Anti-coagulation for COVID-19 treatment: both anti-thrombotic and anti-inflammatory?

Journal of Thrombosis and Thrombolysis - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been linked to a higher risk of mortality compared to influenza, which is mainly...     

Sport therapy for hypertension: why, how, and how much?

Exercise may prevent or reduce the effects of metabolic and cardiovascular diseases, including arterial hypertension. Both acute and chronic exercise, alone or combined with lifestyle modifications, decrease blood pressure and avoid or reduce the need for pharmacologic therapy in patients with hypertension. The hypotensive effect of exercise is observed in a large percentage of subjects, with differences due to age, sex, race, health conditions, parental history, and genetic factors. Exercise regulates autonomic nervous system activity, increases shear stress, improves nitric oxide production in endothelial cells and its bioavailability for vascular smooth muscle, up-regulates antioxidant enzymes. Endurance training is primarily effective, and resistance training can be combined with it. Low-to-moderate intensity training in sedentary patients with hypertension is necessary, and tailored programs make exercise safe and effective also in special populations. Supervised or home-based exercise programs allow a nonpharmacological reduction of hypertension and reduce risk factors, with possible beneficial effects on cardiovascular morbidity.     

Oxaliplatin-related neurotoxicity: how and why?

In early clinical trials, oxaliplatin has demonstrated significant activity against colorectal cancer in combination with 5-fluorouracil (5-FU) and folinic acid (FA), both in metastatic as in radically resected disease. The drug differs from the other two most important platinum compounds (cisplatin and carboplatin) for the absence of nephrotoxicity or for the reduced drug-induced ototoxicity. During its administration, two different types of neurological symptoms can be experienced: the first one occurs during or immediately after the end of the infusion and it appears as a transient peripheral sensory neuropathy manifesting as paresthesias and dysesthesia in the extremities sometimes accompanied by muscular contractions of the extremities or the jaw (triggered or enhanced by exposure to cold). The second one occurs after long-term administration of oxaliplatin presenting with deep sensory loss, sensory ataxia and functional impairment (similar to those observed with cisplatin). This type of neurotoxicity is usually late-onset and correlated with the cumulative-dose of oxaliplatin. The aim of this review is to analyse the mechanism underlying induction of neurotoxicity and the possible treatments to prevent and to treat it.     

Dialysis without membranes: how and why?

Dialysis between two flowing, miscible fluids without an intervening membrane enhances both the transport rate and biocompatibility. Unfortunately, it also presents serious challenges, including the loss of pressure as a driving force for volume transport, the need for sterile dialysate in greater quantity than in conventional dialysis, the possibility of unacceptable protein loss, and even the possibility of blood cell loss. This paper quantifies these advantages and disadvantages, and evaluate the means by which the latter might be surmounted. Preliminary data are provided to show that stable flows of one fluid sheathing another, miscible fluid are achievable and that molecular exchange between the fluids is orderly and in qualitative agreement with the theory. Extension of the concept to other blood purification tasks, especially in the treatment of liver failure and various macromolecular separations, is also discussed. In conclusion, membraneless separations will require a secondary process and a recycle stream. Under these conditions, its advantages can be preserved and its disadvantages controlled.     

Combination therapy for mucormycosis: why, what, and how?

The high mortality rate of mucormycosis with currently available monotherapy, particularly in hematology patients, has stimulated interest in studying novel combinations of antifungal agents to determine whether superior outcomes might be achieved. Combination lipid polyene-echinocandin therapy is the most promising of such regimens based on safety profile, the availability of parenteral formulations of echinocandins, their synergy in murine models of mucormycosis, and observational clinical data that are concordant. Other options include combination lipid polyene plus deferasirox or posaconazole therapy. Definitive, randomized, placebo-controlled phase III clinical trials are needed to determine whether combination therapy with any of these options is superior to monotherapy. Until such studies are conducted, clinicians will continue to be placed in the unacceptable position of not knowing if and when to administer combination therapy. Such a state of confusion may lead to undertreatment if combination therapy is indeed superior but is not used and, conversely, may lead to unacceptable toxicity and cost to patients if combination therapy is not superior but is used. It is critical that sponsors step forward with funding to conduct these clinical trials to determine whether outcomes from these devastating infections can be improved.     

Hydroxychloroquine for the treatment of COVID-19 and its potential cardiovascular toxicity: Hero or villain?

A variety of treatment modalities have been investigated since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic. The use of antimalarials (hydroxychloroquine and chloroquine) for COVID-19 treatment and prevention has proven to be a cautionary tale for widespread, off-label use of a medication during a crisis. The investigation of antimalarials for COVID-19 has also been a driver for a deluge of scientific output in a short amount of time. In this narrative review, we detail the evidence for and against antimalarial use in COVID-19, starting with the early small observational studies that influenced strategies worldwide. We then contrast these findings to later published larger observational studies and randomized controlled trials. We detail the emerging possible cardiovascular risks associated with antimalarial use in COVID-19 and whether COVID-19-related outcomes and cardiovascular risks may differ for antimalarials used in rheumatic diseases.     

Fatty liver: how frequent is it and why?

There is increasing evidence that fatty liver may be the most frequent liver disorder in Western countries. However, the epidemiology of fatty liver is still not fully understood and there is a clear need of better assessing and defining the potential role of the risk factors identified by clinical series in the general population. This article reviews the available data on the epidemiology of fatty liver and addresses some important questions that should be answered in much needed future research.     

School health in rural Nepal: why and how?

School health has been regarded as a high priority intervention in developing countries from the perspective of donor organizations. This paper aims to show why school health is important from the community perspective as well, and how school health programs should be implemented based on a case study by the School and Community Health Project (SCHP) in Nepal. SCHP conducted a needs assessment using a participatory rural appraisal in 28 rural communities (mean household number: 51; mean population: 352) in rural Nepal. As a result, SCHP found 70% of the target communities regarded schools as the most important institutions in their communities. Then, SCHP initiated two school health programs to meet their needs, a Supportive Healthy Environment Program and Child Initiative Program. The community members welcomed them, and all the schools successfully built toilets and water supply systems, and initiated child club activities, even though the school teachers' commitment was limited.