A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation.

The KRAS GTPase plays a critical role in the control of cellular growth. The activity of KRAS is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and also post-translational modification. Lysine 104 in KRAS can be modified by ubiquitylation and acetylation, but the role of this residue in intrinsic KRAS function has not been well characterized. We find that lysine 104 is important for GEF recognition, because mutations at this position impaired GEF-mediated nucleotide exchange. Because the KRAS K104Q mutant has recently been employed as an acetylation mimetic, we conducted a series of studies to evaluate its in vitro and cell-based properties. Herein, we found that KRAS K104Q exhibited defects in both GEF-mediated exchange and GAP-mediated GTP hydrolysis, consistent with NMR-detected structural perturbations in localized regions of KRAS important for recognition of these regulatory proteins. Despite the partial defect in both GEF and GAP regulation, KRAS K104Q did not alter steady-state GTP-bound levels or the ability of the oncogenic KRAS G12V mutant to cause morphologic transformation of NIH 3T3 mouse fibroblasts and of WT KRAS to rescue the growth defect of mouse embryonic fibroblasts deficient in all Ras genes. We conclude that the KRAS K104Q mutant retains both WT and mutant KRAS function, probably due to offsetting defects in recognition of factors that up-regulate (GEF) and down-regulate (GAP) RAS activity.

CIB1 depletion impairs cell survival and tumor growth in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with generally poor prognosis and no available targeted therapies, highlighting a critical unmet need to identify and characterize novel therapeutic targets. We previously demonstrated that CIB1 is necessary for cancer cell survival and proliferation via regulation of two oncogenic signaling pathways, RAF-MEK-ERK and PI3K-AKT. Because these pathways are often upregulated in TNBC, we hypothesized that CIB1 may play a broader role in TNBC cell survival and tumor growth. Methods utilized include inducible RNAi depletion of CIB1 in vitro and in vivo, immunoblotting, clonogenic assay, flow cytometry, RNA-sequencing, bioinformatics analysis, and Kaplan-Meier survival analysis. CIB1 depletion resulted in significant cell death in 8 of 11 TNBC cell lines tested. Analysis of components related to PI3K-AKT and RAF-MEK-ERK signaling revealed that elevated AKT activation status and low PTEN expression were key predictors of sensitivity to CIB1 depletion. Furthermore, CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo. RNA sequence analysis also showed that CIB1 depletion in TNBC cells activates gene programs associated with decreased proliferation and increased cell death. CIB1 expression levels per se did not predict TNBC susceptibility to CIB1 depletion, and CIB1 mRNA expression levels did not associate with TNBC patient survival. Our data are consistent with the emerging concept of non-oncogene addiction, where a large subset of TNBCs depend on CIB1 for cell survival and tumor growth, independent of CIB1 expression levels. Our data establish CIB1 as a novel therapeutic target for TNBC.

Lumbosacral Plexogram: An Aid to Reconstructive Nerve Possibilities in the Lower Extremity.

The lumbosacral plexus is the network of nerves responsible for the motor and sensory function of the pelvis and lower limb. Our observation is that the anatomy of this plexus is less familiar to surgeons than that of the brachial plexus. Damage to the lumbosacral plexus and its terminal branches may have a significant impact on locomotion, posture, and stability. We have designed a visual representation of the lumbosacral plexus to aid clinicians treating peripheral nerve disorders. The utility is illustrated with a case report in which a patient underwent nerve transfers in the lower limb to restore function. A visual representation of the lumbosacral plexus is a valuable adjunct to a clinical examination and helps make sense of clinical signs. The color-coding of each root level and the arrangement of muscles from proximal to distal helps with visual recall. A clear assessment of complex lumbosacral plexus patients is essential for diagnosis and planning. As with the case described, a sound knowledge of the "plexogram" can identify solutions for complex patients and result in significant functional improvements. We hope it helps advance the field of nerve surgery and, particularly, nerve transfers.

Spinal axial torque assessment after surgical correction in adolescent idiopathic scoliosis: a new approach to 3D barycentremetry and mass distribution based on biplanar radiographs.

