A near-miss diagnosis of necrotizing breast fasciitis complicated by atrial fibrillation secondary to septic focus: a case report and brief review of literature.

Necrotizing fasciitis of the breast is a rare, life-threatening entity characterized by a rapidly aggressive infection of the soft tissue. There are few literature reports on necrotizing fasciitis at the level of the breast tissue as the most common locations are within the abdominal wall or extremities, but this entity can lead to sepsis and systemic multiorgan failure if not adequately managed. Here, we report a case that highlights the course of a 68-year-old African American female with a past medical history of hypertension, hyperlipidemia, and poorly controlled diabetes mellitus, who presented with the complaint of a painful right breast abscess with intermittent, purulent drainage. An initial point-of-care ultrasound displayed an area of induration of the right breast as well as soft tissue edema with no identifiable fluid collection. A subsequent CT abdomen and pelvis was obtained given new onset abdominal pain, which demonstrated incidental findings of inflammatory changes and subcutaneous emphysema along with colonic diverticulosis. Surgical intervention was immediately sought for which she underwent debridement and exploration of the right breast with findings that were consistent with necrotizing transformation. The patient was sent back to the OR for an additional surgical debridement the next day. Of note, the patient had post-op atrial fibrillation with rapid ventricular response and had to be admitted to the ICU for conversion to sinus rhythm. She returned to sinus rhythm and was transferred back to medicine before application of a negative pressure wound dressing on discharge. The patient was transitioned from Enoxaparin to Apixaban for anticoagulation control in the setting of atrial fibrillation before being discharged to a Skilled Nursing Facility with long-term antibiotics. This case highlights the difficulty and significance in establishing a prompt diagnosis for necrotizing fasciitis.

Pumping the brakes: rostromedial tegmental inhibition of compulsive cocaine seeking.

Addiction is marked by aberrant decision-making and an inability to suppress inappropriate and often dangerous behaviors. We previously demonstrated that inactivation of the rostromedial tegmental nucleus (RMTg) in rats causes persistent food seeking despite impending aversive footshock, an effect strikingly similar to the punishment resistance observed in people with a history of protracted drug use [1]. Here, we extend these studies to demonstrate chemogenetic silencing of RMTg axonal projections to the ventral tegmental area (VTA) (RMTg→VTA pathway) causes rats to endure significantly more footshock to receive cocaine infusions. To further test whether activation of this circuit is sufficient to suppress reward seeking in the absence of an overtly aversive stimulus, we used temporally specific optogenetic stimulation of the RMTg→VTA pathway as a "punisher" in place of footshock following lever pressing for either food or cocaine reward. While optical stimulation of the RMTg→VTA pathway robustly suppressed lever pressing for food, we found that stimulation of this circuit had only modest effects on suppressing responding for cocaine infusions. Even though optical RMTg→VTA stimulation was not particularly effective at reducing ongoing cocaine use, this experience nevertheless had long-lasting consequences, as reinstatement of drug seeking in response to cocaine-associated cues was profoundly suppressed when tested nearly two weeks later. These results suggest the RMTg may serve as a useful target for producing enduring reductions in drug craving, particularly during periods of abstinence from drug use.

Multicenter investigation of technical and clinical outcomes after thrombectomy for Proximal Medium Vessel Occlusion (pMeVO) by frontline technique.

