Treatment of Thoracoabdominal Aortic Aneurysmal Degeneration Following Aortic Dissections at a Single Surgical Center Using a Physician-Assembled Branched Endovascular Stent Graft.

BACKGROUND: Aneurysmal degeneration of aortic dissection portends significant morbidity and mortality consequences in the subacute and chronic phases of aortic dissection. This article describes the use of a multibranched stent graft system for the treatment of thoracoabdominal aneurysmal degeneration of dissections with visceral segment involvement and reports upon the 30-day and 1-year outcomes for the first 18 patients treated with this design configuration. METHODS: The in-hospital, 30-day and 1-year morbidity and mortality outcomes of 18 consecutive patients treated with the physician-assembled visceral manifold or unitary manifold stent graft systems between 2013 and 2022 were evaluated. RESULTS: A total of 18 patients were treated for aneurysmal changes after aortic dissection. A total of 71 visceral vessels were successfully stented. There were no acute procedural failures. There were no episodes of paraplegia, reinterventions for type I or III endoleaks, patency-related events or mortalities reported in the first 30 days following treatment. One-year, all-cause mortality demonstrated 2/11 (18.2%). CONCLUSIONS: The aneurysmal degeneration of aortic dissection poses significant risks to patients with medically managed aortic dissections and those under surveillance. When these aneurysms develop in the thoracoabdominal region, treatment becomes even more challenging given the problem of visceral vessel patency, as these vessels can originate off the true or false lumens. The physician-designed endovascular stent graft system reported upon here has been successfully deployed in 18 patients with no acute procedural failures and promising clinical results. This treatment modality may offer utility to vascular surgeons whose patients with thoracoabdominal aneurysmal degeneration following aortic dissection have historically had limited endovascular repair prospects.

Novel variants identified in CKAP2L in two siblings with Filippi syndrome.

Pathogenic variants in CKAP2L have previously been reported in Filippi syndrome (FS), a rare autosomal recessive, craniodigital syndrome characterized by microcephaly, syndactyly, short stature, intellectual disability, and dysmorphic facial features. To date, fewer than 10 patients with pathogenic variants in CKAP2L associated with FS have been reported. All of the previously reported probands have presumed loss-of-function variants (frameshift, canonical splice site, starting methionine), and all but one have been homozygous for a pathogenic variant. Here we describe two brothers who presented with microcephaly, micrognathia, syndactyly, dysmorphic features, and intellectual disability. Whole-exome sequencing of the family identified a missense variant, c.2066G > A;p.(Arg689His), in trans with a frameshift variant, c.1169_1173del;p.(Ile390LysfsTer4), in CKAP2L To our knowledge, these are the first patients with FS to be reported with a missense variant in CKAP2L and only the second family to be reported with two variants in trans.

Diagnostic laparoscopy and oophorectomy for ovarian vein thrombosis in a patient with COVID-19: a surgical case report and literature review.

Ovarian vein thrombosis (OVT) is a rare condition most frequently associated with pelvic inflammatory disease (PID), malignancy or the immediate postpartum period. This case study reports on a 56-year-old woman who developed OVT 11 days after a positive COVID-19 diagnosis. Imaging including abdominal/pelvic computed tomography, transvaginal Doppler ultrasound and transabdominal pelvic ultrasound failed to definitively diagnose the thrombotic etiology of the patient's presentation. Ultimately, laparoscopic visualization and subsequent oophorectomy were necessary for diagnostic and therapeutic purposes. The patient did not have underlying malignancy, recent surgical history, history of PID or any history of previous thromboembolic events. Therefore, this report contributes further evidence to the growing knowledge of systemic manifestations associated with COVID-19 that may require surgical intervention.

Combination of mural thrombus and age improves the identification of all-cause mortality following branched endovascular repair.

BACKGROUND: In-hospital and 30-day mortality rates of endovascular repair of thoracoabdominal aortic aneurysms shows a significant improvement over open surgery, although we are not seeing a significant difference at 1 year. We assess the hypothesis that a greater mural thrombus ratio within the aorta could function as an indicator of postoperative mortality. METHODS: The mural thrombus ratio and preoperative comorbidities of 100 consecutive patients from a single center undergoing endo-debranching between 2012 and 2019 were evaluated. Logistic regression, survival analysis, and decision tree methods were used to examine each variable's association with death at 1 year. RESULTS: At the time of analysis, 73 subjects had 1-year outcomes and adequate imaging to assess the parameters. At 1 year, the overall survival for all subjects was 71.2% (21 died, 52 survived). For patients with a favorable mural thrombus ratio (n = 36), the overall 1-year survival was 86.1% (5 died, 31 survived). The subjects with an unfavorable mural thrombus ratio (n = 37), had an overall 1 year survival of 56.8% (16 died, and 21 survived). The only preoperative mortality factor that was statistically significant between the subjects with an unfavorable mural thrombus ratio was age of the patient. The survival for subjects 75 years and older with an unfavorable mural thrombus ratio was 90% (one died, nine survived) vs only 44.4% survival for subjects less than 75 years with an unfavorable mural thrombus ratio (15 died, 12 survived). CONCLUSIONS: This study examined whether a patient's mural thrombus ratio may be an indicator of 1-year survival. These findings suggest that the combination of a patient's aortic mural thrombus ratio and age can function as a preoperative indicator of their underlying cardiac reserve. Identifying patients with low cardiac reserve and fitness to handle the increased cardiac demands owing to the physiologic response to extensive aortic stent grafting before undergoing aortic repair may allow for modification of preoperative patient counseling and postoperative care guidelines to better treat this patient population.