PURPOSE: Barycentremetry in adolescent idiopathic scoliosis (AIS) allows the distribution of masses and their loading of the spine to be studied. In particular, the axial torque on the spine has been studied in AIS, but not after surgical correction. Spinal axial torque was studied in AIS before and after surgery. METHODS: All AIS (Lenke 1 and 3) who underwent posterior spinal fusion surgery at our center in 2019 were included retrospectively. AIS underwent frontal and sagittal biplanar radiographs in the free-standing position before surgery, 4 months after surgery, and at the last follow-up. Their spine and external envelope were reconstructed with validated methods. Spinal axial torque at the apex and the upper and lower end vertebra was calculated. Finally, the preoperative and postoperative values were compared to a previously published reference corridor for asymptomatic subjects. RESULTS: Twenty-nine patients were included (54 ± 11° Cobb angle, 15 ± 2 years old at surgery). The surgical procedure decreased the Cobb angle by 36° ± 11° and decreased the spinal axial torque at the upper end vertebra by 2.5 N/m (95% CI = [1.9; 3]; p < 0.001), at the apex by 0.6 N/m (95% CI = [0.4; 1]; p = 0.004), at the lower end vertebra by 2 N/m (95% CI = [1.5; 2.8]; p < 0.001). Compared to 95th percentile of torque, which was previously evaluated in asymptomatic subjects, more than 90% of patients had higher values at the upper and lower end vertebrae before surgery. Postoperatively, 62% of patients still had higher torque at the upper end vertebra than asymptomatic subjects, while only 38% patients showed abnormal values at the lower junction. CONCLUSION: Results of this study confirm that AIS patients show abnormally high spinal axial torque, especially at the end vertebrae, and that this parameter is normalized postoperatively for only a small number of patients.

The Double-Opposing Adipofascial Interposition Flap: A Novel Technique to Prevent Scar Tethering and Symptomatic Neuroma of the Superficial Radial Nerve After Trauma.

The superficial radial nerve (SRN) is vulnerable to injury following trauma with a high incidence of resultant nerve tether and neuroma formation. The SRN has an anatomical predisposition to neuroma formation, with research indicating that its propensity to neuroma development is out of proportion with its likelihood for injury. In addition, SRN neuromas have been described as one of the more painful and difficult neuromas to manage. Despite this, the published literature to date is chiefly focused on neuroma and scar tether treatment options rather than more impactful work on neuroma prevention, which can be safely delivered at the time of primary surgery. Treatment of established neuroma or nerve tether is notoriously difficult, and existing techniques have inconsistent outcomes, with patients often requiring multiple trips to the theatre. The authors present a novel technique for neuroma and scar tether prevention using an adipofascial flap accompanied by patient examples of our experience using this approach as an adjunct during the primary SRN repair, creating a gliding, interposing layer to prevent subsequent nerve traction pain and symptomatic neuroma. We identified five patients presenting with dorsal wrist injuries involving the SRN and one or more tendons. Patients' follow-up duration was a mean of 3.5 months (one to eight months). All follow-up patients showed no symptoms of a neuroma or nerve tether pain. All patients were discharged without re-referral or further surgery. Our patient sample demonstrates promising results using an adipofascial interposition flap as a prophylactic measure in traumatic injuries to reduce nerve tether pain and symptomatic neuroma formation in the SRN.

Supercharged End-to-Side Nerve Transfer for Ulnar Neuropathy: Redefining Nomenclature and Recommendations for Standardisation of Surgical Technique Description.

