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The importance of having region-specific data when planning health interventions has become evident in recent years. Nonetheless, several world regions, including Latin America and the Caribbean (LAC), still face significant challenges. These regions need to develop strategies specifically designed to consider the inherent characteristics of their population composite and sociodemographic characteristics. More than 20% of the global cancer incidence arises in LAC. Yet, treatment, prevention, and follow-up guidelines in the area are frequently based on studies that mainly include patients from North America, Europe, and Asia. As personalized approaches become ubiquitous in medical practice, the amount of information emerging from LAC has risen considerably. In this review, we seek to present a comprehensive summary of the frequency of germline genetic variants in hereditary cancer syndromes in patients from LAC. The data highlight relevant differences in variants associated with LAC patients, including founder and recurrent variants, while showcasing potential features that might be relevant in oncology practices.

Abstract Pulmonary vascular disease is a frequent complication of chronic liver disease and portal hypertension, affecting up to 30% of patients. There are two distinct pulmonary vascular complications of liver disease: hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). HPS affects 25% of patients with chronic liver disease and is characterized by intrapulmonary vasodilatation and abnormal arterial oxygenation. HPS negatively impacts quality of life and is associated with a 2‐fold increased risk of death compared to controls with liver disease without HPS. Angiogenesis, endothelin‐1 mediated endothelial dysfunction, monocyte influx, and alveolar type 2 cell dysfunction seem to play important roles in disease pathogenesis but there are currently no effective medical therapies. Fortunately, HPS resolves following liver transplant (LT) with improvements in hypoxemia. POPH is a subtype of pulmonary arterial hypertension (PAH) characterized by an elevated mean pulmonary arterial pressure and pulmonary vascular resistance in the setting of normal left‐sided filling pressures. POPH affects 5% to 6% of patients with chronic liver disease. Although the pathogenesis has not been fully elucidated, endothelial dysfunction, inflammation, and estrogen signaling have been identified as key pathways involved in disease pathogenesis. POPH is typically treated with PAH targeted therapy and may also improve with liver transplantation in selected patients. This article highlights what is currently known regarding the diagnosis, management, pathobiology, and outcomes of HPS and POPH. Ongoing research is needed to improve understanding of the pathophysiology and outcomes of these distinct and often misunderstood pulmonary vascular complications of liver disease. © 2021 American Physiological Society. Compr Physiol 12:3281‐3302, 2022.

ABSTRACTBackgroundDespite the general perception of minimal donor‐site morbidity associated with scapular free flaps, the surgical harvest of scapular bone and subsequent reattachment of parascapular muscle have the potential to compromise postoperative shoulder function. A comprehensive assessment of functional impairment remains undocumented in the literature. Therefore, this systematic review was conducted to thoroughly explore both subjective and objective donor‐site morbidity following free flap surgery.MethodsSearches were conducted on PubMed, Embase, and CENTRAL to locate articles addressing functional donor‐site morbidity after the transfer of scapular bone. Qualifying articles reported scapular free flaps which utilized bone, including lateral border, medial border, and scapular tip. Each measured donor‐site morbidity using at least one of these measures: Constant‐Murley score (CM), Disabilities of Arm, Shoulder, and Hand questionnaire (DASH), shoulder range of motion (ROM), and shoulder strength.ResultsThe search culminated in 16 eligible studies, incorporating data from 316 cases. The CM was employed in five studies, yielding mean values from 60.6 to 95, while the DASH was utilized in nine studies, with means ranging from 10.44 to 46.7. Compared to normative values, these CM and DASH scores reflected negligible to mild impairment in shoulder function. Additional evaluations of shoulder ROM, conducted in four studies, revealed modest yet statistically significant reductions in flexion, abduction, and external rotation. Three studies measuring shoulder strength reported associated mild weakening of these motions.ConclusionsThis systematic review enables healthcare providers to characterize the probable scope of shoulder dysfunction following scapular bone harvest. Patient‐reported outcomes imply a high tolerance for the procedure, while objective measures denote the potential for substantial restoration of shoulder function approaching preoperative levels. To augment the understanding of functional recovery, future research should incorporate a comparative analysis of preoperative and postoperative functional metrics for each subject.

