Newly identified roles for PIEZO1 mechanosensor in controlling normal megakaryocyte development and in primary myelofibrosis.

Mechanisms through which mature megakaryocytes (Mks) and their progenitors sense the bone marrow extracellular matrix to promote lineage differentiation in health and disease are still partially understood. We found PIEZO1, a mechanosensitive cation channel, to be expressed in mouse and human Mks. Human mutations in PIEZO1 have been described to be associated with blood cell disorders. Yet, a role for PIEZO1 in megakaryopoiesis and proplatelet formation has never been investigated. Here, we show that activation of PIEZO1 increases the number of immature Mks in mice, while the number of mature Mks and Mk ploidy level are reduced. Piezo1/2 knockout mice show an increase in Mk size and platelet count, both at basal state and upon marrow regeneration. Similarly, in human samples, PIEZO1 is expressed during megakaryopoiesis. Its activation reduces Mk size, ploidy, maturation, and proplatelet extension. Resulting effects of PIEZO1 activation on Mks resemble the profile in Primary Myelofibrosis (PMF). Intriguingly, Mks derived from Jak2V617F PMF mice show significantly elevated PIEZO1 expression, compared to wild-type controls. Accordingly, Mks isolated from bone marrow aspirates of JAK2V617F PMF patients show increased PIEZO1 expression compared to Essential Thrombocythemia. Most importantly, PIEZO1 expression in bone marrow Mks is inversely correlated with patient platelet count. The ploidy, maturation, and proplatelet formation of Mks from JAK2V617F PMF patients are rescued upon PIEZO1 inhibition. Together, our data suggest that PIEZO1 places a brake on Mk maturation and platelet formation in physiology, and its upregulation in PMF Mks might contribute to aggravating some hallmarks of the disease.

Characterization of Glycoproteoforms of Integrins α2 and ß1 in Megakaryocytes in the Occurrence of JAK2V617F Mutation-Induced Primary Myelofibrosis.

Primary myelofibrosis (PMF) is a neoplasm prone to leukemic transformation, for which limited treatment is available. Among individuals diagnosed with PMF, the most prevalent mutation is the JAK2V617F somatic point mutation that activates the Janus kinase 2 (JAK2) enzyme. Our earlier reports on hyperactivity of ß1 integrin and enhanced adhesion activity of the α2ß1 complex in JAK2V617F megakaryocytes (MKs) led us to examine the new hypothesis that this mutation leads to posttranslational modification via changes in glycosylation. Samples were derived from immunoprecipitation of MKs obtained from Vav1-hJAK2V617F and WT mice. Immunoprecipitated fractions were separated by SDS-PAGE and analyzed using LC-MS/MS techniques in a bottom-up glycoproteomics workflow. In the immunoprecipitate, glycopeptiforms corresponding to 11 out of the 12 potential N-glycosylation sites of integrin ß1 and to all nine potential glycosylation sites of integrin α2 were observed. Glycopeptiforms were compared across WT and JAK2V617F phenotypes for both integrins. The overall trend observed is that JAK2V617F mutation in PMF MKs leads to changes in ß1 glycosylation; in most cases, it results in an increase in the integrated area of glycopeptiforms. We also observed that in mutated MKs, changes in integrin α2 glycosylation were more substantial than those observed for integrin ß1 glycosylation, a finding that suggests that altered integrin α2 glycosylation may also affect activation. Additionally, the identification of proteins associated to the cytoskeleton that were co-immunoprecipitated with integrins α2 and ß1 demonstrated the potential of the methodology employed in this study to provide some insight, at the peptide level, into the consequences of integrin activation in MKs. The extensive and detailed glycosylation patterns we uncovered provide a basis for future functional studies of each site in control cells as compared to JAK2V617F-mutated cells. Data are available via ProteomeXchange with identifier PXD030550.

Impact of COVID-19 pandemic and vaccine perceptions on HPV vaccine hesitancy.

