Multiscale Optical Imaging Fusion for Cervical Precancer Diagnosis: Integrating Widefield Colposcopy and High-Resolution Endomicroscopy.

OBJECTIVE: Early detection and treatment of cervical precancers can prevent disease progression. However, in low-resource communities with a high incidence of cervical cancer, high equipment costs and a shortage of specialists hinder preventative strategies. This manuscript presents a low-cost multiscale in vivo optical imaging system coupled with a computer-aided diagnostic system that could enable accurate, real-time diagnosis of high-grade cervical precancers. METHODS: The system combines portable colposcopy and high-resolution endomicroscopy (HRME) to acquire spatially registered widefield and microscopy videos. A multiscale imaging fusion network (MSFN) was developed to identify cervical intraepithelial neoplasia grade 2 or more severe (CIN 2+). The MSFN automatically identifies and segments the ectocervix and lesions from colposcopy images, extracts nuclear morphology features from HRME videos, and integrates the colposcopy and HRME information. RESULTS: With a threshold value set to achieve sensitivity equal to clinical impression (0.98 [p = 1.0]), the MSFN achieved a significantly higher specificity than clinical impression (0.75 vs. 0.43, p = 0.000006). CONCLUSION: Our findings show that multiscale optical imaging of the cervix allows the highly sensitive and specific detection of high-grade precancers. SIGNIFICANCE: The multiscale imaging system and MSFN could facilitate the accurate, real-time diagnosis of cervical precancers in low-resource settings.

Use of Treatments after Recovery from Thumb Carpometacarpal Arthritis Surgery.

BACKGROUND: Which treatments patients continue to use more than 1 year after primary thumb carpometacarpal arthritis surgery, and how such use relates to patient-reported outcomes, is largely unknown. METHODS: The authors identified patients who had isolated primary trapeziectomy alone or with ligament reconstruction ± tendon interposition and were 1 to 4 years postoperative. Participants completed a surgical site-focused electronic questionnaire about what treatments they still used. Patient-reported outcome measures were the Quick Disability of the Arm, Shoulder, and Hand questionnaire and visual analog/numerical rating scales for current pain, pain with activities, and typical worst pain. RESULTS: A total of 112 patients met inclusion and exclusion criteria and participated. At a median of 3 years after surgery, over 40% reported current use of at least one treatment for their thumb carpometacarpal surgical site, with 22% using more than one treatment. Of those who still used treatments, 48% used over-the-counter medications, 34% used home or office-based hand therapy, 29% used splinting, 25% used prescription medications, and 4% used corticosteroid injections. A total of 108 participants completed all patient-reported outcome measures. With bivariate analyses, the authors found that use of any treatment after recovering from surgery was associated with statistically and clinically significantly worse scores for all measures. CONCLUSIONS: Clinically relevant proportions of patients continue to use various treatments a median of 3 years after primary thumb carpometacarpal arthritis surgery. Continued use of any treatment is associated with significantly worse patient-reported outcomes for function and pain.

Impaired Myofibroblast Proliferation is a Central Feature of Pathologic Post-Natal Alveolar Simplification.

Premature infants with bronchopulmonary dysplasia (BPD) have impaired alveolar gas exchange due to alveolar simplification and dysmorphic pulmonary vasculature. Advances in clinical care have improved survival for infants with BPD, but the overall incidence of BPD remains unchanged because we lack specific therapies to prevent this disease. Recent work has suggested a role for increased transforming growth factor-beta (TGFß) signaling and myofibroblast populations in BPD pathogenesis, but the functional significance of each remains unclear. Here, we utilize multiple murine models of alveolar simplification and comparative single-cell RNA sequencing to identify shared mechanisms that could contribute to BPD pathogenesis. Single-cell RNA sequencing reveals a profound loss of myofibroblasts in two models of BPD and identifies gene expression signatures of increased TGFß signaling, cell cycle arrest, and impaired proliferation in myofibroblasts. Using pharmacologic and genetic approaches, we find no evidence that increased TGFß signaling in the lung mesenchyme contributes to alveolar simplification. In contrast, this is likely a failed compensatory response, since none of our approaches to inhibit TGFb signaling protect mice from alveolar simplification due to hyperoxia while several make simplification worse. In contrast, we find that impaired myofibroblast proliferation is a central feature in several murine models of BPD, and we show that inhibiting myofibroblast proliferation is sufficient to cause pathologic alveolar simplification. Our results underscore the importance of impaired myofibroblast proliferation as a central feature of alveolar simplification and suggest that efforts to reverse this process could have therapeutic value in BPD.

