Minimally Invasive Method for Treatment of Syndromic Congenital Vertical Talus Deformity in Children.

BACKGROUND: Congenital Vertical Talus (CVT) is a rare form of rigid flatfoot commonly seen in patients with underlying neurologic syndromes. This study aims to evaluate the long-term effectiveness of the minimally invasive method for correcting CVT deformity in a large cohort of syndromic patients. METHODS: A single author recorded preoperative, 2-week postoperative, 1-year postoperative, and most recent radiographic measurements and complications for 25 patients treated with the minimally invasive method from 2006 to 2021. Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires were administered for 12 patients after January 1, 2015, when the institution began collecting PROMIS in all orthopaedic patients. Average follow-up was 55 months (13-111); 18 patients had minimum 24-month follow-up. RESULTS: Forty feet in 25 patients were analyzed. The average preoperative lateral talar axis-first metatarsal base angle (TAMBA) was 68.7 ± 21.3 vs 12.1 ± 8.9 after initial surgical intervention (P < .0001). There was a statistically significant increase in the lateral TAMBA between the initial postoperative and final follow-up visits (13.0 vs 21.6, P = .02). Radiographic recurrence of talonavicular deformity was noted in 12 feet (30.9%); 7 (15.55%) required corrective surgery. Larger preoperative lateral TAMBA was predictive of recurrence. Notably, patients with arthrogryposis experienced higher radiographic recurrence than other syndromic patients (45.0% vs 14.3%, P = .0384). PROMIS scores were within population norms. CONCLUSION: The study suggests that less than one-third of syndromic CVT patients experienced a radiographic recurrence of talonavicular deformity, with 15% requiring further surgical intervention at an average of 55 months following the initial procedure. A higher incidence of radiographic recurrence occurred in patients with distal arthrogryposis. These findings, along with the satisfactory patient-reported outcomes, suggest that the minimally invasive technique is an effective treatment method for syndromic CVT, underscoring the necessity for clinicians to provide detailed prognoses and consider more intensive follow-up for those at higher risk. LEVEL OF EVIDENCE: Level IV, case series.

Outcomes of Ponseti Method for the Treatment of Clubfeet in Children With Spina Bifida.

INTRODUCTION: While the Ponseti method is the primary treatment for idiopathic clubfoot, its application in treating myelodysplastic clubfeet is less certain. Myelodysplastic clubfoot tends to be more severe and difficult to treat. Although the Ponseti method can initially correct these cases, there is conflicting evidence about recurrence rates and the need for additional treatment. This study aims to assess the effectiveness of the Ponseti method in treating myelodysplastic clubfeet compared with idiopathic clubfeet over a 20-year period. METHODS: The study conducted a retrospective review of medical records from patients treated for clubfoot at a single institution (2002 to 2021), comparing children with myelodysplastic and idiopathic clubfoot. Included patients were under 18, initially treated with Ponseti-casting, and had a minimum 2-year follow-up. Data on demographics, treatment details, recurrence, and Patient-reported Outcomes Measurement Information System (PROMIS) scores were analyzed. RESULTS: Forty-nine myelodysplastic and 512 idiopathic clubfeet in 366 patients met the inclusion criteria. Myelodysplastic cases had a median age of 5 months at presentation versus 2 months for idiopathic cases (P=0.002). Initial correction was achieved in 95% of idiopathic and 87.8% of myelodysplastic feet (P=0.185). Recurrence rates were higher in the myelodysplastic cohort, 65.3% versus 44.1% (P=0.005). Surgery was necessary to treat recurrence in 59.2% of myelodysplastic and 37.7% of idiopathic cases, P=0.003. Follow-up was 3.9±1.8 years for myelodysplastic and 3.3±1.5 years for idiopathic feet, P=0.030. Myelodysplastic feet had lower PROMIS mobility scores; 31.94±7.56 versus 49.21±8.64, P<0.001. CONCLUSIONS: To the best of our knowledge, we report the largest series of myelodysplastic clubfeet treated by Ponseti casting and the first to assess PROMIS data. Overall, the Ponseti method is as effective in obtaining initial correction in myelodysplastic clubfoot as it is in idiopathic clubfoot. However, myelodysplastic clubfeet has a higher risk of relapse and increased need for surgical interventions. Children with spina bifida may need closer follow-ups and more stringent adherence to bracing. LEVEL OF EVIDENCE: Level III-therapeutic studies-investigating the results of treatment.

