Citations

AbstractPersistent chest pain (PCP) following acute COVID‐19 infection is a commonly reported symptom with an unclear etiology, making its management challenging. This scoping review aims to address the knowledge gap surrounding the characteristics of PCP following COVID‐19, its causes, and potential treatments. This is a scoping review of 64 studies, including observational (prospective, retrospective, cross‐sectional, case series, and case–control) and one quasi‐experimental study, from databases including Embase, PubMed/MEDLINE, Cochrane CENTRAL, Google Scholar, Cochrane Database of Systematic Reviews, and Scopus. Studies on patients with PCP following mild, moderate, and severe COVID‐19 infection were included. Studies with patients of any age, with chest pain that persisted following acute COVID‐19 disease, irrespective of etiology or duration were included. A total of 35 studies reported PCP symptoms following COVID‐19 (0.24%–76.6%) at an average follow‐up of 3 months or longer, 12 studies at 1–3 months and 17 studies at less than 1‐month follow‐up or not specified. PCP was common following mild—severe COVID‐19 infection, and etiology was mostly not reported. Fourteen studies proposed potential etiologies including endothelial dysfunction, cardiac ischemia, vasospasm, myocarditis, cardiac arrhythmia, pneumonia, pulmonary embolism, postural tachycardia syndrome, or noted cardiac MRI (cMRI) changes. Evaluation methods included common cardiopulmonary tests, as well as less common tests such as flow‐mediated dilatation, cMRI, single‐photon emission computed tomography myocardial perfusion imaging, and cardiopulmonary exercise testing. Only one study reported a specific treatment (sulodexide). PCP is a prevalent symptom following COVID‐19 infection, with various proposed etiologies. Further research is needed to establish a better understanding of the causes and to develop targeted treatments for PCP following COVID‐19.

At the time of graduation from medical school, medical students have been exposed primarily to adult neurology and have limited exposure to child neurology. Child neurology is a unique field that encompasses caring for children with neurological conditions ranging from routine to rare. There are many opportunities for a variety of unique careers in child neurology including both in the inpatient and outpatient setting. This article aims to provide practical advice for the medical student interested in child neurology to best prepare for a successful match and rewarding career.

AbstractThe fusion of haemagglutinin‐neuraminidase (HN) protein of peste des petits ruminant (PPR) virus with signaling lymphocyte activation molecules (SLAM) host cell receptor consequences the virus entry and multiplication inside the host cell. The use of synthetic SLAM homologous peptides (i.e., molecular decoy for HN protein of PPR virus) may check PPR infection at the preliminary stage. Hence, the predicted SLAM homologous peptides using bioinformatics tools were synthesized by solid phase chemistry with standard Merrifield's 9‐fluorenylmethoxycarbonyl (Fmoc) chemistry and were purified by reverse phase high performance liquid chromatography. The secondary structures of synthesized peptides were elucidated by circular dichroism spectroscopy. The in vitro interactions of these peptides were studied through indirect Enzyme Linked Immuno Sorbent Assay (ELISA) and visual surface plasmon UV‐visible spectroscopy. The SLAM homologous peptides were able to interact with the peste des petits ruminant virus (PPRV) with varying binding efficiency. The interaction of SLAM homologous peptide with the PPR virus was ascertained by the change in the plasmon color from red wine to purple during visual detection and also by bathochromic shift in absorbance spectra under UV‐visible spectrophotometry. The cytotoxic and anti‐PPRV effect of these peptides were also evaluated in B95a cell line using PPR virus (Sungri/96). The cytotoxic concentration 50 (CC50) value of each peptide was greater than 1000 μg mL−1. The anti‐PPRV efficiency of SLAM‐22 was relatively high among SLAM homologous peptides, SLAM‐22 at 25 μg mL−1 concentration showed a reduction of more than log10 3 virus titer by priming of B95a cell line while the use of SLAM‐15 and Muco‐17 at the same concentration dropped virus titer from log10 4.8 to log10 2.5 and log10 3.1 respectively. The concentration of SLAM homologous peptide (25 μg mL−1) to exert its anti‐PPRV effect was much less than its CC50 level (>1000 μg mL−1). Therefore, the synthetic SLAM homologous peptides may prove to be better agents to target PPRV.