Development of Osteopenia During Distal Radius Fracture Recovery.

Purpose: To determine the degree of disuse osteopenia (DO) and factors associated with its development during treatment of distal radius fractures (DRFs). Methods: We retrospectively reviewed charts and radiographs of patients with DRFs treated with and without surgery at 2 health care systems. We defined DO as a >10% drop from initial to 6-week second metacarpal cortical percentage and 6-week absolute second metacarpal cortical percentage <60%. Bivariate analyses were performed to evaluate associations between treatment type, patient and fracture characteristics, and radiographic measurements with odds of developing DO. Significant associations were included in multivariable analyses, adjusting for patient and fracture characteristics. Results: Approximately 18% of 517 included patients met the criteria for development of DO (n = 93). Bivariate analysis showed that surgical treatment was associated with lower odds of developing DO, whereas advancing age was associated with increased odds. In adjusted multivariable models, only advancing age was associated with increased odds of developing DO. Conclusions: A fairly important proportion of patients with DRF develop hand DO 6 weeks after surgical or nonsurgical treatment. The clinical relevance of this finding is uncertain and requires further investigation. Type of study/level of evidence: Prognostic IV.

Development of a multimodal mobile colposcope for real-time cervical cancer detection.

Cervical cancer remains a leading cause of cancer death among women in low-and middle-income countries. Globally, cervical cancer prevention programs are hampered by a lack of resources, infrastructure, and personnel. We describe a multimodal mobile colposcope (MMC) designed to diagnose precancerous cervical lesions at the point-of-care without the need for biopsy. The MMC integrates two complementary imaging systems: 1) a commercially available colposcope and 2) a high speed, high-resolution, fiber-optic microendoscope (HRME). Combining these two image modalities allows, for the first time, the ability to locate suspicious cervical lesions using widefield imaging and then to obtain co-registered high-resolution images across an entire lesion. The MMC overcomes limitations of high-resolution imaging alone; widefield imaging can be used to guide the placement of the high-resolution imaging probe at clinically suspicious regions and co-registered, mosaicked high-resolution images effectively increase the field of view of high-resolution imaging. Representative data collected from patients referred for colposcopy at Barretos Cancer Hospital in Brazil, including 22,800 high resolution images and 9,900 colposcope images, illustrate the ability of the MMC to identify abnormal cervical regions, image suspicious areas with subcellular resolution, and distinguish between high-grade and low-grade dysplasia.

The Syringe External Fixator: Short- and Medium-Term Functional Outcomes From This Inexpensive and Customizable Treatment for Comminuted Intra-Articular Fractures of the Hand.

PURPOSE: Comminuted intra-articular fractures and fracture dislocations of the metacarpophalangeal (MCP) and interphalangeal joints are challenging. Dynamic external fixation, permitting early joint motion while still minimizing forces across the healing joint, can result in acceptable postoperative active range of motion (AROM). However, some fractures are not initially stable enough for early dynamic motion; further, many available dynamic external fixation systems are costly and cumbersome. We reviewed our experience using an external fixator made from a 1-mL syringe and K-wires and report outcomes using it as a static fixator, dynamic fixator, or configured as a static fixator and then converted to a dynamic fixator in the clinic. METHODS: Patients with intra-articular fractures and fracture dislocations of the MCP and proximal interphalangeal (PIP) joints treated between 2014 and 2020 using syringe external fixators were retrospectively reviewed. We reviewed demographics, mechanisms, treatment types and durations, and postoperative AROM, as well as complications including infection, pin loosening, nonunion, hardware failure, and need for further surgery. Patients were analyzed by the level of joint injury (MCP versus PIP) and by treatment pattern. RESULTS: After excluding 23 patients with 25 joint injuries who were lost to follow-up or had inadequate outcome data, 27 patients with 29 joint injuries were reviewed. The average follow-up was 171 days after surgery. The postoperative AROM at the MCP level averaged 55° for static fixation and 30° for static-to-dynamic fixation. The postoperative AROM at the PIP level averaged 64° for static fixation, 66° for static-to-dynamic fixation, and 80° for dynamic fixation. Three pin site infections and 2 loose pins were reported. CONCLUSIONS: The syringe external fixator is an inexpensive, effective, and customizable treatment for intra-articular MCP and interphalangeal fractures and fracture dislocations, and results in acceptable postoperative AROM outcomes and complication rates. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Viral expression of constitutively active AKT3 induces CST axonal sprouting and regeneration, but also promotes seizures.

