Intra-operative evaluation of textured anatomic implant rotation: a prospective study.

BACKGROUND: Textured implants were developed with the goal of reducing rates of capsular contracture and preventing implant malposition (eg., malrotation). Recent evidence has questioned whether textured implants are as resistant to malrotation as previously reported. METHODS: Women presenting to a single healthcare system for removal of textured implants were prospectively enrolled in the study from September 2019 to July of 2022. Patients who underwent removal of an anatomic, textured implant in the operating room were included in the study, while those who did not undergo implant removal, or were found to have a smooth implant, or a round, textured implant were excluded. The degree of implant rotation upon removal of the implant was measured intra-operatively. Implant specific factors, as well as patient demographics, clinical factors, and operative characteristics were collected. RESULTS: A total of 51 patients (80 implants) were included in the study. 45% of implants were malrotated (rotated >30 degrees) and the median degree of rotation was 30. Having more than one previous revision of the breast pocket was predictive of implant rotation (42 degrees) on multivariate linear regression analysis. Patients who presented with a complaint of "aesthetic dissatisfaction" had 2.89 increased odds of having an implant rotated > 30 degrees. CONCLUSION: Our study found a high rate of malrotation of textured, shaped implants upon explantation.

Performance of Near-Infrared Spectroscopy in Detecting Acute Tourniquet-Induced Upper-Extremity Ischemia Across Different Skin Phenotypes.

PURPOSE: Diagnosing acute tissue ischemia is challenging, particularly in patients with higher skin melanin content. We investigated whether near-infrared spectroscopy (NIRS) is effective and consistent in detecting upper extremity ischemia across various skin phenotypes. METHODS: Volunteers underwent tourniquet-induced upper extremity ischemia. Skin color was evaluated by the Fitzpatrick scale (FP, range: I-VI) and the Von Luschan scale (vL, range: 1-36). A NIRS probe was placed on one finger. The tourniquet was inflated to 250 mmHg and perfusion was restricted for 7 minutes, followed by a 10-minute monitored reperfusion period. The percent tissue oxygenation (StO2) was recorded. RESULTS: A total of 55 volunteers were enrolled (22 self-identified as Caucasian, 21 African American, 7 Asian, 2 Latinx, and 2 Biracial). Average starting and ending StO2 for the cohort was 72.2% and 45.9%, respectively. However, there was variability based on skin melanin content. Increasing vL correlated with lower starting StO2, smaller StO2 decrease, and shorter time to reach ischemic steady state. High skin melanin (FP scale IV-VI) was associated with significantly lower starting StO2 (-7.1%) and shorter time to reach ischemic steady state (-0.3 mins). African Americans had lower starting StO2 (-8.6%) and 7.8% lesser total StO2 decrease than other groups. CONCLUSIONS: NIRS can rapidly detect acute onset tissue ischemia in the upper extremity. However, given the lower starting StO2 and smaller total StO2 decrease after tourniquet-induced ischemia for patients with higher skin melanin, using NIRS for clinical detection of acute ischemia may be more challenging in these patients. These inconsistencies may limit use of NIRS clinically for spot identification of ischemia. CLINICAL RELEVANCE: Although NIRS has utility in tracking tissue oxygenation, variable performance with different skin melanin content raises concerns as to whether different cutoff/threshold levels are needed for different groups, and whether NIRS is reliable for spot checks in acute events.

Diagnostic Biomarkers for Upper Extremity Chronic Pain Conditions.

Hand surgery patients often experience chronic pain conditions. However, there are few reliable ways to measure pain, making diagnosis and subsequent management of these conditions notably challenging for the hand surgeon. Various diagnostic biomarkers have been actively studied in the chronic pain management field with promising results. This review discusses the development of diagnostic biomarkers for chronic pain conditions of the upper extremity, including complex regional pain syndrome, osteoarthritis, and neuropathic pain. Techniques involving the measurements of heart rate variability, molecular biomarkers including inflammatory and noninflammatory molecules, metabolites, and exosomes, magnetic resonance imagining and electroencephalography, as well as skin biopsy, are discussed. Future potential applications are proposed.

