One- and 2-Year American Shoulder and Elbow Surgeons Scores Do Not Vary Significantly After Arthroscopic Rotator Cuff Repair: A Prospective Multicenter Analysis of 1,567 Patients.

PURPOSE: To evaluate whether there are clinically significant changes in patient-reported outcomes between 1 and 2 years' postoperatively after arthroscopic rotator cuff repair (RCR). METHODS: A retrospective analysis of prospective, multicenter registry was queried for all patients who underwent RCR. Patients with preoperative, 6-month, 1-year, and 2-year postoperative American Shoulder and Elbow Surgeons (ASES) scores were included. We evaluated mean postoperative ASES scores, Δ (change from preoperative) ASES, and the %MOI (% maximum outcome improvement). We also evaluated achievement of clinically significant outcomes (CSOs) for the ASES score, including the minimal clinically important difference (MCID), substantial clinical benefit, and patient-acceptable symptom state. RESULTS: There were 1,567 patients with complete data through 2-year follow-up. There were small differences in achievement of CSOs from 1 to 2 years: 88% to 91% for MCID, 81% to 83% for substantial clinical benefit, and 65% to 71% for patient-acceptable symptom state. There were statistically significant differences from 1 to 2 years in mean ASES (87 to 88, P < .001), Δ ASES (37 to 39, P < .001), and %MOI (72% to 76%, P < .001); however, these changes were well below the MCID of 11.1. From 1 to 2 years, the mean ASES improved only 1.7 points (P < .001). At 1 year, patients achieved, on average, 97% of their 2-year ASES. CONCLUSIONS: Both patient-reported outcomes and achievement of CSOs show small differences at 1 and 2 years after RCR. Given the large sample size, there were statistical differences, but these are unlikely to be clinically relevant. LEVEL OF EVIDENCE: Level IV, case series.

Impact of COVID-19 on Spinal Diagnosis and Procedural Volume in the United States.

STUDY DESIGN: Retrospective analysis of a national database. OBJECTIVES: COVID-19 resulted in the widespread shifting of hospital resources to handle surging COVID-19 cases resulting in the postponement of surgeries, including numerous spine procedures. This study aimed to quantify the impact that COVID-19 had on the number of treated spinal conditions and diagnoses during the pandemic. METHODS: Using CPT and ICD-10 codes, TriNetX, a national database, was utilized to quantify spine procedures and diagnoses in patients >18 years of age. The period of March 2020-May 2021 was compared to a reference pre-pandemic period of March 2018-May 2019. Each time period was then stratified into four seasons of the year, and the mean average number of procedures per healthcare organization was compared. RESULTS: In total, 524,394 patient encounters from 53 healthcare organizations were included in the analysis. There were significant decreases in spine procedures and diagnoses during March-May 2020 compared to pre-pandemic levels. Measurable differences were noted for spine procedures during the winter of 2020-2021, including a decrease in lumbar laminectomy and anterior cervical arthrodesis. Comparing the pandemic period to the pre-pandemic period showed significant reductions in most spine procedures and treated diagnoses; however, there was an increase in open repair of thoracic fractures during this period. CONCLUSIONS: COVID-19 resulted in a widespread decrease in spinal diagnosis and treated conditions. An inverse relationship was observed between new COVID-19 cases and spine procedural volume. Recent increases in procedural volume from pre-pandemic levels are promising signs that the spine surgery community has narrowed the gap in unmet care produced by the pandemic.

Anticoagulant Usage After Anterior Cruciate Ligament Reconstruction Is Associated With Increased Rate of Manipulation Under Anesthesia.

