Intestinal mucormycosis as a differential diagnosis of small bowel ischemia.

Intestinal mucormycosis is a rare manifestation of the Mucor fungus, associated with high mortality and typically found in immunocompromised patients, though it has also been described in immunocompetent individuals. The mode of acquisition is digestive. It usually presents as abdominal pain, with ischemia and intestinal perforation, and the diagnosis is often histopathological after surgical resection. We present the case of a 54-year-old female patient with recurrent acute myeloid leukemia undergoing treatment with daunorubicin-cytarabine and experiencing febrile neutropenia. She developed patchy and progressive intestinal ischemia that evolved into intestinal necrosis, which was treated with antifungal medications and surgery. Examination of the surgical specimen revealed aseptate wide hyphae with branching at right angles, suggestive of Mucor fungus. This is a rare but highly mortal pathology in which clinical, radiological, and surgical suspicion is essential for early diagnosis and treatment, thus improving the patient's prognosis.

DNA mismatch repair defect and intratumor heterogeneous deficiency differently impact immune responses in diffuse large B-cell lymphoma.

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression profiling. The results showed that genetic dMMR was infrequent in DLBCL and was significantly associated with increased cancer gene mutations and favorable immune microenvironment, but not prognostic impact. Phenotypic dMMR was also infrequent, and MMR proteins were commonly expressed in DLBCL. However, intratumor heterogeneity existed, and increased DLBCL cells with phenotypic dMMR correlated with significantly increased T cells and PD-1+ T cells, higher average nearest neighbor distance between T cells and PAX5+ cells, upregulated immune gene signatures, LE4 and LE7 ecotypes and their underlying Ecotyper-defined cell states, suggesting the possibility that increased T cells targeted only tumor cell subsets with dMMR. Only in patients with MYC¯ DLBCL, high MSH6/PMS2 expression showed significant adverse prognostic effects. This study shows the immunologic and prognostic effects of genetic/phenotypic dMMR in DLBCL, and raises a question on whether DLBCL-infiltrating PD-1+ T cells target only tumor subclones, relevant for the efficacy of PD-1 blockade immunotherapy in DLBCL.

Nephrotoxicity Associated with Cytoreductive Surgery Combined with Cisplatin-Based Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignant Disease: A Systematic Review and Meta-Analysis.

Background: Cisplatin is employed in hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for peritoneal surface malignancies (PSMs). The main concern regarding intraperitoneal cisplatin administration is nephrotoxicity. Numerous reports in this context are available. Our objective was to conduct a systematic review and meta-analysis to assess cisplatin-based HIPEC-related nephrotoxicity (CHRN). Methods: A systematic literature review on CHRN after CRS for the treatment of PSMs was performed. The literature search was carried out using Medline, Cochrane, and Embase. The last day of the search was 23 October 2023. PRISMA guidelines were used. A meta-analysis was then conducted. The main endpoint was the incidence of acute and chronic renal impairment after CHRN. Secondary endpoints included the potential impact of several clinical variables on the primary endpoint and a critical appraisal of the different renal impairment scales employed. Results: Our study included 26 articles with a total sample of 1473 patients. The incidence of acute kidney injury (AKI) was 18.6% (95% CI: 13.6-25%, range of true effects 3-59%). For chronic kidney disease, it was 7% (95% CI: 3-15.3%, range of true effects 1-53%). The variables that statistically influenced these results were the scale used to measure renal insufficiency, the use of nephroprotective agents, and the presence of pre-existing renal disease. Conclusions: The reported incidence of renal impairment following cisplatin-based HIPEC is highly variable. The incidence of renal failure obtained in this meta-analysis should be used as a reference for subsequent reports on this topic. Further prospective studies are warranted to establish optimal and standardized management.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: HIPEC Technologies.

This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.

Ibrutinib and R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma of non-GCB type: Phase II clinical trial of the Spanish GELTAMO group.

PURPOSE: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41-65) and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 - 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

Hipertensión portal no cirrótica por enfermedad vascular porto-sinusoidal: presentación de un caso y revisión de la literatura / Non-cirrhotic portal hypertension due to porto-sinusoidal vascular disease: Case presentation and literature review

La enfermedad vascular porto-sinusoidal es una causa infrecuente de hipertensión portal no cirrótica, fue descrita recientemente y es poco diagnosticada por el desconocimiento entre los médicos. Se considera en casos de hipertensión portal clínicamente significativa, en ausencia de cirrosis. El diagnóstico se basa en los hallazgos de la biopsia. El pronóstico de la enfermedad es mejor que el de los pacientes cirróticos, y el tratamiento es similar al de la hipertensión portal y al de las complicaciones que presentan los pacientes con cirrosis. Se presenta el caso de una paciente con várices esofágicas con estudios de imágenes no compatibles con cirrosis y hallazgos específicos en la biopsia de enfermedad vascular porto-sinusoidal. Este caso muestra el ejercicio diagnóstico en un caso de enfermedad vascular porto-sinusoidal de una paciente de Colombia, así como el resultado de las intervenciones terapéuticas y la evolución en el tiempo.