Treatment of Refractory Radial Sensory Neuroma With Function-Sparing Targeted Muscle Reinnervation to the Extensor Carpi Radialis Brevis.

The radial sensory nerve can be injured during many common procedures, including intravenous cannulation, first extensor compartment release, and radial-sided wrist surgery. Injury to the nerve may result in neuroma formation that can lead to chronic and debilitating pain. Nonsurgical treatments and surgical interventions, including excision of the neuroma and burying the nerve into local muscle, are frequently ineffective. Here, we present a technique for treating recalcitrant neuromas of the radial sensory nerve with targeted muscle reinnervation to a redundant motor nerve branch of the extensor carpi radialis brevis.

Passive Manipulation for Proximal Interphalangeal Joint Extension Contractures.

PURPOSE: We investigated closed passive manipulation as an alternative to surgery for certain proximal interphalangeal (PIP) joint extension contractures. METHODS: We retrospectively reviewed all patients with PIP joint extension contractures treated with passive manipulation at our institution between 2015 and 2019. The included patients were a minimum of 12 weeks from their initial injury/surgery (median 179 days; interquartile range: 130-228 days), had plateaued with therapy, and underwent a 1-time passive manipulation. All included fingers had congruent PIP joints and no indwelling hardware that could have had direct adhesions. Most (80%) patients had a direct injury to the finger ray(s) that led to the contractures. Most (75%) patients had the manipulation performed under local anesthesia in the office. Available measures of passive range of motion (PROM) and active range of motion (AROM) immediately, within 6 weeks, between 6 and 12 weeks, and at >12 weeks after the manipulation were recorded. RESULTS: Twenty-eight patients and 46 digits met the criteria. The median PIP joint PROM improved from 50° to 90° immediately following the manipulation. The median PROM values within 6 weeks, between 6 and 12 weeks, and at >12 weeks following manipulation were 80°, 85°, and 85°, respectively. The median AROM immediately after the manipulation improved from 40° to 90°, and the median AROM values within 6 weeks, between 6 and 12 weeks, and at >12 weeks were 70°, 50°, and 60°, respectively. None of the patients experienced worsening of PIP joint range of motion. One patient who had 4 fingers manipulated had a 45° distal interphalangeal joint extension lag for one of the fingers after the manipulation. Eight fingers underwent later flexor tenolysis or reconstruction to improve AROM after the gains in PROM via manipulation were maintained. CONCLUSIONS: Passive manipulation is an alternative to surgical release for select PIP joint extension contractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Pain Control and Satisfaction With Peripheral Nerve Blocks for Upper Extremity Surgery.

BACKGROUND: Regional anesthesia ("block") is an important component of upper extremity (UE) surgery pain control. However, little is known about patient experience related to perioperative opioid use. This study assessed patient-reported pain control and satisfaction with UE blocks and evaluated how opioid consumption impacted these outcomes before the block "wore off." METHODS: A postoperative phone survey was administered to patients who underwent outpatient UE surgery at a surgery center for more than 16 months. It assessed pain scores (scale 1-10), satisfaction with block duration (scale 1-5), duration until return of UE function, and opioid consumption. Analyses used Mann-Whitney U tests, Fisher exact tests, and bivariate and multivariable linear and ordered logistic regressions to understand relationships between opioid use and outcomes. RESULTS: A total of 509 patients (61%) completed the survey, and 441 (88%) were satisfied with block duration. Initial and final pain scores were significantly higher in patients who took opioids prior to the block wearing off (6 and 4.5, P = .04 and 3.5 and 2, P = .002, respectively). Although satisfaction with block duration was not different in group comparisons (ie, patients who premedicated vs those who did not), in a multivariable analysis, patients who premedicated with opioids had 78% increased odds of reporting the highest level of satisfaction compared with the lower 4 levels (P = .03). CONCLUSIONS: Upper extremity blocks are associated with high overall patient satisfaction and postsurgical pain control. Premedicating before the block wears off may increase patient satisfaction with block duration even if pain is not notably impacted.

