Hint from an Enzymatic Reaction: Superoxide Dismutase Models Efficiently Suppress Colorectal Cancer Cell Proliferation.

Superoxide dismutases (SODs) are essential antioxidant enzymes that prevent massive superoxide radical production and thus protect cells from damage induced by free radicals. However, this concept has rarely been applied to directly impede the function of driver oncogenes, thus far. Here, leveraging efforts from SOD model complexes, we report the novel finding of biomimetic copper complexes that efficiently scavenge intracellularly generated free radicals and, thereby, directly access the core consequence of colorectal cancer suppression. We conceived four structurally different SOD-mimicking copper complexes that showed distinct disproportionation reaction rates of intracellular superoxide radical anions. By replenishing SOD models, we observed a dramatic reduction of intracellular reactive oxygen species (ROS) and adenine 5'-triphosphate (ATP) concentrations that led to cell cycle arrest at the G2/M stage and induced apoptosis in vitro and in vivo. Our results showcase how nature-mimicking models can be designed and fine-tuned to serve as a viable chemotherapeutic strategy for cancer treatment.

Associations of normal fasting glucose levels and of insulin resistance with degenerative rotator cuff tear : Normoglycemia and rotator cuff tear.

BACKGROUND: The upper normoglycemic range has been proposed as a risk factor for degenerative rotator cuff tendon tear (RCT), and insulin resistance has been suggested as a risk factor for tendinopathy. However, no research has established their association with degenerative RCT in the general population. This study aimed to determine whether fasting glucose levels and insulin resistance are risk factors for degenerative RCT in the normoglycemic population and identify the risk range for fasting glucose. METHODS: This study included 418 normoglycemic participants from a rural cohort. Participants completed questionnaires, physical exams, blood tests, and MRI evaluations of both shoulders. Insulin resistance was assessed using a triglyceride/high-density-lipoprotein (TG/HDL) ≥ 3.5. Logistic regression analysis was used to determine the association between fasting glucose level, TG/HDL ≥ 3.5, and other factors and degenerative RCT. The study calculated the areas under the receiver operating characteristic curve (AUC) to determine the more appropriate predicting value between the scale and categorical values of fasting glucose levels, and compared the AUCs using the DeLong method. RESULTS: In the multivariable analyses, both scale and categorical values of fasting glucose levels, and TG/HDL ≥ 3.5 were significantly associated with degenerative RCT. Fasting glucose levels ≥ 90.5 mg/dL (OR: 3.87, 95% CI: 2.10-7.06) in scale value and 90-99 mg/dL (OR: 4.13, 95% CI: 2.87-8.12) in categorical value were significantly associated with degenerative RCT (P < .001). The AUC of the scale value of fasting glucose levels ≥ 90.5 mg/dL was 0.68. The AUC of the categorical value of fasting glucose levels of 90-99 mg/dL was 0.70. Because of the significantly larger AUC of the categorical value of fasting glucose levels of 90-99 mg/dL, those fasting glucose levels were determined to be independently associated with degenerative RCT (P < .001). CONCLUSIONS: High fasting glucose levels within the normal range may link to increase insulin resistance and risk of degenerative RCT. Normoglycemic levels of 90-99 mg/dL and insulin resistance may be risk factors for degenerative RCT. LEVEL OF EVIDENCE: Level III, prognostic study.

Involvement of inflammatory lipoproteinemia with idiopathic adhesive capsulitis accompanying subclinical hypothyroidism.

