Symptom burden guiding invasive electrophysiological study in paroxysmal supraventricular tachycardia: The believe SVT registry.

BACKGROUND AND OBJECTIVE: Patients with palpitations clinically suggestive of paroxysmal supraventricular tachycardia (PSVT) are often managed conservatively until ECG-documentation of the tachycardia, leading to high impact on life quality and healthcare resource utilization. We evaluated results of electrophysiological study (EPS), and ablation when appropriate, among these patients, with special focus on gender differences in management. METHODS: BELIEVE SVT is a European multicenter, retrospective registry in tertiary hospitals performing EPS in patients with palpitations, without ECG-documentation of tachycardia or preexcitation, and considered highly suggestive of PSVT by a cardiologist or cardiac electrophysiologist. We analyzed clinical characteristics, results of EPS and ablation, complications, and clinical outcomes during follow-up. RESULTS: Six-hundred eighty patients from 20 centers were included. EPS showed sustained tachycardia in 60.9% of patients, and substrate potentially enabling AVNRT in 14.7%. No major/permanent complications occurred. Minor/transient complications were reported in 0.84% of patients undergoing diagnostic-only EPS and 1.8% when followed by ablation. During a 3.4-year follow-up, 76.2% of patients remained free of palpitations recurrence. Ablation (OR: 0.34, P < .01) and male gender (OR: 0.58, P = .01) predicted no recurrence. Despite a higher female proportion among patients with recurrence, (77.2% vs 63.5% among those asymptomatic during follow-up, P < .01), 73% of women in this study reported no recurrence of palpitations after EPS. CONCLUSIONS: EPS and ablation are safe and effective in preventing recurrence of nondocumented palpitations clinically suggestive of PSVT. Despite a lower efficacy, this strategy is also highly effective among women and warrants no gender differences in management.

Conduction system pacing and atrioventricular node ablation in heart failure: The PACE-FIB study design.

AIMS: Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction. In this study, the long-term benefits and safety profile of heart rate regularization through left-bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate-control strategy. METHODS AND RESULTS: The PACE-FIB trial is a multicentre, prospective, open-label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all-cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment-related adverse events, among others, will be analysed too. CONCLUSION: LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long-term efficacy and safety of this pace-and-ablate strategy in patients with HFpEF/HFmrEF and permanent AF.

Compatibility of a novel temperature-controlled, irrigated radiofrequency catheter with ultra-high-density mapping.

Background: Compatibility of DiamondTemp (DT) radiofrequency (RF) catheter with the Rhythmia mapping system has not been manufacturer-reported nor its tracking accuracy reported. Methods: Consecutive patients undergoing macroreentrant atrial tachycardia ablation guided by Rhythmia and ablated using DT were prospectively enrolled. Following catheter configuration, ablation lines were performed and remapped to measure the RF tag to effective-ablation-line-center (RFT-ALC) distance. Results: Among 20 consecutive patients (54 maps), 40 ablation lines were evaluated. Overall, the RFT-ALC distance was 3.88 ± 2.95 mm, and the operator assessment of accuracy was high. No complications occurred. Conclusion: The use of DT catheter guided by the Rhythmia mapping system is feasible and accurate.

Systematic Workflow and Electrogram guidance to reduce X-ray Exposure Time during cryoballoon ablation of atrial fibrillation: the SWEET-Cryo strategy.

