A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic cell death (ICD). Although the catalytic function of RIPK1 is required to trigger cell death, its non-catalytic scaffold function mediates strong pro-survival signaling. Accordingly, cancer cells can hijack RIPK1 to block necroptosis and evade immune detection. We generated a small-molecule proteolysis-targeting chimera (PROTAC) that selectively degraded human and murine RIPK1. PROTAC-mediated depletion of RIPK1 deregulated TNFR1 and TLR3/4 signaling hubs, accentuating the output of NF-κB, MAPK, and IFN signaling. Additionally, RIPK1 degradation simultaneously promoted RIPK3 activation and necroptosis induction. We further demonstrated that RIPK1 degradation enhanced the immunostimulatory effects of radio- and immunotherapy by sensitizing cancer cells to treatment-induced TNF and interferons. This promoted ICD, antitumor immunity, and durable treatment responses. Consequently, targeting RIPK1 by PROTACs emerges as a promising approach to overcome radio- or immunotherapy resistance and enhance anticancer therapies.

Early metformin treatment: An effective approach for targeting fragile X syndrome pathophysiology.

Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder engendered by transcriptional silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Given the early onset of behavioral and molecular changes, it is imperative to know the optimal timing for therapeutic intervention. Case reports documented benefits of metformin treatment in FXS children between 2 and 14 y old. In this study, we administered metformin from birth to Fmr1-/y mice which corrected up-regulated mitogen-2 activated protein kinase/extracellular signal-regulated kinase and mammalian/mechanistic target of rapamycin complex 1 signaling pathways and specific synaptic mRNA-binding targets of FMRP. Metformin rescued increased number of calls in ultrasonic vocalization and repetitive behavior in Fmr1-/y mice. Our findings demonstrate that in mice, early-in-life metformin intervention is effective in treating FXS pathophysiology.

Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.

BACKGROUND: Primary resistance to anti-EGFR therapies affects 40% of metastatic colorectal cancer patients harbouring wild-type RAS/RAF. YAP1 activation is associated with this resistance, prompting an investigation into AURKA's role in mediating YAP1 phosphorylation at Ser397, as observed in breast cancer. METHODS: We used transcriptomic analysis along with in vitro and in vivo models of RAS/RAF wild-type CRC to study YAP1 Ser397 phosphorylation as a potential biomarker for cetuximab resistance. We assessed cetuximab efficacy using CCK8 proliferation assays and cell cycle analysis. Additionally, we examined the effects of AURKA inhibition with alisertib and created a dominant-negative YAP1 Ser397 mutant to assess its impact on cancer stem cell features. RESULTS: The RAS/RAF wild-type CRC models exhibiting primary resistance to cetuximab prominently displayed elevated YAP1 phosphorylation at Ser397 primarily mediated by AURKA. AURKA-induced YAP1 phosphorylation was identified as a key trigger for cancer stem cell reprogramming. Consequently, we found that AURKA inhibition had the capacity to effectively restore cetuximab sensitivity and concurrently suppress the cancer stem cell phenotype. CONCLUSIONS: AURKA inhibition holds promise as a therapeutic approach to overcome cetuximab resistance in RAS/RAF wild-type colorectal cancer, offering a potential means to counter the development of cancer stem cell phenotypes associated with cetuximab resistance.

Effectiveness and Safety of Postoperative Hospital at Home for Surgical Patients: A Cohort Study.

