Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.

Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated human induced pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines. Using whole-exome and mitochondrial sequencing, we identified unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines were viable and capable of differentiating into progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS patient-derived cerebral organoids showed defects in neural epithelial bud generation, size and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with abnormal mitochondrial morphology, characterized by fragmentation and disorganization, and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used to study Leigh syndrome.

A patient-centered framework for health systems engineering in gastroenterology: improving inpatient colonoscopy bowel preparation.

BACKGROUND: Inpatient colonoscopy bowel preparation (ICBP) is frequently inadequate and can lead to adverse events, delayed or repeated procedures, and negative patient outcomes. Guidelines to overcome the complex factors in this setting are not well established. Our aims were to use health systems engineering principles to comprehensively evaluate the ICBP process, create an ICBP protocol, increase adequate ICBP, and decrease length of stay. Our goal was to provide adaptable tools for other institutions and procedural specialties. METHODS: Patients admitted to our tertiary care academic hospital that underwent inpatient colonoscopy between July 3, 2017 to June 8, 2018 were included. Our multi-disciplinary team created a protocol employing health systems engineering techniques (i.e., process mapping, cause-effect diagrams, and plan-do-study-act cycles). We collected demographic and colonoscopy data. Our outcome measures were adequate preparation and length of stay. We compared pre-intervention (120 ICBP) vs. post-intervention (129 ICBP) outcomes using generalized linear regression models. Our new ICBP protocol included: split-dose 6-L polyethylene glycol-electrolyte solution, a gastroenterology electronic note template, and an education plan for patients, nurses, and physicians. RESULTS: The percent of adequate ICBPs significantly increased with the intervention from 61% pre-intervention to 74% post-intervention (adjusted odds ratio of 1.87, p value = 0.023). The median length of stay decreased by approximately 25%, from 4 days pre-intervention to 3 days post-intervention (p value = 0.11). CONCLUSIONS: By addressing issues at patient, provider, and system levels with health systems engineering principles, we addressed patient safety and quality of care provided by improving rates of adequate ICBP.

Complications of K-wire fixation in procedures involving the hand and wrist.

PURPOSE: Surgeons often use smooth K-wires for bone stabilization in the hand and wrist. The purposes of this study were to observe the incidence of postoperative complications of K-wire fixation in the hand and wrist and to identify associated risk factors. METHODS: A total of 189 patients underwent bone and soft tissue procedures in the hand and wrist with insertion of 408 smooth K-wires. All patients were instructed to comply with a uniform pin care protocol and were observed for a minimum of 1 examination after pin removal. Complications were categorized as minor or major, with 3 subcategories for infectious complications. We compared total complications and infectious complications with patient age, comorbidities, soft tissue integrity, pin exposure (external or buried), number of pins inserted, pin location, compliance with pin site care, and empiric antibiotic treatment. RESULTS: We found that 39 patients experienced postoperative complications involving 58 K-wires (14% of all pins). Most complications were minor, commonly superficial pin track infection (24 pins, 6% of all pins). Major complications occurred less frequently (11 pins, 3% of all pins) and included complications that led to additional surgery (deep infection, malunion, or nonunion) and fractures through the pin track. The development of an infectious complication was associated with 2 factors: pin location in the hand versus the wrist and poor compliance with pin site care. Patient age, medical comorbidities, soft tissue integrity, pin exposure, number of pins inserted, and empiric antibiotic treatment had no statistically significant relationships to the occurrence of complications. CONCLUSIONS: Complications with smooth K-wire fixation in the hand and wrist are relatively uncommon. Most complications involve minor, superficial pin track infections. Location of pins in the hand as compared with the wrist and poor patient compliance with pin site care may increase the risk of infection.

Comparison of powered drill & manual bone biopsy systems: Does the diagnostic yield justify the cost?

Bone biopsies are traditionally performed using manual drill devices. More recently, powered drill biopsy systems have been developed, ostensibly to improve diagnostic yield. We compare the powered drill biopsy system to traditional manual needle devices on the basis of diagnostic yield, specimen size and material costs. 309 consecutive bone biopsy procedures performed with imaging guidance from a single academic institution were retrospectively reviewed. Specimen diagnostic adequacy, qualitative interpretation of diagnostically inadequate specimens, aggregate specimen volume and material costs were assessed. Econometric analysis was performed to assess the relationship between materials cost and diagnostic yield. Diagnostic yield and average core specimen volume were significantly higher in the powered drill group, with 86% of cases yielding adequate biopsy specimens versus 67% of cases using the manual method. The materials cost associated with the powered drill device was higher than those of any of the manual needle devices with an average difference of $270.19 per case, however, this was offset due to higher diagnostic yield suggesting that the increased diagnostic accuracy achieved by the powered drill does not carry a significant added financial burden. The powered drill bone biopsy system results in a significantly higher yield of diagnostically adequate biopsy specimens compared to traditional manual needles, possibly attributed to larger and more intact obtained core specimen volumes and is more economically viable off-setting the higher cost.

