Citations

The syndrome of episodic angioedema with eosinophilia, first reported over 40 years ago, is a hypereosinophilic disorder that, uniquely, is not associated with end-organ pathology. However, patients develop a constellation of symptoms that include angioedema, urticaria, fatigue, and fever. Episodes are accompanied by massive hypereosinophilia and weight gain. Type II serum cytokine levels (IL-5, IL-13, IL-9, and IL-10) show cyclic variations peaking at or just prior to the peak of eosinophilia and an abnormal Th2 cell phenotype has been reported. Attacks may occur with predictable regularity and have been described in both adults and children. Glucocorticoid therapy reliably reverses symptoms with accompanying diuresis, defervesce, and normalization of the eosinophil count. In this report, a patient who had the syndrome of episodic angioedema with eosinophilia exceeding 20 years is reported. He has had no end-organ damage to date. Testing for the CHIC 2 deletion, a surrogate for the FIP1L1-PDGFRA fusion, was negative. Use of imatinib mesylate, initially as a steroid-sparing agent, and subsequently as a maintenance medication, plus low-dose prednisone has provided long-term control of hypereosinophilia and all clinical manifestations.

Abstract BackgroundOsteoarthritis (OA) is a common shoulder disorder that impacts shoulder functions. Shoulder arthroplasty is often required to restore function and quality of life. Reverse total shoulder arthroplasty (RSA), which was originally designed mainly for irreparable rotator cuff damage, has gained popularity in recent years for the treatment of advanced shoulder OA instead of the clinically standard total shoulder arthroplasty (TSA). However, this RSA has some nonnegligible flaws such as higher complications rate and economic cost, not mention the following problems caused by irreversible physical structural damage. Therefore, the employment of RSA needs to be carefully considered.PurposeThis study aimed to compare TSA and RSA in OA patients with or without rotator cuff damage to better guide clinical decision making. We believe the radical use of RSA in patients without rotator cuff deficiency may cause more harm than good.Study designCross-sectional studyMethodsWe queried the Nationwide Inpatient Sample (NIS) database from 2011 to 2014 to collect information on OA patients who received TSA and RSA. Patients were divided into 2 groups of comparison according to the presence of rotator cuff deficiency and matched with propensity score analysis.Results A total of 57,156 shoulder arthroplasties were identified. RSA patients in the rotator cuff deficiency group had significant higher transfusion rates and longer hospital stays. RSA patients without rotator cuff deficiency had a statistically significantly higher number of implant-related mechanical complications, acute upper respiratory infections and postoperative pain. Overall, RSA incurred higher costs in both groups.ConclusionFor OA patients with rotator cuff deficiencies, RSA has its benefits as complication rates were comparable to TSA. For those patients without rotator cuff deficiencies, the use of RSA should be reconsidered as there were more complications with higher severity.

AbstractTo examine the length of a hexanucleotide expansion in C9orf72, which represents the most frequent genetic cause of frontotemporal lobar degeneration and motor neuron disease, we employed a targeted amplification-free long-read sequencing technology: No-Amp sequencing. In our cross-sectional study, we assessed cerebellar tissue from 28 well-characterized C9orf72 expansion carriers. We obtained 3507 on-target circular consensus sequencing reads, of which 814 bridged the C9orf72 repeat expansion (23%). Importantly, we observed a significant correlation between expansion sizes obtained using No-Amp sequencing and Southern blotting (P = 5.0 × 10−4). Interestingly, we also detected a significant survival advantage for individuals with smaller expansions (P = 0.004). Additionally, we uncovered that smaller expansions were significantly associated with higher levels of C9orf72 transcripts containing intron 1b (P = 0.003), poly(GP) proteins (P = 1.3 × 10− 5), and poly(GA) proteins (P = 0.005). Thorough examination of the composition of the expansion revealed that its GC content was extremely high (median: 100%) and that it was mainly composed of GGGGCC repeats (median: 96%), suggesting that expanded C9orf72 repeats are quite pure. Taken together, our findings demonstrate that No-Amp sequencing is a powerful tool that enables the discovery of relevant clinicopathological associations, highlighting the important role played by the cerebellar size of the expanded repeat in C9orf72-linked diseases.

