Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.

Is Pain in the Uninjured Leg Associated With Unhelpful Thoughts and Distress Regarding Symptoms During Recovery From Lower Extremity Injury?

BACKGROUND: Patients recovering from lower extremity injuries often interpret discomfort associated with increased use of the uninjured leg as a potential indication of harm. If expressed concerns regarding contralateral leg pain are associated with unhelpful thinking regarding symptoms, they can signal orthopaedic surgeons to gently reorient these thoughts to help improve comfort and capability during recovery. QUESTIONS/PURPOSES: We asked: (1) Among people recovering from isolated traumatic lower extremity injury, is pain intensity in the uninjured leg associated with unhelpful thoughts and feelings of distress regarding symptoms, accounting for other factors? (2) Are pain intensity in the injured leg, magnitude of capability, and accommodation of pain associated with unhelpful thoughts and feelings of distress regarding symptoms? METHODS: Between February 2020 and February 2022, we enrolled 139 patients presenting for an initial evaluation or return visit for any traumatic lower extremity injury at the offices of one of three musculoskeletal specialists. Patients had the option to decline filling out our surveys, but because of the cross-sectional design, required fields on the electronic survey tools, and monitored completion, there were few declines and few incomplete surveys. The median age of participants was 41 years (IQR 32 to 58), and 48% (67 of 139) were women. Fifty percent (70 of 139) injured their right leg. Sixty-five percent (91 of 139) had operative treatment of their fracture. Patients completed measures of pain intensity in the uninjured leg, pain intensity in the injured leg, lower extremity-specific magnitude of capability, symptoms of depression, symptoms of health anxiety, catastrophic thinking, and accommodation of pain. Multivariable analysis sought factors independently associated with pain intensity in the uninjured leg, pain intensity in the injured leg, magnitude of capability, and pain accommodation, controlling for other demographic and injury-related factors. RESULTS: Greater pain intensity in the uninjured leg (regression coefficient [RC] 0.09 [95% CI 0.02 to 0.16]; p < 0.01) was moderately associated with more unhelpful thinking regarding symptoms. This indicates that for every one-unit increase in unhelpful thinking regarding symptoms on the 17-point scale we used to measure pain catastrophizing, pain intensity in the uninjured leg increases by 0.94 points on the 11-point scale that we used to measure pain intensity, holding all other independent variables constant. Greater pain intensity in the injured leg (RC 0.18 [95% CI 0.08 to 0.27]; p < 0.01) was modestly associated with more unhelpful thinking regarding symptoms. Greater pain accommodation (RC -0.25 [95% CI -0.38 to -0.12]; p < 0.01) was modestly associated with less unhelpful thinking regarding symptoms. Greater magnitude of capability was not independently associated with less unhelpful thinking regarding symptoms. CONCLUSION: A patient's report of concerns regarding pain in the uninjured limb (such as, "I'm overcompensating for the pain in my other leg") can be considered an indicator of unhelpful thinking regarding symptoms. Orthopaedic surgeons can use such reports to recognize unhelpful thinking and begin guiding patients toward healthier thoughts and behaviors. LEVEL OF EVIDENCE: Level II, prognostic study.

Is Pain in the Uninjured Arm Associated With Unhelpful Thoughts and Distress Regarding Symptoms During Recovery From Upper-Extremity Injury?

PURPOSE: During recovery from upper-extremity injury, patients sometimes express concerns regarding pain associated with increased use of the uninjured limb. Concerns about discomfort associated with increased use may represent a manifestation of unhelpful thoughts such as catastrophic thinking or kinesiophobia. We asked the following questions: (1) Among people recovering from an isolated unilateral upper-extremity injury, is pain intensity in the uninjured arm associated with unhelpful thoughts and feelings of distress regarding symptoms, accounting for other factors? (2) Is pain intensity in the injured extremity, magnitude of capability, or accommodation of pain associated with unhelpful thoughts and feelings of distress regarding symptoms? METHODS: In this cross-sectional study of new or returning patients presenting to a musculoskeletal specialist for care for an upper-extremity injury, the patients completed scales that were used to measure the following: pain intensity in the uninjured arm, pain intensity in the injured arm, upper-extremity-specific magnitude of capability, symptoms of depression, symptoms of health anxiety, catastrophic thinking, and accommodation of pain. Multivariable analysis was used to evaluate factors associated with pain intensity in the uninjured arm, pain intensity in the injured arm, magnitude of capability, and pain accommodation, controlling for other demographic and injury-related factors. RESULTS: Greater pain intensity in both uninjured and injured arms was independently associated with greater unhelpful thinking regarding symptoms. A greater magnitude of capability and pain accommodation were independently associated with less unhelpful thinking regarding symptoms. CONCLUSIONS: Given that greater pain intensity in the uninjured upper extremity is associated with greater unhelpful thinking, clinicians can be attuned to patient concerns about contralateral pain. Clinicians can facilitate recovery from upper-extremity injury by evaluating the uninjured limb as well as identifying and ameliorating unhelpful thinking regarding symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Rate of concomitant cellulitis and osteoarticular infections in a pediatric population.

Concern for infection is a common presentation in pediatric emergency departments. Clinical signs of cellulitis in pediatric patients often lead to a workup for osteoarticular infection despite a lack of evidence to suggest that the two entities commonly co-exist. With this in mind, we asked: (1) What is the rate of concomitant cellulitis and osteoarticular infections in the pediatric population? (2) What factors are associated with concomitant cellulitis and osteoarticular infections? This is a retrospective study of 482 pediatric patients who underwent MRI to evaluate for either cellulitis or an osteoarticular infection at a single tertiary care children's hospital. Data were analyzed to assess the prevalence of osteomyelitis concomitant with cellulitis in our sample population. Concomitant cellulitis and osteoarticular infection were present in 11% of all cases (53/482). Of the concomitant infections, 92% percent (49/53) were present in distal locations (Group 1) and 8% (4/53) were present in proximal locations (Group 2). Bivariate analysis showed that concomitant infections on the distal extremities were significantly more common than concomitant infections on the proximal extremities ( P < 0.001). We found that concomitant cellulitis and osteoarticular infection were (1) uncommon and (2) significantly less common when clinical signs of cellulitis were present in the proximal extremities (proximal to ankle or wrist). This suggests that advanced imaging is most appropriate for patients who present with cellulitis on the distal extremities and can be used more judiciously in patients presenting with cellulitis on the proximal extremities. Level of Evidence - Level III.

Asprosin is a centrally acting orexigenic hormone.

Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.