Citations

BACKGROUND AND OBJECTIVES: Adult spinal deformity (ASD) with fixed sagittal malalignment (FSM) may require a pedicle subtraction osteotomy (PSO) for greater focal lordosis and restoration of global alignment. Despite growing trends in minimizing PSOs given their associated high risks, a considerable portion of patients with ASD still require a lumbar PSO most commonly because of iatrogenic flat back deformity. The purpose of this article is to describe a modified extended PSO technique with additional anterior column support coined the “sandwich” extended PSO (SE-PSO) to promote arthrodesis and report the outcomes in a consecutive case series. METHODS: Patients with ASD treated with a lumbar SE-PSO at a single institution from 2015 to 2020 were analyzed. Complications, radiographic data, and patient-reported outcomes were compared preoperatively, at immediate postoperative follow-up, and at a 2-year postoperative follow-up (FU). RESULTS: Fourteen patients who underwent revision operations for FSM were included. Improvements in segmental lordosis across the PSO site (14.8 ± 6.8 vs 39.9 ± 7.1, P < .0001), overall lumbar lordosis (14.6 ± 15.4 vs 44.6 ± 12.1, P < .0001), sacral slope (21.0 ± 10.5 31.1 ± 10.7, P = .0150), C7 sagittal vertical axis (140.1 ± 59.0 mm vs 35.9 ± 28.5, P < .0001), and spinopelvic mismatch (52.5 ± 21.3 vs 18.6 ± 14.1, P = .0001) were obtained in all patients. Eight patients experienced perioperative complications, with intraoperative durotomy being the most common (n = 7). Eight patients had a 2-year FU and demonstrated improvements in their segmental lordosis across the PSO site (14.3 ± 7.0 vs 41.3 ± 7.3, P = .0003), overall lumbar lordosis (8.7 ± 17.8 vs 46.1 ± 14.2, P = .0014), sacral slope (19.1 ± 12.8 vs 32.3 ± 12.5, P = .0479), C7 sagittal vertical axis (173.6 ± 54.4 mm vs 35.8 ± 30.0, P < .0001), and spinopelvic mismatch (63.0 ± 19.7 vs 21.1 ± 18.3, P < .0001), all of which were maintained at final FU ( P > .05). At 2 years, a significant increase in Scoliosis Research Society-22r total score (2.5 ± 0.8 vs 3.6 ± 0.7, P = .0023 was reported. There were no reports of symptomatic pseudarthrosis or mechanical complications. CONCLUSION: SE-PSO is an effective technique to correct FSM and is associated with low complications, improved patient-reported outcomes, and spinopelvic parameters that are maintained at 2 years.

Background Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far. Methods As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals. Results The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families. Conclusion The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term ‘GDACCF syndrome’ with ‘ZNF148-related neurodevelopmental disorder’.

Abstract Background: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. Methods: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. Results: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88–1.22; MR-Egger OR, 0.89; 95% CI, 0.65–1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90–1.27; MR-Egger OR, 0.93; 95% CI, 0.67–1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. Conclusions: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. Impact: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.

Sex hormone concentrations, particularly testosterone, are primary determinants of sex-based differences in athletic and sports performance, and this relationship may inform fair competition and participation for athletes. This article describes the sex-based dichotomy in testosterone and the implications for sex-based differences in individual sports performance, including factors that relate to athletic performance for transgender individuals, and areas of future investigation.

AbstractHypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG‐induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG‐induced AP or AP in the presence of HTG and determining possible treatments are needed.

AbstractBackgroundDisruption of central circadian rhythms likely mediated by changes in microbiota and a decrease in gut-derived metabolites like short chain fatty acids (SCFAs) negatively impacts colonic barrier homeostasis. We aimed to explore the effects of isolated peripheral colonic circadian disruption on the colonic barrier in a mouse model of colitis and explore the mechanisms, including intestinal microbiota community structure and function.MethodsColon epithelial cell circadian rhythms were conditionally genetically disrupted in mice: TS4Cre-BMAL1lox (cBMAL1KO) with TS4Cre as control animals. Colitis was induced through 5 days of 2% dextran sulfate sodium (DSS). Disease activity index and intestinal barrier were assessed, as were fecal microbiota and metabolites.ResultsColitis symptoms were worse in mice with peripheral circadian disruption (cBMAL1KO). Specifically, the disease activity index and intestinal permeability were significantly higher in circadian-disrupted mice compared with control animals (TS4Cre) (P &lt; .05). The worsening of colitis appears to be mediated, in part, through JAK (Janus kinase)-mediated STAT3 (signal transducer and activator of transcription 3), which was significantly elevated in circadian-disrupted (cBMAL1KO) mice treated with DSS (P &lt; .05). Circadian-disrupted (cBMAL1KO) mice also had decreased SCFA metabolite concentrations and decreased relative abundances of SCFA-producing bacteria in their stool when compared with control animals (TS4Cre).ConclusionsDisruption of intestinal circadian rhythms in colonic epithelial cells promoted more severe colitis, increased inflammatory mediators (STAT3 [signal transducer and activator of transcription 3]), and decreased gut microbiota–derived SCFAs compared with DSS alone. Further investigation elucidating the molecular mechanisms behind these findings could provide novel circadian directed targets and strategies in the treatment of inflammatory bowel disease.

Background: Spinal synovial cysts are cystic dilatations of synovial sheaths that extrude into the spinal canal. Despite their generally benign behavior, they can cause severe symptoms due to compression of neural structures. They are most commonly found in the lumbar spine and are rare in the cervical region, especially at the atlanto-occipital junction. Case Description: A 65-year-old presented with neck pain and headaches. The magnetic resonance imaging (MRI) revealed a degenerative cyst within the anterior foramen magnum causing anterior spinal cord and brainstem compression. Multiple surgical treatment options were discussed, and he was prescribed methylprednisolone and immobilization of his cervical spine with a rigid collar. One month later, the patient reported dramatic improvement of his symptoms, and no surgery was performed. One year later, his pain had remained much improved with the continued use of the collar and pain management (i.e., using anti-inflammatories and muscle relaxants). The 1-year follow-up MRI showed the atlanto-occipital cyst compressing the cervicomedullary junction had completely resolved along with the brainstem compression. Conclusion: A 65-year-old presented with myelopathy attributed to a large anterior foramen magnum atlanto-occipital cyst compressing the cord. Conservative management for 1 month with a rigid cervical collar and steroids resulted in marked neurological improvement; at 1 year follow-up, the patient was markedly improved with an MR that demonstrated spontaneous cyst regression.