Porto-sinusoidal vascular disease is an uncommon cause of non-cirrhotic portal hypertension. It was recently described and is rarely diagnosed due to lack of knowledge among doctors. It is considered in cases of clinically significant portal hypertension in the absence of cirrhosis, and the diagnosis is based on biopsy findings. The prognosis of the disease is better than that of cirrhotic patients, and the treatment is similar to that of portal hypertension, including the management of complications associated with cirrhosis. We present the case of a patient with esophageal varices, whose imaging studies were not compatible with cirrhosis, alongside specific biopsy findings of porto-sinusoidal vascular disease. This case illustrates the diagnostic process in a patient from Colombia with portosinusoidal vascular disease, as well as the outcomes of therapeutic interventions and the patient´s evolution over time.

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis.

BACKGROUND: Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients. METHODS: We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5). RESULTS: By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group. CONCLUSION: Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.

Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

BACKGROUND: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. METHODS: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments. RESULTS: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. CONCLUSION: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.

Kikuchi-Fujimoto disease type lymph node reaction with increased plasmacytoid dendritic cells may appear as a side effect following COVID-19 vaccination: Report of a case and literature review.

Subsequent to mass vaccination programs against COVID-19, diverse side effects have been described, both at the injection site, such as pain, redness and swelling, and systemic effects such as fatigue, headache, muscle or joint pain. On rare occasions, a lymphadenopathic syndrome may develop, raising the clinical suspicion of a lymphoproliferative disorder. We present the case of a 30-year-old woman who developed self-limiting left axillary lymphadenopathy following COVID-19 vaccination. To date, only seven similar cases with a complete clinicopathological description have been published, and fourteen cases have been notified to the European adverse events databases (Eudravigilance) in relationship with vaccination against COVID-19. It is important to be aware of this potential complication when a lymphadenopathic syndrome develops following vaccination, to avoid unnecessary treatment.

From Castleman disease histopathological features to idiopathic multicentric Castleman disease: a multiparametric approach to exclude potential iMCD histopathological mimickers.

AIMS: International consensus diagnostic criteria for idiopathic multicentric Castleman disease (iMCD) includes lymph node Castleman disease (CD) histopathological features as major criteria. Our aim was to apply those criteria in a series of 42 cases with CD to find differences among unicentric CD, iMCD, HHV-8+multicentric CD (HHV-8+MCD) and POEMS/plasma cell neoplasia (PCN)-associated CD. METHODS: Available clinical and laboratory criteria were collected. Histopathological features (germinal centre hyperplasia/regression, plasmacytosis, hypervascularity and follicular dendritic cell (FDC) prominence) were graded and immunohistochemistry with antibodies against CD20, CD3, CD138, HHV-8, Ig isotype (IgG, IgG4, IgA, IgM, IgD), kappa, lambda was performed in all cases. RESULTS: Fourteen cases had hyaline-vascular type unicentric CD, 15 were HHV-8+MCD, 7 cases PCN/POEMS-associated CD and 5 cases were iMCD. One case was consistent with systemic lupus erythematosus (SLE) lymphadenopathy. Differences in grading of the CD-associated histopathological features showed that FDC proliferation was prominent in unicentric CD, hypervascularity was increased in HHV-8 positive MCD and germinal centre hyperplasia was restricted to iMCD cases and SLE. Monotypic plasma cells were readily identifiable in the lymph node biopsies in 43% of PCN/POEMS-associated CD. All three cases had lambda light chain restriction with IgA (two cases) and IgG (one case) isotypes. CONCLUSIONS: HHV-8+ MCD and PCN/POEMS-related CD are the major mimickers of iMCD in lymph node biopsies. Grading of the five histopathological features for CD might be useful to, in conjunction with complete ancillary testing, suggest for specific disease entities.

Feasibility of a selective targeted strategy of HIV testing in emergency departments: a before-after study.