BACKGROUND: Thyroid functional abnormalities are considered risk factors for idiopathic adhesive capsulitis (IAC) though that relationship remains uncertain. Although dyslipidemias are associated with IAC, no readily accessible study has reported associations between dyslipidemias and IAC patients with subclinical hypothyroidism. The purposes of this study were to investigate whether subclinical hypothyroidism is an independently associated factor for IAC and to determine the differences in prevalence of dyslipidemias between two groups of persons with subclinical hypothyroidism: one composed of IAC patients and the other of individuals without IAC. METHODS: This case-control study included a case group of 412 IAC patients without intrinsic shoulder lesions, extrinsic causes, or medication for thyroid dysfunction. The control group comprised 1236 age- and sex-matched persons seeking general checkups at the authors' health promotion center during the same period as the case group. Control subjects had normal shoulder function and no previously diagnosed adhesive capsulitis, no medication for thyroid dysfunction, and no history of trauma or of shoulder surgery. The studied variables were age, gender, obesity, diabetes, dyslipidemias, subclinical hypothyroidism, hypothyroidism, and hyperthyroidism. A conditional logistic regression analysis evaluated the matched sets of subjects to determine odds ratios and 95% confidence intervals for the studied variables. The differences in the prevalence of dyslipidemias between IAC patients with subclinical hypothyroidism and individuals with subclinical hypothyroidism but without IAC were determined with generalized estimating equations, using covariates of age, sex, and diabetes. The P values were set at < 0.05. RESULTS: Subclinical hypothyroidism (odds ratio, 2.10; 95% confidence interval, 1.36-3.15; P = .001) was significantly associated with IAC. Patients with IAC and subclinical hypothyroidism had a significantly higher prevalence of hyper-low-density lipoproteinemia, an inflammatory lipoproteinemia, than individuals with subclinical hypothyroidism but without IAC (P = .002). CONCLUSIONS: Subclinical hypothyroidism is significantly associated with IAC. Hyper-low-density lipoproteinemia, an inflammatory lipoproteinemia, is involved in IAC accompanied by subclinical hypothyroidism.

Are any radiologic parameters independently associated with degenerative postero-superior rotator cuff tears?

BACKGROUND: Several radiologic parameters representing scapular morphology have been proposed as risk factors for degenerative posterosuperior rotator cuff tear (PSRCT). The causes of PSRCT are multifactorial; many reported risk factors are compound entities. However, no determination, made after adjustment with previously reported risk factors, of which radiologic parameters are independent risk factors for degenerative PSRCT, has been reported. Therefore, this study's purpose was to determine which radiologic parameters representing scapular morphology are independent risk factors for degenerative PSRCT in a general population after adjustment with previously suggested risk factors. METHODS: This study involved 629 subjects (629 shoulders) drawn from a cohort of rural residents. PSRCT diagnoses were based on magnetic resonance imaging findings. Logistic regression analysis was used to determine the odds ratios and 95% confidence intervals for the following variables: sex, age, height, weight, waist circumference, dominant-side involvement, smoking, alcohol consumption, manual labor, diabetes, hypertension, metabolic syndrome, thyroid dysfunction, serum lipid profile, high-sensitivity C-reactive protein, and radiologic parameters. The evaluated radiologic parameters were the superior displacement of the humeral head (SDHH) and those representing the scapular morphology. The radiologic parameters representing the scapular morphology were lateral acromial angle, acromial slope, acromial tilt, acromial index, and critical shoulder angle (CSA). Univariate logistic regression analyses for all variables, as well as multivariable logistic regression analyses for variables with significant associations and clinical effect sizes in the univariate logistic regression analyses, were performed. In order to determine the cutoff value for significant radiologic parameters, each pair of candidate cutoff values was obtained as follows: 1 candidate, as the lowest significant ordinal value in a univariate analysis, and the other candidate, according to a receiver operating characteristic curve analysis. Then, the cutoff values were determined by selecting the value in each candidate pair that had the larger area under the receiver operating characteristic curve, using the DeLong test. RESULTS: In the multivariable analyses, CSA was significantly associated with degenerative PSRCT after controlling for the following factors: age, waist circumference, dominant-side involvement, manual labor, diabetes, metabolic syndrome, hypo-high-density lipoproteinemia, and SDHH (P ≤ .033). CSA (odds ratio, 1.58 [95% confidence interval, 1.45-1.72]; P < .001) was the only significantly associated radiologic parameter among the studied radiologic parameters representing scapular morphology. CONCLUSION: CSA (≥35°) is an independent associated factor for degenerative PSRCT after adjustment for the following suggested risk factors: age, waist circumference, dominant-side involvement, manual labor, diabetes, metabolic syndrome, hypo-high-density lipoproteinemia, and SDHH.

Need for early exploration of radial nerve in humeral shaft fractures with radial nerve palsy.

INTRODUCTION: Radial nerve palsy (RNP) associated with humeral shaft fracture (HSF) is the most common nerve complication in long bone fractures. There is still controversy over the need for immediate exploration of the radial nerve (RN) in HSF with RNP. The purpose of the current study was to determine which situations of HSF with RNP require early exploration of the RN. MATERIALS AND METHODS: This is a retrospective study that included 55 patients who had visited the emergency department of the current authors' hospital and had been diagnosed with HSF between March of 2005 and September of 2015. Of these 55 patients, 14 (25.4%) had been diagnosed with HSF with RNP. We reviewed the medical records of those 14 patients and their radiographs to evaluate each fracture's type, location, pattern, energy of trauma, status of RN injury, and time until recovery from RNP. RESULT: All the 14 RNP patients had suffered high-energy trauma. Three had fractures in the proximal third (21.4%), six in the middle third (42.9%), and five in the distal third (35.7%). The three patients (21.4%) with incomplete recovery of RNP all had proximal third fractures; two of these three patients had RN transection. CONCLUSION: Early exploration of the radial nerve should be considered in patients with radial nerve palsy associated with proximal third humeral shaft fracture, regardless of the fracture patterns caused by the high-energy trauma.