Discrepancies in Work Relative Value Unit Assignment Based on Operative Time in Hand Surgery.

BACKGROUND: Work relative value units (wRVUs) are an intricate component of physician reimbursement determination in the United States. This paper assesses whether wRVUs appropriately consider operative time in hand surgery. METHODS: The 50 most common single Current Procedural Terminology code hand surgery cases were queried from the 2013 to 2018 National Surgical Quality Improvement Program database. The average assigned wRVUs and median operative times were calculated for each CPT. Linear regressions were calculated between operative time, wRVUs, and wRVUs per hour. Cases deviating the most from the expected wRVUs based on operative time were identified. RESULTS: In all, 46 800 cases comprising the top 50 most common hand surgery procedures were identified. Among these cases, the median (range) assigned operative time was 62 minutes (18-110), wRVUs were 7.5 (3.5-18.0), and wRVUs per hour was 8.3 (4.9-14.2). There was a positive linear correlation between operative time and wRVUs (R2 = 0.60). Each additional operative hour was associated with an additional 6.3 wRVUs (P < .001). Based on this relationship, the assigned wRVUs for included cases ranged from 59.7% to 172.6% of expected. There was a weak negative relationship between wRVUs per hour and operative time (R2 = 0.25). Cases shorter than 1 hour had more wRVUs per hour than those longer than 1 hour (10.0 vs. 8.1, P = .003). However, this relationship disappeared when considering case turnover. CONCLUSION: This study suggests a moderately strong positive correlation between wRVUs and operative time in hand surgery. Yet, numerous outliers from this trend exist, suggesting some discrepancies in reimbursement.

Global Genome Demethylation Causes Transcription-Associated DNA Double Strand Breaks in HPV-Associated Head and Neck Cancer Cells.

High levels of DNA methylation at CpG loci are associated with transcriptional repression of tumor suppressor genes and dysregulation of DNA repair genes. Human papilloma virus (HPV)-associated head and neck squamous cell carcinomas (HNSCC) have high levels of DNA methylation and methylation has been associated with dampening of an innate immune response in virally infected cells. We have been exploring demethylation as a potential treatment in HPV+ HNSCC and recently reported results of a window clinical trial showing that HNSCCs are particularly sensitive to demethylating agent 5-azacytidine (5-aza). Mechanistically, sensitivity is partially due to downregulation of HPV genes expression and restoration of tumor suppressors p53 and Rb. Here, for the first time, we show that 5-azaC treatment of HPV+ HNSCC induces replication and transcription-associated DNA double strand breaks (DSBs) that occur preferentially at demethylated genomic DNA. Blocking replication or transcription prevented formation of DNA DSBs and reduced sensitivity of HPV-positive head and neck cancer cells to 5-azaC, demonstrating that both replication and active transcription are required for formation of DSBs associated with 5-azaC.

Complete Reoperation in Orthognathic Surgery.

BACKGROUND: Complete reoperation is defined as undergoing reoperative/repeated jaw osteotomies, in a patient who previously underwent orthognathic surgery. The purpose of this study is to (1) describe jaw positions at three time-points (before primary and before and after reoperative surgery), (2) investigate factors necessitating reoperation, and (3) outline the technical challenges. METHODS: Repeated orthognathic surgery cases >1-year out were included. Demographic, radiologic, and perioperative data were compiled. Repeated osteotomies (Le-Fort and/or bilateral split sagittal osteotomy, with or without genioplasty), were compared to their respective primary procedures. Statistical analysis was performed using t tests and z-scores. RESULTS: Fifteen patients were included (28.1 years; 71 percent female). Reoperative/repeated surgery was most often needed to address iatrogenic bony malposition and asymmetry. Relapse was a less common indication. Time between reoperative and primary surgery was 14 months. Sagittal discrepancies (p = 0.029) were the most frequent reason for primary orthognathic surgery (e.g., mandibular hypoplasia (p = 0.023). Reoperative/repeated orthognathic was performed for asymmetry (p = 0.014). Repeated procedures used more 3-dimensional planning (p < 0.001), required all three osteotomies (p = 0.034), had longer operative times (p = 0.078), and all required hardware removal (p < 0.001). Anatomical outcomes were good with 100% patient satisfaction at long-term follow-up. CONCLUSIONS: Reoperative/repeated orthognathic surgery is challenging and underreported in the literature. Whereas primary orthognathic typically addressed sagittal discrepancies, reoperative/repeated osteotomies were needed to correct iatrogenic bone malposition and asymmetries. Challenges include: re-planning, scar burden, need to remove integrated hardware, and repeated osteotomy/fixation. Despite these difficulties, outcomes and patient acceptance were good. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Clockwise and Counterclockwise Le Fort I Movements Influence Nasolabial Morphology Differently.