Increasing the intrinsic growth potential of neurons after injury has repeatedly been shown to promote some level of axonal regeneration in rodent models. One of the most studied pathways involves the activation of the PI3K/AKT/mTOR pathways, primarily by reducing the levels of PTEN, a negative regulator of PI3K. Likewise, activation of signal transducer and activator of transcription 3 (STAT3) has previously been shown to boost axonal regeneration and sprouting within the injured nervous system. Here, we examined the regeneration of the corticospinal tract (CST) after cortical expression of constitutively active (ca) Akt3 and STAT3, both separately and in combination. Overexpression of caAkt3 induced regeneration of CST axons past the injury site independent of caSTAT3 overexpression. STAT3 demonstrated improved axon sprouting compared to controls and contributed to a synergistic improvement in effects when combined with Akt3 but failed to promote axonal regeneration as an individual therapy. Despite showing impressive axonal regeneration, animals expressing Akt3 failed to show any functional improvement and deteriorated with time. During this period, we observed progressive Akt3 dose-dependent increase in behavioral seizures. Histology revealed increased phosphorylation of ribosomal S6 protein within the unilateral cortex, increased neuronal size, microglia activation and hemispheric enlargement (hemimegalencephaly).

Thumb Carpometacarpal Arthritis Surgery: The Patient Experience.

BACKGROUND: Patients with symptomatic recalcitrant thumb carpometacarpal arthritis often undergo surgery. Although most surgical patients do well, the authors anticipated that a substantial portion of their thumb carpometacarpal surgery patients would have unsatisfactory experiences and express unmet expectations, dissatisfaction, and regret, regardless of surgical procedure performed. The authors hypothesized those experiences would correlate with patient-reported outcomes scores. METHODS: The authors identified patients who had undergone trapeziectomy alone or with ligament reconstruction 1 to 4 years previously for primary thumb carpometacarpal arthritis. One hundred twelve patients completed Quick Disabilities of the Arm, Shoulder and Hand and visual analogue scale pain, expectations, satisfaction, and regret questionnaires. RESULTS: More than 40 percent of patients expected to "return to normal" after surgery for pain, strength, and/or function. Including all patients, 7, 19, and 11 percent had unmet expectations for improvement in pain, strength, and function, respectively. Twelve percent expressed dissatisfaction with their outcome. Although just 4 percent regretted undergoing surgery, 13 percent would likely not recommend the procedure to someone they care about. There were no statistically significant differences for any patient-reported outcomes between trapeziectomy-alone (n = 20) and trapeziectomy with ligament reconstruction (n = 92). Visual analogue scale and Quick Disabilities of the Arm, Shoulder and Hand questionnaire scores were both moderately correlated with expectations being met for pain, strength, and function and for satisfaction with surgical outcome. CONCLUSIONS: Patients' thumb carpometacarpal surgical experiences vary considerably. Many express dissatisfaction or a lack of expectations met with the two most common procedures. A thorough understanding and review of expectations preoperatively may be uniquely pertinent for these patients. Further research should determine predictors and potentially modifiable factors for unsatisfactory outcomes.

Comparison of conventional methods with commercially available topical hemostat surgical snow (oxidized cellulose) for achieving hemostasis in canine model of partial splenectomy.

Spleen is highly vascularized organ and bleeding control during partial splenectomy is a big challenge. In this study conventional methods of electrocautery, absorbable suturing and advance methods of topical hemostat Surgicel® were compared to control bleeding during partial splenec- tomy. Twelve healthy dogs (n=4) were divided in A, B and C groups. After partial splenectomy Surgicel®, electrocautery and absorbable horizontal mattress sutures were used to control hemor- rhages in group A, B and C respectively. Bleeding time and loss of blood volume was evaluated during surgery. In addition, blood samples were taken on day 0 pre-surgery and on days 3, 10 and 17 post-surgery to evaluate changes in biochemical parameters after the application of dif- ferent hemostatic techniques. Ultrasonography was also performed at alternative days to check any gross changes in the spleen. Dogs in group A showed minimum bleeding time and loss of blood volume as compared to group B and C. Drop in red blood cells count was compared be- tween group A, B and C showing significant change (p≤0.05) at day 3, 10 and 17, while a sig- nificant decline in hemoglobin was found in group C followed by groups B and A at 3rd and 10th day. There was no difference between platelet counts in various groups. Ultrasonography showed no significant changes in the spleen parenchyma. It was concluded that Surgicel® was an effective material for controlling hemorrhage in veterinary patients.