Outcomes of Ponseti Method for the Treatment of Clubfeet in Children With Arthrogryposis.

INTRODUCTION: The Ponseti serial casting method is the method of choice in treating children with congenital clubfeet. The arthrogrypotic clubfoot has traditionally been considered challenging to treat, with higher rates of recurrence and the need for more corrective surgeries. However, initial reports have found promising results in using the Ponseti method to treat arthrogrypotic feet. This study aims to compare the outcomes of idiopathic versus arthrogrypotic clubfeet following initial treatment with the Ponseti serial casting method. METHODS: A retrospective review of medical records from a single institution was conducted. Data was collected from children ages 0 to 18 with idiopathic or arthrogrypotic clubfoot treated from 2002 to 2022 with Ponseti-style serial casting with a minimum 2-year follow-up. Recurrence was defined as the need for additional casting or subsequent surgeries following initial correction. Data was collected on relevant patient demographics, previous treatment, casting records, Achilles tenotomies, and surgical treatments. RESULTS: A total of 352 patients (546 feet) met inclusion criteria. In all, 334 idiopathic and 18 arthrogrypotic patients were analyzed with an average follow-up duration of 3.4 and 4.2 years, respectively. Twelve patients had distal arthrogryposis, and 6 had amyoplasia. In all, 93.4% of idiopathic and 72.2% of arthrogrypotic patients successfully achieved correction with Ponseti casting and Achilles tenotomy. Recurrence rates were significantly higher in the arthrogrypotic group at 83.3% compared with 44.6% in the idiopathic group ( P =0.001). A posterior or posterior medial release was performed in 35.0% of idiopathic and 66.7% arthrogrypotic feet. CONCLUSIONS: We report the largest series of arthrogrypotic clubfeet treated by Ponseti casting to the best of our knowledge. In contrast to earlier reports, our investigation underscores that while the Ponseti method may be able to secure initial correction in arthrogrypotic clubfeet, on average, at a 3-year follow-up, the prognosis is less favorable. These patients exhibit higher recurrence and often require operative treatment. Notably, a posterior medial release may eventually be needed in up to 6 of 10 patients. LEVEL OF EVIDENCE: Level III-therapeutic studies-investigating the results of treatment.

The Effect of Human Growth Hormone Treatment on the Development of Slipped Capital Femoral Epiphysis: A Cohort Analysis With 6 Years of Follow-up.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a common hip disorder in adolescents that can result in substantial complications, impacting the quality of life. Human Growth Hormone (HGH) administration may elevate the risk of SCFE, though the relationship remains unclear. Clarifying this association could enable better monitoring and earlier diagnosis of SCFE in patients receiving HGH. The aim of the study is to investigate the association between HGH administration and the incidence of SCFE. METHODS: This retrospective cohort study utilized data from the TriNetX research database from January 2003 to December 2022. The study included 2 cohorts: an HGH cohort including 36,791 patients aged below 18 years receiving HGH therapy and a control group consisting of patients who did not receive HGH therapy. A 1:1 propensity score matching technique was employed to ensure comparability between the HGH and no-HGH cohorts. The primary outcome measure was the development of SCFE identified by International Classification of Diseases codes. For comparative analysis, both risk ratios (RR) and hazard ratios were computed to evaluate the association between HGH therapy and the development of SCFE. RESULTS: The HGH cohort had an increased risk of SCFE compared with the no-HGH cohort (RR: 3.5, 95% CI: 2.073, 5.909, P <0.001) and had an increased hazard of developing SCFE (hazard ratio: 2.627, 95% CI: 1.555, 4.437, P <0.001). Patients with higher exposure to HGH (defined as >10 prescriptions) had an RR of 1.914 (95% CI: 1.160, 3.159, P =0.010) when compared with their counterparts with ≤10 prescriptions. CONCLUSIONS: In the largest study to date, HGH administration was associated with an elevated risk of SCFE in children in a dose-dependent manner. LEVEL OF EVIDENCE: Level III-therapeutic retrospective cohort study.

The interplay between MMP-12 and t-PA in the brain after ischemic stroke.