OBJECTIVE: This study evaluated the impact of the COVID-19 pandemic and vaccine perceptions on Human Papillomavirus (HPV) vaccine hesitancy. Secondary endpoints included comparing COVID-19 and HPV vaccination trends regarding time, community of residence, and unmet social needs. METHODS: This was a survey-based, cross-sectional study that included 101 participants who were recruited through the Wyandotte County Public Health Department. Participants were eligible for inclusion in this study if they were a parent/guardian of one or more children aged 13 to 17; English- or Spanish-speaking. This study took place in Wyandotte County, Kansas. Descriptive statistics and chi-square analyses were utilized. RESULTS: There was no difference in completion of COVID-19 and HPV vaccines (p = 0.0975). Significantly more individuals started and did not finish the HPV vaccine series compared to the COVID-19 vaccine series (p = 0.0004). Most participants indicated their opinion on the HPV vaccine had not changed due to the pandemic (71.3 %). Participants who felt familiar with HPV had higher rates of HPV vaccine completion. While 77 % of participants felt extremely or moderately familiar with HPV, 61.4 % were unaware of its association with oropharyngeal cancer. CONCLUSION: There was minimal change in parents' perception of the HPV vaccine due to the COVID-19 pandemic despite decreased rates of vaccination during this time. HPV vaccine series completion was significantly lower than COVID-19 vaccine series completion, highlighting a need to improve HPV vaccine completion counseling. Additionally, patient education should address the knowledge gap discovered regarding the link between HPV infection and oropharyngeal cancer.

Long-Term Clinical Outcomes Following Nonsurgical Management of Salter-Harris Type II Fractures of the Proximal Phalanx of the Small Finger: A Prospective Cohort Study.

PURPOSE: Juxta-physeal fractures at the base of the proximal phalanx (FBPP) of the small finger are one of the most common hand fractures in children. Although many of these fractures are treated nonsurgically, it is unclear which fractures benefit from surgery or the degree of acceptable angulation appropriate for nonsurgical management. Our study aimed to assess long-term, patient-reported outcomes regarding function, appearance, and pain after nonsurgical management of FBPP of the small finger in a pediatric population. METHODS: Our hospital Picture Archiving and Communication Systems database was queried to identify radiographs of the small finger of children between the ages of 8 and 16 years old taken from 2011 to 2021. Displacement on initial injury radiographs was calculated using the diaphyseal-metacarpal head angle. Patient-reported function, appearance, and pain were measured using standardized assessment tools sent to patients and parents electronically. Optional clinical photographs were uploaded by parents and assessed for residual clinical deformity. RESULTS: One hundred eighty-one eligible subjects were identified. Eighty (44%) agreed to participate, and 40 (22%) parent and 38 patient surveys were completed. The mean age at the time of injury was 11 years old (8-14 years), and the mean age at the time of survey completion was 17 years old (11-23 years). Patient T-scores were higher than the average reference T-score on the Patient-Reported Outcomes Measurement Information System Short Form v2.0-Upper Extremity. Overall, greater than 78% of patients and parents reported appearance as 8/10 or above on a VAS. Ninety-five percent (108/114) of patients reported no pain (0/10) for pain during activities and at rest. CONCLUSIONS: Children with up to 26° of initial coronal plane angulation reported better function than a reference population, good appearance, and no pain, at a mean of 6 years after injury. Our findings support nonsurgical management of most FBPP of the small finger in children. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Results of Implementation of Amyloidosis Screening for Patients Undergoing Carpal Tunnel Release.