BACKGROUND: Le Fort I maxillary advancements affect nasal proportions. However, there are no data on the three-dimensional nasal changes that occur with differential lateral plane adjustment (clockwise and counterclockwise movements) during Le Fort I maxillary advancements. This study analyzes and compares nasolabial soft-tissue changes after Le Fort I clockwise and counterclockwise repositioning. METHODS: Single-piece Le Fort I advancements were included. A retrospective study of patients split into clockwise and counterclockwise groups was performed. Preoperative and postoperative three-dimensional photographs (VECTRA 3D) were analyzed. Nasolabial anthropometric measurements were recorded using Mirror software. Statistical analysis involved paired t test to compare preoperative and postoperative measurements. RESULTS: Twenty-four patients were evaluated (12 per group), with 22 distinct nasolabial relationships measured. Counterclockwise movement showed a statistically significant increase in alar width (3.6 mm; p < 0.001), alar base width (1.6 mm; p = 0.009), oral width (3.2 mm; p = 0.02), and lip projection (3.4 mm; p = 0.04). Clockwise movement showed no statistically significant changes, with the largest position changes noted in alar width (2.7 mm; p = 0.07) and alar base width (1.7 mm; p = 0.09). CONCLUSIONS: Clockwise and counterclockwise Le Fort I advancements have a different effect on postoperative nasolabial morphology. Counterclockwise movements exhibit significant changes, widening the alar base and width and the oral and philtral widths. The impact on the nostril morphology and columella was similar between the groups. The differential impact on nasolabial appearance is important to recognize for treatment planning and patient counseling. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Nonvisualization of Sentinel Lymph Nodes by Lymphoscintigraphy in Primary Cutaneous Melanoma: Incidence, Risk Factors, and a Review of Management Options.

BACKGROUND: Lymphoscintigraphy is often performed before sentinel lymph node biopsy, especially in areas likely to have multiple or aberrant drainage patterns. This study aims to determine the incidence and characteristics of melanoma patients with negative lymphoscintigraphic findings and to review the management options and surgical recommendations. METHODS: This is a retrospective study of patients with primary cutaneous melanoma who underwent sentinel lymph node biopsy between 2005 and 2016. Patients with nonvisualized lymph nodes on preoperative lymphoscintigraphy were compared in a 1:4 ratio with a randomly selected unmatched cohort drawn from all melanoma patients who underwent preoperative lymphoscintigraphy within the period of the study. Demographic, clinical, and outcome data were compared between these groups. RESULTS: A negative lymphoscintigraphic scan was seen in 2.3 percent of all cases (25 of 1073). In both univariate and multivariate analyses, predictive patient- and tumor-specific factors for negative lymphoscintigraphy included older age and head and neck location. Patients with a nonvisualized sentinel lymph node had significantly worse overall survival compared with patients who had a visualized sentinel lymph node, but there was no difference in melanoma-specific survival. In 16 of the 25 cases (64 percent), at least one sentinel lymph node was found intraoperatively despite the negative lymphoscintigraphic findings. CONCLUSIONS: Older patients with head and neck melanomas are more likely to experience nodal nonvisualization on lymphoscintigraphy. In patients who have nodal nonvisualization, the surgeon should attempt sentinel lymph node biopsy at the time of excision of the primary lesion because a sentinel lymph node can still be found in a majority of cases, and it offers prognostic information. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

A Quantitative Analysis of Weight Gain Following Mandibular Distraction Osteogenesis in Robin Sequence.

