Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma.

BACKGROUND: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease. OBJECTIVE: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease. METHODS: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome. RESULTS: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P = .0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95% confidence interval 0.21-0.84; P = .0113). LIMITATIONS: This is a multicenter but single institution study of a white population. CONCLUSION: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.

Why Do Patients Stay Longer Than Three Nights Following Hip and Knee Arthroplasty?

BACKGROUND: Prolonged length of stay (PLOS) is frequently cited by secondary data studies as an adverse outcome following hip and knee arthroplasty. Although perhaps indisputable that PLOS increases the cost of hospitalization, it is unknown whether it is an appropriate measure of the quality of an arthroplasty procedure. METHODS: We searched our institution's database for all hip and knee arthroplasty procedures over a 5-year period using MS-DRG (Medicare Severity-Diagnosis Related Group) 469 and 470. Cases with greater than 3 night stays were identified. Charts were manually reviewed by 2 independent reviewers to identify the primary reason for PLOS, and the need for 30-day readmission or reoperation. RESULTS: Of a total 4347 hip and knee arthroplasty cases, 218 (5.0%) were identified with LOS greater than 3 nights. The majority of prolonged stays were due to exclusively medical reasons (81 cases: 37.2%; 95% confidence interval [CI] 31.0-43.7). The second most common cause was inpatient days prior to the arthroplasty procedure (45 cases: 20.6%; 95% CI 15.8-26.5). Orthopedic reasons for PLOS were significantly less common than medical reasons (36 cases: 16.5%; 95% CI 12.2-22.0, P < .0001), most often due to failure to meet therapy goals. Neither readmission (31 cases: 14.2%) nor reoperation (10 cases: 4.6%) was associated with an underlying reason for PLOS. CONCLUSION: When evaluating LOS as a measure of quality of an arthroplasty procedure, readers of secondary "big data" studies should be aware that there are significant limitations to its utility. Even after controlling for potential confounders, we found that PLOS does not necessarily reflect an adverse outcome.

Improving Access to Care Through the Establishment of a Local, Teledermatology Network.

Introduction: Access to dermatologic care is a major issue in the United States, especially within the un- and underinsured populations; technology, including teledermatology, will pay a role in improving access to care. Methods: We performed a prospective study between November 2016 and September 2017. We leveraged a partnership between Mayo Clinic and Mountain Park Health Clinic, a community clinic that primarily serves un- and underinsured populations. We implemented a mobile phone-based store and forward (SAF) teledermatology service, which integrated an external community health clinic to an existing electronic health record (EHR) using standardized data capture forms, real-time support, and simple workflows. Results: Thirty-seven patients were enrolled in the study, 65% female and 35% male with an average age of 47.9 (SD = 15.9). The ethnic breakdown was: 81.1% Hispanic, 13.5% Caucasian, and 5.4% African American. The majority, 62.2%, did not have a high school education, 45.9% were unemployed, and 51.4% were uninsured. 64.9% earned less than $25,000 for annual household income. Teledermatology consultation increased the absolute diagnostic and management concordance by 36.6% (p = 0.01, 95% CI 12.2%-61.0%) and 34.2% (p < 0.01, 95% CI 11%-57%), respectively. Primary care providers had a significant increase in mean confidence in the diagnosis and management of dermatology conditions pre and poststudy (3.60 vs. 3.70 and 3.21 vs. 3.60, respectively; p < 0.01). Ninety-six percent of the primary care providers agreed (52.0%) and strongly agreed (44.0%) that they would send another patient for teleconsultation.Conclusion: We successfully implemented a SAF teledermatology consultative service in a community health clinic outside our EHR. A similar approach can be used by other large health care organizations to provide integrated, high-quality consultation to clinics with rural, un- and underinsured populations.

Distal Metatarsal Articular Angle in Hallux Valgus Deformity. Fact or Fiction? A 3-Dimensional Weightbearing CT Assessment.