OBJECTIVE: To determine the feasibility and effectiveness of a Hospital at Home (HaH) enabled early transfer pathways for surgical patients. BACKGROUND: HaH serves as a safe alternative to traditional hospitalization by providing acute care to patients in their homes through a comprehensive range of hospital-level interventions. To our knowledge, no studies have been published to date reporting a large cohort of early home-transferred patients after surgery through a HaH unit. METHODS: Cohort study enrolling every patient admitted to the HaH unit of a tertiary hospital who underwent any of 6 surgeries with a predefined early transfer pathway and fitting both general and surgery inclusion criteria (clinical and hemodynamic stability, uncomplicated surgery, presence of a caregiver, among others) from November 2021 to May 2023. Protocols were developed for each pathway between surgical services and HaH to deliver the usual postoperative care in the home setting. Discharge was decided according to protocol. An urgent escalation pathway was also established. RESULTS: During the study period, 325 patients were included: 141 were bariatric surgeries, 85 kidney transplants, 45 thoracic surgeries, 37 cystectomies, 10 appendicectomies, and 7 ventral hernia repairs. The overall escalation of care during HaH occurred in 7.3% of patients and 30-day readmissions in 7%. Most adverse events were managed at home and the overall mortality was zero. The total mean length of stay was 8 days (interquartile range 2-14), and patients with HaH were transferred home 3 days (interquartile range 1-6) earlier than the usual pathway; a total of 1551 bed-days were saved. CONCLUSIONS: The implementation of early home transfer pathways for surgical patients through HaH is feasible and effective, with favorable safety outcomes.

Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10.

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.

Short and Long-Term Outcomes of Patients with Pure Membranous Lupus Nephritis Compared to Patients with Proliferative Disease.

OBJECTIVES: Membranous lupus nephritis (MLN) is thought to have a more benign course than proliferative lupus nephritis (PLN). We aimed to determine the differences in short and long-term outcomes between patients with MLN and PLN. METHODS: We included patients with first biopsy-proven MLN and PLN. Short-term outcomes included complete proteinuria recovery (CPR), complete renal response (CRR), and primary efficacy renal response (PERR). Long-term outcomes included a sustained ≥40% reduction in baseline estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), cardiovascular (CV) events, ≥2 increase in SDI, and death. Univariable and multivariable Cox proportional hazard models were used to examine the effect of baseline characteristics on long-term outcomes. RESULTS: Of 215 patients, 51 had pure MLN, and 164 had PLN. We found no significant differences between the two groups in achieving CPR, CRR, and PERR at 1 and 2 years. Median time to outcomes was slightly, but insignificantly, longer in the MLN group.For long-term outcomes, PLN was associated with worse renal and non-renal outcomes, but this was not statistically significant.In the multivariable Cox proportional hazard models, ESKD was associated with the following baseline variables: younger age (HR 0.92, 95% CI 0.87-0.97), higher creatinine (HR 1.01, 95% CI 1.01-1.02), low complement (HR 4.0, 95% CI 1.04-11.10), and higher chronicity index (HR 1.28, 95% CI 1.08-1.51). CONCLUSION: The resolution of proteinuria in LN is slow. MLN is not a benign disease and may be associated with deterioration of renal function, ESKD, damage, CV events, and death.

Opposing effects of the purinergic P2X7 receptor on seizures in neurons and microglia in male mice.