AIMS: Cryoballoon pulmonary vein isolation (CB-PVI) offers similar efficacy to point-by-point radiofrequency PVI for patients with atrial fibrillation (AF), but generally with higher X-ray exposure. Strategies aimed at reducing fluoroscopy mostly rely on other costly imaging techniques, limiting their applicability. We designed a Systematic Workflow and Electrogram guidance to reduce X-ray Exposure Time during CB-PVI (SWEET-Cryo) strategy and analysed its impact on fluoroscopy use and acute procedural and clinical outcomes. METHODS AND RESULTS: We enrolled 100 patients with paroxysmal or persistent AF undergoing CB-PVI by two operators with different levels of expertise. Patients treated with the SWEET-Cryo strategy (prospective cohort; n = 50) or conventional fluoroscopy (retrospective control cohort; n = 50) were compared. When applied by the senior operator, the SWEET-Cryo strategy significantly reduced the mean fluoroscopy time (FT) (2.6 ± 1.25 vs. 20.3 ± 10.8 min) and mean dose area product (DAP) (5.1 ± 3.8 vs. 35.3 ± 22.3 Gy cm2) compared with those of the control group, respectively (P < 0.001). Significant reductions in FT (6.4 ± 2.5 min vs. 32.5 ± 10.05) and DAP (13.9 ± 7.7 vs. 92.3 ± 63.8) were also achieved by the less experienced operator (P < 0.001). No difference was observed in acute and long-term complications or freedom from AF between fluoroscopy strategies during a 33-month median follow-up. Mean FT was maintained below 3 min in randomly selected cases performed during the follow-up period. CONCLUSION: In contrast to conventional protocols and regardless of the operator's experience, the optimized SWEET-Cryo strategy dramatically reduced fluoroscopy exposure during CB-PVI. The efficacy, safety, or added costs of the ablation procedure were not compromised.

Percutaneous radiofrequency ablation is an effective treatment option for small renal masses, comparable to partial nephrectomy.

OBJECTIVES: The standard therapy for small renal masses (SRMs) remains partial nephrectomy (PN), which is associated with relatively high morbidity and complication rate. Therefore, percutaneous radiofrequency ablation (PRFA) emerges as an alternative therapy. This study aimed to compare the efficacy, safety, and oncological outcomes of PRFA versus PN. METHODS: A multicenter non-inferiority study with retrospective analysis of 291 patients with SRMs (N0M0), who underwent PN or PRFA (2:1), recruited prospectively from two hospitals in the Andalusian Public Health System, Spain, between 2014 and 2021. Comparisons of treatment features were evaluated using the t test, Wilcoxon-Mann-Whitney U test, chi-square test, Fisher test, and Cochran-Armitage trend test. Kaplan-Meier curves depicted overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) rates in the overall study population. RESULTS: A total of 291 consecutive patients were identified; 111 and 180 patients underwent PRFA and PN, respectively. Median follow-up time was 38 and 48 months, and mean hospitalization days were 1.04 and 3.57 days, respectively. The variables underpinned with high surgical risk were significantly increased in PRFA compared to those in PN (mean age was 64.56 and 57.47 years, the solitary kidney presence was 12.6% and 5.6%, ASA score ≥ 3 was 36% and 14.5%, respectively). The rest of oncological outcomes were comparable amongst PRFA and PN. Patients undergoing PRFA did not improve OS, LRFS, and MFS compared to those undergoing PN. Limitations comprise retrospective design and limited statistical power. CONCLUSION: PRFA for SMRs in high-risk patients is non-inferior in terms of oncological outcomes and safety compared to PN. CLINICAL RELEVANCE STATEMENT: Our study has a direct clinical application as it proves that radiofrequency ablation is an effective and uncomplicated therapeutic option for patients with small renal masses. KEY POINTS: •There are non-inferiority results in overall survival, local recurrence-free survival, and metastasis-free survival between PRFA and PN. •Our two-center study showed that PRFA is non-inferior to PN in oncological outcomes. •Contrast-enhanced power ultrasound-guided PRFA provides an effective therapy for T1 renal tumors.

mRNA-1273 boost after BNT162b2 vaccination generates comparable SARS-CoV-2-specific functional responses in naïve and COVID-19-recovered individuals.

