Citations

SummaryVenetoclax (VEN) is an FDA‐approved selective inhibitor of B‐cell leukaemia/lymphoma‐2 (BCL‐2), used for treating elderly or unfit acute myeloid leukaemia (AML) patients unable to undergo intensive chemotherapy. Combining VEN with hypomethylating agents (HMAs) has shown impressive response rates in high‐risk myelodysplastic syndromes (MDS) and relapsed/refractory AML. However, the efficacy of VEN and HMAs in treating DDX41‐mutated (mDDX41) MDS/AML patients remains uncertain. Despite the favourable prognostic nature of mDDX41 MDS/AML patients, there is a lack of clinical experience regarding their response to different treatment regimens, leading to an unknown optimal therapeutic approach.

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity—findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.

Background: Atypical fibroxanthoma (AFX) is a dermal-based, low-grade neoplasm with no specific lineage of differentiation. The occurrence of AFX with osteoclast-like giant cells is exceptionally rare. Less than 20 cases have been reported in the literature. Case Presentation: A 77-year-old man with a medical history of multiple basal and squamous cell carcinomas of the skin, presented with a progressively growing erythematous nodule on the sun-damaged right central parietal scalp. A shave biopsy showed a dermal spindle cell proliferation accompanied by numerous osteoclast-like multinucleated giant cells and predominant atypical mitotic figures. The immunohistochemical staining showed a diffuse positive staining for CD68 and SMA, patchy staining for CD10, and negative staining for SOX-10, pan-cytokeratin, CK5/6, S100, CD34, and desmin. The tumor was completely excised with negative margins. A subsequent follow-up over a period of 13 months showed no recurrence. Conclusion: Distinguishing AFX with osteoclast-like giant cells from both malignant and benign skin lesions with osteoclast-like giant cells is crucial. Although AFX tumors display worrisome malignant histologic features, most cases have a favorable prognosis with a local recurrence rate below 5% and exceedingly rare metastasis.

Abstract Background Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer’s disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group). Methods We recruited a population-based cohort of 217 individuals (all aged 70 years, 53% female participants, 119 SCD-memory individuals, 23 SCD-concentration individuals, and 89 controls). AD and CVD were assessed through cerebrospinal fluid levels of the Aβ42/40 ratio and phosphorylated tau, and white matter signal abnormalities on magnetic resonance imaging, respectively. Associations between biomarkers, depressive symptomatology, and SCD were tested via logistic regression and correlation analyses. Results We found a significant association between depressive symptomatology with SCD-memory and SCD-concentration. Depressive symptomatology was not associated with AD and CVD biomarkers. Both the phosphorylated tau biomarker and depressive symptomatology predicted SCD-memory, and the Aβ42/40 ratio and depressive symptomatology predicted SCD-concentration. Conclusions The role of depressive symptomatology in SCD may differ depending on the stage within the spectrum of preclinical AD (as determined by amyloid-beta and tau positivity), and does not seem to reflect AD pathology. Our findings contribute to the emerging field of subclinical depressive symptomatology in SCD and clarify the association of different types of subjective complaints with distinct syndromic and biomarker profiles.

Abstract Female breast cancer is a common cancer in young adults, an age group with the highest uninsured rate. Among 51 675 young adult women (ages 18-39 years) diagnosed with breast cancer between 2011 and 2018 in the National Cancer Database, we estimated changes in guideline-concordant treatment receipt, treatment timeliness, and survival associated with the Affordable Care Act Medicaid expansion. Of young adults with stage I-III estrogen receptor–positive or progesterone receptor–positive breast cancer, Medicaid expansion was associated with a net increase of 2.42 percentage points (95% confidence interval [CI] = 0.56 to 4.28 percentage points) in the percentage receiving endocrine therapy. Among all young adults with stage I-III breast cancer, Medicaid expansion was associated with a net reduction of 1.65 percentage points (95% CI = 0.08 to 3.22 percentage points) in treatment delays defined as treatment initiation of at least 60 days after diagnosis and a net increase of 1.00 percentage points (95% CI = 0.21 to 1.79 percentage points) in 2-year overall survival. Our study provides evidence of benefit in cancer care and outcomes from Medicaid expansion among the young adult population.

Abstract Objective Sellar repair techniques with varying complexity and effectiveness have been employed to reduce the incidence of postoperative cerebrospinal fluid (CSF) leaks following endoscopic transsphenoidal pituitary surgery. This study describes our institutional experience with a minimalistic, highly effective approach to sellar repair. Methods The authors performed a retrospective review of consecutive cases of transsphenoidal pituitary surgery performed at our institution. All included subjects underwent sellar repair with an epidural interlay graft. Relationships between patient and tumor characteristics, incidence of CSF leak, adjunct repair techniques, and endocrine outcomes were examined. Results Three hundred and thirty-four (334) cases were included. Intraoperative CSF leak was encountered in 116 cases (34.7%), and postoperative CSF leak occurred only once (0.3%) early in the series. Seventy intraoperative CSF leaks were successfully repaired with an epidural interlay alone, including 13 high-flow leaks. Our rate of fat graft use (1.2%), nasoseptal flap (3.0%), and lumbar drain placement (6.6%) in the second half of the series showed a significant decline compared with the first half, indicating increased reliance on the interlay graft over time. Our 65% functional macroadenoma remission rate compares favorably with large historical series. Conclusion Simple sellar repair using an epidural interlay graft is highly effective in preventing postoperative CSF leaks, including cases of high-flow intraoperative leaks. More complex repair techniques are reserved for select high-risk cases or those with inadequate sellar bony ledges. With this technique, there has been no postoperative CSF leak at our institution in over 300 consecutive transsphenoidal pituitary surgeries.

