Citations

Abstract Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Methods Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron’s papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). Results In total 1054 patients were included (DM, n = 405; ASyS, n = 649). In the ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic’s hands, Raynaud’s phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P < 0.001), whereas higher frequency of any of four DM-type rashes—heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V-sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%)—differentiated DM from ASyS-DMskin (all P < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both P < 0.001). Conclusion DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Background: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. Aim: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. Methods: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. Results: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). Conclusions: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

BACKGROUND Intraneural cysts involving the tibial nerve in the knee region (popliteal fossa) are rare. According to the articular (synovial) theory, which posits a joint origin for this pathology, these cysts originate from either the superior tibiofibular joint (STFJ) or the tibiofemoral (knee) joint. As tibial intraneural cysts arising from the tibiofemoral joint remain poorly understood, the authors present 2 illustrative cases and a review of the world’s literature on all tibial intraneural ganglion cysts in the knee region. OBSERVATIONS Fourteen cases of tibial intraneural ganglion cysts arising from the tibiofemoral joint were identified in the literature. Different articular branch patterns were demonstrated, which could be explained by the varied, rich articular branch innervation at the knee. Favorable outcomes were observed in cases in which the articular branch had been disconnected and the cyst drained and were comparable to the outcomes seen in tibial intraneural ganglion cysts with an STFJ origin. LESSONS Tibial intraneural cysts in the knee region can be subdivided by their joint of origin: the STFJ or the tibiofemoral joint. Those arising from the tibiofemoral joint originate from different areas of the joint and propagate in predictable patterns, with favorable outcomes following surgical intervention when the joint connection is identified and treated. The origin of tibial intraneural cysts from the tibiofemoral joint are more complex than those originating from the STFJ but seem to have similar propagation patterns and outcomes.

Traumatic brain injury (TBI) remains a major cause of morbidity and death among the pediatric population. Timely diagnosis, however, remains a complex task because of the lack of standardized methods that permit its accurate identification. The aim of this study was to determine whether serum levels of brain injury biomarkers can be used as a diagnostic and prognostic tool in this pathology. This prospective, observational study collected and analyzed the serum concentration of neuronal injury biomarkers at enrollment, 24h and 48h post-injury, in 34 children ages 0–18 with pTBI and 19 healthy controls (HC). Biomarkers included glial fibrillary acidic protein (GFAP), neurofilament protein L (NfL), ubiquitin-C-terminal hydrolase (UCH-L1), S-100B, tau and tau phosphorylated at threonine 181 (p-tau181). Subjects were stratified by admission Glasgow Coma Scale score into two categories: a combined mild/moderate (GCS 9–15) and severe (GCS 3–8). Glasgow Outcome Scale-Extended (GOS-E) Peds was dichotomized into favorable (≤4) and unfavorable (≥5) and outcomes. Data were analyzed utilizing Prism 9 and R statistical software. The findings were as follows: 15 patients were stratified as severe TBI and 19 as mild/moderate per GCS. All biomarkers measured at enrollment were elevated compared with HC. Serum levels for all biomarkers were significantly higher in the severe TBI group compared with HC at 0, 24, and 48h. The GFAP, tau S100B, and p-tau181 had the ability to differentiate TBI severity in the mild/moderate group when measured at 0h post-injury. Tau serum levels were increased in the mild/moderate group at 24h. In addition, NfL and p-tau181 showed increased serum levels at 48h in the aforementioned GCS category. Individual biomarker performance on predicting unfavorable outcomes was measured at 0, 24, and 48h across different GOS-E Peds time points, which was significant for p-tau181 at 0h at all time points, UCH-L1 at 0h at 6–9 months and 12 months, GFAP at 48h at 12 months, NfL at 0h at 12 months, tau at 0h at 12 months and S100B at 0h at 12 months. We concluded that TBI leads to increased serum neuronal injury biomarkers during the first 0–48h post-injury. A biomarker panel measuring these proteins could aid in the early diagnosis of mild to moderate pTBI and may predict neurological outcomes across the injury spectrum.

Abstract Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethenyl)salicylic acid (SANA), a molecule with unprecedented beneficial effects in diet-induced obesity (DIO). SANA reduces DIO, liver steatosis and insulin resistance at doses up to 40 times lower than salicylate. Mechanistically, SANA stimulated mitochondrial respiration and increased creatine-dependent energy expenditure in adipose tissue. Indeed, depletion of creatine resulted in the loss of SANA action. Moreover, we found that SANA binds to creatine kinases CKMT1/2, and downregulation CKMT1 interferes with the effect of SANA in vivo. Together, these data demonstrate that SANA is a first-in-class activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue and emerges as a candidate for the treatment of diabesity.

BACKGROUND Many benign and malignant tissue or bony lesions have been reported as causes of extrinsic or intrinsic posterior interosseous nerve (PIN) neuropathy at the proximal forearm/elbow region. The authors describe an unusual cause of external compression of the PIN due to a ganglion cyst arising from a radial neck pseudarthrosis (a false joint). OBSERVATIONS Decompression of the PIN with the release of the arcade of Frohse was performed with resection of the radial head and the ganglion cyst. By 6 months postoperatively, the patient had a complete neurological recovery. LESSONS This case illustrates a previously unreported cause of extraneural compression of the PIN from a pseudarthrosis. The mechanism for compression in this case from the radial head pseudarthrosis is likely attributable to the sandwich effect, in which the PIN is sandwiched between the arcade of Frohse at the supinator from above and the cyst below.