Tissue-type plasminogen activator (t-PA) expression is known to increase following transient focal cerebral ischemia and reperfusion. Previously, we reported downregulation of t-PA upon suppression of matrix metalloproteinase-12 (MMP-12), following transient focal cerebral ischemia and reperfusion. We now present data on the temporal expression of t-PA in the brain after transient ischemia, as well as the interaction between MMP-12 and t-PA, two proteases associated with the breakdown of the blood-brain barrier (BBB) and ischemic brain damage. We hypothesized that there might be reciprocal interactions between MMP-12 and t-PA in the brain after ischemic stroke. This hypothesis was tested using shRNA-mediated gene silencing and computational modeling. Suppression of t-PA following transient ischemia and reperfusion in rats attenuated MMP-12 expression in the brain. The overall effect of t-PA shRNA administration was to attenuate the degradation of BBB tight junction protein claudin-5, diminish BBB disruption, and reduce neuroinflammation by decreasing the expression of the microglia/macrophage pro-inflammatory M1 phenotype (CD68, iNOS, IL-1ß, and TNFα). Reduced BBB disruption and subsequent lack of infiltration of macrophages (the main source of MMP-12 in the ischemic brain) could account for the decrease in MMP-12 expression after t-PA suppression. Computational modeling of in silico protein-protein interactions indicated that MMP-12 and t-PA may interact physically. Overall, our findings demonstrate that MMP-12 and t-PA interact directly or indirectly at multiple levels in the brain following an ischemic stroke. The present findings could be useful in the development of new pharmacotherapies for the treatment of stroke.

Increased Cerebrospinal Fluid Amyloid-ß During Sleep Deprivation in Healthy Middle-Aged Adults Is Not Due to Stress or Circadian Disruption.

BACKGROUND: Concentrations of soluble amyloid-ß (Aß) oscillate with the sleep-wake cycle in the interstitial fluid of mice and cerebrospinal fluid (CSF) of humans. Further, the concentration of Aß in CSF increases during sleep deprivation. Stress and disruption of the circadian clock are additional mechanisms hypothesized to increase CSF Aß levels. Cortisol is a marker for stress and has an endogenous circadian rhythm. Other factors such as glucose and lactate have been associated with changes in sleep-wake activity and/or Aß. OBJECTIVE: In this exploratory study, we used samples collected in a previous study to examine how sleep deprivation affects Aß, cortisol, lactate, and glucose in plasma and CSF from healthy middle-aged adults (N = 11). METHODS: Eleven cognitively normal participants without evidence of sleep disturbance were randomized to sleep deprivation or normal sleep control. All participants were invited to repeat the study. Cortisol, lactate, glucose, and Aß were measured in 2-h intervals over a 36-h period in both plasma and CSF. All concentrations were normalized to the mean prior to calculating mesor, amplitude, acrophase, and other parameters. RESULTS: One night of sleep deprivation increases the overnight concentration of Aß in CSF approximately 10%, but does not significantly affect cortisol, lactate, or glucose concentrations in plasma or CSF between the sleep-deprived and control conditions. CONCLUSION: These data suggest that sleep deprivation-related changes in CSF Aß are not mediated by stress or circadian disruption as measured by cortisol.

Multi-Modal Home Sleep Monitoring in Older Adults.

The gold standard for sleep monitoring is attended in-lab polysomnography; however, this method may be cost-prohibitive and inconvenient for patients and research participants. Home sleep testing has gained momentum in the field of sleep medicine due to its convenience and lower cost, as well as being more naturalistic. The accuracy and quality of home sleep testing, however, may be variable because studies are not monitored by sleep technologists. There has been some success in improving the accuracy of home sleep studies by having trained sleep technicians assist participants inside their homes with putting on the devices, but this can be intrusive and time-consuming for those involved. In this protocol, participants undergo at-home sleep monitoring with multiple devices: 1) a single-channel EEG device; 2) a home sleep test for sleep-disordered breathing and periodic limb movements; 3) actigraphy; and 4) sleep logs. A major challenge of this study is obtaining high-quality sleep monitoring data on the first attempt in order to minimize participant burden. This protocol describes the implementation of educational manuals with step-by-step instructions and photos. The goal is to improve the quality of home sleep testing.