Abstract Triggering receptor expressed on myeloid cell 2 (TREM2) is a surface receptor that, in the central nervous system, is exclusively expressed on microglia. TREM2 variants have been linked to increased risk for neurodegenerative diseases, but the functional effects of microglial TREM2 remain largely unknown. To this end, we investigated TAR-DNA binding protein 43 kDa (TDP-43)-related neurodegenerative disease via viral-mediated expression of human TDP-43 protein (hTDP-43) in mice or inducible expression of hTDP43 with defective nuclear localization signals in transgenic mice. We found that TREM2 deficiency impaired microglia phagocytic clearance of pathological TDP-43, and enhanced neuronal damage and motor function impairments. Mass cytometry analysis revealed that hTDP-43 induced a TREM2-dependent subpopulation of microglia with high CD11c expression and higher phagocytic ability. Using mass spectrometry, we further demonstrated an interaction between TDP-43 and TREM2, in vitro and in vivo, in hTDP-43-expressing transgenic mouse brains. We computationally identified the region within hTDP-43 that interacts with TREM2 and observed the potential interaction in ALS patient tissues. Our data reveal the novel interaction between TREM2 and TDP-43, highlighting that TDP-43 is a potential ligand for microglial TREM2 and the interaction mediates neuroprotection of microglial TREM2 in TDP-43-related neurodegeneration.

Abstract BackgroundHepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than do those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scare. Therefore, the present study aimed to investigate the outcomes of this group of patients.MethodsThirty patients with caudate HCC who underwent definitive PBT between February 2001 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose.ResultsThe median follow-up period was 37.5 (range, 3.0–152.0) months. The overall survival rates at 1, 3, and 5 years were 86.6%, 62.8%, and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P < 0.01), having a single tumour (P = 0.02), and a low serum alpha-fetoprotein level (P < 0.01) were significant factors predicting longer survival. The local control rates at 1, 3, and 5 years were 100.0%, 85.9%, and 85.9%, respectively, while the corresponding progression-free survival rates were 65.0%, 27.5%, and 22.0%, respectively. No grade 3 or worse adverse events were observed.ConclusionsPBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.

Background The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end‐systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end‐diastolic trough of trabeculation‐to‐epicardium (X):peak of trabeculation‐to‐epicardium (Y) ratio <0.5 (Chin criteria) by echocardiography; and end‐diastolic noncompacted:compacted ratio >2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction <50% was present in 57% of patients and isolated apical noncompaction in 48%. During a median follow‐up of 6.3 years, 59 patients died. On multivariable Cox regression analysis, age (hazard ratio [HR] 1.04; 95% CI, 1.02–1.06), left ventricular ejection fraction <50% (HR, 2.37; 95% CI, 1.17–4.80), and noncompaction extending from the apex to the mid or basal segments (HR, 2.11; 95% CI, 1.21–3.68) were associated with all‐cause mortality. Compared with the expected survival for age‐ and sex‐matched US population, patients with LVNC had reduced overall survival ( P <0.001). However, patients with LVNC with preserved left ventricular ejection fraction and patients with isolated apical noncompaction had similar survival to the general population. Conclusions Overall survival is reduced in patients with LVNC compared with the expected survival of age‐ and sex‐matched US population. However, survival rate in those with preserved left ventricular ejection fraction and isolated apical noncompaction was comparable with that of the general population.

Study Design. Retrospective review of prospectively collected data. Objective. To determine if the addition of L5-S1 interbody support in long fusion deformity constructs is associated with superior long-term clinical and radiographic outcomes. To compare the 5-year clinical and radiographic outcomes and complications between long fusion constructs with L5-S1 interbody support versus posterolateral fusion (PLF) alone. Summary of Background Data. Cadaveric biomechanical studies have suggested that an interbody fusion at L5-S1 is beneficial in long fusion constructs with sacropelvic fixation. However, there is limited data reflecting the superiority of interbody support augmentation in optimizing arthrodesis and deformity correction relative to PLF alone. Methods. Eighty-eight consecutive adults with spinal deformity who underwent at minimum T11-pelvis posterior pedicle screw instrumentation with 5-year follow-up were included. Two cohorts were compared based on technique used at the lumbosacral junction (L5-S1): (A) no interbody (PLF; n = 23), or (B) interbody support at L5-S1 (IB; n = 65). Radiographic measurements and clinical outcome measures were compared at multiple time points. Complications were recorded and compared. Results. No differences in baseline patient characteristics between cohorts. One nonunion occurred at L5-S1 in the PLF group (P = 0.091). Initial postop sagittal alignment was better in the IB group (PLF: 6.46 cm, IB: 2.48 cm, P = 0.007); however, this was not maintained over long-term follow-up. No significant differences in proximal junctional kyphosis (PLF: 7/23, IB: 9/65, P = 0.076). Proximal junctional failure was more frequent in the PLF group (PLF: 6/23, IB: 6/65, P = 0.043). No significant differences in complications were found. Both cohorts had improvement from baseline pain and functional scores. Conclusion. There is no absolute long-term advantage for lumbar interbody support in adult spinal deformity patients undergoing spinal arthrodesis to the pelvis. Level of Evidence: 3