PURPOSE: Many patients with amyloidosis undergo carpal tunnel release (CTR) before amyloidosis diagnosis and before developing cardiac or other serious disease manifestations. The purposes of this study were to examine if our patient population had a similar prevalence of positive amyloidosis diagnoses to that in prior studies and to describe the results of implementing a screening program for amyloidosis. METHODS: We retrospectively reviewed the biopsy results and subsequent interventions for all patients who underwent screening tenosynovial biopsy during CTR from March 2020 through December 2021. Amyloid screening was offered to patients who met the criteria for increased risk of disease using an appropriateness screening algorithm. RESULTS: Seventy-five (48%) of 156 patients who underwent CTR met the eligibility criteria for amyloidosis testing. Of the 62 patients who agreed to undergo tenosynovial biopsy, 14 had amyloid-positive biopsy specimens (10 men and 4 women). All patients with positive tenosynovial biopsies had bilateral carpal tunnel syndrome and wild-type transthyretin amyloid subtype. One patient was diagnosed and started treatment for otherwise asymptomatic cardiac amyloidosis. CONCLUSIONS: The incidence of amyloid-positive tenosynovial biopsy results from CTR was 22.5% in patients using the criteria from an appropriateness screening algorithm, which was higher than previously reported. Implementation of a screening program for patients undergoing CTR requires a multidisciplinary approach and may result in early diagnosis and lifesaving interventions for patients with amyloidosis. TYPE OF STUDY/LEVEL OF EVIDENCE: Differential diagnosis/symptom prevalence study, II.

Adhesion to fibronectin via α5ß1 integrin supports expansion of the megakaryocyte lineage in primary myelofibrosis.

Excessive accumulation of extracellular matrix (ECM) is a hallmark of bone marrow (BM) milieu in primary myelofibrosis (PMF). Because cells have the ability to adhere to the surrounding ECM through integrin receptors, we examined the hypothesis that an abnormal ECM-integrin receptor axis contributes to BM megakaryocytosis in JAK2V617F+ PMF. Secretion of ECM protein fibronectin (FN) by BM stromal cells from PMF patients correlates with fibrosis and disease severity. Here, we show that Vav1-hJAK2V617F transgenic mice (JAK2V617F+) have high BM FN content associated with megakaryocytosis and fibrosis. Further, megakaryocytes from JAK2V617F+ mice have increased cell surface expression of the α5 subunit of the α5ß1 integrin, the major FN receptor in megakaryocytes, and augmented adhesion to FN compared with wild-type controls. Reducing adhesion to FN by an inhibitory antibody to the α5 subunit effectively reduces the percentage of CD41+ JAK2V617F+ megakaryocytes in vitro and in vivo. Corroborating our findings in mice, JAK2V617F+ megakaryocytes from patients showed elevated expression of α5 subunit, and a neutralizing antibody to α5 subunit reduced adhesion to FN and megakaryocyte number derived from CD34+ cells. Our findings reveal a previously unappreciated contribution of FN-α5ß1 integrin to megakaryocytosis in JAK2V617F+ PMF.

Incidence of Infection in Operatively Treated Distal Radius Fractures After Conversion From External to Internal Fixation.

PURPOSE: The purpose of this study was to report the incidence of infection after conversion from external fixation (EF) to internal fixation (IF) of distal radius fractures and to evaluate the relationship between infection and secondary variables, including time to conversion from EF to IF, internal hardware overlapping EF pin sites, and definitive fixation with a dorsal-spanning bridge plate. METHODS: A retrospective review was performed at 2 level 1 trauma centers including all patients aged ≥18 years from 2006 to 2019 with a distal radius fracture treated initially with EF followed by subsequent IF. The patients were excluded from analysis if they had <10 weeks of clinical follow-up, a history of prior distal radius surgery, or evidence of infection before EF to IF conversion. Patient demographic data, mechanism of injury, presence of hardware overlapping pin sites, and timing to definitive fixation were obtained from the medical records. Infection was defined as positive intraoperative cultures or documented return to the operating room for debridement after IF. RESULTS: A total of 64 fractures in 61 patients with a median age of 50 years (range, 18-75 years) were included. Infections developed in 6 patients (6 of 64 fractures). The incidence of infection was higher in patients with a time to conversion from EF to IF of >14 days (infection in 2 of 5 patients vs 4 of 59 patients). The incidence of infection was similar in patients with and without hardware overlapping EF pin sites (3 of 27 vs 3 of 37, respectively). CONCLUSIONS: Infections occurred in 6 of 64 distal radius fractures following conversion from EF to IF, and delay in conversion of >14 days was associated with an increased infection risk. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Self-initiated learning reveals memory performance and electrophysiological differences between younger, older and older adults with relative memory impairment.