BACKGROUND: The purinergic ATP-gated P2X7 receptor (P2X7R) is increasingly recognized to contribute to pathological neuroinflammation and brain hyperexcitability. P2X7R expression has been shown to be increased in the brain, including both microglia and neurons, in experimental models of epilepsy and patients. To date, the cell type-specific downstream effects of P2X7Rs during seizures remain, however, incompletely understood. METHODS: Effects of P2X7R signaling on seizures and epilepsy were analyzed in induced seizure models using male mice including the kainic acid model of status epilepticus and pentylenetetrazole model and in male and female mice in a genetic model of Dravet syndrome. RNA sequencing was used to analyze P2X7R downstream signaling during seizures. To investigate the cell type-specific role of the P2X7R during seizures and epilepsy, we generated mice lacking exon 2 of the P2rx7 gene in either microglia (P2rx7:Cx3cr1-Cre) or neurons (P2rx7:Thy-1-Cre). To investigate the protective potential of overexpressing P2X7R in GABAergic interneurons, P2X7Rs were overexpressed using adeno-associated virus transduction under the mDlx promoter. RESULTS: RNA sequencing of hippocampal tissue from wild-type and P2X7R knock-out mice identified both glial and neuronal genes, in particular genes involved in GABAergic signaling, under the control of the P2X7R following seizures. Mice with deleted P2rx7 in microglia displayed less severe acute seizures and developed a milder form of epilepsy, and microglia displayed an anti-inflammatory molecular profile. In contrast, mice lacking P2rx7 in neurons showed a more severe seizure phenotype when compared to epileptic wild-type mice. Analysis of single-cell expression data revealed that human P2RX7 expression is elevated in the hippocampus of patients with temporal lobe epilepsy in excitatory and inhibitory neurons. Functional studies determined that GABAergic interneurons display increased responses to P2X7R activation in experimental epilepsy. Finally, we show that viral transduction of P2X7R in GABAergic interneurons protects against evoked and spontaneous seizures in experimental temporal lobe epilepsy and in mice lacking Scn1a, a model of Dravet syndrome. CONCLUSIONS: Our results suggest a dual and opposing action of P2X7R in epilepsy and suggest P2X7R overexpression in GABAergic interneurons as a novel therapeutic strategy for acquired and, possibly, genetic forms of epilepsy.

And how do LGB adults rate their orgasms in a relational context?

BACKGROUND: Subjective orgasm experience (SOE) refers to the perception, assessment, and/or sensation of orgasm on a psychological level, with the particularity that the study of SOE in nonheterosexual populations is currently very scarce. AIM: The study sought to analyze differences in SOE dimensions, comparing the intensity of each adjective of the Orgasm Rating Scale (ORS) and creating a ranking of the adjectives that better represent it in LGB men and women. METHODS: In a sample of 1475 adults organized into 4 groups according to the type of sexual relationships reported, comparisons were made using multivariate analysis of variance and chi-square tests. OUTCOMES: Differences were obtained in the intensity of all the SOE dimensions, and in 23 of the 25 ORS adjectives. RESULTS: Lesbians and bisexual women reported higher intensity in SOE compared with bisexual and gay men. CLINICAL IMPLICATIONS: Because the ORS has been established as a good tool for detecting orgasmic difficulties in nonheterosexual populations, this study could provide LGBT affirmative psychotherapy with evidence on how these individuals evaluate their orgasms in a relational context. STRENGTHS AND LIMITATIONS: This study extends prior limited knowledge about how LGB people evaluate their orgasmic experiences in the context of sexual relationships. Despite this, the study poses limitations such as nonprobability sampling or the inclusion of exclusively cisgender and young individuals, making it difficult to generalize the results. CONCLUSION: Although significant differences were found between LGB men and women, all groups agree on the adjectives they use to describe the subjective experience of orgasm in the context of sexual relationships; therefore, evidence is provided about how LGB people evaluate their orgasmic experiences in this context.

Variations in tumor growth, intra-individual biological variability, and the interpretation of changes.

OBJECTIVES: The identification of changes in tumor markers (TMs) in cancer patients that indicate response to treatment, stabilization or disease progression is a challenge for laboratory medicine. Several approaches have been proposed: assessing percentage increases, applying discriminant values, and estimating half-life (t1/2) or doubling time (DT). In all of them it is assumed that the TM is a surrogate of the variation in tumor size. In general this variation is time-dependent, but this is not the case of intraindividual biological variability (CVi), which can range from 6 % in CA15-3 to 22 % in CA125. When decisions are made on the basis of DT or t1/2, these values can be affected by the CVi; if it is very large, the growth rate very slow and the period of time between determinations very short, the result obtained for DT may be due mainly to the CVi. The aim of this study is to establish the relationship between the CVi and temporal variables. METHODS: We related equations for calculating DT and t1/2 to the reference change values in tumor markers. RESULTS: The application of the formula obtained allows the calculation of the optimal time between measurements to ensure that the influence of the CVi is minimal in different types of tumors and different scenarios. CONCLUSIONS: Intraindividual variation affects the calculation of DT and t1/2. It is necessary to establish the minimum time between two measurements to ensure that the CVi does not affect their calculation or lead to misinterpretation.