Early Outcomes of Endoscopic Versus Open Carpal Tunnel Release.

PURPOSE: To compare the short-term outcomes of endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR), including patient-reported outcomes, pain and satisfaction scores, return to work, and postoperative prescription pain medication use. METHODS: We included all patients over 18 years of age undergoing carpal tunnel release at a single hand center between January 2018 and December 2019. The carpal tunnel release method was driven by variations in surgeon practice. Data from patient-reported outcomes measurement information system (PROMIS) questionnaires and brief Michigan hand outcomes questionnaires and data on patient-reported pain levels, satisfaction with care, return to work, and postoperative prescription pain medication use were collected at preoperative visits and the first follow-up visit between postoperative days 7 and 14. RESULTS: We included 678 (586 ECTR and 92 OCTR) patients. The median age was 58 years, and 75% of the patients were women. At early follow up, patients who underwent OCTR reported significantly lower postoperative PROMIS upper-extremity scores than those who underwent ECTR (median, 32 vs 36 points, respectively) but similar postoperative PROMIS pain interference, global physical health, global mental health, and brief Michigan hand outcomes questionnaire scores. The postoperative pain and satisfaction scores were similar between the 2 groups. In multivariable models, patients who underwent OCTR had 62% lower odds of returning to work and 30% greater odds of remaining on a postoperative pain prescription at the first follow-up visit. CONCLUSIONS: This study found no evidence suggesting the definitive superiority of 1 surgical technique with regard to clinical outcomes in the early postoperative period. However, OCTR was associated with lower postoperative PROMIS upper-extremity scores of unclear clinical significance, higher odds of remaining on pain medication, and lower odds of returning to work by the first postoperative visit. Endoscopic carpal tunnel release may be preferred in patients who need to return to work within the first 2 weeks after the procedure. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Patient Satisfaction After Discharge Is Discordant With Reported Inpatient Experience.

Patient satisfaction measures are commonly used to evaluate clinical performance. However, research on the correlation between patient satisfaction scores and actual patient experience is limited. This study aimed to determine the concordance between patient satisfaction reported as an inpatient and patient satisfaction reported after discharge. The study enrolled 231 adult orthopedic patients at least 48 hours after admission to an academic hospital. Study participants rated their overall inpatient experience on a scale of 0 to 10, followed by open-ended questions on their hospital experience. Participants were then randomized to a second survey by either phone or mail at 4 to 6 weeks after discharge. Statistical and qualitative techniques were used to assess concordance in satisfaction scores and the agreement and association between patient experiences and patient satisfaction scores. The median overall patient satisfaction scores were 9.5 as inpatients (interquartile range [IQR], 8-10) and 10 at follow-up (IQR, 8-10), with a poor concordance between the inpatient and follow-up satisfaction scores (ρc=0.28). This study raises concerns regarding the validity of patient satisfaction measures to accurately quantify inpatient experience and the limitations related to its modes of administration. The authors observed poor agreement between the reported experience as an inpatient and the recollection of the inpatient experience after discharge. [Orthopedics. 2021;44(3):e427-e433.].

Assessing the Relationship Between Bone Density and Loss of Reduction in Nonsurgical Distal Radius Fracture Treatment.