Older adults display difficulties in encoding and retrieval of information, resulting in poorer memory. This may be due to an inability of older adults to engage elaborative encoding strategies during learning. This study examined behavioural and electrophysiological effects of explicit cues to self-initiate learning during encoding and subsequent recognition of words in younger adults (YA), older control adults (OA) and older adults with relative memory impairment (OD). The task was a variation of the old/new paradigm, some study items were preceded by a cue to learn the word (L) while others by a do not learn cue (X). Behaviourally, YA outperformed OA and OD on the recognition task, with no significant difference between OA and OD. Event-related potentials at encoding revealed enhanced early visual processing (70-140 ms) for L- versus X-words in young and old. Only YA exhibited a greater late posterior positivity (LPP; 200-500 ms) for all words during encoding perhaps reflecting superior encoding strategy. During recognition, only YA differentiated L- versus X-words with enhanced frontal P200 (150-250 ms) suggesting impaired early word selection for retrieval in older groups; however, OD had enhanced P200 activity compared to OA during L-word retrieval. The LPP (250-500 ms) was reduced in amplitude for L-words compared to both X- and new words. However, YA showed greater LPP amplitude for all words compared to OA. For older groups, we observed reduced left parietal hemispheric asymmetry apparent in YA during encoding and recognition, especially for OD. Findings are interpreted in the light of models of compensation and dedifferentiation associated with age-related changes in memory function.

Use of an Automated Mobile Phone Messaging Robot in Postoperative Patient Monitoring.

BACKGROUND: Mobile phone messaging software robots allow clinicians and healthcare systems to communicate with patients without the need for human intervention. The purpose of this study was to (1) describe a method for communicating with patients postoperatively outside of the traditional healthcare setting by utilizing an automated software and mobile phone messaging platform and to (2) evaluate the first week of postoperative pain and opioid use after common ambulatory hand surgery procedures. MATERIALS AND METHODS: The investigation was a prospective, multicenter investigation of patient-reported pain and opioid usage after ambulatory hand surgery. Inclusion criteria included any adult with a mobile phone capable of text messaging, who was undergoing a common ambulatory hand surgical procedure at one of three tertiary care institutions. Participants received daily, automated text messages inquiring about their pain level and how many tablets of prescription pain medication they had taken in the past 24 h. Initial 1-week response rate was assessed and compared between different patient demographics. Patient-reported pain and opioid use were also quantified for the first postoperative week. Statistical significance was set as p < 0.05. RESULTS: Forty-seven (n = 47) patients were enrolled in this investigation. Total response rate of both pain and opioid medication questions through 7 days was 88.3%. Pain trended down on a daily basis for the first postoperative week, with the highest levels of pain being reported in the first 48 h after surgery. Patients reported an average use of 15.9 ± 14.8 tablets of prescription opioid pain medication. CONCLUSIONS: We find that a mobile phone messaging software robot allows for effective data collection of postoperative pain and pain medication use. Patients undergoing common ambulatory hand procedures utilized an average of 16 tablets of opioid medication in the first postoperative week.

Incidence of Treatment for Infection of Buried Versus Exposed Kirschner Wires in Phalangeal, Metacarpal, and Distal Radial Fractures.