Severe Food Protein-Induced Enterocolitis Syndrome After Hematopoietic Stem Cell Transplantation: Pediatric Case Report.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. In the last few years, after the publication of the consensus guidelines, with refined diagnostic criteria and improved awareness, FPIES is diagnosed with increased frequency. However, despite having a background of immune dysregulation, this complication has just been described once in the posttransplant setting, in an adult patient. To the best of our knowledge, there are no reports of pediatric patients developing FPIES after a hematopoietic stem cell transplant (HCT). METHODS: Retrospective review of a pediatric patient who developed severe FPIEs after a HCT. RESULTS: In this case report, the clinical presentation and diagnosis challenges of a pediatric patient who developed severe FPIES after HCT are described. The patient developed severe vomiting, diarrhea, lethargy, and shock and required admission to the pediatric intensive care unit in three occasions before the diagnosis was made. CONCLUSIONS: To the best of our knowledge, this is the first report of severe FPIES post-HCT in a pediatric patient. Physicians who are looking after pediatric patients in the post-HCT setting need to be aware of this possibility and include this entity in the differential diagnosis in order to reduce its associated morbidity.

Lettre to editor: Case report of an ictal asystole as debut in new onset epilepsy.

The case report describes a 65-year-old man with arterial hypertension and a metallic aortic valve who presented to the emergency room for a loss of consciousness event and memory impairment. The electroencephalographic recording showed right temporal epileptiform activity followed by a 9 s asystole with quick consciousness recovery. The patient was diagnosed with right temporal epilepsy with asystole and was prescribed levetiracetam to prevent new events. A pacemaker was indicated in the follow-up for the long duration of the asystole, preventing major morbidity. Ictal asystole (IA) is a rare phenomenon of epilepsy that leads to syncope. It is observed in focal epilepsy, especially in left temporal epilepsy. Underlying cardiac pathology may facilitate IA, especially when the onset of the epilepsy is new. Knowledge of focal temporal semiology is key, concerning our case report, the memory impairment points to temporal pathology, and ictal vomiting in the non-dominant hemisphere. Anti-seizures drugs must be initiated in all patients, and there is a recommendation to avoid those with negative inotropic and arrhythmogenic effects (such as phenytoin, carbamazepine, and lacosamide). There is a discussion about pacemaker indication, however, it is highly recommended in non-controlled epilepsy and in ictal asystoles that last for more than 6 s to reduce morbidity.

A clinical practice guideline for the management of the foot and ankle in rheumatoid arthritis.

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created including a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improving short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis.

Performance of risk scores in predicting mortality at 3, 6, and 12 months in patients diagnosed with community-acquired pneumonia.

BACKGROUND: Risk scores (RS) evaluate the likelihood of short-term mortality in patients diagnosed with community-acquired pneumonia (CAP). However, there is a scarcity of evidence to determine the risk of long-term mortality. This article aims to compare the effectiveness of 16 scores in predicting mortality at three, six, and twelve months in adult patients with CAP. METHODS: A retrospective cohort study on individuals diagnosed with CAP was conducted across two hospitals in Colombia. Receiver Operating Characteristic (ROC) curves were constructed at 3, 6, and 12 months to assess the predictive ability of death for the following scoring systems: CURB-65, CRB-65, SCAP, CORB, ADROP, NEWS, Pneumonia Shock, REA-ICU, PSI, SMART-COP, SMRT-CO, SOAR, qSOFA, SIRS, CAPSI, and Charlson Comorbidity Index (CCI). RESULTS: A total of 3688 patients were included in the final analysis. Mortality at 3, 6, and 12 months was 5.2%, 8.3%, and 16.3% respectively. At 3 months, PSI, CCI, and CRB-65 scores showed ROC curves of 0.74 (95% CI: 0.71-0.77), 0.71 (95% CI: 0.67-0.74), and 0.70 (95% CI: 0.66-0.74). At 6 months, PSI and CCI scores showed performances of 0.74 (95% CI: 0.72-0.77) and 0.72 (95% CI: 0.69-0.74), respectively. Finally at 12 months, all evaluated scores showed poor discriminatory capacity, including PSI, which decreased from acceptable to poor with an ROC curve of 0.64 (95% CI: 0.61-0.66). CONCLUSION: When predicting mortality in patients with CAP, at 3 months, PSI, CCI, and CRB-65 showed acceptable predictive performances. At 6 months, only PSI and CCI maintained acceptable levels of accuracy. For the 12-month period, all evaluated scores exhibited very limited discriminatory ability, ranging from poor to almost negligible.