BACKGROUND AND IMPORTANCE: The rates of hidden infection and late diagnosis of HIV still remain high in Western countries. Missed diagnostic opportunities represent the key point in changing the course of the epidemic. OBJECTIVE: To evaluate the feasibility and results of implementation of a selective strategy to test for HIV in the emergency department (ED) in patients with six pre-defined medical situations: sexually transmitted infections, herpes zoster, community-acquired pneumonia, mononucleosis syndrome, practice of chemsex (CS) or request of post-exposure prophylaxis. DESIGN: This quasi-experimental longitudinal study evaluated the pre- and post-implementation results of HIV testing in the six aforementioned clinical scenarios. SETTINGS AND PARTICIPANTS: Patients attended 34 Spanish EDs. INTERVENTION OR EXPOSURE: The intervention was an intensive educational program and pathways to facilitate and track orders and results were designed. We collected and compared pre- and post-implementation ED census and diagnoses, and HIV tests requested and results. OUTCOME MEASURES AND ANALYSIS: The main outcome was adherence to the recommendations. Secondary outcomes were to evaluate the effectiveness of the program by the rate of positive test and the new HIV diagnoses. Differences between first and second periods were assessed. The magnitude of changes (absolute and relative) was expressed with the 95% confidence interval (CI). MAIN RESULTS: HIV tests increasing from 7080 (0.42% of ED visits) to 13 436 (relative increase of 75%, 95% CI from 70 to 80%). The six conditions were diagnosed in 15 879 and 16 618 patients, and HIV testing was ordered in 3393 (21%) and 7002 (42%) patients (increase: 97%; 95% CI: 90-104%). HIV testing significantly increased for all conditions except for CS. The positive HIV test rates increased from 0.92 to 1.67%. Detection of persons with undiagnosed HIV increased from 65 to 224, which implied a 220% (95% CI: 143-322%) increase of HIV diagnosis among all ED comers and a 71% (95% CI: 30-125%) increase of positive HIV tests. CONCLUSION: Implementation of a strategy to test for HIV in selective clinical situations in the ED is feasible and may lead to a substantial increase in HIV testing and diagnoses.

POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1.

The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO-GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co-localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer-related deaths, POTEE could represent a potential therapeutic target for these types of cancer.

Primary cutaneous CD30+ lymphoproliferative disorders with DUSP22 translocation.

Primary cutaneous CD30+ lymphoproliferative disorders (LPD) encompass a broad category of clonal T cell proliferations with varied clinical presentations. Classically, lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (ALCL) have been recognized as distinct clinicopathological entities according to their differing clinical features. Recently, a subset of LyP and both cutaneous and systemic ALCL have been shown to carry a DUSP22 translocation [1-3], a defining molecular feature for the novel entity "LyP with DUSP22t" [1]. In cutaneous biopsies, both primary cutaneous DUSP22-translocated ALCL and LyP with DUSP22 rearrangements are characterized by a biphasic pattern with significant small cell epidermotropism. A distinct protein expression profile with preserved T Cell Receptor (TCR) expression, positivity for CD30, LEF1, HLA, and CD58, and negativity for cytotoxic marker expression as well as phospho-STAT3 protein is consistently found in these cases.

Mortality due to non-AIDS-defining cancers among people living with HIV in Spain over 18 years of follow-up.

PURPOSE: Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors. METHODS: We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004-2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors. RESULTS: Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use. CONCLUSION: Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population.

CTNNB1 somatic mutations drive Wnt pathway activation in a case of incidental intranodal palisaded myofibroblastoma.

Intranodal palisaded myofibroblastoma (IPM) is a rare stroma-derived spindle-cell neoplasm of the lymph node with myofibroblastic differentiation and CTNNB1 (ß-catenin gene) somatic mutations. We present a case of IPM found incidentally in the staging of lung adenocarcinoma. We describe the major histopathological and phenotypic features, including a palisaded bland spindle cell proliferation with myofibroblastic differentiation and Wnt pathway activation by immunohistochemistry, including ß-catenin expression. Production of osteoid-like collagen directly from tumor cells was observed. We confirmed p.Gly34Arg CTNNB1 mutation by direct sequencing. We also reviewed the literature for similar cases.

Seven Epidemic Waves of COVID-19 in a Hospital in Madrid: Analysis of Severity and Associated Factors.

(1) Background: COVID-19 has evolved during seven epidemic waves in Spain. Our objective was to describe changes in mortality and severity in our hospitalized patients. (2) Method: This study employed a descriptive, retrospective approach for COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) until 31 December 2022. (3) Results: A total of 5510 admissions for COVID-19 were recorded. The first wave accounted for 1823 (33%) admissions and exhibited the highest proportion of severe patients: 65% with bilateral pneumonia and 83% with oxygen saturation under 94% during admission and elevated levels of CRP, IL-6, and D-dimer. In contrast, the seventh wave had the highest median age (79 years) and comorbidity (Charlson: 2.7), while only 3% of patients had bilateral pneumonia and 3% required intubation. The overall mortality rate was 10.3%. The first wave represented 39% of the total. The variables related to mortality were age (OR: 1.08, 1.07-1.09), cancer (OR: 1.99, 1.53-2.60), dementia (OR: 1.82, 1.20-2.75), the Charlson index (1.38, 1.31-1.47), the need for high-flow oxygen (OR: 6.10, 4.94-7.52), mechanical ventilation (OR: 11.554, 6.996-19.080), and CRP (OR: 1.04, 1.03-1.06). (4) Conclusions: The variables associated with mortality included age, comorbidity, respiratory failure, and inflammation. Differences in the baseline characteristics of admitted patients explained the differences in mortality in each wave. Differences observed between patients admitted in the latest wave and the earlier ones suggest that COVID-19 has evolved into a distinct disease, requiring a distinct approach.