PURPOSE: Whether low bone mineral density affects loss of reduction for distal radius fractures (DRFs) managed without surgery is unknown. Our purpose was to understand how bone mineral density, based on second metacarpal cortical percentage (2MCP) measurement, affects DRF healing after nonsurgical treatment. METHODS: We retrospectively reviewed 304 patients from 2 health systems with DRFs treated without surgery. The AO classification, 2MCP (<50% indicating osteoporosis), and fracture stability based on Lafontaine criteria were determined from prereduction radiographs. Radial inclination, radial height, volar tilt, ulnar variance, and intra-articular stepoff were measured on initial and 6-week final follow-up radiographs and compared. Bivariate analysis was used to evaluate the association between Lafontaine criteria or 2MCP and changes in radiographic parameters. Radiographic parameters with significant associations in bivariate analysis were evaluated in multivariable models adjusted for age, sex, initial radiographic parameters, reduction status, and AO fracture type. RESULTS: Across all patients, after 6 weeks of nonsurgical treatment, ulnar variance (shortening of the radius) increased by an average of 1.4 mm. Bivariate analysis showed that lower 2MCP and unstable fractures per Lafontaine criteria were each significantly associated with an increase in ulnar variance (P < .05). In adjusted multivariable models, having both 2MCP less than 50% and an unstable fracture together was associated with an additional 1.2-mm increase in ulnar variance (P < .05). CONCLUSIONS: A 2MCP in the osteoporosis range and unstable fractures by Lafontaine criteria were each associated with a significant increase in ulnar variance after nonsurgical treatment for DRFs. Patients with unstable fractures and 2MCP less than 50% are likely to have an additional increase of greater than 1 mm in ulnar variance at the end of nonsurgical fracture treatment than patients with similar injuries, but without these features. Using initial radiographs to identify patients with low bone mineral density that may be at risk for more substantial loss of reduction can assist with decision making for managing DRFs. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Variation in Postoperative Opioid Prescribing Among Upper-Extremity Surgery Providers.

Purpose: To identify targets for corrective interventions and guide improved opioid stewardship, we studied opioid prescribing patterns of attending surgeons compared with surgical trainees for 2 upper-extremity surgeries: open reduction internal fixation (ORIF) of distal radius fractures (DRF), and carpal tunnel release (CTR). Methods: We retrospectively reviewed records for all patients who underwent CTR or DRF ORIF at 6 hospitals across a large health system from 2016 to 2018. We collected prescriber training level (attending vs trainee), analgesic prescribed, and amount initially prescribed after surgery converted to oral morphine equivalents (OMEs). Regression models evaluated OMEs by prescriber and surgery type. Our final models included an interaction term between prescriber training level and year of surgery to assess group changes over time. No prescription guidelines or formal training was provided during the study period. Results: We included 707 CTR and 383 DRF ORIF patients. Opioids prescribed by trainees ranged from 90 to 300 OMEs (median, 180 OMEs). Opioids prescribed by attendings ranged from 100 to 225 OMEs (median, 150 OMEs). Early in the analyses, trainees prescribed significantly more than attendings (320 versus 180). Over time, trainees reduced overprescribing significantly more, by an additional 40 OME/y. By the end of the analysis period, trainees were prescribing less OME than were attendings (112.5 vs 150). Both groups continued to prescribe more than recently suggested amounts for both procedures. Conclusions: Our study found that both attendings and trainees overprescribed opioids after surgery. Trainees prescribed more than attendings over the study period; however, when analyzing for improvement over time and with no formal intervention or training, trainees showed greater improvement, eventually dropping to levels at or below that of attendings. Considering that most change was seen at the trainee level, education for established providers may be an area in which more improvement can be made. Clinical relevance: Understanding which providers are more likely to overprescribe opioids can help guide interventions that improve opioid stewardship.

Algorithm to quantify nuclear features and confidence intervals for classification of oral neoplasia from high-resolution optical images.

Purpose: In vivo optical imaging technologies like high-resolution microendoscopy (HRME) can image nuclei of the oral epithelium. In principle, automated algorithms can then calculate nuclear features to distinguish neoplastic from benign tissue. However, images frequently contain regions without visible nuclei, due to biological and technical factors, decreasing the data available to and accuracy of image analysis algorithms. Approach: We developed the nuclear density-confidence interval (ND-CI) algorithm to determine if an HRME image contains sufficient nuclei for classification, or if a better image is required. The algorithm uses a convolutional neural network to exclude image regions without visible nuclei. Then the remaining regions are used to estimate a confidence interval (CI) for the number of abnormal nuclei per mm 2 , a feature used by a previously developed algorithm (called the ND algorithm), to classify images as benign or neoplastic. The range of the CI determines whether the ND-CI algorithm can classify an image with confidence, and if so, the predicted category. The ND and ND-CI algorithm were compared by calculating their positive predictive value (PPV) and negative predictive value (NPV) on 82 oral biopsies with histopathologically confirmed diagnoses. Results: After excluding the images that could not be classified with confidence, the ND-CI algorithm had higher PPV (65% versus 59%) and NPV (78% versus 75%) than the ND algorithm. Conclusions: The ND-CI algorithm could improve the real-time classification of HRME images of the oral epithelium by informing the user if an improved image is required for diagnosis.

