Confocal Assessment of Pigmented-Mucosal Lesions: A Monocentric, Retrospective Evaluation of Lip and Genital Area.

INTRODUCTION: Pigmentation of lip and/or genitalia is mainly due to the development of benign melanotic macules, with a less occurrence of melanocytic and other non-melanocytic lesions. Mucosal melanoma has worse prognosis compared with cutaneous counterpart, hence identification of atypical features for an early diagnosis is crucial. OBJECTIVES: The aim of this study was to report further data of confocal features characterizing pigmented mucosal lesions of genital area and of the lips and test the diagnostic role of the reflectance confocal microscopy (RCM)lip score. METHODS: Clinical, dermoscopic and RCM images of histologically proven pigmented lesions, involving the genital area (vulva or glans penis) and lip, were retrospectively reviewed. RCM images were evaluated for malignant criteria, and statistical analysis was conducted for categorical variables. RESULTS: Seventy pigmented lesions were included in the study and divided into two groups based on the body area location: lip (17) and genital area (53). Architectural disarray (P = 0.002), dendritic (P = 0.031) and roundish cells in epidermis (P < 0.0001), interpapillary dendritic cells (P = 0.039) and junctional atypical cells (P = 0.002) were associated to genital melanoma. Melanoma involving the lip was characterized by roundish cells in epidermis, a criterion found in one labial benign lesion, only (P = 0.005). Main limitations of the study are the inclusion of low melanomas and the presence of epidermal dendritic cells in melanosis and melanoma, as a confusing factor in imaging. CONCLUSIONS: Dermatologists should consider confocal microscopy as an adjunctive tool to dermoscopy in the differential diagnosis of pigmented mucosal lesions, especially in presence of clinical and dermoscopic findings suspicious for malignancy.

Operative strategies for acute mitral regurgitation as a mechanical complication of myocardial infarction.

Severe mitral regurgitation secondary to papillary muscle rupture is one of the mechanical complications after an acute myocardial infarction. Surgical strategies represent the cornerstone of treatment in this disease; in addition to surgical valve replacement, approaches involving surgical valve repair have been reported over time in different clinical scenarios to restore valve competency, improve cardiac function and reduce mechanical prosthesis-related risks. Moreover, in recent years, percutaneous trans-catheter procedures have emerged as an important alternative in high risk or inoperable patients.

Surgical treatment for post-infarction papillary muscle rupture: a multicentre study.

OBJECTIVES: Papillary muscle rupture (PMR) is a rare but potentially fatal complication of acute myocardial infarction. The aim of this study was to analyse the patient characteristics and early outcomes of the surgical management of post-infarction PMR from an international multicentre registry. METHODS: Patients underwent surgery for post-infarction PMR between 2001 through 2019 were retrieved from database of the CAUTION study. The primary end point was in-hospital mortality. RESULTS: A total of 214 patients were included with a mean age of 66.9 (standard deviation: 10.5) years. The posteromedial papillary muscle was the most frequent rupture location (71.9%); the rupture was complete in 67.3% of patients. Mitral valve replacement was performed in 82.7% of cases. One hundred twenty-two patients (57%) had concomitant coronary artery bypass grafting. In-hospital mortality was 24.8%. Temporal trends revealed no apparent improvement in in-hospital mortality during the study period. Multivariable analysis showed that preoperative chronic kidney disfunction [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.07-6.45, P = 0.036], cardiac arrest (OR: 3.99, 95% CI: 1.02-15.61, P = 0.046) and cardiopulmonary bypass duration (OR: 1.01, 95% CI: 1.00-1.02, P = 0.04) were independently associated with an increased risk of in-hospital death, whereas concomitant coronary artery bypass grafting was identified as an independent predictor of early survival (OR: 0.38, 95% CI: 0.16-0.92, P = 0.031). CONCLUSIONS: Surgical treatment for post-infarction PMR carries a high in-hospital mortality rate, which did not improve during the study period. Because concomitant coronary artery bypass grafting confers a survival benefit, this additional procedure should be performed, whenever possible, in an attempt to improve the outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03848429.

Right ventricular failure after left ventricular assist device implantation: a review of the literature.