Mandibular distraction osteogenesis (MDO) is an effective treatment modality for children suffering from upper airway obstruction from Robin Sequence (RS). Mandibular distraction osteogenesis has been shown to have positive effects on oral feeding and for relieving respiratory obstruction, but its effects on postoperative weight gain are poorly understood. This study quantitatively analyzes weight gain following MDO. A retrospective chart review identified 22 RS children who underwent MDO. Patient weight data, feeding methods pre- and postoperatively, and polysomnography data pre- and postoperatively were collected. Each patient's weight plotted over time was then compared with his or her closest standardized growth curve, and linear regression analysis was utilized to quantify patient growth by calculating actual and expected average daily weight gain (g/d). Percentile changes were analyzed as well. Children gained significantly less weight than expected from birth to time of MDO and significantly more weight than expected from MDO to device removal, MDO to 6 months postoperatively, and MDO to 12 months postoperatively. The average growth percentile for the cohort was 37.3 at birth, declined to 22.7 by MDO, and increased to 28.5 and 33.5 at device removal and 6 months postoperatively, respectively. More than 70% of children were exclusively orally fed within 6 months of MDO. Children with isolated Robin Sequence had superior weight gain than children with syndromic Robin Sequence following surgery. In conclusion, MDO helps improve weight gain following surgery, particularly for infants with isolated Robin Sequence, and has positive effects on oral feeding and respiration.

Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer.

Purpose: DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation, and survival. Here, we determined activity of a global DNA-demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in preclinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC.Experimental Design: Sensitivity of HNSCC cells to 5-aza treatment was determined, and then 5-aza activity was tested in vivo using xenografted tumors in a mouse model. Finally, tumor samples from patients enrolled in a window clinical trial were analyzed to identify activity of 5-aza therapy in patients with HPV+ HNSCC.Results: Clinical trial and experimental data show that 5-aza induced growth inhibition and cell death in HPV+ HNSCC. 5-aza reduced expression of HPV genes, stabilized p53, and induced p53-dependent apoptosis in HNSCC cells and tumors. 5-aza repressed expression and activity of matrix metalloproteinases (MMP) in HPV+ HNSCC, activated IFN response in some HPV+ head and neck cancer cells, and inhibited the ability of HPV+ xenografted tumors to invade mouse blood vessels.Conclusions: 5-aza may provide effective therapy for HPV-associated HNSCC as an alternative or complement to standard cytotoxic therapy. Clin Cancer Res; 23(23); 7276-87. ©2017 AACR.

Carpal Tunnel Syndrome Following Corrective Osteotomy for Distal Radius Malunion: A Rare Case Report and Review of the Literature.

BACKGROUND: Although median nerve neuropathy and carpal tunnel syndrome (CTS) are known complications of both untreated and acutely treated distal radius fracture, median neuropathy after correction of distal radius malunion is not commonly reported in hand surgery literature. We describe a patient with severe CTS after corrective osteotomy, open reduction internal fixation (ORIF) with a volar locking plate (VLP), and bone grafting for distal radius malunion. METHODS: We report a case of severe acute CTS as a complication of corrective osteotomy with bone grafting for distal radius malunion. RESULTS: The patient was treated with surgical exploration of the median nerve and carpal tunnel release. CONCLUSION: The authors report a case of acute CTS after ORIF with VLP for a distal radius malunion warranting surgical exploration and carpal tunnel release. Treatment teams must be aware of this potential complication so that the threshold for reoperation is low and irreversible damage to the median nerve is prevented.

Selective antitumor activity of roscovitine in head and neck cancer.