Introduction: COVID-19 vaccines based on mRNA have represented a revolution in the biomedical research field. The initial two-dose vaccination schedule generates potent humoral and cellular responses, with a massive protective effect against severe COVID-19 and death. Months after this vaccination, levels of antibodies against SARS-CoV-2 waned, and this promoted the recommendation of a third vaccination dose. Methods: We have performed an integral and longitudinal study of the immunological responses triggered by the booster mRNA-1273 vaccination, in a cohort of health workers previously vaccinated with two doses of the BNT162b2 vaccine at University Hospital La Paz located in Madrid, Spain. Circulating humoral responses and SARS-CoV-2-specific cellular reactions, after ex vivo restimulation of both T and B cells (cytokines production, proliferation, class switching), have been analyzed. Importantly, all along these studies, the analyses have been performed comparing naïve and subjects recovered from COVID-19, addressing the influence of a previous infection by SARS-CoV-2. Furthermore, as the injection of the third vaccination dose was contemporary to the rise of the Omicron BA.1 variant of concern, T- and B-cell-mediated cellular responses have been comparatively analyzed in response to this variant. Results: All these analyses indicated that differential responses to vaccination due to a previous SARS-CoV-2 infection were balanced following the boost. The increase in circulating humoral responses due to this booster dropped after 6 months, whereas T-cell-mediated responses were more stable along the time. Finally, all the analyzed immunological features were dampened in response to the Omicron variant of concern, particularly late after the booster vaccination. Conclusion: This work represents a follow-up longitudinal study for almost 1.5 years, analyzing in an integral manner the immunological responses triggered by the prime-boost mRNA-based vaccination schedule against COVID-19.

Atrioventricular block following prolonged focal cryoablation for parahisian premature ventricular complexes.

A 54-year-old woman with symptomatic premature ventricular contractions (PVC) was referred for electrophysiological study. The earliest activation was located at the parahisian area, so it was decided to ablate using cryoenergy. No AV conduction impairment was observed during cryomapping. PVCs were abolished after the first 15 seconds of cryoablation, without recurrence. However, after 354 seconds of cryoablation, a mild PR prolongation was followed by first degree and 2-to-1 AV block. Termination of cryoablation led to complete recovery without definitive damage and with elimination of the PVC. This case illustrates how lesion formation using cryoenergy can continue to evolve even after several minutes, highlighting the need of monitoring throughout the whole target duration.

Caracterización de la enfermedad renal crónica subclínica en Chile

Contexto al realizar cribado en la población de riesgo se encontró que la enfermedad renal crónica subclínica (ERCs) está escasamente caracterizada en Chile y su conocimiento contribuiría al mejor manejo y tratamiento precoz, atenuando sus consecuencias. Objetivo describir las características epidemiológicas y clínicas de la población con ERCs en Chile. Metodología estudio descriptivo transversal en una población de 1032 sujetos provenientes de tres regiones de Chile: Coquimbo (n = 902), Metropolitana (n = 70) y De Los Ríos (n = 60), provenientes de programas cardiovasculares, otros programas de APS y familiares directos de pacientes en diálisis. A los pacientes se les aplicó: un consentimiento informado, una encuesta, un examen físico (presión arterial, peso y talla) y se realizaron exámenes de laboratorio (creatininemia y albuminuria/creatininuria). Se definió ERC por guía KDOQI-2012 y velocidad de filtración glomerular según MDRD. La albuminuria se midió mediante relación albuminuria/creatininuria de primera micción (mg/g). VFG < 60 ml/min o albuminuria ≥ 30 mg/g, definieron ERCs. Se determinaron frecuencias y comparaciones (chi-cuadrado, t student y Anova), con un nivel de significancia de p < 0,05. Resultados presentaron ERCs 205 sujetos (19,9 %), siendo significativamente más frecuente en ≥ 65 años (35,7 %), quienes alcanzaron estudios básicos (26,6 %), labores de servicio doméstico (44 %), pensionados (40 %), quienes tenían familiares en diálisis (24,6 %) y diabéticos insulino-requirentes (70,6 %). En el grupo ≥ 65 años hubo una significativa menor frecuencia de ERCs en aquellos que realizaban actividad física, comparado con los sedentarios (48,8 %). A mayor intensidad de HTA y presión de pulso (PP) se observó una mayor frecuencia de ERCs. Conclusiones estos datos aportan información epidemiológica útil para la programación de mejores estrategias de detección de ERCs en Chile.

