139, 29 %). Throughout the disease, patients with a poor QoL experienced clinically significant impairment in emotional functioning, nausea and vomiting, and pain. They also had significant cognitive impairment, dyspnea, and diarrhea. Patients with a good QoL had clinically meaningful diarrhea for the first 7 months, while those with the best QoL had clinically important nausea and vomiting during the first 2 months since diagnosis. Noteworthy, all groups experienced significant financial difficulties throughout their follow-up. Regular alcohol consumption at diagnosis (aOR [adjusted odds ratio] 1.64; 95 % CI [confidence interval] 1.02–2.65) and HER2-positive BC (aOR 2.53; 95 % CI 1.35–4.73) were independent factors associated with classification to the poor and good groups, respectively. Conclusion: This study underscores the variability in QoL among YWBC and the importance of ongoing monitoring. Strategies to improve access to economic resources, manage treatment-related adverse effects, and support patients in discontinuing modifiable risk factors are needed.

Colonization by multidrug-resistant (MDR) bacteria and related bloodstream infections (BSI) are associated with a high rate of mortality in patients with hematological malignancies after intensive chemotherapy and allogeneic stem cell transplantation (allo-SCT). In this retrospective study, we analyzed the outcomes of patients colonized with MDR bacteria (primarily carbapenem-resistant klebsiella pneumoniae, KPC), before allo-SCT. We also investigated the feasibility and safety of an antimicrobial de-escalating approach in these patients. Since 2021, 106 patients have been undergoing allo-SCT in our department, and 34 (32%) of them were colonized by MDR bacteria before allo-SCT. In the pre-engraftment period, 84% received an empiric antibiotic therapy (EAT) active against MDR bacteria and 16% were treated with a conventional EAT. The MDR translocation rate was null, and the overall de-escalation rate was 79%, with 75% in patients with fever of unknown origin (FUO). Among the cohort of patients with MDR-positive rectal swabs just before allo-SCT (n = 18), the de-escalation rate was 100%. The all-cause mortality rates at 30 and 100 days for the whole MDR patient population were 6% (2/34) and 12% (4/34), respectively. Day +30 infection-related mortality rate was 3%. In this study, we confirm the safety of the de-escalation approach in patients with previous MDR infection after allo-SCT. This could reduce the exposure time to EAT antibiotics, reducing the selective pressure.

Summary: The commercial poultry industry has expanded and profited from intensively rearing birds, but it is not without consequences. Coccidiosis is an intestinal disease caused by Eimeria species that is well recognized by poultry producers because of the resulting health implications that often contribute to reduced welfare of birds, meat production and profitability. Strict host specificity of these parasites (infection of one host species only) is often assumed; however, examples of Eimeria spp. capable of infecting multiple galliform hosts have been described. Despite the relevance of coccidiosis in commercial poultry production, the number and extent of such cross-infections remain poorly understood, potentially limiting the species considered during diagnoses. In the present study, the host specificity of Eimeria spp. isolated from chukar partridges, turkeys and chickens were assessed by cross-infecting the coccidia of each host in chukar partridges, Northern bobwhites or turkeys. While the coccidia from chickens and chukar partridges demonstrated strict host specificity, some Eimeria spp. from turkeys infected multiple hosts: Eimeria dispersa and E. innocua were shed by both chukar partridges and Northern bobwhites; and, oocysts of E. adenoeides were recovered from chukar partridges only. Turkeys infected with E. dispersa or E. innocua shed more oocysts in each case than Northern bobwhites that received the same inoculation dose. Despite being less productive in Northern bobwhites, infections of these Eimeria spp. could potentially contribute to cases of coccidiosis in captive populations of susceptible gamebirds reared at high densities and in close proximity to domestic or wild turkeys.

ABSTRACTIndividuals with Inflammatory Bowel Disease (IBD) are more susceptible to experiencing severe complications of COVID-19 if infected. Nevertheless, sub-optimal immunization rates have been reported among these patients. Our study aims to assess COVID-19 VH among a global population of patients with IBD and to investigate the role of healthcare professionals, particularly gastroenterologists, in promoting immunization. Twenty-six studies were systematically selected from scientific articles in the MEDLINE/PubMed, WoK, and Scopus databases from January 1, 2020, to September 15, 2023. The pooled prevalence of COVID-19 VH was 27.2% (95%CI = 20.6–34.2%). A significant relationship was evidenced between COVID-19 vaccine compliance and receiving advice from gastroenterologists or healthcare providers (OR = 2.77; 95%CI = 1.79–4.30). By leveraging their knowledge of IBD, familiarity with patient histories, and trusted patient-doctor relationships, gastroenterologists are pivotal in promoting vaccination. This patient-centered care is crucial in increasing vaccine acceptance among individuals with IBD, contributing to better public health outcomes.

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A non-functional middle mediastinal paraganglioma is a rare entity. We describe a case of a 67-year-old woman with a diagnosis of a big mediastinal paraganglioma by endobronchial ultrasound transbronchial needle aspiration after chest CT and 18F-fluorodeoxyglucose positron-emission tomography. The nine centimeter in length tumor was located between the superior vena cava and the posterior portion of the ascending aorta, compressing the left atrium and the trachea and main left bronchus, posteriorly, surrounding the right pulmonary artery. Uniportal right video-thoracoscopic biopsy was unconclusive and complicated by severe hemorrhage, however controlled. Surgical resection was performed via a trans-sternal trans-pericardial approach followed by cardiopulmonary bypass and ascending aorta resection which allows an excellent exposure and greater control of great vessels and heart. Complete resection of the tumor was achieved without perioperative complication except for the left vocal cord palsy. Twelve months late the patient is disease free and in good general conditions.