Supercharged end-to-side (SETS) nerve transfers have been described as a treatment option for ulnar neuropathy, however, there is inconsistency in the nomenclature used to describe the microsurgical technique. The purpose of this article is to systematically review the available literature on the SETS nerve transfer technique and to provide an overview of the technical variations to facilitate standardisation of surgical method. A literature review was performed through PubMed, MEDLINE, and Ovid databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that reported surgical technique of anterior interosseous nerve (AIN) to ulnar nerve SETS transfer were included. Studies were excluded when not referencing SETS/reverse end-to-side (RETS) nerve transfers, studies referencing nerve transfers other than AIN to motor fascicle bundle of the ulnar nerve (MUN), animal studies, and studies not reporting technique. Of the 168 studies found, 14 articles were included. In five articles, distal visualisation of the MUN in Guyon's canal was specifically cited. In the four studies that commented on donor preparation, sharp neurectomy proximal to the AIN branching point was undertaken. Recipient preparation was commented on in seven of the included studies. Two studies referred to an epineurial window only while five specifically recommended a perineurial window. Coaptation site was specified in four studies and all studies used sutures for coaptation, with four articles stipulating that 9-0 nylon was used. Additionally, fibrin glue was used in conjunction with suture technique in four studies. Consistency in nomenclature used to describe SETS microsurgical technique is needed before case series measuring outcome can be reliably interpreted. This review allowed for the development of suggestions for standardisation of nomenclature and minimal reporting requirements when describing SETS technique. Standardisation of technique will allow for reproducibility and facilitate future evaluations of outcome in prospective randomised control trials.

Combined latissimus dorsi transfer and deltoid flap for irreparable rotator cuff tear: A retrospective analysis.

PURPOSE: This study will evaluate the outcomes of the combined latissimus dorsi tendon transfer and deltoid flap for the management of irreparable posterosuperior rotator cuff tears. METHODS: This is a retrospective study of 15 patients who have undergone double transfer surgery for their irreparable posterosuperior rotator cuff tears. These patients were followed up in three periods. Functional outcomes such as the constant score (CS), subjective shoulder value (SSV), and range of motion were assessed as well as radiographic outcomes such as the acromio-humeral distance. RESULTS: Fifteen patients were included in the early and intermediate follow-up while only 8 remained at the latest follow-up. At the early follow-up the SSV (p = 0.001), CS (p = 0.021), and A-H distance (p = 0.008) showed a statistically significant improvement from their pre-operative values. At the latest follow-up, only the external rotation decreased from its value at the intermediate follow-up (p = 0.027). CONCLUSION: The double transfer technique showed sustainable improvement of the functional outcomes except for the external rotation. However, the loss of external rotation did not affect the remaining outcomes. Trials comparing this technique to other surgical managements or MIRCTs are needed to confirm these results.

The Clinical Outcomes of Spinal Accessory to Suprascapular Nerve Transfer Through a Posterior Approach.

BACKGROUND: Spinal accessory nerve (SAN) to suprascapular nerve (SSN) transfer can restore function to the rotator cuff following brachial plexus injuries. The traditional anterior approach using the lateral branch of the SAN causes denervation of the lateral trapezius limiting shoulder elevation. Suprascapular nerve pathology at the suprascapular notch may be missed resulting in poor reinnervation of the rotator cuff. The posterior approach uses the medial SAN and allows decompression and visualization of the SSN at the notch and nerve transfer coaptation closer to the target muscles with a shorter reinnervation distance. METHODS: This is a review of 28 patients from 2014 to February 2020 who underwent SAN to SSN nerve transfer via a posterior approach. Patients were evaluated for SSN pathology, external rotation power, and range of motion. Data were evaluated for high-energy trauma (HET) and low-energy trauma/nontraumatic etiology subsets. RESULTS: A total of 8 HET (40%) patients had pathology identified at the suprascapular notch during the posterior approach, including SSN scarring, ruptures, neuromata-in-continuity, and ossification of ligaments. British Medical Research Council grade greater than or equal to 4 shoulder external rotation was achieved in 75% patients with median range of motion 137.5°. CONCLUSIONS: Spinal accessory nerve to SSN transfer using a posterior approach allows visualization of pathology involving the SSN and coaptation of a medial SAN transfer close to the target muscles. Following HET, 8 cases (40%) had posterior pathology identified. Spinal accessory nerve to SSN transfer through a posterior approach shows improved external rotation power and range of motion.

Motor and sensory nerve transfers in the lower extremity: Systematic review of current reconstructive possibilities.