PURPOSE: To determine whether there is a difference in the incidence of infection between exposed and buried K-wires when used to treat phalangeal, metacarpal, and distal radius fractures. METHODS: We conducted a retrospective review identifying all patients aged greater than 16 years who underwent fixation of phalangeal, metacarpal, or distal radius fractures with K-wires between 2007 and 2015. We recorded patient demographic data, fracture location, number of K-wires used, whether K-wires were buried or left exposed, and duration of K-wire placement. RESULTS: A total of 695 patients met inclusion criteria. Surgeons buried K-wires in 207 patients and left K-wires exposed in 488. Infections occurred more frequently in exposed K-wire cases than in buried K-wire ones. Subgroup analysis based on fracture location revealed a significantly increased risk of being treated for infection when exposed K-wires were used for metacarpal fractures. CONCLUSIONS: Patients with exposed K-wires for fixation of phalangeal, metacarpal, or distal radius fractures were more likely to be treated for a pin-site infection than those with K-wires buried beneath the skin. Metacarpal fractures treated with exposed K-wires were 2 times more likely to be treated for a pin-site infection (17.6% of exposed K wire cases vs 8.7% of buried K wire cases). TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Junctional adhesion molecule A promotes epithelial tight junction assembly to augment lung barrier function.

Epithelial barrier function is maintained by tight junction proteins that control paracellular fluid flux. Among these proteins is junctional adhesion molecule A (JAM-A), an Ig fold transmembrane protein. To assess JAM-A function in the lung, we depleted JAM-A in primary alveolar epithelial cells using shRNA. In cultured cells, loss of JAM-A caused an approximately 30% decrease in transepithelial resistance, decreased expression of the tight junction scaffold protein zonula occludens 1, and disrupted junctional localization of the structural transmembrane protein claudin-18. Consistent with findings in other organs, loss of JAM-A decreased ß1 integrin expression and impaired filamentous actin formation. Using a model of mild systemic endoxotemia induced by i.p. injection of lipopolysaccharide, we report that JAM-A(-/-) mice showed increased susceptibility to pulmonary edema. On injury, the enhanced susceptibility of JAM-A(-/-) mice to edema correlated with increased, transient disruption of claudin-18, zonula occludens 1, and zonula occludens 2 localization to lung tight junctions in situ along with a delay in up-regulation of claudin-4. In contrast, wild-type mice showed no change in lung tight junction morphologic features in response to mild systemic endotoxemia. These findings support a key role of JAM-A in promoting tight junction homeostasis and lung barrier function by coordinating interactions among claudins, the tight junction scaffold, and the cytoskeleton.

Dorsal Approach Decreases Operative Time for Complex Metacarpophalangeal Dislocations.

PURPOSE: Complex metacarpophalangeal (MCP) dislocations require open surgical reduction, but surgeons disagree about the best surgical approach. We hypothesized that a dorsal approach would require less operative time than would a volar approach and result in a decreased need for a secondary approach. METHODS: We performed a retrospective chart review of all isolated irreducible dorsal MCP dislocations treated at 2 level 1 trauma centers between 2005 and 2015. We recorded the initial surgical approach (volar or dorsal), total operative time, and whether the surgeon used a second surgical approach. Operative times for initial volar approach versus initial dorsal approach, hand surgeon versus non-hand surgeon, and thumb versus other digits were compared using the 2-tailed Student t test. We used Fisher exact test to compare the need for a second approach between the volar and dorsal approach groups. RESULTS: A total of 21 patients (22 digits) with MCP dislocations required surgical reduction. Average operative time was longer for the 14 patients who underwent the initial volar approach (70 minutes) than for the 7 who underwent an initial dorsal approach (45 minutes). Six of the 14 MCP joints approached volarly (42%) required a second dorsal approach. None of the 7 patients in the dorsal group required a second approach. CONCLUSIONS: Using a dorsal approach to reduce complex MCP dislocations reduces operative time and decreases the need for a secondary approach. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The relative balance of GM-CSF and TGF-ß1 regulates lung epithelial barrier function.

Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-ß1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-ß1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-ß1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-ß1 alone caused an ∼ 25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions ("spikes") containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼ 20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-ß1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-ß1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-ß1. Critically, patients who survived had significantly higher GM-CSF/TGF-ß1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-ß1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-ß1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS.

Effect of Rurality in Head and Neck Cancer: A Scoping Review.