Background: Prompt seeking of emergency medical services (EMS) assistance at stroke onset is critical to minimize poststroke disability. Objective: The aim was to study how racial differences in EMS decision-relevant factors and EMS use impact stroke care and disability outcomes. Design: A prospective observational study. Participants: A total of 1168 acute ischemic stroke patients discharged from April 2016 to October 2017 at a safety net hospital were included; 108 patients were surveyed before discharge. Measures: (1) Prehospital delay: EMS use, timely hospital arrival; (2) Stroke care: alteplase receipt and inpatient rehab; (3) Outcomes: Functional improvement at discharge (admission minus discharge scores on National Institutes of Health Stroke Scale), 90-day modified Rankin Scale; (4) EMS decision-relevant factors: Stroke symptom knowledge, source of knowledge, unfavorable past EMS/care experiences, and financial barriers to EMS use. Results: Despite more Black patients using EMS than Whites/Asians (56% vs. 48%, P=0.003), their timely hospital arrival was 30% less likely. Adjusted for stroke severity, receipt of alteplase, and inpatient rehab were similar, but Black patients fared worse on functional improvement at discharge (among severe strokes, 2.4 National Institutes of Health Stroke Scale points less improvement, P<0.01), and on functional normalcy at 90 days (modified Rankin Scale score 0–1 being 60% less likely across severity categories) (P<0.01). Fewer Black patients knew any stroke symptoms before the stroke (72% vs. 87%, P=0.03), and fewer learned about stroke from providers (P=0.01). Financial barriers and provider mistrust were similar. Conclusions: Black patients had less knowledge of stroke symptoms, more care-seeking delay, and poorer outcomes. Including stroke education as a standard of chronic disease care may mitigate stroke outcome disparities.

BACKGROUND AND OBJECTIVES: Nerve sheath tumors of the brachial plexus frequently distort the local anatomy, increasing the difficulty of safe exposure and resection. However, lateral displacement of the phrenic nerve has not been previously described. The purpose of this study was thus to illustrate the abnormal lateral displacement of the phrenic nerve in 2 cases of patients undergoing brachial plexus tumor resection and provide a possible mechanism for this observation. METHODS: Two patients underwent surgical resection of clinically progressing C5 schwannomas. During exposure, the phrenic nerve was found to be significantly more superficial and lateral than typical. This structural relationship persisted even after complete resection of the lesion. Both patients did well postoperatively. RESULTS: The phrenic nerve traverses along the anterolateral aspect of the anterior scalene. However, in these 2 cases of C5 nerve sheath tumors, the phrenic was found to be significantly more lateral and superficial than usual, draping across the medial aspect of the tumor. We believe that the C5-phrenic communicating branch may act as a functional tether that mobilizes the phrenic nerve laterally as the tumor grows. The mass effect on the anterior scalene by the underlying C5 tumor may further contribute to the anterolateral and superficial displacement of the nerve. CONCLUSION: The phrenic nerve may be seen markedly more laterally and superficially displaced in cases of C5 nerve sheath tumors. It is important for surgeons who operate on lesions of the brachial plexus to be aware of this phenomenon.

BACKGROUND AND OBJECTIVES: Nongeneral anesthesia (non-GA) spine surgery is growing in popularity and has facilitated earlier postoperative recovery, reduced cost, and fewer complications compared with spine surgery under general anesthesia (GA). Changes in reimbursement policies have been demonstrated to correlate with clinical practice; however, they have yet to be studied for GA vs non-GA spine procedures. We aimed to investigate trends in physician reimbursement for GA vs non-GA spine surgery in the United States. METHODS: We queried the ACS-NSQIP for GA and non-GA (regional, epidural, spinal, and anesthesia care/intravenous sedation) spine surgeries during 2011–2020. Work relative value units per operative hour (wRVUs/h) were retrieved for decompression or stabilization of the cervical, thoracic, and lumbar spine. Propensity score matching (1:1) was performed using all baseline variables. RESULTS: We included 474 706 patients who underwent spine decompression or stabilization procedures. GA was used in 472 248 operations, whereas 2458 operations were non-GA. The proportion of non-GA spine operations significantly increased during the study period. Operative times ( P < .001) and length of stays ( P < .001) were shorter in non-GA when compared with GA procedures. Non-GA lumbar procedures had significantly higher wRVUs/h when compared with the same procedures performed under GA (decompression; P < .001 and stabilization; P = .039). However, the same could not be said about cervicothoracic procedures. Lumbar decompression surgeries using non-GA witnessed significant yearly increase in wRVUs/h ( P < .01) contrary to GA ( P = .72). Physician reimbursement remained stable for procedures of the cervical or thoracic spine regardless of the anesthesia. CONCLUSION: Non-GA lumbar decompressions and stabilizations are associated with higher and increasing reimbursement trends (wRVUs/h) compared with those under GA. Reimbursement for cervical and thoracic surgeries was equal regardless of the type of anesthesia and being relatively stable during the study period. The adoption of a non-GA technique relative to the GA increased significantly during the study period.