Radiation and chemotherapy that are commonly used to treat human cancers damage cellular DNA. DNA damage appears to be more toxic to cancer cells than normal cells, most likely due to deregulated checkpoint activation and/or deficiency in DNA repair pathways that are characteristics of many tumors. However, unwanted side effects arise as a result of DNA damage to normal cells during the treatment.Here, we show that roscovitine, a cyclin-dependent kinase (CDK) inhibitor that inhibits CDK-1, CDK-2, CDK-5, CDK-7, and CDK-9 due to competitive binding to the ATP site on the kinases, causes significant DNA damage followed by p53-dependent cell death in human papilloma virus (HPV)-positive, but not in HPV-negative, head and neck cancer cells. Since HPV positivity was a molecular marker for increased sensitivity of cells to roscovitine, we reasoned that systemic roscovitine administration would not be toxic to healthy HPV-negative tissue. Indeed, low roscovitine doses significantly inhibited the growth of HPV-associated xenografted tumors in mice without causing any detectable side effects.Given that inhibition of CDKs has been shown to inhibit replication of several viruses, we suggest that roscovitine treatment may represent a selective and safe targeted therapeutic option against HPV-positive head and neck cancer.

Normalization of brain morphology after surgery in sagittal craniosynostosis.

OBJECT Nonsyndromic craniosynostosis (NSC) is associated with significant learning disability later in life. Surgical reconstruction is typically performed before 1 year of age to correct the cranial vault morphology and to allow for normalized brain growth with the goal of improving cognitive function. Yet, no studies have assessed to what extent normalized brain growth is actually achieved. Recent advances in MRI have allowed for automated methods of objectively assessing subtle and pronounced brain morphological differences. The authors used one such technique, deformation-based morphometry (DBM) Jacobian mapping, to determine how previously treated adolescents with sagittal NSC (sNSC) significantly differ in brain anatomy compared with healthy matched controls up to 11.5 years after surgery. METHODS Eight adolescent patients with sNSC, previously treated via whole-vault cranioplasty at a mean age of 7 months, and 8 age- and IQ-matched control subjects without craniosynostosis (mean age for both groups = 12.3 years), underwent functional 3-T MRI. Statistically significant group tissue-volume differences were assessed using DBM, a whole-brain technique that estimates morphological differences between 2 groups at each voxel (p < 0.01). Group-wise Jacobian volume maps were generated using a spacing of 1.5 mm and a resolution of 1.05 × 1.05 × 1.05 mm(3). RESULTS There were no significant areas of volume reduction or expansion in any brain areas in adolescents with sNSC compared with controls at a significance level of p < 0.01. At the more liberal threshold of p < 0.05, two areas of brain expansion extending anteroposteriorly in the right temporooccipital and left frontoparietal regions appeared in patients with sNSC compared with controls. CONCLUSIONS Compared with previous reports on untreated infants with sNSC, adolescents with sNSC in this cohort had few areas of brain dysmorphology many years after surgery. This result suggests that comprehensive cranioplasty performed at an early age offers substantial brain normalization by adolescence, but also that some effects of vault constriction may still persist after treatment. Specifically, few areas of expansion in frontoparietal and temporooccipital regions may persist. Overall, data from this small cohort support the primary goal of surgery in allowing for more normalized brain growth. Larger samples, and correlating degree of normalization with cognitive performance in NSC, are warranted.

Förster resonance energy transfer as a probe of membrane protein folding.

The folding reaction of a ß-barrel membrane protein, outer membrane protein A (OmpA), is probed with Förster resonance energy transfer (FRET) experiments. Four mutants of OmpA were generated in which the donor fluorophore, tryptophan, and acceptor molecule, a naphthalene derivative, are placed in various locations on the protein to report the evolution of distances across the bilayer and across the protein pore during a folding event. Analysis of the FRET efficiencies reveals three timescales for tertiary structure changes associated with insertion and folding into a synthetic bilayer. A narrow pore forms during the initial stage of insertion, followed by bilayer traversal. Finally, a long-time component is attributed to equilibration and relaxation, and may involve global changes such as pore expansion and strand extension. These results augment the existing models that describe concerted insertion and folding events, and highlight the ability of FRET to provide insight into the complex mechanisms of membrane protein folding. This article is part of a Special Issue entitled: Membrane protein structure and function.