Introduction subclinical chronic kidney disease (CKDs), performing screening in at-risk populations, is poorly characterized in Chile. Its knowledge would contribute to better management and early treatment, mitigating its consequences. Objective to describe the epidemiological and clinical characteristics of the population with CKDs in Chile. Methodology cross-sectional descriptive study in a population of 1,032 subjects from three regions of Chile; Coquimbo (n=902), Metropolitana (n=70) and De Los Ríos (n=60), from cardiovascular programs, other Primary Care programs and direct relatives of dialysis patients. Informed consent, survey, physical examination (blood pressure, weight and height) and laboratory tests (creatinine and albumin/creatinine urinary ratio) were performed. CKD was defined by KDOQI-2012 guideline and Glomerular Filtration Rate according to MDRD formula. Albuminuria by relation albumin/creatinine of first urination (mg/g). eVFG <60 ml/min and/or Albuminuria ≥ 30 mg/g, defined CKDs. Frequencies and comparisons were determined (chi-square, t student and ANOVA), with a significance level of p < 0.05. Results 205 subjects (19.9%) presented CKDs, being significantly more frequent in ≥65 years (35.7%), who achieved elementary school studies (26.6%), domestic service workers (44%), retired workers (40%), having a family member on dialysis (24.6%) and insulin-requesting diabetics (70.6%). In the ≥65 year-old group, there was a significantly lower frequency of CKDs in those who performed physical activity, compared to sedentary (48.8%). The higher the intensity of hypertension and pulse pressure (PP), the higher the frequency of CKDs. Conclusions These data provide useful epidemiological information for the programming of better detection strategies for CKDs in Chile.

Differential Immune Checkpoint and Ig-like V-Type Receptor Profiles in COVID-19: Associations with Severity and Treatment.

Identifying patients' immune system status has become critical to managing SARS-CoV-2 infection and avoiding the appearance of secondary infections during a hospital stay. Despite the high volume of research, robust severity and outcome markers are still lacking in COVID-19. We recruited 87 COVID-19 patients and analyzed, by unbiased automated software, 356 parameters at baseline emergency department admission including: high depth immune phenotyping and immune checkpoint expression by spectral flow cytometry, cytokines and other soluble molecules in plasma as well as routine clinical variables. We identified 69 baseline alterations in the expression of immune checkpoints, Ig-like V type receptors and other immune population markers associated with severity (O2 requirement). Thirty-four changes in these markers/populations were associated with secondary infection appearance. In addition, through a longitudinal sample collection, we described the changes which take place in the immune system of COVID-19 patients during secondary infections and in response to corticosteroid treatment. Our study provides information about immune checkpoint molecules and other less-studied receptors with Ig-like V-type domains such as CD108, CD226, HVEM (CD270), B7H3 (CD276), B7H5 (VISTA) and GITR (CD357), defining these as novel interesting molecules in severe and corticosteroids-treated acute infections.

Survival study and factors associated with mortality in Chilean patients on peritoneal dialysis infected with SARS-CoV-2.