OBJECTIVES: This scoping review sought to evaluate the current literature regarding the following outcomes in relation to rurality: stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes of head and neck cancer (HNC). DATA SOURCES: A literature search was performed using PubMed (MEDLINE), Science Direct, EMBASE, SCOPUS, and Web of Science databases. REVIEW METHODS: A 20-year study cutoff from the initial search was used to increase the comparability of the studies regarding population and standards of clinical care. These searches were designed to capture all primary studies reporting HNC incidence, presenting characteristics, treatments, and treatment outcomes. Two reviewers independently screened abstracts, selected articles for exclusion, extracted data, and appraised studies. Critical appraisal was done according to the Joanna Briggs Institute Quality Assessment Tool for Cohort Studies. FINDINGS: Twenty eligible original articles were included. Stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes were measured. Our review indicates that although this relationship is unclear, there may be variations in treatment choice for laryngeal cancer based on geographic location and rural residency status. The studies assessing HNC outcomes related to stage at diagnosis, clinical characteristics, treatment characteristics, and overall survival demonstrated conflicting findings, indicating a need for further research examining HNC outcomes with a focus on rurality as the main exposure. CONCLUSIONS: The relationship between HNC and rural-urban status remains unclear. More studies are needed, along with a consistent metric for measuring rurality and recruitment of comparable populations from both rural and urban areas. Laryngoscope, 2024.

Charcot Arthropathy of the Digit: A Report of 2 Cases.

CASE: Charcot arthropathy (CA) is a progressive degenerative joint disease typically affecting lower extremity weight-bearing joints, with only a few cases reported in the fingers. We present 2 cases of interphalangeal joint CA: the long finger distal interphalangeal joint in a 73-year-old man with severe carpal tunnel syndrome and the ring finger proximal interphalangeal joint of a 71-year-old woman with diabetic neuropathy. CONCLUSION: Two cases of CA of the digits were treated with splinting with resolution of symptoms and no wound complications.

Incidence of Loss of Reduction After Open Reduction Internal Fixation of Metacarpal Shaft Fractures.

BACKGROUND: This study compared the incidence of loss of reduction (LOR) between metacarpal fractures fixed with screws alone and those fixed with plates and screws. Secondary aims included identifying patient or fracture characteristics associated with increased risk of LOR. METHODS: We retrospectively reviewed 138 metacarpal fractures in 106 patients treated with open reduction internal fixation with screws (60 fractures) or plates and screws (78 fractures) with a mean radiographic follow-up of 50 days for evidence of LOR. We compared the incidence of LOR between the screw and plate groups using a χ2 test. We performed logistic regression analysis to determine whether patient age, sex, metacarpal location (index, long, ring, small), the presence of multiple metacarpal fractures, or fracture pattern were associated with increased incidence of LOR. RESULTS: Loss of reduction occurred in 19 (13.8%) of 138 fractures, with no statistically significant difference between lag screw (7 of 60, 11.6%) and plate fixation (12 of 78, 15.4%). Neither fracture pattern nor the presence of multiple metacarpal fractures was associated with an increased incidence of LOR, but patients experienced a 7% increase in the risk of LOR for each additional year of age. Loss of reduction occurred most frequently in index metacarpal fractures (4 of 12, 33%), although this did not reach statistical significance. CONCLUSIONS: We found no difference in LOR incidence between lag screw fixation and plate fixation. The overall incidence of LOR was higher in this study than previously reported and increased with increasing patient age.

Infectious Flexor Tenosynovitis Following Trigger Finger Release: Incidence and Risk Factors.