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon.

BACKGROUND: Bone mineral density of the humeral head is an independent determining factor for postoperative rotator cuff tendon healing. Bisphosphonates, which are commonly used to treat osteoporosis, have raised concerns regarding their relationships to osteonecrosis of the jaw and to atypical fracture of the femur. In view of the prevalence of rotator cuff tear in osteoporotic elderly people, it is important to determine whether bisphosphonates affect rotator cuff tendon healing. However, no studies have investigated bisphosphonates' cytotoxicity to human rotator cuff tendon fibroblasts (HRFs) or bisphosphonates' effects on rotator cuff tendon healing. The purpose of this study was to evaluate the cytotoxicity of alendronate (Ald), a bisphosphonate, and its effects on HRF wound healing. METHODS: HRFs were obtained from human supraspinatus tendons, using primary cell cultures. The experimental groups were control, 0.1 µM Ald, 1 µM Ald, 10 µM Ald, and 100 µM Ald. Alendronate exposure was for 48 h, except during a cell viability analysis with durations from 1 day to 6 days. The experimental groups were evaluated for cell viability, cell cycle and cell proliferation, type of cell death, caspase activity, and wound-healing ability. RESULTS: The following findings regarding the 100 µM Ald group contrasted with those for all the other experimental groups: a significantly lower rate of live cells (p < 0.01), a higher rate of subG1 population, a lower rate of Ki-67 positive cells, higher rates of apoptosis and necrosis, a higher number of cells with DNA fragmentation, higher caspase-3/7 activity (p < 0.001), and a higher number of caspase-3 positive staining cells. In scratch-wound healing analyses of all the experimental groups, all the wounds healed within 48 h, except in the 100 µM Ald group (p < 0.001). CONCLUSIONS: Low concentrations of alendronate appear to have little effect on HRF viability, proliferation, migration, and wound healing. However, high concentrations are significantly cytotoxic, impairing cellular proliferation, cellular migration, and wound healing in vitro.

Hypo-High-Density Lipoproteinemia Is Associated With Preoperative Tear Size and With Postoperative Retear in Large to Massive Rotator Cuff Tears.

PURPOSE: To evaluate any association of specific subtypes of dyslipidemia with increments of preoperative tear size and with structural integrity after arthroscopic rotator cuff repair (ARCR). METHODS: One surgeon's consecutive patients who underwent ARCR from January 2011 to June 2018 were reviewed. The inclusion criteria were minimum 1-year follow-up ultrasonography, blood tests, physical examination, and provision of informed consent. The exclusion criteria were incomplete laboratory tests, history of acute trauma, previous shoulder surgery, isolated subscapularis tendon tear, inappropriate radiographs, no 1-year follow-up ultrasonography, and medication with lipid-lowering drugs. Associated preoperative factors for the increments of tear size and for retear after ARCR were determined using logistic regression analysis. Statistical significance was set at P < .05. RESULTS: Of the 502 ARCR patients from the study period, 195 patients (195 shoulders), with a mean age of 60.5 ± 7.5 years, met the inclusion and exclusion criteria. Age (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.1-1.3), diabetes (OR, 3.6; 95% CI, 1.7-7.5), and hypo-high-density lipoproteinemia (hypo-HDLemia) (OR, 2.9; 95% CI, 1.5-5.6) were significantly associated with increments of preoperative tear size (P ≤ .01). Diabetes (OR, 3.0; 95% CI, 1.3-6.6), critical shoulder angle (OR, 2.0; 95% CI, 1.4-3.0), and tear size (OR, 2.1; 95% CI, 1.3-3.4) were significantly associated with retear after ARCR in overall study subjects (P = .01). Diabetes (OR, 3.8; 95% CI, 1.3-11.4), hypo-HDLemia (OR, 3.0; 95% CI, 1.1-8.8), and critical shoulder angle (OR, 1.5; 95% CI, 1.1-2.3) had significant associations with retear after ARCR in patients with a large to massive preoperative tear size (P ≤ .04). CONCLUSIONS: Preoperative hypo-HDLemia (high-density lipoprotein level < 40 mg/dL in male patients and < 50 mg/dL in female patients) has a significant association with the increments of preoperative tear size and with retear after ARCR in large- to massive-sized rotator cuff tears. LEVEL OF EVIDENCE: Level IV, case series.