BACKGROUND: Peripheral nerve injuries (PNI) are predominantly treated by anatomical repair or reconstruction with autologous nerve grafts or allografts. Motor nerve transfers for PNI in the upper extremity are well established; however, this technique is not yet widely used in the lower extremity. This literature review presents an overview of the current options and postoperative results for nerve transfers as a treatment for nerve injury in the lower extremity. METHODS: A systematic search in PubMed and Embase databases was performed. Full-text English articles describing surgical procedures and postoperative outcomes of nerve transfers in the lower extremity were included. The primary outcome was postoperative muscle strength measured using the British Medical Research Council (MRC) scale, with MRC> 3 considered good and postoperative return of sensation reported according to the modified Highet classification. RESULTS: A total of 36 articles for motor nerve transfer and 7 for sensory nerve transfer were included. Sixteen articles described motor nerve transfers for treating peroneal nerve injury, 17 for femoral nerve injury, 2 for tibial nerve injury, and one for obturator nerve injury. Transfers of multiple branches to restore deep peroneal nerve function led to a good outcome in 58% of patients and 43% when a single branch was used as a donor. The transfer of multiple branches for femoral nerve or obturator nerve repair was performed in all reported patients with a good outcome. CONCLUSIONS: The transfer of motor nerves for the recovery of PNI is a feasible technique with relatively low risks and great benefits. The correct indication, timing, and surgical technique are essential for optimizing results.

Resect, rewire, and restore: Nerve transfer salvage of neurological deficits associated with soft tissue tumors in a retrospective cohort series at a tertiary reconstructive center.

AIMS: We aimed to explore the effectiveness of nerve transfer as an intervention to restore neurological deficits caused by extremity tumors through direct nerve involvement, neural compression, or as a consequence of oncological surgery. METHODS: A retrospective cohort study of consecutive cases was conducted, including all patients who underwent nerve transfers to restore functional deficits in limbs following soft tissue tumor resection. The threshold for a successful nerve transfer was a BMRC motor grade of 4/5 and sensory grade of 3-3+/4 with protective sensation. RESULTS: In total, 29 nerve transfers (25 motor and 4 sensory) were completed in 11 patients, aged 12-70 years at referral, over a 6-year period to 2020. This included 22 upper limb and 3 lower limb motor nerve transfers. The timing of delayed nerve transfer reconstructions was 1-15 months following primary oncological resection, with immediate simultaneous reconstructions performed in 4 cases. The threshold for success was achieved in 82% of upper limb and 33% of lower limb motor nerve transfers, while all sensory transfers were successful in restoring protective sensation. CONCLUSION: Nerve transfer surgery, a well-established technique in restoring deficits following traumatic nerve injury, is further demonstrably relevant in extremity oncological reconstruction, especially as it can be performed remotely to the tumor location or resection site and introduces a healthy nerve or fascicle to rapidly reinnervate distal muscles without sacrificing major function. This study further illustrates the importance of early recognition and referral to specialist services where multi-disciplinary surgical resection and reconstructive planning can be conducted. LEVEL OF EVIDENCE: IV Clinical Case Series.

Outcomes Following Surgery for Common Peroneal Nerve Intraneural Ganglion Cysts: A Case Series and Systematic Review.

Background: Intraneural ganglia are a rare cause of common peroneal nerve palsy. Although several treatment modalities exist, surgical intervention is recommended, especially in the setting of neurological dysfunction. We present a case series and systematic review on the clinical outcomes following surgical excision of common peroneal nerve intraneural ganglia. Methods: We performed a retrospective chart review of all patients who had undergone surgery for common peroneal nerve intraneural ganglia at Queen Elizabeth Hospital in Birmingham, UK, from 2012 to 2022. Demographic and pre- and postoperative findings were collected. A comprehensive literature search of MEDLINE and EMBASE databases was also performed to identify similar studies. Data were subsequently extracted from included studies and qualitatively analyzed. Results: Five patients at our center underwent procedures to excise intraneural ganglia. There was a male preponderance. Pain, foot drop, and local swelling were the common presenting features. Postoperatively, all patients who completed follow-up demonstrated improved motor function with no documented cyst recurrence. The systematic review identified 6 studies involving 128 patients with intraneural ganglia treated with surgery. Similar findings were reported, with objective and subjective measures of foot and ankle function and symptoms improving after surgical intervention. The recurrence rate varied from 0% to 25%, although most recurrences were extraneural. Conclusions: Excision of intraneural ganglia is associated with symptomatic relief and functional improvement. Recurrence rates are relatively low and are rarely intraneural.

