Citations

AbstractBackgroundPathogenic variants in AXIN2 have been associated with tooth agenesis, colon polyps, and colon cancer. Given the rare nature of this phenotype, we set out to collect additional genotypic and phenotypic information.MethodsData were collected via a structured questionnaire. Sequencing was performed in these patients mostly due to diagnostic purpose. A little more than half of the AXIN2 variant carriers were identified by NGS; other six were family members.ResultsHere, we report 13 individuals with a heterozygous AXIN2 pathogenic/likely pathogenic variant who have a variable expression of oligodontia‐colorectal cancer syndrome (OMIM 608615) or oligodontia‐cancer predisposition syndrome (ORPHA 300576). Three individuals from one family also had cleft palate, which might represent a new clinical feature of AXIN2 phenotype, also given the fact that AXIN2 polymorphisms have been found in association with oral clefting in population studies. AXIN2 has already been added to multigene cancer panel tests; further research should be conducted to determine whether it should be added to cleft lip/palate multigene panels.ConclusionMore clarity about oligodontia‐colorectal cancer syndrome, about the variable expression, and associated cancer risks is needed to improve clinical management and to establish guidelines for surveillance. We collected information about the surveillance that was advised, which might support clinical management of these patients.

Introduction Contiguous non-mass enhancement (NME) often coexists with a solid tumor component on MRI, but it can be challenging to predict whether NME represents invasive breast cancer, ductal carcinoma in situ (DCIS), benign disease, or biopsy site reaction. The purpose of this study was to determine the association between the size/extent of NME and the presence of invasive cancer and/or DCIS on final pathology. Methods This was a single institution retrospective analysis of a prospectively maintained breast cancer registry (2010-2020). Female patients who underwent surgical resection were included if they had a diagnosis of invasive breast cancer (with or without DCIS) and had an MRI showing both a solid mass and contiguous NME. The size of NME on MRI was compared with the size of invasive cancer and/or DCIS on the final pathology. Results From a total of 3443 patients, 225 patients were included. 86.2% had invasive ductal carcinoma (IDC), and 12.0% had invasive lobular carcinoma 76.9% were ER+, 16.4% were HER2+, and 13.3% were triple negative breast cancer (TNBC). 18.7% received neoadjuvant chemotherapy (NCT) of whom 31% achieved a complete radiographic/pathologic response. Pearson correlation coefficients (r) between the size of NME and invasive cancer/DCIS showed a strong and positive correlation of MRI NME with DCIS on pathology in patients without NCT. Subgroup analysis showed the strongest correlations for NME and DCIS among non-white (r = .70) and HER2 + patients (r = .74) who did not receive NCT. Conclusions Strong correlations between NME and DCIS were found for HER2 + disease and non-white patients, but only modest correlations were found for other patient/disease characteristics. These correlations may impact decisions in surgical approach.

This review article summarizes the basic principles of vascular anatomy, physiology, diagnostic work-up and treatment for patients with nontraumatic upper extremity vascular disorders. Vascular disorders can be considered vasospastic or occlusive. The most commonly encountered vasospastic condition is Raynaud’s Phenomenon secondary to scleroderma. While historically this has been managed medically with vasodilators, more advanced cases can benefit from surgical treatment to improve blood flow and minimize tissue loss, with compelling evidence that earlier surgical intervention can modify disease process and should be considered. Occlusive disease can present as aneurysm or thrombosis and often requires surgical treatment with resection of the occluded segment with or without vascular reconstruction. In advanced atherosclerotic disease or end stage ischemia, arterialization of the venous system can be considered to avoid more proximal amputations.

Abstract Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here we extend molecular work to energy metabolism and sex hormone signaling in mice and humans. We found spaceflight-induced changes in insulin and estrogen signaling in rodents and humans. Murine changes were most prominent in the liver, where we observed inhibition of insulin and estrogen receptor signaling with concomitant hepatic insulin resistance and steatosis. Based on the metabolic demand, metabolic pathways mediated by insulin and estrogen vary among muscles, specifically between the soleus and extensor digitorum longus. In humans, spaceflight induced changes in insulin and estrogen related genes and pathways. Pathway analysis demonstrated spaceflight-induced changes in insulin resistance, estrogen signaling, stress response, and viral infection. These data strongly suggest the need for further research on the metabolic and reproductive endocrinologic effects of space travel, if we are to become a successful interplanetary species