Association between fasting glucose levels and adhesive capsulitis in a normoglycemic population: a case-control study.

BACKGROUND: Hyperglycemia is the most commonly cited risk factor for adhesive capsulitis. However, no study has established whether fasting glucose levels within the normoglycemic range are associated with idiopathic adhesive capsulitis (IAC). This study hypothesized that increments of fasting glucose levels within the normoglycemic range would be linked to IAC. This study investigated any association between normoglycemic fasting glucose levels and IAC. METHODS: This case-control study comprised a group of 151 patients with IAC without intrinsic shoulder lesions, extrinsic causes, or known metabolic risk factors such as diabetes, dyslipidemia, and thyroid dysfunction. The control group comprised 453 age- and sex-matched persons seeking general check-ups at the authors' health promotion center during the same period as the case group. Control subjects had normal shoulder function, no previous diagnosis of adhesive capsulitis or of metabolic disease, and no history of trauma or of shoulder surgery. The studied variables were body mass index, serum lipid profiles, thyroid hormone levels, fasting glucose levels, glycosylated hemoglobin A1c, and high-sensitivity C-reactive protein. Fasting glucose levels were studied as scale data and categorical data (<85, 85-89, 90-94, and 95-99 mg/dL). Multivariable conditional logistic regression analysis evaluated the matched sets of subjects. Odds ratios and 95% confidence intervals were determined for various potentially associated factors. RESULTS: Fasting glucose level, hypercholesterolemia, and high-sensitivity C-reactive protein were significantly associated with IAC (P ≤ .030). Fasting glucose levels in the <85 mg/dL quartile were significantly negatively associated with IAC (P ≤ .001). In contrast, fasting glucose levels in the 90-94 mg/dL quartile or higher were significantly positively associated with IAC (P ≤ .034). CONCLUSION: IAC is positively associated with fasting glucose levels of 90-99 mg/dL, which are currently considered normoglycemic.

N-acetylcysteine reduces glutamate-induced cytotoxicity to fibroblasts of rat supraspinatus tendons.

Purpose: Neuronal theory regarding rotator cuff degeneration has developed from the findings that glutamate, an amino acid and an excitatory neurotransmitter, is present in increased concentrations in tendon tissues with tendinopathy and that glutamate induces cell death in fibroblasts of origin in rat supraspinatus tendon. The purpose of the current study was to determine whether N-acetylcysteine (NAC) has cytoprotective effects against glutamate-induced fibroblast death. Materials and Methods: Primary cultured fibroblasts were obtained from rat supraspinatus tendons. Varying concentrations of glutamate (0.5, 1, 5, and 10 mM) and of NAC (0.5, 1, 2, and 5 mM) were used for evaluation of cytotoxicity. Cell viability, cell cycles, types of cell death, intracellular ROS production, expressions of caspase-3/7, and Ca2+ influx were evaluated. Results: Glutamate significantly induced cell death, apoptosis, and Ca2+ influx and significantly increased caspase-3/7 activity and intracellular ROS production (p < 0.001). NAC significantly reduced the glutamate-induced cell death, apoptosis, Ca2+ influx, caspase-3/7 activity, and intracellular ROS production (p < 0.001). Conclusions: The glutamate-induced cytotoxic effects can be reduced by NAC, an antioxidant, through the reduction of intracellular oxidative stress and/or Ca2+ influx.

Association of high sensitivity C-reactive protein with tearing of the long head of the biceps tendon.