Background: Trigger finger release (TFR) is one of the most commonly performed hand procedures and typically results in restoration of normal finger function. However, uncommon postoperative complications such as deep infection can have devastating consequences. The goal of this study was to evaluate the incidence, risk factors, and characteristics of infectious flexor tenosynovitis occurring after TFR. Methods: We searched billing records for the Current Procedural Terminology code for TFR to identify all adult patients who underwent TFR at our institution over a 10-year period. We defined infectious tenosynovitis as any case where the patient underwent tendon sheath drainage or postoperative wound debridement within 6 months of the index TFR procedure. Medical records were reviewed to obtain patient demographic information, body mass index (BMI), tobacco use, history of diabetes mellitus, surgical setting (clinic vs outpatient surgery center), and surgical digit for all patients. In those patients treated for infection, we recorded hospital length of stay, number of operative procedures, and any culture results. Results: We identified a total of 18 infections out of 2307 procedures (1827 patients), for an incidence of 0.99%. Current smokers had a significantly higher incidence of infection than nonsmokers (1.77% vs 0.29%). On univariate analysis, smoking was closely associated with infection (P ≤ .05). All infections occurred in overweight or obese patients by BMI criteria, but there was no difference in average BMI between patients with and without infection. History of diabetes, in-office surgery, patient age, and patient sex were not associated with a higher incidence of infection. Patients with infections spent an average of 4.1 days in the hospital, and 40% required multiple surgical procedures. The most common infectious organism cultured was Staphylococcus aureus, which was present in 67% of infections. Patients with isolated methicillin-sensitive S aureus on culture showed signs of infection within 3 weeks of the index procedure, whereas polymicrobial, coagulase-negative staphylococci or beta hemolytic streptococci were identified in patients presenting with infectious symptoms later. Conclusion: Infections after TFR are uncommon but are more likely to occur in patients who are current smokers and overweight or obese by BMI criteria. Methicillin-sensitive S aureus is the most likely causative organism, especially in patients presenting during the early postoperative course.

Quality of Life in Caregivers, Spouses, and Partners of Total Laryngectomees: A Scoping Review.

PURPOSE: The purpose of this study was to (a) review methods used to assess quality of life (QOL) in caregivers, partners, and spouses of those who have undergone total laryngectomy (TL); (b) identify patterns in caregiver QOL changes postoperatively; and (c) review previously proposed interventions for caregivers. METHOD: PubMed, EMBASE, and CINAHL Complete were searched using the Medical Subject Heading terms laryngectomy, spouse, caregiver, and partner. Two reviewers independently screened and identified records meeting inclusion criteria. This scoping review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Initial search returned 143 results and 12 met inclusion criteria. Eight studies assessed postoperative QOL changes in categories such as psychological health, physical health, sexuality, and interpersonal relationships. Four studies proposed interventions for caregivers perioperatively. There were no consistently used inventories, and only one intervention was formally tested. CONCLUSIONS: The literature available on TL caregiver QOL contains inconsistent inventories and study design. There are few interventions available, and it would be beneficial to develop a standardized QOL inventory for this population to better target caregiver needs. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19287887.

Development and Validation of Machine Learning Models for Predicting Occult Nodal Metastasis in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Importance: Given that early-stage oral cavity squamous cell carcinoma (OCSCC) has a high propensity for subclinical nodal metastasis, elective neck dissection has become standard practice for many patients with clinically negative nodes. Unfortunately, for most patients without regional metastasis, this risk-averse treatment paradigm results in unnecessary morbidity. Objectives: To develop and validate predictive models of occult nodal metastasis from clinicopathological variables that were available after surgical extirpation of the primary tumor and to compare predictive performance against depth of invasion (DOI), the currently accepted standard. Design, Setting, and Participants: This diagnostic modeling study collected clinicopathological variables retrospectively from 7 tertiary care academic medical centers across the US. Participants included adult patients with early-stage OCSCC without nodal involvement who underwent primary surgical extirpation with or without upfront elective neck dissection. These patients were initially evaluated between January 1, 2000, and December 31, 2019. Exposures: Largest tumor dimension, tumor thickness, DOI, margin status, lymphovascular invasion, perineural invasion, muscle invasion, submucosal invasion, dysplasia, histological grade, anatomical subsite, age, sex, smoking history, race and ethnicity, and body mass index (calculated as weight in kilograms divided by height in meters squared). Main Outcomes and Measures: Occult nodal metastasis identified either at the time of elective neck dissection or regional recurrence within 2 years of initial surgery. Results: Of the 634 included patients (mean [SD] age, 61.2 [13.6] years; 344 men [54.3%]), 114 (18.0%) had occult nodal metastasis. Patients with occult nodal metastasis had a higher frequency of lymphovascular invasion (26.3% vs 8.1%; P < .001), perineural invasion (40.4% vs 18.5%; P < .001), and margin involvement by invasive tumor (12.3% vs 6.3%; P = .046) compared with those without pathological lymph node metastasis. In addition, patients with vs those without occult nodal metastasis had a higher frequency of poorly differentiated primary tumor (20.2% vs 6.2%; P < .001) and greater DOI (7.0 vs 5.4 mm; P < .001). A predictive model that was built with XGBoost architecture outperformed the commonly used DOI threshold of 4 mm, achieving an area under the curve of 0.84 (95% CI, 0.80-0.88) vs 0.62 (95% CI, 0.57-0.67) with DOI. This model had a sensitivity of 91.7%, specificity of 72.6%, positive predictive value of 39.3%, and negative predictive value of 97.8%. Conclusions and Relevance: Results of this study showed that machine learning models that were developed from multi-institutional clinicopathological data have the potential to not only reduce the number of pathologically node-negative neck dissections but also accurately identify patients with early OCSCC who are at highest risk for nodal metastases.