AbstractPeripheral T‐cell lymphoma (PTCL) is a clinically heterogeneous group that represents 10%–15% of all lymphomas. Despite improved genetic and molecular understanding, treatment outcomes for PTCL have not shown significant improvement. Although Janus kinase‐2 (JAK2) plays an important role in myeloproliferative neoplasms, the critical role of JAK isoforms in mediating prosurvival signaling in PTCL cells is not well defined. Immunohistochemical analysis of PTCL tumors (n = 96) revealed high levels of constitutively active JAK3 (pJAK3) that significantly (p < 0.04) correlated with the activation state of its canonical substrate STAT3. Furthermore, constitutive activation of JAK3 and STAT3 positively correlated, at least in part, with an oncogenic tyrosine phosphatase PTPN11. Pharmacological inhibition of JAK3 but not JAK1/JAK2 significantly (p < 0.001) decreased PTCL proliferation, survival and STAT3 activation. A sharp contrast was observed in the pJAK3 positivity between ALK+ (85.7%) versus ALK‐negative (10.0%) in human PTCL tumors and PTCL cell lines. Moreover, JAK3 and ALK reciprocally interacted in PTCL cells, forming a complex to possibly regulate STAT3 signaling. Finally, combined inhibition of JAK3 (by WHI‐P154) and ALK (by crizotinib or alectinib) significantly (p < 0.01) decreased the survival of PTCL cells as compared to either agent alone by inhibiting STAT3 downstream signaling. Collectively, our findings establish that JAK3 is a therapeutic target for a subset of PTCL, and provide rationale for the clinical evaluation of JAK3 inhibitors combined with ALK‐targeted therapy in PTCL.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that typically manifests with debilitating symptoms that progressively worsen, negatively impacting patients’ quality of life. Fatigue is a multifactorial and burdensome MF-related symptom due to its severity, persistence, and prevalence, with anemia a contributing factor and major unmet need. Clinical trials of the Janus kinase (JAK)1/JAK2/activin A receptor type 1 inhibitor momelotinib have shown consistent anemia benefits, in addition to improvements in MF-related symptoms. The phase 3 MOMENTUM trial in symptomatic and anemic patients met its primary end point, with a greater proportion having a Myelofibrosis Symptom Assessment Form (MFSAF) Total Symptom Score (TSS) reduction ≥50% at week 24 with momelotinib versus danazol. To support the positive primary end point result, we conducted longitudinal, responder, and time-to-event analyses of patient-reported outcomes from MOMENTUM, as measured by the MFSAF, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Patient-Reported Outcomes Measurement Information System (PROMIS) assessments. These analyses demonstrated rapid and durable response benefits with momelotinib, with achievement of first TSS response by day 29 and continued improvement over time. Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701 .

AbstractBackground/ObjectivesUlceration is a common complication of infantile hemangioma (IH). Severe, persistent ulceration occurs in a minority of patients. This study aims to characterize the clinical features of IH with aggressive ulceration (AU).MethodsMulticenter retrospective study of clinical features of IH with AU.ResultsThirty‐five patients with AU were identified and included in the study. The majority of AU occurred in segmental IH (23/35, 65%). Segmental IH with AU were large (≥10 cm2; 16/23, 69%, p < .001) with a thin (<3 mm) superficial component (16/23, 69%, p < .001). Localized IH with AU had a thick (>3 mm) superficial component (11/12, 92%, p < .001).All diaper area IH with AU (9/35) were segmental with thin superficial component (100%, p = .02). IH with AU in the head/neck (10/35) were more commonly localized (67%) and mixed (62.5%), while segmental, thick superficial morphology was more common on trunk (9/35) and upper extremities (7/35).ConclusionsIH resulting in AU differ in clinical features by anatomic site. Those in the diaper area are nearly always segmental with thin superficial component, whereas other sites tend to be localized, mixed, with thick superficial component. These distinct phenotypes may prove useful in the clinical setting for physicians to identify patterns of IH ulceration with increased risk of aggressive, persistent ulceration.