BACKGROUND: Arthrofibrosis after anterior cruciate ligament reconstruction (ACLR) is a notable but uncommon complication of ACLR. To improve range of motion after ACLR, aggressive physical therapy, arthroscopic/open lysis of adhesions, and revision surgery are currently used. Manipulation under anesthesia (MUA) is also a reasonable choice for an appropriate subset of patients with inadequate range of motion after ACLR. Recently, the correlation between anticoagulant usage and arthrofibrosis after total knee arthroplasty has become an area of interest. The purpose of this study was to determine whether anticoagulant use has a similar effect on the incidence of MUA after ACLR. METHODS: The Mariner data set of the PearlDiver database was used to conduct this retrospective cohort study. Patients with an isolated ACLR were identified by using Current Procedural Terminology codes. Patients were then stratified by MUA within 2 years of ACLR, and the use of postoperative anticoagulation was identified. In addition, patient demographics, medical comorbidities, and timing of ACLR were recorded. Univariate and multivariable analyses were used to model independent risk factors for MUA. RESULTS: We identified 216,147 patients who underwent isolated ACLR. Of these patients, 3,494 (1.62%) underwent MUA within 2 years. Patients who were on anticoagulants after ACLR were more likely to require an MUA (odds ratio [OR]: 2.181; P < 0.001), specifically low-molecular-weight heparin (OR: 2.651; P < 0.001), warfarin (OR: 1.529; P < 0.001), and direct factor Xa inhibitors (OR: 1.957; P < 0.001). DISCUSSION: In conclusion, arthrofibrosis after ACLR is associated with the use of preoperative or postoperative thromboprophylaxis. Healthcare providers should be aware of increased stiffness among these patients and treat them aggressively.

Is seizure disorder a risk factor for complications following surgical treatment of hip dysplasia in the pediatric population?

The impact of seizure disorders on pediatric patients who undergo hip dysplasia surgery has yet to be elucidated. This study focused on identifying the effect of seizure disorders on the incidence of complications following surgical management of hip dysplasia. Pediatric patients undergoing surgical treatment for hip dysplasia from 2012 to 2019 were identified in the National Surgical Quality Improvement Program-Pediatric database. Patients were divided into two cohorts: patients with and patients without a seizure disorder. Patient demographics, comorbidities and postoperative outcomes were compared between the two groups. Bivariate and multivariate analyses were performed. Of 10 853 pediatric patients who underwent hip dysplasia surgery, 8117 patients (74.8%) did not have a seizure disorder whereas 2736 (25.2%) had a seizure disorder. Bivariate analyses revealed that compared to patients without a seizure disorder, patients with a seizure disorder were at increased risk of developing surgical site infections, pneumonia, unplanned reintubation, urinary tract infection, postoperative transfusion, sepsis, extended operation time and length of stay and readmission ( P < 0.05 for all). Following adjustment for patient demographics and comorbidities on multivariate analysis, there were no differences in any postoperative complications between pediatric patients with and without a seizure disorder. There were no differences in 30-day postoperative complications in patients with and without a seizure disorder. Due to potential decreased bone mineral density as an effect of antiepileptic drugs and the risk of femur fracture during surgery for hip dysplasia, pediatric patients with a seizure disorder should be closely monitored as they may be more susceptible to injury. Level of Evidence: III.

The Association between Bleeding Disorders and Postoperative Complications Following Operative Treatment of Distal Radius Fracture.

Background While previous studies have investigated the association between bleeding disorders and outcomes with hip or knee surgeries, no studies have investigated the association between bleeding disorders and outcomes in upper extremity surgery. Questions/Purposes The purpose of this study was to investigate if a past history of bleeding disorders is associated with which, if any postoperative complications for patients receiving distal radius fracture open reduction internal fixation. Patients and Methods Patients undergoing operative treatment for distal radius fracture from 2007 to 2018 were identified in the National Surgical Quality Improvement Program database. Patients were stratified into two cohorts: patients with a bleeding disorder and patients without a bleeding disorder. In this analysis, 30-day postoperative complications were assessed, as well as mortality, extended length of stay, reoperation, and readmission. Bivariate and multivariate analyses were performed. Results Of the 16,489 total patients undergoing operative treatment for distal radius fracture, 16,047 patients (97.3%) did not have a bleeding disorder, whereas 442 (2.7%) had a bleeding disorder. Following adjustment on multivariate analyses, an increased risk of postoperative transfusion requirement (odds ratio [OR] 17.437; p = 0.001), extended length of hospital stay more than 3 days (OR 1.564; p = 0.038), and readmission (OR 2.515; p < 0.001) were seen in patients with a bleeding disorder compared to those without a bleeding disorder. Conclusion History of bleeding disorders is an independent risk factor for transfusions, extended length of stay, and readmission. We recommend a multidisciplinary team approach to addressing bleeding disorders before patients receive distal radius fracture open reduction internal fixation. Level of Evidence Level III, retrospective study.

The transition to outpatient shoulder arthroplasty: a systematic review.