BACKGROUND: This study proposed to investigate whether high-sensitivity C-reactive protein (hs-CRP) is an independent risk factor for long head of biceps tendon (LHBT) tear and whether hs-CRP can increase accuracy in diagnosing LHBT tear. METHODS: This study involved 582 shoulders of 557 consecutive patients who received arthroscopic examinations at the authors' institution between January 2010 and July 2018. The strengths of associations between LHBT tear and various factors were determined by calculating the odds ratios (ORs), with 95% confidence intervals (CIs), using logistic regression analyses. The studied variables were demographic, physical, social, metabolic, comorbidity, hs-CRP, and pain on a visual analog scale (VAS) factors, as well as those related to rotator cuff tear (RCT). Significant factors in the multivariable logistic analysis were evaluated to determine their diagnostic values, including their likelihood ratios and post-test probabilities for LHBT tear. RESULTS: In the multivariable analysis, five variables were significant: age, retraction degree of Patte, subscapularis tendon tear, hs-CRP > 1 mg/L, and pain VAS (p ≤ 0.01). The best combination of determinations for diagnosing LHBT tear, which yielded a strong positive likelihood ratio of 19.07 and a high post-test probability of 96%, was age ≥ 67 years, subscapularis tendon tear, grade of Patte ≥2, hs-CRP > 1, and pain VAS ≥ 7. CONCLUSIONS: Serum hs-CRP > 1 mg/L is an independent risk factor for LHBT tear, along with the expected risk factors of age, subscapularis tendon tear, retraction degree of Patte, and pain VAS. Serum hs-CRP > 1 mg/L increases the diagnostic accuracy for LHBT tear. LEVEL OF EVIDENCE: Level IV, Clinical case series.

Association of steroid injection with soft-tissue calcification in lateral epicondylitis.

BACKGROUND: Steroid injections are among the most commonly used conservative treatments for lateral epicondylitis (LE). Although soft-tissue calcification has been reported as a steroid injection complication in certain tendons, such an association in LE has not been established. This study's purpose was to determine any association of both a history of steroid injection and the number of steroid injections with the types of calcification found in LE. METHODS: This study included 110 patients (110 elbows) with LE diagnosed from February 2016 to October 2017. We categorized calcifications seen on standard elbow radiographs as soft-tissue calcifications or enthesophytes using the classification of Shillito et al. Using logistic regression analyses, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for various factors possibly affecting calcification in LE: age, sex, body mass index, dominant-side involvement, occupation, symptom duration, hand-grip power, pain score on a visual analog scale, and treatment methods. The evaluated treatments included stretching exercise, extracorporeal shockwave therapy, and steroid injections. RESULTS: In the univariate analysis, the visual analog scale pain score, a history of steroid injection, and the number of steroid injections were significantly associated with soft-tissue calcification (P ≤ .020). In the multivariable analysis, a history of steroid injection (OR, 7.63; 95% CI, 1.63-35.72) and the number of steroid injections (OR, 1.18; 95% CI, 1.06-1.32) were significantly associated with soft-tissue calcification (P ≤ .010). CONCLUSIONS: The significant association of steroid injections with soft-tissue calcification in LE suggests that this calcification is likely to be an iatrogenic complication of steroid injection.

What Serum Lipid Abnormalities Are Associated with Adhesive Capsulitis Accompanied by Diabetes?

BACKGROUND: Adhesive capsulitis is common and can cause stiffness and pain. Diabetes and dyslipidemia are known to be associated with adhesive capsulitis. However, there is no report of any association between serum lipid profiles and adhesive capsulitis accompanied by diabetes. QUESTION/PURPOSE: Which serum lipid abnormalities are associated with adhesive capsulitis accompanied by diabetes? METHODS: This is a case-control study with two control groups. Our case group included 37 patients with newly diagnosed adhesive capsulitis accompanied by newly diagnosed diabetes who had no other diagnosed systemic diseases or rotator cuff tears. The two control groups each had 111 age- and sex-matched individuals with normal shoulder function (bilaterally pain-free, with full range of motion and no shoulder muscle weakness), no thyroid dysfunction, and no previously diagnosed systemic diseases. Individuals in the first control group had neither adhesive capsulitis nor diabetes. Individuals in the second control group had newly diagnosed diabetes without adhesive capsulitis. We evaluated any association between adhesive capsulitis accompanied by diabetes and serum lipid profile, including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and nonhigh-density lipoprotein (nonHDL). Conditional logistic regression analysis was used to evaluate the strengths of associations between serum lipid levels and adhesive capsulitis accompanied by diabetes, as determined by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Low-density lipoprotein and nonHDL were associated with adhesive capsulitis accompanied by diabetes. Specifically, patients with adhesive capsulitis and diabetes had greater odds ratios of hyperlow-density lipoproteinemia when compared with individuals with neither adhesive capsulitis nor diabetes (OR, 3.19; 95% CI, 1.21-8.38; p = 0.019) and when compared with individuals without adhesive capsulitis but with newly diagnosed diabetes (OR, 5.76; 95% CI, 1.67-19.83; p = 0.005). Similarly, patients with adhesive capsulitis accompanied by diabetes had greater odds ratios of hypernonhigh-density lipoproteinemia when compared with individuals with neither adhesive capsulitis nor diabetes (OR, 7.39; 95% CI, 2.72-20.09; p < 0.001) and when compared with individuals without adhesive capsulitis but with newly diagnosed diabetes (OR, 3.26; 95% CI, 1.40-7.61; p = 0.006). CONCLUSIONS: Inflammatory lipoproteinemias, particularly hyperlow-density lipoproteinemia and hypernonhigh-density lipoproteinemia, are associated with adhesive capsulitis accompanied by diabetes. Further research is needed to evaluate whether inflammatory lipoproteinemias are a cause, a related cofactor, or an aggravating factor in the development of adhesive capsulitis in people who have diabetes. LEVEL OF EVIDENCE: Level III, prognostic study.