Versatility of the double fascicular transfer in reconstruction of elbow flexion paralysis: Intermediate term follow-up and patient-related outcome measures.

OBJECTIVES: The use of fascicle transfers in the reconstruction of traumatic brachial plexus injury is well established, but limited evidence is available regarding their use in atraumatic elbow flexion paralysis. This retrospective case review aimed to verify whether median and ulnar fascicle transfers are similarly effective in atraumatic versus traumatic elbow flexion paralysis when measured using the British Medical Research Council (MRC) scale, Brachial plexus Assessment Tool (BrAT) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) scores at long-term follow-up. METHODS: All median and ulnar fascicle transfer cases performed at the Queen Elizabeth Hospital Birmingham between August 2007 and November 2018 were reviewed to compare the outcomes of transfers performed for traumatic and atraumatic indications. Data on patient demographics, mechanism and nature of injury, date of injury or symptom onset, date of operation, and other nerve transfers performed were collected. Outcome measures collected included the British MRC scale and two patient-reported outcome measures (PROMs), BrAT and SPONEA. RESULTS: In total, 34 patients with 45 median and ulnar fascicle transfers were identified. This included 27 traumatic and seven atraumatic brachial plexus insults. Thirty patients had sufficient follow-up to be included in MRC analysis and 17 patients had sufficient follow-up to be included in PROM analysis. No significant differences were found between traumatic and atraumatic subgroups for median MRC, BrAT, or SPONEA scores. CONCLUSIONS: This study suggests that nerve transfers might be considered effective reconstructive options in atraumatic pathology and provides validation for further research on the subject.

Sensory nerve transfers in the upper limb after peripheral nerve injury: a scoping review.

Nerve transfer for motor nerve paralysis is an established technique for treating complex nerve injuries. However, nerve transfer for sensory reconstruction has not been widely used, and published research on this topic is limited compared to motor nerve transfer. The indications and outcomes of nerve transfer for the restoration of sensory function remain unproven. This scoping review examines the indications, outcomes and complications of sensory nerve transfer. In total, 22 studies were included; the major finding is that distal sensory nerve transfers are more successful than proximal ones in succeeding protective sensation. Although the risk of extension of the sensory deficit with donor site loss and morbidity from neuromas remain a barrier to wider adoption, these complications were not reported in the review. Further, the scarcity of studies and small patient series limit the ability to determine sensory nerve transfer success. However, sensory restoration remains an opportunity for surgeons to pursue.Level of evidence: II.

COVID-19 Prevention Behaviours and Vaccine Acceptability, and Their Association with a Behaviour Change Campaign in Somalia: Analysis of a Longitudinal Cohort.

Somalia experienced its first wave of COVID-19 infections in March 2020 and has experienced fluctuating infection levels since. Longitudinal data on suspected cases of COVID-19, attitudes, and behaviours were collected by telephone interviews of cash-transfer programme beneficiaries from June 2020-April 2021. A multi-media Social and Behaviour Change Communication (SBCC) campaign was designed and implemented from February 2021 to May 2021. Between the end of the first wave and the onset of the second the perceived threat from COVID-19 increased, with the proportion of respondents viewing it as a major threat increasing from 46% to 70% (p = 0.021). Use of face coverings increased by 24% (p < 0.001) and hand shaking and hugging for social greeting decreased, with 17% and 23% more people abstaining from these practices (p = 0.001). A combined preventative behaviour score (PB-Score) increased by 1.3 points (p < 0.0001) with a higher score in female respondents (p < 0.0001). During wave 2, vaccine acceptance was reported by 69.9% (95% CI 64.9, 74.5), overall. Acceptance decreased with increasing age (p = 0.009) and was higher in males (75.5%) than females (67.0%) (p = 0.015). Awareness of the SBCC campaign was widespread with each of the 3 key campaign slogans having been heard by at least 67% of respondents. Awareness of 2 specific campaign slogans was independently associated with an increased use of face coverings (aOR 2.31; p < 0.0001) and vaccine acceptance (aOR 2.36; p < 0.0001). Respondents reported receiving information on the pandemic from a wide range of sources with mobile phones and radio the most common. Trust in different sources ranged widely.