Assessing Prognostic Value of Quantitative Neck Dissection Quality Measures in Patients With Clinically Node-Negative Oral Cavity Squamous Cell Carcinoma.

Importance: In clinically localized (T1-2) oral cavity squamous cell carcinoma (OCSCC), regional lymph node metastasis is associated with a poor prognosis. Given the high propensity of subclinical nodal disease in these patients, upfront elective neck dissections (END) for patients with clinically node-negative disease are common and associated with better outcomes. Unfortunately, even with this risk-adverse treatment paradigm, disease recurrence still occurs, and our understanding of the factors that modulate this risk and alter survival have yet to be fully elucidated. Objective: To investigate the prognostic value of lymph node yield (LNY), lymph node ratio (LNR), and weighted LNR (wLNR) in patients with clinically node-negative T1-2 OCSCC. Design, Setting, and Participants: In this cohort study, data were collected retrospectively from 7 tertiary care academic medical centers. Overall, 523 patients with cT1-2N0 OCSCC who underwent elective neck dissections after primary surgical extirpation were identified. Exposures: Lymph node yield was defined as the number of lymph nodes recovered from elective neck dissection. Lymph node ratio was defined as the ratio of positive nodes against total LNY. Weighted LNR incorporated information from both LNY and LNR into a single continuous metric. Main Outcomes and Measures: Locoregional control (LRC) and disease-free survival (DFS) were both evaluated using nonparametric Kaplan-Meier estimators and semiparametric Cox regression. Results: On multivariable analysis, LNY less than or equal to 18 lymph nodes was found to be significantly associated with decreased LRC (aHR, 1.53; 95% CI, 1.04-2.24) and DFS (aHR, 1.46; 95% CI, 1.12-1.92) in patients with pN0 disease, but not those with pN-positive disease. Importantly, patients with pN0 disease with LNY less than or equal to 18 and those with pN1 diseasehad nearly identical 5-year LRC (69.7% vs 71.4%) and DFS (58.2% vs 55.7%). For patients with pN-positive disease, LNR greater than 0.06 was significantly associated with decreased LRC (aHR, 2.66; 95% CI, 1.28-5.55) and DFS (aHR, 1.65; 95% CI, 1.07-2.53). Overall, wLNR was a robust prognostic variable across all patients with cN0 disease, regardless of pathologic nodal status. Risk stratification via wLNR thresholds demonstrated greater optimism-corrected concordance compared with American Joint Committee on Cancer (AJCC) 8th edition nodal staging for both LRC (0.61 vs 0.57) and DFS (0.61 vs 0.58). Conclusions and Relevance: Movement toward more robust metrics that incorporate quantitative measures of neck dissection quality and regional disease burden, such as wLNR, could greatly augment prognostication in cT1-2N0 OCSCC by providing more reliable and accurate risk estimations.