Outcomes of Arthroscopic Rotator Cuff Repair in Patients Who Are 70 Years of Age or Older Versus Under 70 Years of Age: A Sex- and Tear Size-Matched Case-Control Study.

PURPOSE: To compare the structural and clinical outcomes after arthroscopic rotator cuff repair (ARCR) of a case group aged 70 and above with those of a control group younger than 70, with the 2 groups matched for sex and tear size. METHODS: The case group, comprising 53 patients 70 or older, and the control group, comprising 159 patients younger than 70, all received ARCR to 1 shoulder with symptomatic full-thickness rotator cuff tear. The case and the control subjects, who were matched for sex and tear size to minimize bias related to tendon healing, received ARCR during the same period. The mean age was 71.8 ± 2.6 years in the case group and 59.3 ± 7.1 years in the control group. The minimum follow-up period was 1 year in both groups. Cuff integrity was evaluated using ultrasonography. Structural and clinical outcomes of the 2 groups were compared. RESULTS: Regarding structural outcomes, the complete healing, partial-thickness retear, and full-thickness retear rates were 66% (35/53), 15% (8/53), and 19% (10/53) in the case group, and 68% (108/159), 19% (30/159), and 13% (21/159), respectively, in the control group. The 2 groups had no significantly different retear rates (P = .52). Regarding clinical outcomes, the mean improvements in range of motion, pain, muscle strength, and age- and sex-matched Constant scores were not significantly different between the 2 groups (P > .37). The preoperative tear size was significantly associated with retear in both studied groups (P = .02). CONCLUSIONS: The clinical and structural outcomes of ARCR in patients 70 or older with symptomatic full-thickness rotator cuff tear are comparable with those in patients younger than 70 with at least 1-year follow-up. Preoperative tear size, a biological factor, is a strong predictor for retear. LEVEL OF EVIDENCE: Level III, a retrospective comparative (case-control) study.

Accurate application of a precontoured-locking plate for proximal humeral fractures in Asians: a cadaveric study.

OBJECTIVES: The purpose of this study was to identify the optimal position for a precontoured-locking plating (PHILOS(®)) of the proximal humerus in Asians in terms of conformity and to determine the prevalence of screw exits in the position of the highest conformity. METHODS: Twenty adult humeri and 14 cadaveric shoulders were included in this study. After placing the precontoured plate in the well-fitted position on the humerus, we measured the distance between the upper margin of the plate and the tip of greater tuberosity (GT) (distance A) and the distance between the anterior margin of the plate and lateral border of the bicipital groove (BG) (distance B). The prevalence of K-wire exits was assessed. In the 14 cadaver shoulders, the mutual relation between the most inferior locking sleeve of the optimally positioned plate and the axillary nerve was evaluated to assess the potential for axillary nerve injury. RESULTS: The precontoured plate was well-fitted and remained in a relatively constant position in all specimens. Distance A was an average of 3.6 mm (range 1.4-5.5 mm), and distance B was an average of 2.5 mm (range 0-4.6 mm). The K wire closest to the BG pierced it in four cases (20 %), and most inferior K wires exited at an average distance of 3.8 mm (range 1.6-9.0 mm) from the inferior articular margin of the humeral head. Regarding involvement of the BG, articular width was the only significant variable in the logistic regression model, with an odds' ratio of 0.610. The axillary nerve was located at an average vertical distance of 59.7 mm (range 51.8-66.9 mm) from the tip of the GT in a vertically neutral position. The results did not differ between the left and right sides (t = 0.326, p = 0.755). Although the axillary nerve was slightly inferior to the most inferior locking holes of the proximal humerus, it was located in the path of their locking sleeves on the deltoid muscle. CONCLUSION: The optimal position for the highest conformity led to ideal fixation of the proximal humerus and inferomedial support screw in Asians. However, the precontoured plate sometimes had screw exits that involved the BG, and articular width had a large impact on involvement of the BG. If locking sleeves for the most inferior holes were introduced on the deltoid muscle in a neutral position, there was high potential for injury to the axillary nerve in Koreans.