Detection of QT prolongation using a novel electrocardiographic analysis algorithm applying intelligent automation: prospective blinded evaluation using the Cardiac Safety Research Consortium electrocardiographic database.

BACKGROUND: The Cardiac Safety Research Consortium (CSRC) provides both "learning" and blinded "testing" digital electrocardiographic (ECG) data sets from thorough QT (TQT) studies annotated for submission to the US Food and Drug Administration (FDA) to developers of ECG analysis technologies. This article reports the first results from a blinded testing data set that examines developer reanalysis of original sponsor-reported core laboratory data. METHODS: A total of 11,925 anonymized ECGs including both moxifloxacin and placebo arms of a parallel-group TQT in 181 subjects were blindly analyzed using a novel ECG analysis algorithm applying intelligent automation. Developer-measured ECG intervals were submitted to CSRC for unblinding, temporal reconstruction of the TQT exposures, and statistical comparison to core laboratory findings previously submitted to FDA by the pharmaceutical sponsor. Primary comparisons included baseline-adjusted interval measurements, baseline- and placebo-adjusted moxifloxacin QTcF changes (ddQTcF), and associated variability measures. RESULTS: Developer and sponsor-reported baseline-adjusted data were similar with average differences <1 ms for all intervals. Both developer- and sponsor-reported data demonstrated assay sensitivity with similar ddQTcF changes. Average within-subject SD for triplicate QTcF measurements was significantly lower for developer- than sponsor-reported data (5.4 and 7.2 ms, respectively; P < .001). CONCLUSION: The virtually automated ECG algorithm used for this analysis produced similar yet less variable TQT results compared with the sponsor-reported study, without the use of a manual core laboratory. These findings indicate that CSRC ECG data sets can be useful for evaluating novel methods and algorithms for determining drug-induced QT/QTc prolongation. Although the results should not constitute endorsement of specific algorithms by either CSRC or FDA, the value of a public domain digital ECG warehouse to provide prospective, blinded comparisons of ECG technologies applied for QT/QTc measurement is illustrated.

Wireless remote monitoring of reconstructed 12-lead ECGs after ablation for atrial fibrillation using a hand-held device.

OBJECTIVE: Atrial fibrillation (AF) surveillance using a wireless handheld monitor capable of 12-lead electrocardiogram reconstruction was performed, and arrhythmia detection rate was compared with serial Holter monitoring. METHODS: Twenty-five patients were monitored after an AF ablation procedure using the hand-held monitor for 2 months immediately after and then for 1 month approximately 6 months postablation. All patients underwent 12-lead 24-hour Holter monitoring at 1, 2, and 6 months postablation. RESULTS: During months 1-2, 425 of 2942 hand-held monitor transmissions from 21 of 25 patients showed AF/atrial flutter (Afl). The frequency of detected arrhythmias decreased by month 6 to 85/1128 (P < .01) in 15 of 23 patients. Holter monitoring diagnosed AF/Afl in 8 of 25 and 7 of 23 patients at months 1-2 and month 6, respectively (P < .01 compared with wireless hand-held monitor). Af/Afl diagnosis by wireless monitoring preceded Holter detection by an average of 24 days. CONCLUSIONS: Wireless monitoring with 12-lead electrocardiogram reconstruction demonstrated reliable AF/Afl detection that was more sensitive than serial 12-lead 24-hour Holter monitoring.

Clinical outcomes following neurolysis and porcine collagen extracellular matrix wrapping of scarred nerves in revision carpal tunnel decompression.

Scar tether after primary nerve decompression can impair physiological nerve glide and vascularity of the nerve. Revision decompression in the setting of neurostenalgia should address the scarred mesoneurium in order to prevent further entrapment and tether. This study reports on the clinical outcomes of 12 patients with neurostenalgia following carpal tunnel decompression (CTD), treated with revision CTD and a porcine submucosa extracellular matrix nerve wrap (PECM) (Axoguard® nerve protector, Axogen Inc., Alachua, FL). Eleven patients had one primary decompression procedure prior to revision surgery; one patient previously had two operations for CTD. There was a significant reduction in visual analogue pain scores (VAS) and improvement in patients' satisfaction rating and symptom resolution. Patient-reported outcome measures were recorded using the Impact of Hand Nerve Disorders (I-HaND) Scale (Version 2), which demonstrated a significant reduction in hand disability. There were no complications attributable to the procedure and no re-revision procedures necessary at the latest follow-up.