Crohn's Disease in a Patient with Tuberculosis: A Diagnostic and Therapeutic Challenge

Introduction: Crohn's disease (CD) is unusual in Colombia. Tuberculosis (TB) occurs more frequently, but intestinal involvement is rare. Differentiating these two entities and treating the cases in which they coexist is a challenge. Clinical case: A 28-year-old man with three months of constitutional, respiratory, and GI symptoms was initially diagnosed with pulmonary tuberculosis, and all the clinical manifestations were attributed to this entity. Given the absence of improvement with treatment and the sum of radiological, endoscopic, and pathological findings, CD was confirmed. Treatment was complex due to the coexistence of the two entities, although he finally went into remission with the use of biologicals. Discussion: Diagnosing CD requires the sum of clinical and paraclinical findings. A therapeutic test may be necessary to differentiate it from intestinal TB. The treatment of CD in a patient with TB has some limitations; steroids are not contraindicated, and biologicals must be initiated cautiously. Conclusions: Differentiating CD from intestinal TB is a diagnostic challenge. Therapeutic management when these two entities coexist requires an interdisciplinary approach.

Introducción: la enfermedad de Crohn (EC) es inusual en Colombia. La tuberculosis (TB) se presenta con mayor frecuencia, pero el compromiso intestinal es raro. Diferenciar estas dos entidades y el tratamiento de los casos en los que coexisten es un reto. Caso clínico: hombre de 28 años con 3 meses de síntomas constitucionales, respiratorios y gastrointestinales al que en un inicio se le confirmó el diagnóstico de tuberculosis pulmonar y se le atribuyó a esta entidad todas las manifestaciones clínicas. Ante la ausencia de mejoría con el tratamiento y la suma de hallazgos radiológicos, endoscópicos y patológicos, se confirmó EC. El tratamiento fue difícil debido a la coexistencia de las dos entidades, aunque finalmente presentó remisión con el uso de biológicos. Discusión: diagnosticar la EC requiere de la sumatoria de hallazgos clínicos y paraclínicos. Para diferenciarla de TB intestinal puede llegar a ser necesaria una prueba terapéutica. El tratamiento de EC en un paciente con TB tiene algunas limitaciones, los esteroides no se contraindican de manera absoluta y el inicio de biológicos debe hacerse con precaución. Conclusiones: diferenciar la EC de la TB intestinal es un reto diagnóstico. El enfoque terapéutico cuando coexisten estas dos entidades requiere un abordaje interdisciplinario.

Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events.

BACKGROUND: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. METHODS: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. FINDINGS: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/µL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/µL, a CD8 count ≥1500 cells/µL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. INTERPRETATION: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/µL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. FUNDING: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.

Microbiome-derived cobalamin and succinyl-CoA as biomarkers for improved screening of anal cancer.

Human papillomavirus can cause preinvasive, high-grade squamous intraepithelial lesions (HSILs) as precursors to cancer in the anogenital area, and the microbiome is suggested to be a contributing factor. Men who have sex with men (MSM) living with human immunodeficiency virus (HIV) have a high risk of anal cancer, but current screening strategies for HSIL detection lack specificity. Here, we investigated the anal microbiome to improve HSIL screening. We enrolled participants living with HIV, divided into a discovery (n = 167) and validation cohort (n = 46), and who were predominantly (93.9%) cisgender MSM undergoing HSIL screening with high-resolution anoscopy and anal biopsies. We identified no microbiome composition signatures associated with HSILs, but elevated levels of microbiome-encoded proteins producing succinyl coenzyme A and cobalamin were significantly associated with HSILs in both cohorts. Measurement of these candidate biomarkers alone in anal cytobrushes outperformed anal cytology as a diagnostic indicator for HSILs, increasing the sensitivity from 91.2% to 96.6%, the specificity from 34.1% to 81.8%, and reclassifying 82% of false-positive results as true negatives. We propose that these two microbiome-derived biomarkers may improve the current strategy of anal cancer screening.