Tenosynovial and Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release.

BACKGROUND: Patients with cardiac amyloidosis often have carpal tunnel syndrome that precedes cardiac manifestations by several years. However, the prevalence of cardiac involvement at the time of carpal tunnel surgery has not been established. OBJECTIVES: The authors sought to identify the prevalence and type of amyloid deposits in patients undergoing carpal tunnel surgery and evaluate for cardiac involvement. The authors also sought to determine if patients with soft tissue transthyretin (TTR) amyloid had abnormal TTR tetramer kinetic stability. METHODS: This was a prospective, cross-sectional, multidisciplinary study of consecutive men age ≥50 years and women ≥60 years undergoing carpal tunnel release surgery. Biopsy specimens of tenosynovial tissue were obtained and stained with Congo red; those with confirmed amyloid deposits were typed with mass spectrometry and further evaluated for cardiac involvement with biomarkers, electrocardiography, echocardiography with longitudinal strain, and technetium pyrophosphate scintigraphy. Additionally, serum TTR concentration and tetramer kinetic stability were examined. RESULTS: Of 98 patients enrolled (median age 68 years, 51% male), 10 (10.2%) had a positive biopsy for amyloid (7 ATTR, 2 light chain [AL], 1 untyped). Two patients were diagnosed with hereditary ATTR (Leu58His and Ala81Thr), 2 were found to have cardiac involvement (1 AL, 1 ATTR wild-type), and 3 were initiated on therapy. In those patients who had biopsy-diagnosed ATTR, there was no difference in plasma TTR concentration or tetramer kinetic stability. CONCLUSIONS: In a cohort of patients undergoing carpal tunnel release surgery, Congo red staining of tenosynovial tissue detected amyloid deposits in 10.2% of patients. Concomitant cardiac evaluation identified patients with involvement of the myocardium, allowing for implementation of disease-modifying therapy. (Carpal Tunnel Syndrome and Amyloid Cardiomyopathy; NCT02792790).

Small Finger to Ring Finger Ray Transposition: Modern Surgical Technique and Case-based Review of the Literature.

Ray transposition for central digital amputation has been performed following traumatic injury to the hand for decades. Small finger to ring finger ray transposition has been well described in the literature, with good functional and aesthetic outcomes reported. Originally described by Bunnell, the fourth metacarpal can be disarticulated and the fifth metacarpal base transposed with reconstruction of the intermetacarpal ligament allowing progressive closure between the third and fifth rays. However, osteotomy-based transpositions are utilized placing the osteotomy at the level of the metacarpal, followed by transposition and fixation of the small finger to the base of the ring finger metacarpal; or, by making an intracarpal wedge-osteotomy of the hamate with subsequent radial translocation of the entire small finger ray. Recent literature has suggested the intracarpal wedge osteotomy to be superior technically, and with less postoperative complications. However, for this somewhat uncommon reconstructive procedure, no high-level evidence exists to determine which of these techniques is truly more favorable. Here, we present an interesting case of ray amputation and transposition following an isolated fourth metacarpal traumatic firearm injury, and comprehensive modern surgical technique. Upon review of the literature, small to ring finger ray transposition has been shown to have acceptable functional and aesthetic outcomes regardless of the osteotomy technique used, and should be considered when the nature of presenting injury and the patient's lifestyle and postoperative expectations are appropriate.

Do Magnetic Resonance Imaging Characteristics of Full-Thickness Rotator Cuff Tears Correlate With Sleep Disturbance?

BACKGROUND: Many patients with rotator cuff tears suffer from nocturnal shoulder pain, resulting in sleep disturbance. PURPOSE: To determine whether rotator cuff tear size correlated with sleep disturbance in patients with full-thickness rotator cuff tears. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with a diagnosis of unilateral full-thickness rotator cuff tears (diagnosed via magnetic resonance imaging [MRI]) completed the Pittsburgh Sleep Quality Index (PSQI), a visual analog scale (VAS) quantifying their shoulder pain, and the American Shoulder and Elbow Surgeons (ASES) questionnaire. Shoulder MRI scans were analyzed for anterior-posterior tear size (mm), tendon retraction (mm), Goutallier grade (0-4), number of tendons involved (1-4), muscle atrophy (none, mild, moderate, or severe), and humeral head rise (present or absent). Bivariate correlations were calculated between the MRI characteristics and baseline survey results. RESULTS: A total of 209 patients with unilateral full-thickness rotator cuff tears were included in this study: 112 (54%) female and 97 (46%) male (mean age, 64.1 years). On average, shoulder pain had been present for 24 months. The mean PSQI score was 9.8, and the mean VAS score was 5.0. No significant correlations were found between any of the rotator cuff tear characteristics and sleep quality. Only tendon retraction had a significant correlation with pain. CONCLUSION: Although rotator cuff tears are frequently associated with nocturnal pain and sleep disruption, this study demonstrated that morphological characteristics of full-thickness rotator cuff tears, such as size and tendon retraction, do not correlate with sleep disturbance and have little to no correlation with pain levels.

Period2 3'-UTR and microRNA-24 regulate circadian rhythms by repressing PERIOD2 protein accumulation.