Nonsense pathogenic variants in exon 1 of PHOX2B lead to translational reinitiation in congenital central hypoventilation syndrome.

Pathogenic variants in PHOX2B lead to congenital central hypoventilation syndrome (CCHS), a rare disorder of the nervous system characterized by autonomic dysregulation and hypoventilation typically presenting in the neonatal period, although a milder late-onset (LO) presentation has been reported. More than 90% of cases are caused by polyalanine repeat mutations (PARMs) in the C-terminus of the protein; however non-polyalanine repeat mutations (NPARMs) have been reported. Most NPARMs are located in exon 3 of PHOX2B and result in a more severe clinical presentation including Hirschsprung disease (HSCR) and/or peripheral neuroblastic tumors (PNTs). A previously reported nonsense pathogenic variant in exon 1 of a patient with LO-CCHS and no HSCR or PNTs leads to translational reinitiation at a downstream AUG codon producing an N-terminally truncated protein. Here we report additional individuals with nonsense pathogenic variants in exon 1 of PHOX2B. In vitro analyses were used to determine if these and other reported nonsense variants in PHOX2B exon 1 produced N-terminally truncated proteins. We found that all tested nonsense variants in PHOX2B exon 1 produced a truncated protein of the same size. This truncated protein localized to the nucleus and transactivated a target promoter. These data suggest that nonsense pathogenic variants in the first exon of PHOX2B likely escape nonsense mediated decay (NMD) and produce N-terminally truncated proteins functionally distinct from those produced by the more common PARMs.

Concise Review: Fat and Furious: Harnessing the Full Potential of Adipose-Derived Stromal Vascular Fraction.

Due to their capacity to self-renew, proliferate and generate multi-lineage cells, adult-derived stem cells offer great potential for use in regenerative therapies to stop and/or reverse degenerative diseases such as diabetes, heart failure, Alzheimer's disease and others. However, these subsets of cells can be isolated from different niches, each with differing potential for therapeutic applications. The stromal vascular fraction (SVF), a stem cell enriched and adipose-derived cell population, has garnered interest as a therapeutic in regenerative medicine due to its ability to secrete paracrine factors that accelerate endogenous repair, ease of accessibility and lack of identified major adverse effects. Thus, one can easily understand the rush to employ adipose-derived SVF to treat human disease. Perhaps faster than any other cell preparation, SVF is making its way to clinics worldwide, while critical preclinical research needed to establish SVF safety, efficacy and optimal, standardized clinical procedures are underway. Here, we will provide an overview of the current knowledge driving this phenomenon, its regulatory issues and existing studies, and propose potential unmapped applications. Stem Cells Translational Medicine 2017;6:1096-1108.

Effects of fatigue on bilateral ground reaction force asymmetries during the squat exercise.

Physical performance and injury risk have been related to functional asymmetries of the lower extremity. The effect of fatigue on asymmetries is not well understood. The goal of this investigation was to examine asymmetries during fatiguing repetitions and sets of the free-weight barbell back squat exercise. Seventeen healthy recreationally trained men and women (age = 22.3 ± 2.5 years; body mass = 73.4 ± 13.8 kg; squat 8 repetition maximum [8RM] = 113 ± 35% body mass [mean ± SD]) performed 5 sets of 8 repetitions with 90% 8RM while recording bilateral vertical ground reaction force (GRFv). The GRFv asymmetry during the first 2 (R1 and R2) and the last 2 (R7 and R8) repetitions of each set was calculated by subtracting the % load on the right foot from that of the left foot. Most subjects placed more load on their left foot (also their preferred non-kicking foot). Average absolute asymmetry level across all sets was 4.3 ± 2.5 and 3.6 ± 2.3% for R1 and R2 and R7 and R8, respectively. There were no effects of fatigue on GRFv asymmetries in whole-group analysis (n = 17). However, when initially highly symmetric subjects (±1.7% Left-Right) were removed, average absolute GRFv asymmetry dropped from the beginning to the end of a set (n = 12, p = 0.044) as did peak instantaneous GRFv asymmetry when exploring general shifts toward the left or right leg (n = 12, p = 0.042). The GRFv asymmetries were highly repeatable for 8 subjects that repeated the protocol (Cronbach's α ≥ 0.733, p ≤ 0.056). These results suggest that functional asymmetries, though low, are present in healthy people during the squat exercise and remain consistent. Asymmetries do not increase with fatigue, potentially even decreasing, suggesting that healthy subjects load limbs similarly as fatigue increases, exposing each to similar training stimuli.