Old plasma dilution reduces human biological age: a clinical study.

This work extrapolates to humans the previous animal studies on blood heterochronicity and establishes a novel direct measurement of biological age. Our results support the hypothesis that, similar to mice, human aging is driven by age-imposed systemic molecular excess, the attenuation of which reverses biological age, defined in our work as a deregulation (noise) of 10 novel protein biomarkers. The results on biological age are strongly supported by the data, which demonstrates that rounds of therapeutic plasma exchange (TPE) promote a global shift to a younger systemic proteome, including youthfully restored pro-regenerative, anticancer, and apoptotic regulators and a youthful profile of myeloid/lymphoid markers in circulating cells, which have reduced cellular senescence and lower DNA damage. Mechanistically, the circulatory regulators of the JAK-STAT, MAPK, TGF-beta, NF-κB, and Toll-like receptor signaling pathways become more youthfully balanced through normalization of TLR4, which we define as a nodal point of this molecular rejuvenation. The significance of our findings is confirmed through big-data gene expression studies.

Case Report: Therapeutic and immunomodulatory effects of plasmapheresis in long-haul COVID.

Many patients with COVID-19 experience a range of debilitating symptoms months after being infected, a syndrome termed long-haul COVID. A 68-year-old male presented with lung opacity, fatigue, physical and cognitive weaknesses, loss of smell and lymphocytopenia. After rounds of therapeutic plasma exchange (TPE), the patient returned to normal activities and work. Mechanistically in the patient's peripheral blood mononuclear cells (PBMCs), markers of inflammatory macrophages diminished and markers of lymphocytes, including natural killer (NK) cells and cytotoxic CD8 T-cells, increased. Circulating inflammatory proteins diminished, while positive regulators of tissue repair increased. This case study suggests that TPE has the capacity to treat long-haul COVID.

Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin.

Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a "neutral" age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.

Stylocarotid artery syndrome.

Stylocarotid artery syndrome is a rare condition that results from compression of the internal or external carotid artery by the styloid process of the temporal bone. Here we present the case of a patient suffering from syncope, monoparesis of the right arm, and dysarthria due to recurrent transient ischemic attacks that resulted from severe compression of the midsegment of the left extracranial internal carotid artery between an elongated styloid process and a C2 vertebral body osteophyte. This case demonstrates successful surgical management of a condition rarely encountered by the vascular surgeon.

A case of intra-operative ventricular fibrillation: Electro-cauterization, undiagnosed Takotsubo cardiomyopathy or long QT syndrome?

INTRODUCTION: Cardiac arrest in the perioperative setting is an extremely serious event that is estimated to occur between 4.6 and 19.7 per 10,000 anesthetics.(1-5) While risk factors for cardiac complications can be identified pre- operatively, in many cases workup of risk factors are not indicated by standard pre-operative testing guidelines. PRESENTATION OF CASE: We present a case of a 47-year-old female undergoing an elective bilateral mastectomy who suddenly converted to ventricular fibrillation. While ventricular fibrillation is not a unique finding, our search for its etiology revealed two previously undiagnosed cardiac conditions, and possible electro- cautery induced ventricular fibrillation. DISCUSSION: In this case study, we discuss the possible etiology of ventricular fibrillation in our patient and highlight the importance pre-operative patient investigation and history provide. CONCLUSION: Searching for the potential causes that may have contributed to the cardiac arrest is an extremely useful exercise as it allows us to better prepare patients pre-operatively, improve intra-operative care, and prevent future cardiac events.

Cerebral hyperperfusion syndrome after carotid intervention: a review.

Cerebral hyperperfusion syndrome (CHS) after carotid surgery, although rare, is a well-described phenomenon. Although originally described after carotid endarterectomy, it has now also been described after carotid artery stenting. It is classically described as an acute neurologic deficit occurring several days after a carotid procedure, associated with severe hypertension and preceded by a severe headache. CHS represents a spectrum of clinical symptoms ranging from severe unilateral headache, to seizures and focal neurologic defects, to intracerebral hemorrhage in its most severe form. The exact mechanism leading to CHS is unknown; however, it seems to be related to increased regional cerebral blood flow secondary to loss of cerebrovascular autoregulation. Given the significant morbidity associated with CHS, researchers have been trying to identify which patients are most at risk. This is a difficult task given the rarity of the disease and the multiple confounding factors in the patient population who undergo carotid intervention. The goal was to determine those patients most at risk preoperatively, so that they may be more closely monitored postoperatively to prevent the development of CHS and its associated morbidity. The purpose of this review was to summarize the data currently available in the literature on CHS, with emphasis on pathophysiology, risk factor assessment, diagnostic modalities, and disease management, to provide insight for future research to better elucidate how to reduce the morbidity and mortality caused by CHS.

Detection of transient events in the presence of background noise.

We describe a method to detect and count transient burstlike signals in the presence of a significant stationary noise. To discriminate a transient signal from the background noise, an optimum threshold is determined using an iterative algorithm that yields the probability distribution of the background noise. Knowledge of the probability distribution of the noise then allows the determination of the number of transient events with a quantifiable error (wrong-positives). We apply the method, which does not rely on the choice of free parameters, to the detection and counting of transient single-molecule fluorescence events in the presence of a strong background noise. The method will be of importance in various ultra sensing applications.