OBJECTIVE Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) has been used to treat degenerative lumbar spondylolisthesis and is associated with expedited recovery, reduced operative blood loss, and shorter hospitalizations compared to those with traditional open TLIF. However, the impact of MI-TLIF on long-term patient-reported outcomes (PROs) is less clear. Here, the authors compare the outcomes of MI-TLIF to those of traditional open TLIF for grade I degenerative lumbar spondylolisthesis at 60 months postoperatively. METHODS The authors utilized the prospective Quality Outcomes Database registry and queried for patients with grade I degenerative lumbar spondylolisthesis who had undergone single-segment surgery via an MI or open TLIF method. PROs were compared 60 months postoperatively. The primary outcome was the Oswestry Disability Index (ODI). The secondary outcomes included the numeric rating scale (NRS) for back pain (NRS-BP), NRS for leg pain (NRS-LP), EQ-5D, North American Spine Society (NASS) satisfaction, and cumulative reoperation rate. Multivariable models were constructed to assess the impact of MI-TLIF on PROs, adjusting for variables reaching p < 0.20 on univariable analyses and respective baseline PRO values. RESULTS The study included 297 patients, 72 (24.2%) of whom had undergone MI-TLIF and 225 (75.8%) of whom had undergone open TLIF. The 60-month follow-up rates were similar for the two cohorts (86.1% vs 75.6%, respectively; p = 0.06). Patients did not differ significantly at baseline for ODI, NRS-BP, NRS-LP, or EQ-5D (p > 0.05 for all). Perioperatively, MI-TLIF was associated with less blood loss (108.8 ± 85.6 vs 299.6 ± 242.2 ml, p < 0.001) and longer operations (228.2 ± 111.5 vs 189.6 ± 66.5 minutes, p < 0.001) but had similar lengths of hospitalizations (MI-TLIF 2.9 ± 1.8 vs open TLIF 3.3 ± 1.6 days, p = 0.08). Discharge disposition to home or home health was similar (MI-TLIF 93.1% vs open TLIF 91.1%, p = 0.60). Both cohorts improved significantly from baseline for the 60-month ODI, NRS-BP, NRS-LP, and EQ-5D (p < 0.001 for all comparisons). In adjusted analyses, MI-TLIF, compared to open TLIF, was associated with similar 60-month ODI, ODI change, odds of reaching ODI minimum clinically important difference, NRS-BP, NRS-BP change, NRS-LP, NRS-LP change, EQ-5D, EQ-5D change, and NASS satisfaction (adjusted p > 0.05 for all). The 60-month reoperation rates did not differ significantly (MI-TLIF 5.6% vs open TLIF 11.6%, p = 0.14). CONCLUSIONS For symptomatic, single-level grade I degenerative lumbar spondylolisthesis, MI-TLIF was associated with decreased blood loss perioperatively, but there was no difference in 60-month outcomes for disability, back pain, leg pain, quality of life, or satisfaction between MI and open TLIF. There was no difference in cumulative reoperation rates between the two procedures. These results suggest that in appropriately selected patients, either procedure may be employed depending on patient and surgeon preferences.

Abstract Background Deep brain stimulator (DBS)–related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections. Methods This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester. Results There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9–6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure. Conclusions Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.

ObjectiveRecent evidence supports a link between increased TDP‐43 burden and the presence of an APOE4 gene allele in Alzheimer's disease (AD); however, it is difficult to conclude the direct effect of APOE on TDP‐43 pathology due to the presence of mixed AD pathologies. The goal of this study is to address how APOE isoforms impact TDP‐43 pathology and related neurodegeneration in the absence of typical AD pathologies.MethodsWe overexpressed human TDP‐43 via viral transduction in humanized APOE2, APOE3, APOE4 mice, and murine Apoe‐knockout (Apoe‐KO) mice. Behavior tests were performed across ages. Animals were harvested at 11 months of age and TDP‐43 overexpression‐related neurodegeneration and gliosis were assessed. To further address the human relevance, we analyzed the association of APOE with TDP‐43 pathology in 160 postmortem brains from autopsy‐confirmed amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with motor neuron disease (FTLD‐MND) in the Mayo Clinic Brain Bank.ResultsWe found that TDP‐43 overexpression induced motor function deficits, neuronal loss, and gliosis in the motor cortex, especially in APOE2 mice, with much milder or absent effects in APOE3, APOE4, or Apoe‐KO mice. In the motor cortex of the ALS and FTLD‐MND postmortem human brains, we found that the APOE2 allele was associated with more severe TDP‐43‐positive dystrophic neurites.InterpretationOur data suggest a genotype‐specific effect of APOE on TDP‐43 proteinopathy and neurodegeneration in the absence of AD pathology, with the strongest association seen with APOE2. ANN NEUROL 2023;93:830–843