Management of Gunshot Injuries of Mandible with Open Reduction and Internal Fixation versus Closed Reduction and Maxillo-mandibular Fixation.

Background/objectives Gunshot injuries are known to cause severe morbidity and mortality when facial regions are involved. Management of the gunshot wounds of the face comprises of securing an airway, controlling hemorrhage, identifying other injuries and definite repair of the traumatic facial deformities. The objective of the present study was to compare the clinical outcome (infection and nonunion) of open reduction and internal fixation versus closed reduction and maxillo-mandibular fixation (CR-MMF) in the treatment of gunshot injuries of the mandible. Materials & methods This study was conducted at Oral and Maxillofacial Surgery Department of Shaheed Zulfiqar Ali Bhutto Medical University/Pakistan Institute of Medical Sciences Islamabad, Pakistan. Ninety gunshot mandibular fractures were randomly allocated in two equal groups. In group-A, 45 patients were treated by open reduction and internal fixation while in group-B, 45 patients were also managed by closed reduction and maxillo-mandibular fixation. Post-operative complications (infection, non-union) were evaluated clinically and radiographically in both groups. Results Patients treated by open reduction and internal fixation were having more complications in terms of infection (17.8%) as compared to closed reduction (4.4%) with a p-value 0.044. Whereas non-union was more in closed reduction (15.6%) as compared to open reduction and internal fixation group (2.2%) with a significant p-value 0.026. Conclusion Both the treatment modalities can be used in the management of gunshot injuries of mandible and there is need for further studies to have clear guideline in this regard in best interest of patients, community and health care providers.

Syringe External Fixator: An Inexpensive Static-to-Dynamic Treatment for Comminuted Intra-Articular Phalangeal Fractures.

Comminuted intra-articular phalanx fractures are complicated injuries often treated with external fixation. The ideal external fixation system should be affordable, readily available, adaptable, and easy to use. The use of dynamic external fixation has advanced the care of these injuries but can be difficult to implement. The authors present a case example of a patient with a comminuted intra-articular phalangeal fracture of the left small finger treated using a syringe as a static uniplanar fixator that was converted to a dynamic fixator during postoperative recovery.

Prospective evaluation of oral premalignant lesions using a multimodal imaging system: a pilot study.

BACKGROUND: Multimodal optical imaging, incorporating reflectance and fluorescence modalities, is a promising tool to detect oral premalignant lesions in real-time. METHODS: Images were acquired from 171 sites in 66 patient visits for clinical evaluation of oral lesions. An automated algorithm was used to classify lesions as high- or low-risk for neoplasia. Biopsies were acquired at clinically indicated sites and those classified as high-risk by imaging, at the surgeon's discretion. RESULTS: Twenty sites were biopsied based on clinical examination or imaging. Of these, 12 were indicated clinically and by imaging; 58% were moderate dysplasia or worse. Four biopsies were indicated by imaging evaluation only; 75% were moderate dysplasia or worse. Finally, four biopsies were indicated by clinical evaluation only; 75% were moderate dysplasia or worse. CONCLUSION: Multimodal imaging identified more cases of high-grade dysplasia than clinical evaluation, and can improve detection of high grade precancer in patients with oral lesions.

Outcomes of the Medial Femoral Trochlea Osteochondral Free Flap for Proximal Scaphoid Reconstruction.