Reliability of the classification and treatment of dislocations of the acromioclavicular joint.

BACKGROUND: We evaluated interobserver and intraobserver reliability of the classification and treatment of acromioclavicular (AC) joint dislocations and assessed the impact of adding 3-dimensional computed tomography (3D CT) on the reliability of classification and treatment choice. METHODS: Ten surgeons independently reviewed plain radiographs and 3D CT in 28 cases with AC joint dislocation. Images from each case were randomly presented to the observers, with plain radiographs alone being presented first, followed by plain radiographs plus 3D CT 2 weeks later. Four weeks later, they repeated the same survey to evaluate intraobserver reliability. Reliability was assessed on the basis of Fleiss κ values. RESULTS: On the basis of plain radiographs alone, interobserver and intraobserver reliability of the Rockwood classification were fair (κ = .214) and moderate (κ = .474), respectively. Interobserver and intraobserver reliability of treatment were both fair (κ = .213 and .399, respectively). On the basis of a combination of plain radiographs and 3D CT, interobserver and intraobserver reliability of the Rockwood classification were slight (κ = .177) and moderate (κ = .565), respectively. Interobserver and intraobserver reliability of treatment were fair (κ = .253) and moderate (κ = .554), respectively. There were no significant differences in reliability between the two groups in terms of any κ values. CONCLUSION: This study suggests an overall lack of reliability of the Rockwood classification of AC joint dislocations and of decisions regarding their treatment. There is especially poor agreement between experienced shoulder surgeons. The addition of 3D CT did not improve reliability of classification and treatment of AC joint dislocations.

Protective and Regenerative Effects of Reconstituted HDL on Human Rotator Cuff Fibroblasts under Hypoxia: An In Vitro Study.

Hypoxia and hypo-high-density lipoproteinemia (hypo-HDLemia) are proposed risk factors for rotator cuff tear. HDL is recognized for its potential benefits in ischemia-driven angiogenesis and wound healing. Nevertheless, research on the potential benefits of reconstituted HDL (rHDL) on human rotator cuff fibroblasts (RCFs) under hypoxia is limited. This study investigates the cytoprotective and regenerative effects of rHDL, as well as N-acetylcysteine (NAC), vitamin C (Vit C), and HDL on human RCFs under hypoxic conditions. Sixth-passage human RCFs were divided into normoxia, hypoxia, and hypoxia groups pretreated with antioxidants (NAC, Vit C, rHDL, HDL). Hypoxia was induced by 1000 µM CoCl2. In the hypoxia group compared to the normoxia group, there were significant increases in hypoxia-inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1), and Bcl-2/E1B-19kDa interacting protein 3 (BNIP3) expressions, along with reduced cell viability, elevated reactive oxygen species (ROS) production, apoptosis rate, expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase-1 (PARP-1), vascular endothelial growth factors (VEGF), and matrix metalloproteinase-2 (MMP-2), as well as decreased collagen I and III production, and markedly lower cell proliferative activity (p ≤ 0.039). These responses were significantly mitigated by pretreatment with rHDL (p ≤ 0.046). This study suggests that rHDL can enhance cell proliferation and collagen I and III production while reducing apoptosis in human RCFs under hypoxic conditions.

Factors associated with long head of the biceps tendon tear severity and predictive insights for grade II tears in rotator cuff surgery.