The Covid-19 pandemic has been responsible for millions of deaths worldwide. Patients with comorbidities- such as those on peritoneal dialysis (PD)- present higher morbidity and mortality than the general population. We prospectively evaluated all Chilean patients on PD (48 centres) and followed those who had Covid-19 from the beginning of the Covid-19 pandemic in Chile (March 2020) to January 2021 (start of vaccination campaign). We described demographic history, comorbidities, factors related to infection, need for hospitalisation and death due to Covid-19. During the study period, 106 adults on PD were infected by SARS-CoV-2, with a mean age of 53.1 (±16.3) and of which 53.9% were female. From that group, 54.8% required hospitalisation and 24.5% (n = 26) died due to Covid-19. Most of the patients (63.4%) were infected at home and 22.8% during hospitalisation for other reasons. There was a significant association for Covid-19 mortality with: being ≥60 years old, diabetes, time on PD ≥5 years, need for hospitalisation and hospital-acquired infection. At 90 days of follow-up, all deaths associated to Covid-19 occurred before 40 days. We conclude that patients on PD without Covid-19 vaccination have a high mortality and need for hospitalisation associated to Covid-19. To avoid this negative outcome, it is necessary to intensify strategies to avoid contagion, especially in those ≥60 years old, with diabetes and/or ≥5 years spent on PD.

Prevalence, Clinical Characteristics, and Management of Episodic Dyspnea in Advanced Lung Cancer Outpatients: A Multicenter Nationwide Study-The INSPIRA-DOS Study.

Background: Episodic dyspnea (ED) is a common problem in patients with advanced lung cancer (LC). However, the prevalence of ED and other related aspects in this patient population is not known. Objectives: To assess and describe the prevalence, clinical features, treatment, and risk factors for ED in outpatients with advanced LC. Design: Multicenter cross-sectional study. Subjects: Consecutive sample of adult outpatients with advanced LC. Measurements: We assessed background dyspnea (BD), the characteristics, triggers, and management of ED. Potential ED risk factors were assessed through multivariate logistic regression. Results: A total of 366 patients were surveyed. Overall, the prevalence of ED was 31.9% (90% in patients reporting BD). Patients reported a median of one episode per day (interquartile range [IQR]: 1-2), with a median intensity of 7/10 (IQR: 5-8.25). ED triggers were identified in 89.9% of patients. ED was significantly associated with chronic obstructive pulmonary disease (p = 0.011), pulmonary vascular disease (p = 0.003), cachexia (p = 0.002), and palliative care (p < 0.001). Continuous oxygen use was associated with higher risk of ED (odds ratio: 9.89; p < 0.001). Opioids were used by 44% patients with ED. Conclusions: ED is highly prevalent and severe in outpatients with advanced LC experiencing BD. The association between intrathoracic comorbidities and oxygen therapy points to alveolar oxygen exchange failure having a potential etiopathogenic role in ED in this population. Further studies are needed to better characterize ED in LC to better inform treatments and trial protocols.

Cellular and humoral functional responses after BNT162b2 mRNA vaccination differ longitudinally between naive and subjects recovered from COVID-19.

We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost 8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.

Case Report: Bilateral Valsalva Retinopathy in an Acutely Anemic Patient.

SIGNIFICANCE: The Valsalva maneuver is known to cause pre-retinal hemorrhages, which have a predilection to affect the macula. Certain conditions may increase the risk of developing Valsalva retinopathy including anemia. Knowing these associations can aid in uncovering underlying systemic conditions for which a patient may not otherwise be aware. PURPOSE: This case report reviews the presentation of Valsalva retinopathy and the impacts of acute anemia on retinal findings. Recommendations for management are also reviewed and reported. CASE REPORT: A 30-year-old Hispanic man presented to the emergency department for progressing weakness over the previous month. He had a history of polysubstance abuse and had not been eating for the previous month except for water intake. He was diagnosed with unconjugated hyperbilirubinemia, anemia, thrombocytopenia, hypercoagulable state, hypokalemia, and hypomagnesia and admitted to the intensive care unit for treatment and observation. He was referred to the eye clinic to be examined for Kayser-Fleischer rings because of concern for Wilson disease. On ophthalmological examination, the patient had reduced vision in both eyes attributed to bilateral subinternal limiting membrane macular hemorrhages likely due to Valsalva, with acute anemia and thrombocytopenia as contributing factors. The patient was referred to a retinal specialist, and observation was recommended with follow-up in 3 months. The patient, unfortunately, never followed up despite multiple attempts to reschedule. CONCLUSIONS: Patient history and the common location of retinal hemorrhages aid in diagnosing Valsalva retinopathy. In this case, the patient had a known history of acute anemia and thrombocytopenia with a recent history of straining. Anemia, among other systemic conditions, can increase the risk of developing retinopathy after a Valsalva maneuver. Although Valsalva retinopathy can occur in healthy patients without underlying conditions, it is important to rule out other conditions that might present with retinal hemorrhage or that may increase the risk of Valsalva retinopathy.