PURPOSE: To describe the radiographic, functional, and patient-reported outcomes (PROs) of medial femoral trochlea (MFT) osteochondral free flap reconstruction of the proximal scaphoid at approximately 2 years follow-up. METHODS: Eleven patients who underwent MFT reconstruction of the proximal scaphoid returned for clinical examination, radiographs, and completion of PROs questionnaires. For another 10 patients who were unable to return, data were gathered remotely or from the medical record. RESULTS: Mean radiographic follow-up was 2.0 years and mean examination follow-up ranged from 2.6 to 2.8 years. Mean follow-up for several PROs ranged from 2.8 to 2.9 years. On average, carpal collapse did not progress, and radiolunate angle was significantly improved by 9.5°. Wrist flexion (41.6°; -6%) and extension (43.8°; -7%) were only slightly changed, and dominance-corrected postoperative pinch and grip strength were 77% and 72% of the uninjured side, respectively. Mean postoperative Disabilities of the Arm, Shoulder, and Hand (DASH) score was 10.7. In patients with both pre- and postoperative scores available, DASH significantly improved by 15 points. Knee donor-site morbidity was measured on the Knee Injury and Osteoarthritis Outcome Score (KOOS)-Sports and Recreation and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scales. The Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health, Physical Function, Pain Intensity, Pain Interference, and Pain Behavior scores reflected good postoperative patient health and function and low pain levels. Higher body mass index (BMI) was found to be predictive of inferior lower extremity and global PROs. CONCLUSIONS: An MFT reconstruction of proximal scaphoid nonunion has the potential to restore normal functional radiocarpal anatomy, improve function, and relieve pain without causing wrist stiffness or weakness. Donor-site morbidity has been further delineated in this study. Caution is warranted when considering this procedure in patients with elevated BMI because they may be at increased risk for donor-site morbidity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Autofluorescence Imaging to Monitor the Progression of Oral Potentially Malignant Disorders.

Patients with oral potentially malignant disorders (OPMD) must undergo regular clinical surveillance to ensure that any progression to malignancy is detected promptly. Autofluorescence imaging (AFI) is an optical modality that can assist clinicians in detecting early cancers and high-grade dysplasia. Patients with OPMD undergoing surveillance for the development of oral cancer were examined using AFI at successive clinic visits. Autofluorescence images acquired at 133 clinical visits from sites in 15 patients who met inclusion criteria were analyzed quantitatively using an algorithm to calculate the red-to-green pixel intensity (RG ratio). A quantitative AFI threshold for high risk of progression was defined based on the RG ratio and was compared with expert clinical impression and with histopathology when available. Patients were divided into two groups based on their endpoint: surveillance (n = 6) or surgery (n = 9). In the surveillance group, 0 of 6 (0%) of patients were clinically identified as high risk for progression prior to the study endpoint, whereas 1 of 6 (17%) of patients were deemed at high risk for progression based on AFI during the same time period. In the surgery group, 9 of 9 (100%) of patients were clinically identified as high risk prior to the study endpoint, whereas 8 of 9 (89%) of patients were at high risk for progression based on AFI during the same time period. AFI results tracked over time were comparable with expert clinical impression in these patient groups. AFI has the potential to aid clinicians in noninvasively monitoring oral precancer and evaluating OPMDs that require increased surveillance.

Machine learning enables detection of early-stage colorectal cancer by whole-genome sequencing of plasma cell-free DNA.

BACKGROUND: Blood-based methods using cell-free DNA (cfDNA) are under development as an alternative to existing screening tests. However, early-stage detection of cancer using tumor-derived cfDNA has proven challenging because of the small proportion of cfDNA derived from tumor tissue in early-stage disease. A machine learning approach to discover signatures in cfDNA, potentially reflective of both tumor and non-tumor contributions, may represent a promising direction for the early detection of cancer. METHODS: Whole-genome sequencing was performed on cfDNA extracted from plasma samples (N = 546 colorectal cancer and 271 non-cancer controls). Reads aligning to protein-coding gene bodies were extracted, and read counts were normalized. cfDNA tumor fraction was estimated using IchorCNA. Machine learning models were trained using k-fold cross-validation and confounder-based cross-validations to assess generalization performance. RESULTS: In a colorectal cancer cohort heavily weighted towards early-stage cancer (80% stage I/II), we achieved a mean AUC of 0.92 (95% CI 0.91-0.93) with a mean sensitivity of 85% (95% CI 83-86%) at 85% specificity. Sensitivity generally increased with tumor stage and increasing tumor fraction. Stratification by age, sequencing batch, and institution demonstrated the impact of these confounders and provided a more accurate assessment of generalization performance. CONCLUSIONS: A machine learning approach using cfDNA achieved high sensitivity and specificity in a large, predominantly early-stage, colorectal cancer cohort. The possibility of systematic technical and institution-specific biases warrants similar confounder analyses in other studies. Prospective validation of this machine learning method and evaluation of a multi-analyte approach are underway.