Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This article outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.     

Subjective Cognitive Complaints and Functional Disability in Patients With Borderline Personality Disorder and Their Nonaffected First-Degree Relatives

Objective:

To examine the contributions of subjective cognitive complaints to functional disability in patients with borderline personality disorder (BPD) and their nonaffected relatives.

Method:

Patients with BPD (n = 26), their first-degree biological relatives (n = 17), and nonpsychiatric control subjects (n = 31) completed a self-report measure of cognitive difficulties and rated the severity of their functional disability on the World Health Organization Disability Assessment Schedule 2.0.

Results:

After accounting for group differences in age and severity of depressive symptoms, patients and relatives endorsed more inattention and memory problems than control subjects. Whereas probands reported greater disability than relatives and control subjects across all functional domains, relatives described more difficulties than control subjects in managing multiple life activities, including domestic activities and occupational and academic functioning, and participating in society. For both probands and relatives, inattention and memory problems were linked primarily to difficulties with life activities, independent of depression and other comorbid psychiatric disorders.

Conclusions:

Problems with inattention and forgetfulness may lead to difficulties carrying out activities of daily living and occupational or academic problems in patients with BPD, as well as their nonaffected first-degree relatives.     

Outcome after major dissection during coronary angioplasty using the perfusion balloon catheter

Coronary artery dissection is an infrequent but serious complication of coronary angioplasty that can lead to periprocedural vessel occlusion, emergency bypass surgery, myocardial infarction or death. Recently, a perfusion balloon catheter was developed that permits passive perfusion of blood through the central lumen of the catheter. It enables prolonged balloon inflations to be performed and has been used to provide distal blood flow after coronary occlusion. To evaluate the effectiveness of the perfusion balloon catheter in patients with major coronary dissections, 36 consecutive patients treated with the perfusion balloon catheter were compared with 46 consecutive patients treated before its availability. The 2 groups were similar in terms of clinical, angiographic and initial procedural characteristics. Use of the perfusion balloon catheter permitted a significantly longer inflation than standard balloon inflation (average 18 +/- 5 min). Angiographic success was significantly greater with the perfusion balloon catheter (84 vs 62% for conventional therapy), whereas complications were markedly reduced (48 vs 78%). With the perfusion balloon catheter there were fewer deaths (2 vs 6%), myocardial infarctions (14 vs 40%) and emergency bypass operations (11 vs 25%). The findings of this retrospective comparison demonstrate that the perfusion balloon catheter is effective for the management of major dissections after coronary angioplasty. The use of the perfusion balloon catheter should be considered when a major coronary dissection occurs and when emergency bypass surgery is contemplated.     

Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage,etiology and vaccination

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.     

Dermoscopy of an acral congenital melanocytic nevus

Congenital melanocytic nevi carry a risk for malignant transformation into melanoma, therefore early detection of suspicious features is crucial to reduce mortality rates. Dermoscopy improves the early detection of melanoma while reducing the number of unnecessary excisions of benign pigmented skin lesions. Dermoscopically, congenital melanocytic nevi are often characterized by the presence of a cobblestone pattern, but to date, little is known about the dermoscopic features of acral congenital melanocytic nevi. We report an acral congenital melanocytic nevus typified by the presence of three different dermoscopic patterns that are commonly seen in acquired melanocytic nevi of palms and soles.     

Optical computation of a spin glass dynamics with tunable complexity

Spin glasses (SGs) are paradigmatic models for physical, computer science, biological, and social systems. The problem of studying the dynamics for SG models is nondetermistic polynomial-time (NP) hard; that is, no algorithm solves it in polynomial time. Here we implement the optical simulation of an SG, exploiting the N segments of a wavefront-shaping device to play the role of the spin variables, combining the interference downstream of a scattering material to implement the random couplings between the spins (the Jij matrix) and measuring the light intensity on a number P of targets to retrieve the energy of the system. By implementing a plain Metropolis algorithm, we are able to simulate the spin model dynamics, while the degree of complexity of the potential energy landscape and the region of phase diagram explored are user defined, acting on the ratio P/N=α . We study experimentally, numerically, and analytically this Hopfield-like system displaying a paramagnetic, ferromagnetic, and SG phase, and we demonstrate that the transition temperature Tg to the glassy phase from the paramagnetic phase grows with α . We demonstrate the computational advantage of the optical SG where interaction terms are realized simultaneously when the independent light rays interfere on the detector’s surface. This inherently parallel measurement of the energy provides a speedup with respect to purely in silico simulations scaling with N .