Impact of Coronavirus Disease 2019 on Cardiac Arrhythmia Care: Experience of a Spanish Tertiary Hospital During the Health Crisis Triggered by the First Wave of the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in a deep restructuring of cardiovascular care, especially in the setting of cardiac arrhythmia units, which are characterized by a wide variety of clinical and interventional activities. We describe the experience of a large university hospital deeply hit during the COVID-19 health crisis (first outbreak of the pandemic), focusing on the exceptional measures implemented and their impact in terms of outcomes. We performed a retrospective study comparing the human and structural resources and the activity of a cardiac arrhythmia unit in a Spanish tertiary hospital for two consecutive periods: from January 12, 2020, to March 8, 2020 ("pre-COVID stage"), and from March 9, 2020, to May 2, 2020 ("COVID stage"). Data were contextualized within the number of confirmed COVID-19 cases in the region of Madrid. The measures implemented were promotion of non-face-to-face consultations, selection of urgent procedures, design of a "COVID-free" circuit for outpatient interventions, and protocolization for patients with COVID-19. A total of 3,526 consultations and 362 procedures were performed. During the COVID stage, the number of consultations remained stable, and the electrophysiology rooms' activity decreased by 55.2% with a relative increase in the number of urgent-hospitalized cases attended (11.8% COVID-19-positive patients). The electrophysiology rooms' activity returned to "normal" in the last week of the COVID stage, with no contagion being detected among patients or professionals. In conclusion, the measures implemented allowed us to respond safely and efficiently to the health care needs of patients with arrhythmias during the COVID-19 crisis and may be useful for other institutions facing similar situations.

Complete interatrial block in a left-atrial dependent atrioventricular node.

INTRODUCTION: A middle-age woman underwent an electrophysiologic study due to recurrent atypical atrial flutter. METHODS AND RESULT: Radiofrequency ablation of cavotricuspid isthmus and anterior mitral line was performed. During energy delivery on the anterior left atrial wall, interatrial dissociation and complete block of the sinus impulse to the atrioventricular (AV) node was observed. AV node activation became dependent on a subsidiary left atrial rhythm. CONCLUSION: Anatomical location of intra and inter-atrial connections must be taken into account when performing extensive ablation procedures, specially in cases with prior cardiac surgeries.

SARS-CoV-2 Proteins Induce Endotoxin Tolerance Hallmarks: A Demonstration in Patients with COVID-19.

According to a large number of reported cohorts, sepsis has been observed in nearly all deceased patients with COVID-19. We and others have described sepsis, among other pathologies, to be an endotoxin tolerance (ET)-related disease. In this study, we demonstrate that the culture of human blood cells from healthy volunteers in the presence of SARS-CoV-2 proteins induced ET hallmarks, including impairment of proinflammatory cytokine production, low MHC class II (HLA-DR) expression, poor T cell proliferation, and enhancing of both phagocytosis and tissue remodeling. Moreover, we report the presence of SARS-CoV-2 blood circulating proteins in patients with COVID-19 and how these levels correlate with an ET status, the viral RNA presence of SARS-CoV-2 in plasma, as well as with an increase in the proportion of patients with secondary infections.

Potential Role of the Galectin-9/TIM-3 Axis in the Disparate Progression of SARS-CoV-2 in a Married Couple: A Case Report.

We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.