We previously created two PER2::LUCIFERASE (PER2::LUC) circadian reporter knockin mice that differ only in the Per2 3'-UTR region: Per2::Luc, which retains the endogenous Per2 3'-UTR and Per2::LucSV, where the endogenous Per2 3'-UTR was replaced by an SV40 late poly(A) signal. To delineate the in vivo functions of Per2 3'-UTR, we analyzed circadian rhythms of Per2::LucSV mice. Interestingly, Per2::LucSV mice displayed more than threefold stronger amplitude in bioluminescence rhythms than Per2::Luc mice, and also exhibited lengthened free-running periods (∼24.0 h), greater phase delays following light pulse, and enhanced temperature compensation relative to Per2::Luc Analysis of the Per2 3'-UTR sequence revealed that miR-24, and to a lesser degree miR-30, suppressed PER2 protein translation, and the reversal of this inhibition in Per2::LucSV augmented PER2::LUC protein level and oscillatory amplitude. Interestingly, Bmal1 mRNA and protein oscillatory amplitude as well as CRY1 protein oscillation were increased in Per2::LucSV mice, suggesting rhythmic overexpression of PER2 enhances expression of Per2 and other core clock genes. Together, these studies provide important mechanistic insights into the regulatory roles of Per2 3'-UTR, miR-24, and PER2 in Per2 expression and core clock function.

The Nature of Foot Ray Deficiency in Congenital Fibular Deficiency.

BACKGROUND: Absent lateral osseous structures in congenital fibular deficiency, including the distal femur and fibula, have led some authors to refer to the nature of foot ray deficiency as "lateral" as well. Others have suggested that the ray deficiency is in the central portion of the midfoot and forefoot.We sought to determine whether cuboid preservation and/or cuneiform deficiency in the feet of patients with congenital fibular deficiency implied that the ray deficiency is central rather than lateral in patients with congenital fibular deficiency. METHODS: We identified all patients with a clinical morphologic diagnosis of congenital fibular deficiency at our institution over a 15-year period. We reviewed the records and radiographs of patients who had radiographs of the feet to allow determination of the number of metatarsals, the presence or absence of a cuboid or calcaneocuboid fusion, the number of cuneiforms present (if possible), and any other osseous abnormalities of the foot. We excluded patients with 5-rayed feet, those who had not had radiographs of the feet, or whose radiographs were not adequate to allow accurate assessment of these radiographic features. We defined the characteristic "lateral (fifth) ray present" if there was a well-developed cuboid or calcaneocuboid coalition with which the lateral-most preserved metatarsal articulated. RESULTS: Twenty-six patients with 28 affected feet met radiographic criteria for inclusion in the study. All affected feet had a well-developed cuboid or calcaneocuboid coalition. The lateral-most ray of 25 patients with 26 affected feet articulated with the cuboid or calcaneocuboid coalition. One patient with bilateral fibular deficiency had bilateral partially deficient cuboids, and the lateral-most metatarsal articulated with the medial remnant of the deformed cuboids. Twenty-one of 28 feet with visible cuneiforms had 2 or 1 cuneiform. CONCLUSIONS: Although the embryology and pathogenesis of congenital fibular deficiency remain unknown, based on the radiographic features of the feet in this study, congenital fibular deficiency should not be viewed as a global "lateral lower-limb deficiency" nor the foot ray deficiency as "lateral." LEVEL OF EVIDENCE: Level IV-prognostic study.

The High Risk of Infection With Delayed Treatment of Open Seymour Fractures: Salter-Harris I/II or Juxta-epiphyseal Fractures of the Distal Phalanx With Associated Nailbed Laceration.

BACKGROUND: To describe treatment methods and complication rates of all open Seymour fractures (Salter-Harris I/II or juxta-epiphyseal fractures of the distal phalanx of the hand with associated nailbed laceration) treated at or referred to a pediatric level 1 trauma center over a 10-year time period. We hypothesized that delayed treatment of Seymour fractures results in higher infectious complication rates. METHODS: We identified all patients treated for open Seymour fractures at the orthopaedic hand clinic at our level 1 pediatric trauma center between August 2002 and December 2012. All charts were reviewed retrospectively. Patients were divided into groups based on timing and completeness of treatment. "Appropriate" treatment was defined as irrigation and debridement, fracture reduction, and antibiotic administration. "Partial" treatment was defined as any type of incomplete treatment; "Acute" treatment was defined as management within 24 hours of the injury; and "Delayed" as having received treatment after 24 hours from the time of injury. Statistical comparisons were performed using the Fisher exact test. RESULTS: A total of 34 patients treated for 35 Seymour fractures met the inclusion criteria. In total, 31% (11/35) received acute, appropriate treatment, 37% (13/35) received acute, partial treatment, and 31% (11/35) received delayed treatment. There were 7 infectious complications: 2 superficial and 5 osteomyelitis. No infections occurred in the acutely, appropriately treated group (infection rate 0%, 0/11), 2 occurred in the acutely, partially treated group (15%, 2/13), and 5 occurred in the delayed treatment group (45%, 5/11). CONCLUSIONS: The timing and quality of treatment of open Seymour fractures significantly influences infection rates. This study highlights the importance of timely and appropriate treatment of this seemingly innocuous fracture. LEVEL OF EVIDENCE: Level III-retrospective study, therapeutic.

Disconnected circadian and cell cycles in a tumor-driven cell line.

Cell division occurs at a specific time of day in numerous species, suggesting that the circadian and cell cycles are coupled in vivo. By measuring the cell cycle rhythm in real-time, we recently showed that the circadian and cell cycles are not coupled in immortalized fibroblasts, resulting in a rapid rate of cell division even though the circadian rhythm is normal in these cells. Here we report that tumor-driven Lewis lung carcinoma (LLC) cells have perfectly temperature compensated circadian clocks, but the periods of their cell cycle gene expression rhythms are temperature-dependent, suggesting that their circadian and cell cycles are not connected. These data support our hypothesis that decoupling of the circadian and cell cycles may underlie aberrant cell division in tumor cells.