BACKGROUND AND HYPOTHESIS: Transitioning shoulder arthroplasty (SA) from an inpatient to outpatient procedure is associated with increased patient satisfaction and potentially decreased costs; however, concerns exist about complications following same-day discharge. We hypothesized that outpatient SA would be associated with low rates of failed discharges, readmissions, and complications, rendering it a safe and effective option for SA. METHODS: A systematic review of the outpatient SA literature identified 16 of 447 studies with level III and IV evidence that met the inclusion criteria with at least 90 days of follow-up. Data on patient demographic characteristics, preoperative and postoperative protocols, surgery characteristics, failed discharges, complications, and readmissions were collected and pooled for analysis. RESULTS: A total of 990 patients were included in our analysis. Many studies identified specific institutional protocols for determining eligibility for outpatient SA, including preoperative clearance from an anesthesiologist; identification of a perioperative caretaker; and exclusion of patients based on cardiac, pulmonary, or hematologic risk factors. Failed same-day discharge occurred in only 0.9% of patients (7 of 788), and 2.1% of patients (9 of 418) and 0.79% of patients (2 of 252) presented to an emergency department or urgent care facility for a perioperative concern. The readmission rate for periprosthetic fracture, arthrofibrosis, infection, subscapularis rupture, and anterior subluxation was 1.3% (7 of 529 patients). Complications occurred in 7.0% of patients (70 of 990), with 5.4% of patients (53 of 990) experiencing a surgical complication and 1.7% (17 of 990) having a medical complication. There were 28 total reoperations (2.9%, 28 of 955 patients). DISCUSSION AND CONCLUSION: Outpatient SA is associated with low rates of failed discharges, readmissions, and complications. Additionally, the medical and surgical complications that occur after outpatient SA are unlikely to be prevented by the short inpatient stay characteristic of traditional SA. With careful screening measures to identify appropriate candidates for same-day discharge, outpatient SA represents a safe approach to prevent unnecessary hospitalizations and to decrease costs associated with SA.

Diagnostic performance of the second-generation molecular tests in the assessment of indeterminate thyroid nodules: A systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the diagnostic performance of the second-generation molecular tests in the diagnosis of thyroid nodules with indeterminate fine-needle aspiration biopsy results. METHODS: We searched PubMed, Google Scholar, Scopus, and Cochrane Library for studies published between January 2017 and March 2021. Inclusion criteria were indeterminate thyroid results from fine-needle aspiration (FNA) that included Bethesda categories III and IV, use of Afirma GSC, Thyroseq v3, and ThyGeNext as an index test, and conclusive histopathological results. Studies with no post-surgical diagnoses were excluded. For each included study, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were obtained. Sensitivity and specificity were pooled jointly using a bivariate binomial random-effects model. Statistical significance was indicated at p-value less than 0.05. RESULTS: Our search yielded 431 non-duplicate articles, of which 15 were included in the study (7 GSC, 6 Thyroseq v3, and 2 ThyGeNext). ThyGeNext studies were excluded from the meta-analysis due to the small sample size. Pooled data for GSC studies on 472 thyroid nodules showed a sensitivity of 96.6 (95% confidence interval: 89.7-98.9%), specificity of 52.9% (23.4-80.5%), PPV of 63% (51-74%), and NPV of 96% (94-98%). Pooled data for ThyroSeq studies on 530 thyroid nodules showed a sensitivity of 95.1% (91.1-97.4%), specificity of 49.6% (29.3-70.1%), PPV of 70% (55-83%), and NPV of 92% (86-97%). There was no statistically significant difference in diagnostic performances of the two tests (p-values for sensitivity = 0.89, specificity = 0.82, PPV = 0.43, NPV = 0.17). CONCLUSION: High sensitivity and high NPV in GSC and Thyroseq v3 have potential to help rule out malignancy among thyroid nodules with indeterminate cytology results. There was no difference in diagnostic performances between the two molecular tests indicating that either test is appropriate to determine the malignancy of thyroid nodules. Further long-term outcome data are warranted to make a clear recommendation.

Evaluating the Association of Anesthesia Type With Postoperative Complications in Patients Undergoing Ankle Fracture Repair.