Background. The current model for end-stage liver disease (MELD) exception policies for portopulmonary hypertension (POPH) require serial right heart catheterizations (RHCs) every 3 mo to maintain exception points. RHC is necessary for the initial diagnosis of POPH, but the utility of serial catheterizations has not been studied. In patients with POPH MELD exceptions, we sought to compare noninvasive and invasive hemodynamics and determine the sensitivity of echocardiography for the detection of hemodynamically severe POPH that would preclude liver transplant. Methods. We performed a single-center retrospective cohort study of patients with POPH MELD exceptions who underwent liver transplant from December 2008 to January 2024. Results were validated at an external center. Echocardiograms and RHCs performed within 1 mo were compared. Pearson correlation coefficient and Bland-Altman plots assessed the association between echocardiogram and RHC variables. We examined varied echocardiographic parameters to optimize sensitivity for the detection of hemodynamically severe POPH. Results. Twenty-two individuals underwent 60 follow-up RHCs with paired echocardiograms. Right ventricular systolic pressure (RVSP) and cardiac index estimated with echocardiogram were not strongly correlated with RHC measurements at follow-up (RVSP and RHC pulmonary artery systolic pressure: R = 0.30, P = 0.02; cardiac index: R = 0.17, P = 0.21). However, echocardiograms with RVSP ≥48 mm Hg had 100% sensitivity for detecting hemodynamically severe POPH, with 100% negative predictive value. In external validation of 13 paired echocardiograms and RHCs, our algorithm had 64% specificity and 100% negative predictive value. Conclusions. Although echocardiogram and RHC hemodynamic estimates were not strongly correlated, these results could potentially negate the current requirement for repeat RHC every 3 mo to maintain POPH MELD exception.

Introduction. Non-cystic fibrosis bronchiectasis is a complex medical condition with multiple etiologies, characterized by chronic productive cough and radiologic evidence of airway lumen dilation and wall thickening. Associated exacerbations and declining lung function contribute to increasing disability and mortality. There are no data about the prevalence of non-cystic fibrosis bronchiectasis etiologies in the Colombian population.Objective. To investigate non-cystic fibrosis bronchiectasis etiology and clinical characteristics in adults evaluated in the southwest of Colombia.Materials and methods. We conducted a cross-sectional, non-interventional study. Subjects diagnosed with non-cystic fibrosis bronchiectasis were referred to by theirhealthcare providers and then enrolled between October 2018 and April 2021. Medical records and radiological studies were evaluated. Participants underwent laboratory tests, including complete blood count, serum immunoglobulin levels, and, in some cases, additional tests.Results. We included 161 subjects. The average age was 50 years old, and 59% were females. Bronchiectasis etiology was identified in 84.6% of the cases. Postinfectious(34.6%) and immune disorders (25.3%), represented by autoimmunity (13.6%) and immunodeficiency (11.7%), were the leading causes. Gender differences were noted in autoimmune (females: 18.8% versus males: 6.1%, p = 0.021) and immunodeficiency-related bronchiectasis (males: 21.2% versus females 5.2%, p = 0.002). Immunodeficiencies-associated bronchiectases were more frequent in subjects under 50 years of age, while chronic obstructive pulmonary disease-associated bronchiectases were common in subjects over 50 years of age.Discussion. The etiologies of non-cystic fibrosis bronchiectasis in Colombia are diverse, exhibiting notable differences from other global regions. Serum immunoglobulin levels and clinical immunologist consultation should be prioritized in diagnosing patients with unclear bronchiectasis etiology, particularly those with recurrent sinopulmonary infections.

OBJECTIVE: To determine the impact of point-of-care ultrasound (POCUS)-guided resuscitation on clinical outcomes in adult patients with shock. DATA SOURCE: We searched MEDLINE, Embase, and unpublished sources from inception to December 2023. STUDY SELECTION: We included randomized controlled trials (RCTs) that examined the use of POCUS to guide resuscitation in patients with shock. DATA EXTRACTION: We collected data regarding study and patient characteristics, POCUS protocol, control group interventions, and outcomes. DATA SYNTHESIS: We identified 18 eligible RCTs. POCUS slightly influences physicians’ plans for IV fluid (IVF) and vasoactive medication prescription (moderate certainty), but results in little to no changes in the administration of IVF (low to high certainty) or inotropes (high certainty). POCUS may result in no change in the number of CT scans performed (low certainty) but probably reduces the number of diagnostic echocardiograms performed (moderate certainty). POCUS-guided resuscitation probably reduces 28-day mortality (relative risk [RR] 0.88; 95% CI, 0.78–0.99), the duration of vasoactive medication (mean difference –0.73 d; 95% CI, –1.16 to –0.30), and the need for renal replacement therapy (RRT) (RR 0.80; 95% CI, 0.63–1.02) (low to moderate certainty evidence), and lactate clearance (high certainty evidence). POCUS-guided resuscitation may results in little to no difference in ICU or hospital admissions, ICU and hospital length of stay, and the need for mechanical ventilation (MV) (low to moderate certainty evidence). There is an uncertain effect on the risk of acute kidney injury and the duration of MV or RRT (very low certainty evidence). CONCLUSIONS: POCUS-guided resuscitation in shock may yield important patient and health system benefits. Due to lack of sufficient evidence, we were unable to explore how the thresholds of operator competency, frequency, and timing of POCUS scans impact patient outcomes.