Long-term retrospective study of patients with idiopathic clubfoot treated with posterior medial-lateral release.

BACKGROUND: It has been demonstrated that an important component of clubfoot deformity is related to pathologic external rotation of the talus with respect to the remainder of the foot. The purpose of the present study was to review the long-term results for a cohort of patients with idiopathic clubfoot who were managed by a single surgeon with a uniform surgical protocol consisting of extensive posterior medial-lateral release in addition to the use of a temporary Kirschner wire to derotate the talus prior to fixation. METHODS: Eighty patients (120 clubfeet) with idiopathic clubfoot without previous surgery were managed with posterior medial-lateral release. At an average of twenty-one years postoperatively, patients underwent a detailed physical examination and completed four quality-of-life surveys (the Short Form-36, the Laaveg and Ponseti scale, the Foot Function Index, and the modified Atar scale). RESULTS: Thirty-two clubfeet (27%) had required additional procedures at the time of follow-up, with only one patient requiring complete revision posterior medial-lateral release and none requiring subtalar or triple arthrodesis. In patients with unilateral clubfoot, clinical examination demonstrated a significant decrease in the range of motion (p < 0.001), foot length (p = 0.045), and calf circumference (p = 0.008) on the affected side as compared with the unaffected, contralateral side. The results on all four quality-of-life scales remained durable, with no decline in relation to the time from the index procedure (p ≥ 0.48). Significantly worse scores were found for patients who required additional surgical procedures (p ≤ 0.03). CONCLUSIONS: Previous studies have demonstrated inconsistent long-term results following the treatment of clubfoot with extensive soft-tissue releases. With our technique, thirty-two clubfeet (27%) required additional procedures and only one clubfoot required revision posterior medial-lateral release. We demonstrate that our technique, which involves aggressive posterior medial-lateral soft-tissue release in addition to manual derotation of the talus with a Kirschner wire to correct pathologic external rotation, produces acceptable results.

Nerve block of the infrapatellar branch of the saphenous nerve in knee arthroscopy: a prospective, double-blinded, randomized, placebo-controlled trial.

BACKGROUND: With the rising use of outpatient knee arthroscopy over the past decade, interest in peripheral nerve blocks during arthroscopy has increased. Femoral nerve blocks are effective but are associated with an inherent risk of the patient falling postoperatively because of quadriceps weakness. We studied blocks of the infrapatellar branch of the saphenous nerve, which produce analgesia in the knee that is similar to that resulting from a femoral nerve block but without associated quadriceps weakness. METHODS: Thirty-four patients were enrolled into each arm of this prospective, randomized, double-blinded trial comparing 10 mL of 0.25% bupivacaine used as a block of the infrapatellar branch of the saphenous nerve with a placebo during simple knee arthroscopy. Immediate outcome measures included Numeric Rating Scale (NRS) pain scores (0 to 10 points), mobility and discharge times, opioid usage, subjective adverse side effects, and forty-eight-hour anesthesia recovery surveys. Short-term measures included one-week and twelve-week Lysholm knee scores. RESULTS: No adverse effects or increased quadriceps weakness were observed following use of the nerve block. Improvement in early NRS scores and subjective nausea (p = 0.03) were detected. Patients for whom the block was successful also had improved twelve-week Lysholm knee scores (p = 0.04). No differences in opioid usage, mobility time, forty-eight-hour anesthesia recovery scores, or one-week Lysholm knee scores were found. CONCLUSIONS: No significant adverse effect or disadvantage was identified for blocks of the infrapatellar branch of the saphenous nerve used in simple knee arthroscopy. In addition to decreased early NRS scores and nausea, blocks of the infrapatellar branch of the saphenous nerve demonstrated potential benefit at twelve weeks after simple knee arthroscopy.

Double lateral band transfer for treatment of traumatic hyperextension instability of the proximal interphalangeal joint: a report of two cases.

Post-traumatic hyperextension instability of the proximal interphalangeal joint may lead to pain, difficulty with initiating finger flexion, and a swan-neck deformity. Most techniques to correct a traumatic hyperextension deformity of the proximal interphalangeal joint require a window in the flexor retinaculum, retraction of the flexor tendons, and manipulation of the joint capsule with a conceivable potential for joint stiffness, tendon adhesions, and tendon bowstringing. We describe an extra-articular lateral band transfer technique that utilizes strips of both lateral bands and preserves the functional integrity of the flexor tendon sheath.