BACKGROUND: Endovascular thrombectomy(EVT) is the standard of care for large vessel occlusion(LVO) stroke. Data on technical and clinical outcome in proximal medium vessel occlusions(pMeVOs) comparing frontline techniques remain limited. METHODS: We report an international multicenter retrospective study of patients undergoing EVT for stroke at 32 centers between 2015-2021. Patients were divided into LVOs(ICA/M1/Vertebrobasilar) or pMeVOs(M2/A1/P1) and categorized by thrombectomy technique. Primary outcome was 90-day good functional outcome(mRS ≤ 2). Multivariate logistic regressions were used to evaluate the impact of technical variables on clinical outcomes. Propensity score matching was used to compare outcome in patients with pMeVO treated with aspiration versus stent-retriever. RESULTS: In the cohort of 5977 LVO and 1287 pMeVO patients, pMeVO did not independently predict good-outcome(p = 0.55). In pMeVO patients, successful recanalization irrespective of frontline technique(aOR = 3.2,p < 0.05), procedure time ≤ 1-h(aOR = 2.2,p < 0.05), and thrombectomy attempts ≤ 4(aOR = 2.8,p < 0.05) were independent predictors of good-outcomes.In a propensity-matched cohort of aspiration versus stent-retriever pMeVO patients, there was no difference in good-outcomes. The rates of hemorrhage were higher(9%vs.4%,p < 0.01) and procedure time longer(51-min vs. 33-min,p < 0.01) with stent-retriever, while the number of attempts was higher with aspiration(2.5vs.2,p < 0.01). Rates of hemorrhage and good-outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group compared to attempts in the stent-retriever group. CONCLUSIONS: Clinical outcomes following EVT for pMeVO are comparable to those in LVOs. The golden hour or 3-pass rules in LVO thrombectomy still apply to pMeVO thrombectomy. Different techniques may exhibit different futility metrics; SR thrombectomy was more influenced by attempts whereas aspiration was more dependent on procedure time.

Impact of Increasing Aspiration Catheter Size and Refinement of Technique: Experience of Over 1000 Strokes Treated With ADAPT.

BACKGROUND: We present longitudinal data regarding the outcomes and evolution of mechanical thrombectomy (MT) using a direct aspiration first pass technique. OBJECTIVE: To evaluate the impact of increasing aspiration catheter size. METHODS: This is a planned analysis of a prospective cohort study that enrolled all patients who underwent a direct aspiration first pass technique MT in a comprehensive stroke center from January 2013 to December 2020. We did exploratory analysis of the characteristics and outcomes of patients who had intracranial internal carotid artery or M1 segment of middle cerebral artery occlusion based on the aspiration catheter bore size (small [041, 054, 058, and 060 inch] vs medium [0.064 and 0.068 inch] and medium vs large [0.071, 0.072, and 0.074 inch]). RESULTS: During the 8-year study period, a total of 1004 patients were included. Median age was 69 years, 49% were female patients, and 60.6% were White. Symptomatic hemorrhagic transformation was observed in 47 patients (4.7%), and 366 patients (36.5%) achieved the modified Rankin scale of 0 to 2 at 90 days after the stroke. For patients with intracranial internal carotid artery or M1 occlusion, medium-bore aspiration catheters were more likely to achieve successful recanalization after first aspiration attempt (63.9% vs 51.4%, P = .015) and had a faster groin-to-reperfusion time (16 vs 20 minutes, P = .001) when compared with small-bore catheters. However, these differences were not significant when comparing medium-bore with large-bore catheters. CONCLUSION: Medium-bore catheters had better performance measures compared with small-bore catheters. However, large-bore catheters did not show significantly better performance results that suggest a plateau effect.

Entopeduncular Nucleus Projections to the Lateral Habenula Contribute to Cocaine Avoidance.