Abstract To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (>75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P < 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine–deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P < 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy. Significance: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody–drug conjugate combinations with potential implications for treatment decisions in relapsed HL.

8634 Background: Patients with unresectable non-small cell lung cancer (NSCLC) with an inadequate response to immune checkpoint inhibitors (ICI) have limited therapeutic options and expected median overall survival (mOS) of 11.6 to 14.5m (PMID: 35658002 ). The immunosuppressive tumor microenvironment and the lack of a specific T cell response underpin inadequate clinical response. CAN-2409 is a replication-defective adenovirus encoding the HSV-tk gene. Transduced cells activate orally delivered valacyclovir, resulting in immunogenic cell death, and in situ immunization against the patient’s tumor antigens, eliciting a specific immune response against the injected tumor and uninjected metastases. Methods: NCT04495153 is an open-label, phase 2 clinical trial of CAN-2409 + valacyclovir in combination with continued ICI in patients with non-resectable, stage III/IV NSCLC, refractory or resistant to anti-PD-(L)1. Patients were enrolled in 2 cohorts (C) depending on disease status at enrolment: C1, stable disease or C2, progressive disease. Two doses of CAN-2409 (5x1011vp) were given 5-7w apart via bronchoscopic or percutaneous injection into lung tumor, disease-positive lymph node, or peripheral metastasis, each followed by oral prodrug. Patients were assessed for safety, immunologic biomarkers, and OS. Results: As of 16Jan2024, 73 patients were treated (safety population: ≥1 dose of CAN-2409) and 44 were evaluable per protocol (received 2 doses of CAN-2409+ valacyclovir and 12-week CT scan). Baseline treated pt median age was 67 [43-88] yrs, 44% female, 68% on aPD(L)1 alone and 32% aPD(L)1 + pemetrexed regimen. We observed no dose-limiting toxicities or ≥grade 4 treatment-related AEs. mOS of the evaluable population was estimated as 22.0m (95% CI: 14.3m, NA; median follow up (mFU) time of 18.2m). In C2 (n = 38) mOS was 20.6 (mFU 19.2.m) and in C1 (n = 6) was N.A. (mFU 15.2m). mOS in the safety population (n = 73) was 14.3.m (mFU16.8m). 64% of evaluable patients had systemic clinical response with shrinkage of both injected and uninjected lesions. We found a significant correlation between increases in T cell populations after the second injection of CAN-2409 (circulating memory and effector memory CD4+ and CD8+T cells, CD4+ Ki67+IFNg+ and CD4+granzymeB+ T cells, CD8+granzymeB+Ki67+ T cells, T regulatory cells) and subsequent OS (R2 between 0.181 and 0.354 and p = 0.043 and 0.004). Conclusions: Experimental treatment with CAN-2409+valacyclovir in NSCLC pts following an inadequate response to ICI is well tolerated and results in the induction of a cytotoxic and memory circulating T cell response associated with shrinkage of injected and uninjected lesions and a raised tail of the survival curve. mOS of the evaluable population was estimated as 22.0m, markedly longer than the expected mOS of 11.6-14.5m. Clinical trial information: NCT04495153 .

AbstractObjectiveCartilaginous tumors of the larynx are rare, representing less than 1% of all laryngeal tumors. Chondromas are benign mesenchymal tumors characterized by a slow‐paced growth, primarily originated in the cricoid cartilage, followed by the thyroid, arytenoid, and epiglottic cartilages. This scoping review aims to understand the extent of evidence on the epidemiology, clinical characteristics, morbidity, and recurrence of the laryngeal chondroma (LC).Data sourcesMEDLINE (Ovid), Embase (Elsevier), Web of Science (Clarivate), Cochrane Central Register of Controlled Trials and Systematic Reviews, Lilacs, Scopus, and Google Scholar databases.Review methodsThe scoping review was conducted from 1816 to 2023, for observational studies describing LC. Titles and abstracts were screened for relevance, followed by an evaluation of the full text for eligibility. The data were collected from the qualifying articles, and a narrative summary of the outcomes was prepared.ResultsOne hundred and nineteen studies met the inclusion criteria. Ninety‐four case reports, 22 case series, and 3 cohorts. Two hundred and four participants with a diagnosis of LC were described. Male:female ratio was 2.8:1. The most common localization was the cricoid (113; 47.08%), followed by the thyroid (45; 18.75%), and the arytenoid cartilage (27; 11.25%). Dyspnea (78.85%) and hoarseness (74.28%) were the most reported symptoms. The recurrence rate was 11.25%, and complications were uncommon following the resection.ConclusionThis scoping review found a low‐frequency rate over all the cartilaginous laryngeal tumors. Most patients were treated with resection, with a low rate of malignancy conversion. This population has low attributable mortality, morbidity, and recurrence according to the current literature.