The solution of large combinatorial problems demands novel hardware architectures enabling faster and inherently parallel calculation. An emerging trend is that of pairing an optical layer with a specific digital or analog computation scheme, in order to improve performance while reducing computational costs and processing times. Optical computing promises parallel processing and high bandwidth that may be eventually performed in free space, with limited power consumption (e.g., Fourier transform performed by a lens). Optical computation is an emerging scheme in quantum transport (1), quantum simulation (2), and machine learning (3), and can be implemented on different platforms including free space, photonic chips (4), and optical fibers (5). One of the advantages brought by optics is that certain operations can be performed at the “speed of light.” Indeed, the evaluation of a matrix product can be estimated in the time needed for a properly shaped light beam to pass through a diffractive pattern opportunely tailored to mimic the requested transfer matrix (6). By exploiting last-generation optical modulation devices, millions of light rays can be driven simultaneously between several states and within a microsecond time frame, thus potentially providing a scalable optical platform that only needs to be properly projected onto the relevant and computationally hard problem.Spin glasses (7) serve as prototype models, capable of providing nontrivial equilibrium and off-equilibrium phenomenology (8, 9). In particular, the dynamics in an energy landscape with many equilibrium states and the origin of (multiple) relaxation times in finite dimensional systems are open questions in modern statistical mechanics (10 –13). Complex systems from diverse fields fall into the spin glass universality class, like, for example, brain functions (14), random lasers (15, 16), and quantum chromodynamics (17). Indeed, novel methods for the calculation of the equilibrium states and of the dynamics of a spin glass system are highly desiderate.Here we propose an optical system able to compute the energy of a given spin glass state. We integrated such an optical layer onto a standard digital computation layer to realize an optical spin glass (OSG) dynamics simulation. Our idea stems from the observation that the overall intensity I=∑ν=1PI(ν) [1]at P given points (ν) on a screen placed at the downstream of a strongly scattering medium shone with N coherent light rays from a single laser can be formally written as a spin glass Hamiltonian. Thus scattering, coupled with an adaptive optical element, has been proposed as an instrument to access the spin glass dynamics and employed for low-complexity (small P values) simulations (18). This approach is revealed to be very promising and has been successively employed to find ground-state transmission matrices (19).     

Suppressing T cell motility induced by anti–CTLA-4 monotherapy improves antitumor effects

A promising strategy for cancer immunotherapy is to disrupt key pathways regulating immune tolerance, such as cytotoxic T lymphocyte–associated protein 4 (CTLA-4). However, the determinants of response to anti–CTLA-4 mAb treatment remain incompletely understood. In murine models, anti–CTLA-4 mAbs alone fail to induce effective immune responses to poorly immunogenic tumors but are successful when combined with additional interventions, including local ionizing radiation (IR) therapy. We employed an established model based on control of a mouse carcinoma cell line to study endogenous tumor-infiltrating CD8⁺ T lymphocytes (TILs) following treatment with the anti–CTLA-4 mAb 9H10. Alone, 9H10 monotherapy reversed the arrest of TILs with carcinoma cells in vivo. In contrast, the combination of 9H10 and IR restored MHC class I–dependent arrest. After implantation, the carcinoma cells had reduced expression of retinoic acid early inducible–1 (RAE-1), a ligand for natural killer cell group 2D (NKG2D) receptor. We found that RAE-1 expression was induced by IR in vivo and that anti-NKG2D mAb blocked the TIL arrest induced by IR/9H10 combination therapy. These results demonstrate that anti–CTLA-4 mAb therapy induces motility of TIL and that NKG2D ligation offsets this effect to enhance TILs arrest and antitumor activity.