BACKGROUND: The Distal Metatarsal Articular Angle (DMAA) was previously described as an increase in valgus deformity of the distal articular surface of the first metatarsal (M1) in hallux valgus (HV). Several studies have reported poor reliability of this measurement. Some authors have even called into question its existence and consider it to be the consequence of M1 pronation resulting in projection of the round-shaped lateral edge of M1 head.Our study aimed to compare the DMAA in HV and control populations, before and after computer correction of M1 pronation and plantarflexion with a dedicated weightbearing CT (WBCT) software. We hypothesized that after computerized correction, DMAA will not be increased in HV compared to controls. METHODS: We performed a retrospective case-control study including 36 HV and 20 control feet. In both groups, DMAA was measured as initially described on conventional radiographs (XR-DMAA) and WBCT by measuring the angle between the distal articular surface and the longitudinal axis of M1. Then, the DMAA was measured after computerized correction of M1 plantarflexion and coronal plane rotation using the α angle (3d-DMAA). RESULTS: The XR-DMAA and the 3d-DMAA showed higher significant mean values in HV group compared to controls (respectively 25.9 ± 7.3 vs 7.6 ± 4.2 degrees, P < .001, and 11.9 ± 4.9 vs 3.3 ± 2.9 degrees, P < .001).Comparing a small subset of precorrected juvenile HV (n=8) and nonjuvenile HV (n=28) demonstrated no significant difference in the measure DMAA values. On the other hand, the α angle was significantly higher in the juvenile HV group (21.6 ± 9.9 and 11.4 ± 3.7 degrees; P = .0046). CONCLUSION: Although the valgus deformity of M1 distal articular surface in HV is overestimated on conventional radiographs, comparing to controls showed that an 8.6 degrees increase remained after confounding factors' correction. CLINICAL RELEVANCE: After pronation computerized correction, an increase in valgus of M1 distal articular surface was still present in HV compared to controls. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Coronal Plane Rotation of the Medial Column in Hallux Valgus: A Retrospective Case-Control Study.

BACKGROUND: We previously reported an increase in pronation of the first metatarsal (M1) head relative to the ground in hallux valgus (HV) patients compared to controls. Still, the origin and location of this hyperpronation along the medial column is unknown. Recent studies showed that presence of progressive collapsing foot deformities (PCFDs), which is a condition frequently associated with HV, can strongly influence the medial column coronal plane alignment. The objective of this study was to assess the coronal rotation of the medial column bones in HV feet, HV feet with radiologic markers of PCFD, and controls. We hypothesized that hyperpronation in HV will originate from a combination of M1 intrinsic torsion and first tarsometatarsal joint malposition. METHODS: The same cohort of 36 HV and 20 controls matched on age, gender, and body mass index was used. Previously, a validation of the measurements was carried out through a cadaveric study. Using these metrics, we assessed the coronal plane rotation of the navicular, medial cuneiform, and the M1 at its base and head with respect to the ground using weightbearing CT images. We measured the Meary angle and the calcaneal moment arm in our 36 HV subjects. We subdivided our cohort into an HV group and a potential PCFD HV group according to these measurements. Comparisons on medial column bones coronal rotation were performed between HV, PCFD HV, and control groups. RESULTS: Twenty-two HV cases were included in the HV group and 14 in the PCFD HV group. Both groups presented an increase in pronation of the first metatarsal head relative to the ground when compared to the control group (P < .001). Comparing HV and controls showed an 8.3 degrees increase in pronation of M1 intrinsic torsion (P < .001) and a 4.7 degrees pronated malposition of the first tarsometatarsal joint (P = .02) in HV. A 9.7 degrees supinated malposition of the first naviculocuneiform joint (P < .001) was also observed in HV. Comparing PCFD HV and controls showed a significant increase in pronation of the navicular (respectively, 17.2 ± 5.4 and 12.3 ± 3.4 degrees, P = .007) and a 5.5 degrees increase in pronation of M1 intrinsic torsion (P = .02) in PCFD HV, without malposition of the first tarsometatarsal and naviculocuneiform joints. CONCLUSION: Hyperpronation of the M1 head relative to the ground originated from both increases in pronation of M1 intrinsic torsion and first tarsometatarsal joint malposition in HV, although partially counterbalanced by a supinated malposition of the first naviculocuneiform joint. On the other hand, PCFD HV patients showed a generalized pronated position throughout the medial column from the navicular to the M1 head and may be related to the midfoot and hindfoot deformities frequently present in PCFD. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Impact of standardized templates and skin cancer learning modules for teledermatology consultations.

BACKGROUND: Little research has been done in teledermatology to examine the effects of standardized templates and subject-specific learning modules. METHODS: We performed a prospective study examining the effects of standardized templates and standardized cutaneous oncology learning modules on teledermatology referrals at Mayo Clinic. This data was then compared to previous teledermatology referrals before standardized templates were adopted. RESULTS: A total of 42 teledermatology consultations were performed during the 4-month study period. The use of standardized templates resulted in an absolute reduction in face-to-face referrals. Teledermatology consultation increased the absolute diagnostic and management concordance by 26.2% (P = 0.02) and 33.3% (P < 0.01), respectively, and decreased the absolute diagnostic and management discordance by 19.1% (P = 0.03) and 31.0% (P < 0.01), respectively. The largest knowledge gaps were identified in cutaneous oncology. Educational intervention improved theoretical referral rates and confidence in diagnosis and management overall. CONCLUSION: The implementation of standardized intake templates reduces the rate of face-to-face referrals. Teledermatology improves primary care-based dermatological care and reduces theoretical referral rates.

Deletions in the fifth alpha helix of HIV-1 matrix block virus release.

The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1-α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release.