SAFETY OF SKIN-TO-SKIN CONTACT WITH UMBILICAL VENOUS CATHETER IN PRETERM INFANTS: A PROSPECTIVE STUDY.

Objective For many healthcare providers, an umbilical venous catheter (UVC) may be a contraindication for skin-to-skin contact (SSC). Our aim was to assess the safety of the procedure. Study Design Prospective observational study in newborns less than 35 weeks' gestation. UVC-related adverse events were compared between neonates who performed SSC and those who didn't. The incidence of catheter-related displacement, leak, loss, hemorrhage, malfunction and bloodstream infection (CRBSI) was studied. Results From 226 patients, 171 performed SSC with UVC. Their first contact was earlier than in those who remained in incubator (SSC-UVC 29 hours (IQR 21-53); vs No SSC-UVC 132 hours (IQR 96-188); p<0.001). Both groups were similar in gestational age (p = 0.331) and birth weight (p = 0.2). Studied complications were not more frequent in patients who performed SSC. In fact, although it was not statistically significant, a lower overall incidence of adverse events (SSC-UVC 13.5% vs No SSC-UVC 20%; p=0.237) and catheter-related bloodstream infection (SSC-UVC 4.7% vs No SSC-UVC 10.9%; p=0.111) was observed in this group. Conclusion SSC with an UVC is a safe procedure and there are no more complications in newborns who perform SSC compared to those who remain in the incubator. Due to its demonstrated benefits, SSC should be promoted in the premature newborn regardless of the type of catheter.

Continuous Temperature Telemonitoring of Patients with COVID-19 and Other Infectious Diseases Treated in Hospital-at-Home: Viture® System Validation.

Body temperature must be monitored in patients receiving Hospital-at-Home (HaH) care for COVID-19 and other infectious diseases. Continuous temperature telemonitoring (CTT) detects fever and patient deterioration early, facilitating decision-making. We performed a validation clinical study assessing the safety, comfort, and impact on healthcare practice of Viture®, a CTT system, compared with a standard digital axillary thermometer in 208 patients with COVID-19 and other infectious diseases treated in HaH at the Navarra University Hospital (HUN). Overall, 3258 pairs of measurements showed a clinical bias of -0.02 °C with limits of agreement of -0.96/+0.92 °C, a 95% acceptance rate, and a mean absolute deviation of 0.36 (SD 0.30) °C. Viture® detected 3 times more febrile episodes and revealed fever in 50% more patients compared with spot measurements. Febrile episodes were detected 7.23 h (mean) earlier and modified the diagnostic and/or therapeutic approach in 43.2% of patients. Viture® was validated for use in a clinical setting and was more effective in detecting febrile episodes than conventional methods.

Walking the talk for dementia: A unique immersive, embodied, and multi-experiential initiative.