The aversive properties associated with drugs of abuse influence both the development of addiction and relapse. Cocaine produces strong aversive effects after rewarding effects wear off, accompanied by increased firing in the lateral habenula (LHb) that contributes to downstream activation of the rostromedial tegmental nucleus (RMTg). However, the sources of this LHb activation are unknown, as the LHb receives many excitatory inputs whose contributions to cocaine aversion remain uncharacterized. Using cFos activation and in vivo electrophysiology in male rats, we demonstrated that the rostral entopeduncular nucleus (rEPN) was the most responsive region to cocaine among LHb afferents examined and that single cocaine infusions induced biphasic responses in rEPN neurons, with inhibition during cocaine's initial rewarding phase transitioning to excitation during cocaine's delayed aversive phase. Furthermore, rEPN lesions reduced cocaine-induced cFos activation by 2-fold in the LHb and by a smaller proportion in the RMTg, while inactivation of the rEPN or the rEPN-LHb pathway attenuated cocaine avoidance behaviors measured by an operant runway task and by conditioned place aversion (CPA). These data show an essential but not exclusive role of rEPN and its projections to the LHb in processing the aversive effects of cocaine, which could serve as a novel target for addiction vulnerability.SIGNIFICANCE STATEMENT Cocaine produces well-known rewarding effects but also strong aversive effects that influence addiction propensity, but whose mechanisms are poorly understood. We had previously reported that the lateral habenula (LHb) is activated by cocaine and contributes to cocaine's aversive effects, and the current findings show that the rostral entopeduncular nucleus (rEPN) is a major contributor to this LHb activation and to conditioned avoidance of cocaine. These findings show a critical, though not exclusive, rEPN role in cocaine's aversive effects, and shed light on the development of addiction.

Three Rostromedial Tegmental Afferents Drive Triply Dissociable Aspects of Punishment Learning and Aversive Valence Encoding.

Persistence of reward seeking despite punishment or other negative consequences is a defining feature of mania and addiction, and numerous brain regions have been implicated in such punishment learning, but in disparate ways that are difficult to reconcile. We now show that the ability of an aversive punisher to inhibit reward seeking depends on coordinated activity of three distinct afferents to the rostromedial tegmental nucleus (RMTg) arising from cortex, brainstem, and habenula that drive triply dissociable RMTg responses to aversive cues, outcomes, and prediction errors, respectively. These three pathways drive correspondingly dissociable aspects of punishment learning. The RMTg in turn drives negative, but not positive, valence encoding patterns in the ventral tegmental area (VTA). Hence, punishment learning involves pathways and functions that are highly distinct, yet tightly coordinated.

Valence-encoding in the lateral habenula arises from the entopeduncular region.

Lateral habenula (LHb) neurons are activated by negative motivational stimuli and play key roles in the pathophysiology of depression. Prior reports suggested that rostral entopeduncular nucleus (rEPN) neurons drive these responses in the LHb and rostromedial tegmental nucleus (RMTg), but these influences remain untested. Using rabies viral tracers, we demonstrate disynaptic projections from the rEPN to RMTg, but not VTA, via the LHb in rats. Using in vivo electrophysiology, we find that rEPN or LHb subpopulations exhibit activation/inhibition patterns after negative/positive motivational stimuli, similar to the RMTg, while temporary inactivation of a region centered on the rEPN decreases LHb basal and burst firing, and reduces valence-related signals in LHb neurons. Additionally, excitotoxic rEPN lesions partly diminish footshock-induced cFos in the LHb and RMTg. Together, our findings indicate an important role of the rEPN, and possibly immediately adjacent hypothalamus, in driving basal activities and valence processing in LHb and RMTg neurons.

Generality and opponency of rostromedial tegmental (RMTg) roles in valence processing.

The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has been hypothesized to be broadly activated by aversive stimuli. However, this encoding pattern has only been demonstrated for a limited number of stimuli, and the RMTg influence on ventral tegmental (VTA) responses to aversive stimuli is untested. Here, we found that RMTg neurons are broadly excited by aversive stimuli of different sensory modalities and inhibited by reward-related stimuli. These stimuli include visual, auditory, somatosensory and chemical aversive stimuli, as well as "opponent" motivational states induced by removal of sustained rewarding or aversive stimuli. These patterns are consistent with broad encoding of negative valence in a subset of RMTg neurons. We further found that valence-encoding RMTg neurons preferentially project to the DA-rich VTA versus other targets, and excitotoxic RMTg lesions greatly reduce aversive stimulus-induced inhibitions in VTA neurons, particularly putative DA neurons, while also impairing conditioned place aversion to multiple aversive stimuli. Together, our findings indicate a broad RMTg role in encoding aversion and driving VTA responses and behavior.