Right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation remains a major complication which may significantly impair patient outcome. The genesis of RVF is, however, multifactorial, and the mechanisms underlying such a condition have not been fully elucidated, making its prevention challenging and the course not always predictable. Although preoperative risks factors can be associated with RV impairment, the physiologic changes after the LV support, can still hamper the function of the RV. Current medical treatment options are limited and sometimes, patients with a severe post-LVAD RVF may be unresponsive to pharmacological therapy and require more aggressive treatment, such as temporary RV support. We retrieved 11 publications which we assessed and divided in groups based on the RV support [extracorporeal membrane oxygenation (ECMO), right ventricular assist device (RVAD), TandemHeart with ProtekDuo cannula]. The current review comprehensively summarizes the main studies of the literature with particular attention to the RV physiology and its changes after the LVAD implantation, the predictors and prognostic score as well as the different modalities of temporary mechanical cardio-circulatory support, and its effects on patient prognosis for RVF in such a setting. In addition, it provides a decision making of the pre-, intra and post-operative management in high- and moderate- risk patients.

Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen's disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.

COVID-19 and Extracorporeal Membrane Oxygenation.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. In SARS-CoV-2 patients with refractory respiratory failure, there may be a role for veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a life-saving rescue intervention. METHODS: This review summarizes the evidence gathered until June 12, 2020; electronic databases were screened for pertinent reports on coronavirus and V-V ECMO. Search was conducted by two independent investigators; keywords used were SARS-CoV-2, COVID-19, ECMO, and extracorporeal life support (ECLS). RESULTS: Many patients with COVID-19 experience moderate symptoms and a relatively quick recovery, but others must be admitted into the intensive care unit due to severe respiratory failure and often must be mechanically ventilated. Further deterioration may require institution of extracorporeal oxygenation. Infection mechanisms may trigger "cytokine storm," an inflammatory disorder notable for multi-organ system failure; together with other metabolic and hematological changes, these amplify the changes pertinent to ECMO therapy, often exaggerating blood coagulation disorders. Thirty-two studies were found describing experiences with ECMO in the treatment of COVID-19. Of 4,912 COVID-19 patients, 2,119 (43%) developed ARDS and 2,086 (42%) were transferred to the ICU; 1,015 patients (21%) were treated with ECMO. While in an overall cohort, observed mortality was 640 (13%), the mortality within ECMO subgroups reached up to 34.6% (range 0-100%). CONCLUSION: The efficacy of ECMO treatment for COVID-19 is largely dependent on the expertise of the center in ECLS due to the interplay between the changes in hematological and inflammatory modulators associated with both COVID-19 and ECMO. In order to support gas exchange during early infection with SARS-CoV-2, ECMO has a strong rationale for the treatment of the most critically ill patients. Due to the limited resources during a global pandemic, ECMO should be reserved for only the most severe cases of COVID-19.

Mortality Predictors in Elderly Patients With Cardiogenic Shock on Venoarterial Extracorporeal Life Support. Analysis From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Because significantly higher mortality is observed in elderly patients undergoing venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock, decision-making in this setting is challenging. We aimed to elucidate predictors of unfavorable outcomes in these elderly (≥ 70 yr) patients. DESIGN: Analysis of international worldwide extracorporeal life support organization registry. SETTING: Refractory cardiogenic shock due to various etiologies (cardiac arrest excluded). PATIENTS: Elderly patients (≥ 70 yr). INTERVENTIONS: Venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Three age groups (70-74, 75-79, ≥80 yr) were in-depth analyzed. Uni- and multivariable analysis were performed. From January 1997 to December 2018, 2,644 patients greater than or equal to 70 years (1,395 [52.8%] 70-74 yr old, 858 [32.5%] 75-79 yr, and 391 [14.8%] ≥ 80 yr old) were submitted to venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock with marked increase in the most recent years. Peripheral access was applied in majority of patients. Median extracorporeal membrane oxygenation support duration was 3.5 days (interquartile range: 1.6-6.1 d), (3.9 d [3.7-4.6 d] in patients ≥ 80 yr) (p < 0.001). Weaning from extracorporeal membrane oxygenation was possible in 1,236 patients (46.7%). Overall in-hospital mortality was estimated at 68.3% with highest crude mortality rates observed in 75-79 years old subgroup (70.1%). Complications were mostly cardiovascular and bleeding, without apparent differences between subgroups. Airway pressures, 24-hour pH after extracorporeal membrane oxygenation start, extracorporeal membrane oxygenation duration, and renal replacement therapy were predictive of higher mortality. In-hospital mortality was lower in heart transplantation recipients, posttranscatheter aortic valve replacement, and pulmonary embolism; conversely, higher mortality followed extracorporeal membrane oxygenation institution after coronary artery bypass + valve and in decompensated chronic heart failure, and nearly 100% mortality followed in extracorporeal membrane oxygenation for sepsis. CONCLUSIONS: This study confirmed the remarkable increase of venoarterial extracorporeal membrane oxygenation use in elderly affected by refractory cardiogenic shock. Despite in-hospital mortality remains high, venoarterial extracorporeal membrane oxygenation should still be considered in such setting even in elderly patients, since increasing age itself was not linked to increased mortality, whereas several predictors may guide indication and management.

