A predominately pulmonary activation of complement in a mouse model of severe COVID-19.

Evidence from in vitro studies and observational human disease data suggest the complement system plays a significant role in SARS-CoV-2 pathogenesis, although how complement dysregulation develops in patients with severe COVID-19 is unknown. Here, using a mouse-adapted SARS-CoV-2 virus (SARS2-N501YMA30) and a mouse model of severe COVID-19, we identify significant serologic and pulmonary complement activation following infection. We observed C3 activation in airway and alveolar epithelia, and in pulmonary vascular endothelia. Our evidence suggests that while the alternative pathway is the primary route of complement activation, components of both the alternative and classical pathways are produced locally by respiratory epithelial cells following infection, and increased in primary cultures of human airway epithelia in response to cytokine exposure. This locally generated complement response appears to precede and subsequently drive lung injury and inflammation. Results from this mouse model recapitulate findings in humans, which suggest sex-specific variance in complement activation, with predilection for increased C3 activity in males, a finding that may correlate with more severe disease. Our findings indicate that complement activation is a defining feature of severe COVID-19 in mice and lay the foundation for further investigation into the role of complement in COVID-19.

Proximal femoral fractures. A perspective from developing countries.

The approach to hip fractures in the developing world has been reviewed to give perspective to the problem on a larger scale. Hip fracture treatment in the developing world is a paradigm for treatment of other orthopedic problems as well as for medical care in general. The most successful approach has been to use the resources as sparingly as possible so as to provide care for the greatest number of people. Reliance on simpler, more basic techniques of nonoperative treatment reduces the complication rate and seems to provide a safer, more cost-effective approach, but the nonunion rate may be 30%-70%. The situation in which technical development exceeds resources is not unique to the developing world, although it is perhaps more apparent there because of a lower resource level. The "developed" world faces the same dilemma, the only real difference perhaps being a higher minimum. Probably no society today can provide the medical care it is technically capable of producing for all of its members. When viewed from a world-wide scale, the task of providing high-technology medical care seems daunting indeed. Development of more sophisticated, expensive technology may not be the appropriate direction; a more fundamental or preventive approach might in the long run be the most effective.

Standardizing methods of measurement of foot shape by including the effects of subtalar rotation.

At the present time, there is no easily performed method of measuring foot shape that can quantitatively differentiate types of feet. We studied 44 feet of individuals with normal appearing asymptomatic feet and flat symptomatic feet to find criteria for measurement of foot shape. We found that measurements of footprints are unreliable. Radiographic methods must include measurements in different positions, or at least specify the position of subtalar rotation to be meaningful, since the height of the arch can change just by rotating the tibia. Traditional measurements of talocalcaneal angles have no precision and are unreproducible.

Posterior roentgenogram of the foot.

A present there is no reliable way to define the position of the heel in relationship to the tibia during weight bearing. Many surgical and nonsurgical procedures are done to correct a varus or valgus heel without a standard method to define the problem or measure the results. This is a report on a posterior roentgenographic technique which defines the position of the heel with respect to the talus, tibia, and forefoot. This technique allows for measurement of the position of the heel and can be performed in any X-ray facility.

Indicators of recovery from fractures of the hip.

Patients with similar injuries who were at a similar level of function before the injury differ in the extent of recovery. In an attempt to identify important factors that affect recovery, we collected extensive physical, psychological and sociological data on a group of 108 elderly people with fractures of the hip in order to study the influence of the many variables on their recovery. We found that of all the items studied, those that best indicated the degree of recovery were: (1) the physical therapist's rating of functional ability; (2) how often the patient got outside the home prior to injury; (3) the patient's mental clarity.