Abstract The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1x10− 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP’s age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.

Introduction: COVID-19 pandemic has had an unprecedented impact worldwide, co-infections with neglected tropical diseases like Malaria can occur and affect the heart. Objective: Describe a unique case of Malaria and SARS CoV2 infection occurring concurrently with cardiac complications. Clinical Case: A 69-year-old male, retired canoeing athlete, with well-controlled arterial hypertension, presented odynophagia, cough, and dyspnea on slight exertion for 2 days. On examination, O2 saturation was 91%, blood pressure 100/60 mmHg, regular heart rate of 110 bpm, positive PCR for SARS-CoV-2, elevated D-Dimer, and chest X-ray with evidence of viral pneumonia. He received supplemental oxygen, steroids, and paracetamol. Two days later, he presented with choluria, afternoon episodes of high fever preceded by chills and myalgia, and a thick blood smear showed Plasmodium falciparum (PF) trophozoites. Antimalarial treatment was started with primaquine 15mg, 20 mg of artemether, and 120 mg of Lumefantrine daily with the disappearance of fever until day 14 of onset of symptoms when he presented with acute heart failure (AHF) with a reduced ejection fraction of 45%. NYHA Class IV, arterial hypotension, sudden onset palpitations, and afternoon febrile episode. The electrocardiogram showed atrial fibrillation (AF) with a rapid irregular ventricular response of 120 bpm; The echocardiogram revealed a 7mm circumferential pericardial effusion, right ventricular dysfunction. Treatment with colchicine, enoxaparin, spironolactone, and bisoprolol was started. A new thick smear demonstrated the persistence of PF. A new antimalarial regimen was restarted, with the disappearance of the fever 48 hours after its onset, with the reversion of AF to sinus rhythm. Discussion: A unique case of concurrent COVID-19 and Malaria, which cause challenges to the heart and lead to cardiovascular complications. Conclusion: An exceptional case is presented, the coexistence of SARS-CoV-2 and PF infection-associated complications of myocarditis, pericarditis, new-onset AF, and AHF. This interaction should not go unnoticed, physicians’ awareness is key, and early diagnosis and treatment can be lifesaving, mitigate and offer the best chance of cure.

Introduction: Leadless pacing(LP) technology has been expanding in recent practice as an alternative to traditional pacing This technology is associated with reduce complications such as infection, dislodgment, and hardware burden. There has been recent reports on effusions with its implantation .Historically the manufacturer has recommend bolus of heparin or infusions We present the results and operative outcomes of patients who received a LP without initial heparinization or infusion from 2016 to 2021 at a single center. Objective We sought to describe the outcomes of LP implantation without the need of heparin administration. Methods: We report the clinical outcomes and operative findings of 200 patients who underwent LP implantation without initial heparin loading or infusions . An aggressive flushing strategy of the sheaths before and during the procedures was performed Data recorded include indication, ejection fraction (EF) R waves, capture thresholds, ventricular ectopy on deployment,recaptures, procedure times, and complications. Patients on chronic anticoagulation were excluded Results: A total of 200 patients were included , average age was 77 years and 20 (10%) had a reduced EF (<40%) pre-procedure. The most common indications included complete AV block (97, 48.5%) and atrial fibrillation with slow ventricular response (76, 38%). All patients (100%) had successful establishment of ventricular pacing with no short-term complications postoperatively. Average R waves after deployment were 9.7 with average capture thresholds of 0.84 @ 0.24 Ventricular ectopy was seen for 134 (67%) of patients upon deployment with 62 (31%) patients requiring recaptures, and 29 (14.5%) requiring more than one recapture. There was no evidence of thrombus in the sheaths or implanting instruments . There were no embolic or thrombotic complications. Conclusions: LP implantation is highly effective and efficacious in establishing single-chamber ventricular pacing for a variety of conduction pathologies with minimal complications postoperatively. It appears that an aggressive flushing strategy of the implanting equipment & sheaths is safe & effective without the need of heparinization. Further studies will be require to validate this strategy

ObjectiveThis scoping review aims to explore the current body of literature to characterize how short‐term surgical trips (STSTs) in Otolaryngology‐Head and Neck Surgery (OtoHNS) contribute to surgical, educational, and sustainability‐based outcomes in low‐ and middle‐income countries (LMICs). We aim to use these data to synthesize aspects of STSTs that are successful with the hopes of shaping future global efforts.Data SourcesData sources included Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus.Review MethodsA comprehensive search was conducted on several databases from inception to October 14, 2021. We included primary studies exploring any surgical or educational outcomes of global short‐term surgical endeavors within LMICs. Data were then extracted to evaluate the heterogenous body of literature that exists, characterizing the surgical, educational, and sustainability‐based outcomes.ResultsForty‐Seven studies were included in the final analysis. Most publications were focused on surgical interventions (39 of 47; 82.9%); 13 (27.7%) studies included education as the primary aim and 12 (25.5%) considered sustainability a significant aim. Of the 94 first and last authors, there were zero first authors and only one last author with an LMIC affiliation. Twenty‐six studies (55%) mentioned that any patients were seen in follow‐up, ranging from one day to five years.ConclusionOur scoping review demonstrates that most STSTs have focused primarily on surgical procedures with a lack of appropriate long‐term follow‐up. However, the available outcome‐based information presented helps identify factors that characterize a strong short‐term global surgical program.Level of EvidenceNA Laryngoscope, 134:32–39, 2024