Reflectance confocal microscopy and its role in the follow-up of a topical treatment for lentigo maligna.

BACKGROUND: In recent years, there has been an ongoing interest in topical treatment for lentigo maligna (LM) as imiquimod 5% cream owing to the localization of this tumor and the advanced age of patients; however, the efficacy of imiquimod 5% cream is controversial, and the rate of local relapses is about 25-53%. Reflectance confocal microscopy (RCM) is a noninvasive diagnostic tool useful not only for diagnostic purpose but also for monitoring the response to the local treatment of LM. Our aim was to demonstrate the role of RCM in the follow-up of a topical treatment with imiquimod 5% cream in clinical practice. METHODS: We report three patients with histopathologically confirmed LM who were not candidates for surgery and were successfully treated with imiquimod 5% cream. In such patients, dermatoscopic images and reflectance confocal microscopy were useful to evaluate treatment response and to verify long-term clinical benefits during the follow-up visits. RESULTS: No relapses were observed in our patients 18 months after the end of treatment; although, continuous follow-up visits are needed in these patients. CONCLUSIONS: In the case series presented herein, we highlight the importance of RCM as a noninvasive tool to monitor the efficacy of imiquimod to treat LM during and after treatment. Detailed confocal images of two of our patients allowed us to establish the persistence of atypical cells and to continue treatment, although clinical and dermatoscopic examinations showed "apparent complete remission" after the first cycle of therapy.

Dynamic extracorporeal life support: A novel management modality in temporary cardio-circulatory assistance.

Extracorporeal life support (ECLS) is a temporary mechanical assistance method employed in acute respiratory, cardiocirculatory, and cardio-respiratory failure, refractory to conventional treatments. Patient's hemodynamic, respiratory and metabolic condition, or situations related to ECLS support or performance, may change during ECLS treatment. Provision of an additional drainage or perfusion cannula, or even of an additional associated device, for example, transaortic suction device or intra-aortic balloon pump (IABP), may be required to improve the ECLS/patient interaction and effects. Besides such a modified ECLS mode, however, a potential asset is represented by the "dynamic ECLS," which is the change of the flow direction (drainage or perfusion) in the already implanted cannula during the ECLS run. This particular management may be achieved in venous femoral or jugular cannulation, but it finds an even more appealing potential with the pulmonary artery (PA) cannulation. The PA allows the institution of a multitasking ECLS circuit, ranging from enhanced left ventricle (LV) unloading (drainage from the PA) to a right ventricular support or "central" veno-venous ECLS (perfusing the PA), tailored according to the patient hemodynamic, gas exchange, metabolic state, underlying cardiac involvement, and ECLS performance. Dynamic ECLS may, therefore, represent an additional option in ECLS management, particularly including the PA cannulation. Based on this new dynamic management of ECLS mode, we propose the Extracorporeal Life Support Organization nomenclature update.

Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.

COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza's characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.

Mechanical circulatory support for life-threatening arrhythmia: A systematic review.