ABSTRACT Background Since the Accreditation Council for Graduate Medical Education (ACGME) established the designated institutional official (DIO) role in 1998, there have been major changes in sponsoring institutions (SIs) and DIO responsibilities. Yet there remains a large gap in our knowledge regarding baseline SI and DIO characteristics as well as a need for institutions wanting to increase diversity in the DIO role and other leadership positions within the medical education community. Objective We sought to characterize demographics of DIOs and the SIs they oversee. Methods We identified SIs and DIOs on the ACGME website on February 15, 2020. Reviewed data included SI accreditation status, number of programs and resident/fellow positions, and DIO characteristics. Results We identified 831 SIs. SIs with continued accreditation sponsored more programs (median 4.0) than SIs with initial accreditation (median 1.0, P &lt; .001). DIO age ranged from 29–81 years (median 57 years). Two-hundred eighty-three of 831 (34%) DIOs were women. Of 576 DIOs with known academic rank, 356 (62%) DIOs held senior academic rank. A higher proportion of male DIOs had senior academic rank (68% vs 52%; OR 1.90 [95% CI 1.34–2.70]; P &lt; .001) and professor rank (39% vs 24%; OR 2.01 [95% CI 1.38–2.94]; P &lt; .001) compared to female DIOs. Female gender was associated with a greater number of ACGME-accredited programs and filled resident/fellow positions per SI (P &lt; .001 for both). Conclusions This study describes characteristics of DIOs and SIs and offers insights for those pursuing a DIO position.

Abstract High-specificity colorectal cancer screening is desirable to triage patients &lt;50 years for colonoscopy; however, most endorsed colorectal cancer screening tests have not been rigorously evaluated in younger populations. This prospective cross-sectional study determined the specificity of the multitarget stool DNA (mt-sDNA) test in an average-risk screening population of 45 to 49 year-olds. Specificity was the primary outcome and was measured in participants without colorectal cancer or advanced precancerous lesions [APL– advanced adenomas (AA), and sessile serrated lesions ≥10 mm], and in the subgroup of participants with negative colonoscopic findings. APL sensitivity was a secondary outcome. The evaluable cohort included those who completed the study without protocol deviations and had a usable mt-sDNA test. Of 983 enrolled participants, 816 formed the evaluable cohort, with a mean age of 47.8 (SD, 1.5) years; 47.7% were women. No participants had colorectal cancer, 49 had APL, 253 had nonadvanced adenomas (NAA), and 514 had negative colonoscopic findings. mt-sDNA test specificity was 95.2% (95% CI, 93.4–96.6) in participants with NAA or negative findings [96.3% (confidence interval (CI), 94.3%–97.8%)] in those with negative findings, and did not differ by sex (P = 0.75) or race (P = 0.36) in participants with NAA or negative findings. Sensitivity for APL was 32.7% (CI, 19.9–47.5%), with most APL (83.7%) measuring 10–19 mm and none having high-grade dysplasia. The area under the ROC curve for discriminating between APL and lesser findings was 0.72 (CI, 0.64–0.81). mt-sDNA's high specificity would help minimize risk from unnecessary diagnostic procedures in this age group. This study shows that mt-sDNA has high specificity among average-risk 45 to 49-year olds, supporting its use as a noninvasive option for colorectal cancer screening. Prevention Relevance: This study shows that mt-sDNA has high specificity among average-risk 45–49 year olds, supporting its use as a non-invasive option for colorectal cancer screening.

Objectives/HypothesisThe purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality.Study DesignDelphi method‐based survey series.MethodsA multidisciplinary, multi‐institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work‐up.ResultsThe international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18).ConclusionThis consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best‐practice applications of systemic bevacizumab for patients with early‐onset or less‐severe disease phenotypes.Level of Evidence5 Laryngoscope, 131:E1941–E1949, 2021