Outcomes of anterior interosseous nerve transfer to restore intrinsic muscle function after high ulnar nerve injury.

Traumatic high ulnar nerve injuries have historically resulted in long-term loss of hand function due to the long re-innervation distance to the intrinsic muscles. Transfer of the anterior interosseous nerve (AIN) to the deep motor branch of the ulnar nerve (MUN) is proving promising in these patients. The purpose of this study was to evaluate the outcomes and efficacy of this procedure in our series. Eligible high ulnar nerve injury patients who underwent AIN to MUN nerve transfer were evaluated with a mean follow-up of 17 months. Data including demographics, injury details, surgical procedures, and outcomes were collected. A review of the current literature was performed for comparison. Sixteen patients had AIN to MUN transfer, mean age of 39.4 years, and a median delay from injury to nerve transfer of 0.8 months. The injury site was above the elbow in 5 cases, at the elbow in 8 cases, and in the proximal forearm in 3 cases. The majority were sharp transection, with the remaining from blast injuries, traumatic traction, and one post-traumatic neuroma resection. Transfer was performed end-to-end in 7 cases, hemi end-to-end in 7 cases, and supercharged end-to-side in 2 cases. Five patients achieved intrinsic muscle recovery of MRC 4+ and thirteen gained MRC 3 or above. The AIN to MUN nerve transfer provides meaningful intrinsic recovery in the majority of traumatic high ulnar nerve injuries. This procedure should be routinely considered, however, warrants further research to validate the optimum technique.

Congenital scoliosis: a narrative review and proposal of a treatment algorithm.

Congenital scoliosis (CS) is a spinal deformity resulting from underlying spinal malformations with an incidence of 0.5-1/1000 births. CS makes up 10% of scoliotic deformities, of which 25% do not progress, 25% progress mildly and 50% need treatment depending on the age, curve characteristics and magnitude and type of anomaly. CS is associated with non-vertebral anomalies (genitourinary, musculoskeletal, cardiac, ribs anomalies, etc.) and intraspinal anomalies (syrinx and tethered cord). Imaging should include whole spine X-rays, CT scanner with reconstruction to better delineate the vertebral anomalies and MRI to visualize the neural elements. Treatment of CS in the majority of cases is non-surgical and relies on fusion techniques (in situ fusion and hemiepiphysiodeis), resection techniques (hemiverterba resection), and growth-friendly techniques (distraction and instrumentation without fusion).

Major implications of single nucleotide polymorphisms in human carboxylesterase 1 on substrate bioavailability.

The number of studies and reviews conducted for the Carboxylesterase gene is limited in comparison with other enzymes. Carboxylesterase (CES) gene or human carboxylesterases (hCES) is a multigene protein belonging to the α/ß-hydrolase family. Over the last decade, two major carboxylesterases (CES1 and CES2), located at 16q13-q22.1 on human chromosome 16 have been extensively studied as important mediators in the metabolism of a wide range of substrates. hCES1 is the most widely expressed enzyme in humans, and it is found in the liver. In this review, details regarding CES1 substrates include both inducers (e.g. Rifampicin) and inhibitors (e.g. Enalapril, Diltiazem, Simvastatin) and different types of hCES1 polymorphisms (nsSNPs) such as rs2244613 and rs71647871. along with their effects on various CES1 substrates were documented. Few instances where the presence of nsSNPs exerted a positive influence on certain substrates which are hydrolyzed via hCES1, such as anti-platelets like Clopidogrel when co-administered with other medications such as angiotensin-converting enzyme (ACE) inhibitors were also recorded. Remdesivir, an ester prodrug is widely used for the treatment of COVID-19, being a CES substrate, it is a potent inhibitor of CES2 and is hydrolyzed via CES1. The details provided in this review could give a clear-cut idea or information that could be used for further studies regarding the safety and efficacy of CES1 substrate.