BACKGROUND: The use of temporary mechanical circulatory support (tMCS) during arrhythmia is increasing, although available evidence for this indication is limited, with significant gaps of knowledge regarding appropriate timing, management and configuration. This systematic review sought to analyze the use of tMCS in patients with life-threatening arrhythmia. METHODS: A systematic literature search identified 2529 references published until September 2019. Adult and pediatric patients diagnosed with all kind of life-threatening arrhythmia were included. tMCS was primarily compared to conventional non-tMCS therapies. Primary outcome measure was in-hospital or 30-day mortality. RESULTS: 19 non-randomized studies were selected, including 2465 adult and 82 pediatric patients. Primary outcome in tMCS patients varied widely (4-62%) with differences based on the use of prophylactic tMCS (4-21%) or rescue tMCS (58-62%). A substantial mortality benefit was observed among high-risk patients, as identified with PAINESD risk score or suffering from electrical storm and treated with prophylactic tMCS. During ablation procedures, tMCS patients showed higher rates of induced ventricular tachycardias (VTs), ablated VTs, VT termination and non-inducibility after ablation. Extracorporeal membrane oxygenation (ECMO) was applied in pediatric cases as hemodynamic protection for aggressive antiarrhythmic medical treatment with >80% survival. CONCLUSIONS: Prophylactic tMCS is associated with improved survival as compared to rescue or no-tMCS in patients with life-threatening arrhythmia, and may be considered in patients with high PAINESD risk score or suffering from electrical storm. ECMO can be advised as rescue and support therapy in pediatric cases requiring aggressive antiarrhythmic medical treatment.

Temporary Mechanical Circulatory Support in Acute Heart Failure.

Cardiogenic shock (CS) is a challenging syndrome, associated with significant morbidity and mortality. Although pharmacological therapies are successful and can successfully control this acute cardiac illness, some patients remain refractory to drugs. Therefore, a more aggressive treatment strategy is needed. Temporary mechanical circulatory support (TCS) can be used to stabilise patients with decompensated heart failure. In the last two decades, the increased use of TCS has led to several kinds of devices becoming available. However, indications for TCS and device selection are part of a complex process. It is necessary to evaluate the severity of CS, any early and prompt haemodynamic resuscitation, prior TCS, specific patient risk factors, technical limitations and adequacy of resources and training, as well as an assessment of whether care would be futile. This article examines options for commonly used TCS devices, including intra-aortic balloon pumps, a pulsatile percutaneous ventricular assist device (the iVAC), veno-arterial extra-corporeal membrane oxygenation and Impella (Abiomed) and TandemHeart (LivaNova) percutaneous ventricular assist device.

Extracorporeal membrane oxygenation without therapeutic anticoagulation in adults: A systematic review of the current literature.

Extracorporeal membrane oxygenation is essential for the treatment of refractory cardiopulmonary failure. Its use may be complicated by worse haemorrhagic complications exacerbated by extracorporeal membrane oxygenation-related therapeutic anticoagulation. Progressive technological advancements have made extracorporeal membrane oxygenation components less thrombogenic, potentially allowing its application with temporary avoidance of systemic anticoagulants. A systematic review of all the available experiences, reporting the use of extracorporeal membrane oxygenation without systemic anticoagulation in the published literature was performed. Only patient series were included, irrespective of the clinical indication. The survival, extracorporeal membrane oxygenation system-related dysfunction and complications rates, as well as in-hospital outcome, were analysed. Six studies were selected for the analysis. Veno-arterial extracorporeal membrane oxygenation was used in 84% of patients, while veno-venous extracorporeal membrane oxygenation was applied in the remaining cases. Anticoagulation was avoided because of the high risk of bleeding after cardiac surgery (64%), active major bleeding (23%) or presence of severe traumatic injury (9%). Duration of support ranged from 0.3 to 1128 h. Heparin was antagonized by protamine in all the post-cardiotomy cases. Successfully extracorporeal membrane oxygenation weaning was achieved in 74% of the treated cases, with a hospital discharge of 58% of patients. Rates of extracorporeal membrane oxygenation malfunctioning due to clot formation and blood transfusion requirement varied remarkably in the published series. Extracorporeal membrane oxygenation without systemic anticoagulation appears feasible in selected circumstances. Further investigations are warranted to elucidate actual aspects regarding extracorporeal membrane oxygenation system performance, related adverse events and benefits associated with this management.