Opposing effects of mu opioid receptors on dopamine D1 and D2 receptor expressing neurons in opioid mediated antinociception

There is extensive interaction between systems involved in pain processing and motivation, where the aberrant functioning of salience circuits likely contributes to chronic pain, as well as increased susceptibility to opioid misuse and opioid use disorder. This study asks to what extent mu opioid receptors (MORs) in dopamine D1 receptor (D1R), D2 receptor (D2R) or adenosine A2a receptor (A2aR) expressing neurons contribute to the expression of pain and opioid antinociception. We ablated MORs in dopamine receptor expressing neurons by breeding D1R, D2R or A2aR-cre with MORloxP mice, which was confirmed by RNAscope multiplex fluorescent in situ hybridization. To determine the role of these MORs in nociception, we assessed the nociceptive responses in the hot plate and formalin tests with and without treatment with oxycodone (3 mg/kg, i.p.). Pain-like behavior in a thermal assay, mechanical thresholds following nerve injury, and the formalin test were not altered by genotype. However, oxycodone-induced antinociception in the formalin test was differentially altered. Opioid antinociception was attenuated in mice that lacked MORs in D1R neurons, but was enhanced when MORs were ablated in either the D2R and A2aR neurons. In contrast, there was no effect of genotype on oxycodone-induced antinociception in the thermal nociceptive test. Together, these data show that MORs in D1R expressing neurons is necessary for opioid-induced antinociception in a model of tonic inflammatory pain, but not acute thermal pain. Whereas, MOR in D2R and A2aR expressing neurons had a tonic inhibitory tone on opioid-mediated antinociception in the formalin test. PERSPECTIVE: This article presents evidence that mu opioid receptors in dopamine receptor containing neurons differentially modulate opioid antinociception in the formalin test but not threshold evoked phasic pain. The endogenous opioid system in these neuronal populations does not appear to modulate various pain behaviors

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Spontaneous compartment syndrome of all limbs: A case report

Compartment syndrome is a serious condition that results from increased pressure in a closed muscle compartment segment, which affects tissue perfusion and leads to necrosis. It can be acute because of fracture and crush injury or chronic due to recurrent transient increases in the intra-compartmental pressure that occurs during exertional activities. Rhabdomyolysis is a rare cause of compartment syndrome; clinicians should be aware of different atypical presentations of compartment syndrome and should have a low threshold for such a case. Early diagnosis and intervention may lead to better clinical outcome and may prevent any possible complication or future morbidity and disabilities. We are presenting a rare case of spontaneous atraumatic four-limb compartment syndrome in a patient post-minimal exertion, which was managed by urgent surgical fasciotomy and compartment decompression. 29 months follow-up; patient regained full function of both upper extremity without residual motor or sensory deficit, while he had bilateral foot drop without sensory deficit, and he was walking using bilateral ankle foot orthotic (AFO). We hypothesize that his compartment syndrome developed due to rhabdomyolysis, which was extenuated by dehydration.</jats:p

Nosebleed No More: Recognizing and Diagnosing Factor VIII Inhibitor

Acquired hemophilia is a condition characterized by the unexpected onset of severe bleeding due to an issue with coagulation factors. Typically, this disorder results from the production of autoantibodies against the Factor VIII coagulation factor. Although acquired hemophilia is an extremely rare condition, with an annual incidence of just 1.5 cases per million, it is crucial to recognize and understand it. This is because diagnosing this disorder is intricate, and if left undiagnosed and untreated, it can lead to high levels of morbidity and mortality. This case stands out as the condition typically targets older adults, with around 80% of patients being 65 years or older, with the median age ranging from 73.9 years to 78 years. In this particular case, the patient is a 56-year-old Hispanic female. This underscores the importance of considering this diagnosis in younger individuals as well, as it can impact those under the age of 65. Acquired hemophilia provides valuable lessons for healthcare providers and remains an intriguing subject for ongoing research, as there are still many aspects of this condition that continue to elude our full understanding. Notably, nearly half of the diagnosed cases of acquired hemophilia have no identifiable cause or precipitating factor. Meanwhile, the other half encompasses a wide range of etiologies, with the most common cause, accounting for approximately 17-18% of cases, being the association with immunologic disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and various other autoimmune diseases

The Association Between Gender and Clinical Outcomes in Patients With Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Introduction Traumatic brain injuries (TBIs) are a significant cause of morbidity and mortality in the United States. but have a disproportionate impact on patients based on gender. This systematic review and meta-analysis aim to compare gender differences in clinical outcomes between male and female adult trauma patients with moderate and severe TBI. Methods Studies assessing gender differences in outcomes following TBIs on PubMed, Google Scholar, EMBASE, and ProQuest were searched. Meta-analysis was performed for outcomes including in-hospital mortality, hospital length of stay, intensive care unit length of stay, and Glasgow outcome scale (GOS) at 6 mo. Results Eight studies were included for analysis with 26,408 female and 63,393 male patients. Meta-analysis demonstrated that males had a significantly lower risk of mortality than females (RR: 0.88; 95% CI 0.78, 0.99; P = 0.0001). Females had a shorter hospital length of stay (mean difference −1.4 d; 95% CI - 1.6 d, −1.2 d). No significant differences were identified in intensive care unit length of stay (mean difference −3.0 d; 95% CI -7.0 d, 1.1 d; P = 0.94) or GOS at 6 mo (mean difference 0.2 d; 95% CI -0.9 d, 1.4 d; P = 1). Conclusions Compared to male patients, female patients with moderate and severe TBI had a significantly higher in-hospital mortality risk. There were no significant differences in long-term outcomes between genders based on GOS at 6 mo. These findings warrant further investigation into the etiology of these gender disparities and their impact on additional clinical outcome measures