BACKGROUND: In rotator cuff repair, the long head of the biceps tendon (LHB) is commonly used as graft material. However, factors influencing LHB tear severity are poorly understood, and predicting grade II LHB tears is challenging. This study aimed to identify these factors preoperatively. METHODS: The demographics, medical parameters, and pain severity of 750 patients who underwent arthroscopic surgery from January 2010 to February 2021 were evaluated to determine the factors associated with LHB tear severity and grade II tears. Both overall and largeto-massive rotator cuff tear (RCT) cohorts underwent ordinal and binary logistic regression analyses. Predictive accuracy for grade II LHB tears was determined using the area under the receiver operating characteristic curve (AUC). RESULTS: In the overall cohort, high-sensitivity C-reactive protein (hs-CRP) >1 mg/L (P<0.001), subscapularis tear (P<0.001), hypothyroidism (P=0.031), and the tangent sign (P=0.003) were significantly associated with LHB tear severity, and hs-CRP>1 mg/L, subscapularis tear, and Patte retraction degree were significantly associated with grade II LHB tears (P<0.001). In the large-to-massive RCT cohort, hs-CRP>1 mg/L, hypertension, and age ≥50 years (P<0.05) were significantly associated with LHB tear severity, and hs-CRP>1 mg/L (P<0.001) and hypertension (P=0.026) were significantly associated with grade II LHB tears. In both cohorts, hs-CRP >1 mg/L demonstrated good predictive accuracy for grade II LHB tears (AUCs: 0.72 and 0.70). CONCLUSIONS: Serum hs-CRP >1 mg/L is associated with LHB tear severity and serves as a reliable predictor of grade II LHB tears, facilitating preoperative assessment of the LHB as potential graft material in arthroscopic rotator cuff repair. Level of evidence: III.

Prediction of the location of the anterior branch of the axillary nerve, using correlations with physical factors: a cadaveric study.

BACKGROUND: Although axillary nerve injury is a catastrophic surgical complication, there is little data for precise prediction of the location of that nerve's anterior branch. To address that, the authors searched for a useful correlation between the acromion-axillary nerve distance (AAND) and one or more physical factors. METHODS: The heights, humeral lengths, AAND, and axillary nerve indexes (ANI: ratio between AAND and humeral length) of 25 male and 20 female cadavers were determined. Any gender differences in the mean measurements were determined. The correlations of each AAND with height, humeral length, and ANI were determined. The authors determined that using the ANI and the humeral length allowed the shortest prediction of the AAND. RESULTS: The mean AAND, cadaver height, and humeral length were 6.5 ± 0.8, 164.9 ± 10.0, and 33.5 ± 2.7 cm, respectively. An independent t test revealed significant gender differences in the mean AAND (P = .003), height (P = .000), and humeral length (P = .000), but not in the mean ANI (P = .564). The Pearson coefficients for the associations of the AAND with height (r = .767), humeral length (r = .797) and ANI (r = .732) demonstrated strong correlations (P < .001), especially with humeral length. The use of the ANI with the humeral length yielded the shortest predictions of AAND, with a 97.8% probability of safety. CONCLUSION: There is a strong correlation between AAND and humeral length. In clinical practice, humeral length and ANI are useful for predicting the location of the anterior branch of the axillary nerve, when the arm is positioned at the side in neutral rotation.

Inflammatory cytokines are overexpressed in the subacromial bursa of frozen shoulder.

BACKGROUND: Frozen shoulder is a debilitating condition characterized by gradual loss of glenohumeral motion with chronic inflammation and capsular fibrosis. Yet its pathogenesis remains largely unknown. We hypothesized that the subacromial bursa may be responsible for the pathogenesis of frozen shoulder by producing inflammatory cytokines. MATERIALS AND METHODS: We obtained joint capsules and subacromial bursae from 14 patients with idiopathic frozen shoulder and from 7 control subjects to determine the expression levels of interleukin (IL) 1α, IL-1ß, IL-6, tumor necrosis factor α (TNF-α), cyclooxygenase (COX) 1, and COX-2 by real-time reverse transcriptase-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: IL-1α, IL-1ß, TNF-α, COX-1, and COX-2 were expressed at significantly high levels in the joint capsules of the frozen shoulder group compared with those of the control group. Intriguingly, IL-1α, TNF-α, and COX-2 were also expressed at significantly high levels in the subacromial bursae of the frozen shoulder group compared with those of the control group. Immunohistochemical analysis showed increased expression of COX-2 in both the joint capsules and subacromial bursae of the frozen shoulder group. CONCLUSIONS: These findings imply that elevated levels of inflammatory cytokines in the subacromial bursa may be associated with the pathogenesis of inflammation evolving into fibrosis.

Use of intramedullary nonvascularized fibular graft with external fixation for revisional Charcot ankle fusion: a case report.

We describe a case of Charcot ankle arthropathy in a 43-year-old male patient who underwent revision surgery for tibiotalocalcaneal arthrodesis with a retrograde intramedullary nonvascularized fibular graft. After 3 months of postoperative stabilization with a ring external fixator, successful radiographic union was identified. The findings obtained at 33 months postoperatively showed maintenance of solid fusion and restoration of hindfoot alignment without any complications.