Coping with dementia requires an integrated approach encompassing personal, health, research, and community domains. Here we describe "Walking the Talk for Dementia," an immersive initiative aimed at empowering people with dementia, enhancing dementia understanding, and inspiring collaborations. This initiative involved 300 participants from 25 nationalities, including people with dementia, care partners, clinicians, policymakers, researchers, and advocates for a 4-day, 40 km walk through the Camino de Santiago de Compostela, Spain. A 2-day symposium after the journey provided novel transdisciplinary and horizontal structures, deconstructing traditional hierarchies. The innovation of this initiative lies in its ability to merge a physical experience with knowledge exchange for diversifying individuals' understanding of dementia. It showcases the transformative potential of an immersive, embodied, and multi-experiential approach to address the complexities of dementia collaboratively. The initiative offers a scalable model to enhance understanding, decrease stigma, and promote more comprehensive and empathetic dementia care and research.

Congenital LMNA-Related Muscular Dystrophy in Paediatrics: Cardiac Management in Monozygotic Twins.

Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias.

Foreign body in a Zenker's diverticulum.

Zenker's diverticulum (ZD) is an uncommon disorder that can cause dysphagia with risk of aspiration. While surgical treatment has been the mainstay for many years, endoscopic diverticulotomy has emerged as a first-line option with favorable outcomes. We present the case of a 93-year-old woman with no significant past medical history who was diagnosed with a 6 cm ZD. Due to dysphagia, she experienced significant weight loss and was at risk of malnutrition. She developed aspiration pneumonia and required admission to our center. Given her condition and inability to swallow, a nasogastric tube was placed under radiological guidance for nutritional support pending definitive treatment. On radiographic localization of the ZD, a radiopaque metallic density image was observed that had not been identified in previous imaging. Suspecting a possible retained foreign body in the large diverticulum, a gastroscopy was performed. During the procedure, the ZD was accessed and a 10 mm metallic object was identified. The object was extracted using a Roth net, confirming the suspicion of a foreign body lodged in the ZD. The metallic piece was later identified as a patient's dental prosthesis. After resolution of the aspiration pneumonia, endoscopic-assisted diverticulotomy was performed. The procedure was carried out under deep sedation with cricopharyngeal myotomy without immediate complications. After 48 hours of hospitalization, the patient was discharged without requiring a nasogastric tube for feeding.

Sweet Syndrome: Clinical Presentation, Malignancy Association, Autoinflammatory Disorders and Treatment Response in a Cohort of 93 Patients with Long-term Follow-up.

Sweet syndrome is a neutrophilic dermatosis associated with multiple disorders. This retrospective case-series study of patients with Sweet syndrome in a tertiary hospital in Spain from 2001 to 2021, explores clinicopathological characteristics of Sweet syndrome and variables associated with malignancy, presence of autoinflammatory disorders and differences between histological subtypes. A total of 93 patients were identified: 30% idiopathic, 34% malignancy-associated, 29% reactive to infections or drug-associated, and 6% with an autoimmune/inflammatory condition. Acute myeloid leukaemia was the most common malignancy (16/93) followed by myelodysplastic syndrome (7/93). Patients with acute myeloid leukaemia presented isolated flares, marked cytopaenia and rapid response to treatment, whereas myelodysplastic syndrome followed a chronic-recurrent course. The most frequent associated medications and inflammatory  disorders were filgrastim and hydroxyurea (n = 2);  and inflammatory bowel disease (n = 4). In addition, 3 patients were diagnosed with VEXAS syndrome. Male sex (p = 0.006), fever (p = 0.034), increased erythrocyte sedimentation rate (p < 0.001), anaemia (p < 0.001), and thrombocytopaenia (p < 0.001) were associated with malignancy. Histologically, patients were classified as classic (60%), histiocytoid (22.5%) or subcutaneous (15%), with pain (p = 0.011) and nodules (p < 0.001) being associated with subcutaneous-Sweet syndrome. Sweet syndrome in the context of cytopaenia should alert the presence of malignancy. An  acquired autoinflammatory condition should be explored  in relapsing Sweet syndrome with myelodysplastic syndrome. A minimum follow-up of 6 months is recommended.