General and neuraxial anesthesia are both successful anesthesia techniques used in many orthopedic procedures. The purpose of this study was to compare the complications and length of hospital stay between patients who underwent general anesthesia versus neuraxial anesthesia during the repair of ankle fractures. Patients undergoing open reduction and internal fixation for ankle fracture from 2014 to 2018 were identified in the National Surgical Quality Improvement Program database. Patients were stratified into 2 cohorts: general anesthesia and neuraxial anesthesia. In this analysis, demographics data, comorbidities, and postoperative complications were collected and compared between the two cohorts. Bivariate analyses and multivariable logistical regression were performed. Of 3585 patients who underwent operative treatment for ankle fracture, 3315 patients (92.5%) had general anesthesia and 270 (7.5%) had neuraxial anesthesia. On bivariate analyses, patients who had neuraxial anesthesia were more likely to develop pulmonary complications (p = .173) or extended length of stay more than 5 days (p = .342) compared to the general anesthesia group. Following adjustment on multivariate analyses, the neuraxial anesthesia cohort no longer had increased likelihood of pulmonary complications or extended length of stay compared to the general anesthesia group. Healthy ankle fracture patients could also benefit from neuraxial anesthetic methods, and they should be considered for this anesthetic type regardless of their lack of comorbidities.

Comparing postoperative outcomes using electrocautery versus cold-knife de-epithelialization of dermal fat graft in parotidectomy reconstruction.

PURPOSE: The present study was developed to evaluate the effectiveness of a simple rapid technique for de-epithelializing cutaneous flaps and grafts in parotidectomy reconstruction. MATERIALS AND METHODS: 109 patients who underwent a parotidectomy with abdominal free dermal fat graft (FDFG) reconstruction between 2018 and 2021 were evaluated based on demographic factors, past medical/surgical history, type of parotidectomy performed, operative factors, and post-operative complications. These data were then stratified based on de-epithelialization technique as well as tumor malignancy status to determine any differences in complication rates or perioperative factors between electrocautery (EC) and cold knife (CK) techniques within both benign and malignant subgroups. RESULTS: 77 of the 109 participants underwent FDFG de-epithelialization using monopolar electrocautery (EC) and the remaining 32 participants underwent de-epithelialization using traditional cold knife (CK) technique. There was no statistical difference among the two groups in overall complication rate. The EC group had a significantly shorter operation time ("EC vs. CK": 144.2 min vs. 174.7 min; p = 0.031). Additionally, histopathologic samples showed that both techniques left the underlying dermis intact and without damage. CONCLUSIONS: This study demonstrated that there is no difference in complication rate or histology of FDFGs de-epithelialized using EC compared to CK. It was also shown that when controlling for confounders by looking solely at the benign subgroup of patients, EC de-epithelialization was a faster technique than CK. These findings suggest that EC is just as effective as CK, and may actually be a more efficient surgical technique to accomplish de-epithelialization of FDFG.

Pig-a gene mutation database.

Mutations in the X-linked phosphatidylinositol glycan, class A gene (Pig-a) lead to loss of glycosylphosphatidylinositol (GPI) anchors and GPI-anchored proteins from the surface of erythrocytes and other mammalian cells. The Pig-a gene mutation assay quantifies in vivo gene mutation by immunofluorescent labeling and flow cytometry to detect the loss of GPI-anchored proteins on peripheral blood erythrocytes. As part of the regulatory acceptance of the assay, a public database has been created that provides detailed information on Pig-a gene mutation assays conducted in rats and mice. A searchable version of the database is available through a website designed and hosted by the University of Maryland School of Pharmacy. Currently, the database contains only mouse and rat data, but it is anticipated that it will expand to include data from other species, including humans. A major purpose in developing the database was to aid in the preparation of a Retrospective Performance Analysis and Detailed Review Paper required for Organisation for Economic Co-operation and Development Test Guideline acceptance. We anticipate, however, that it also will be useful for accessing and comparing Pig-a data to data from other assays and for conducting quantitative assessments of Pig-a gene mutation responses. Environ. Mol. Mutagen., 60:759-762, 2019. © 2019 Wiley Periodicals, Inc.

Genome-wide mutation detection by interclonal genetic variation.

Genetic toxicology assays estimate mutation frequencies by phenotypically screening for the activation or inactivation of endogenous or exogenous reporter genes. These reporters can only detect mutations in narrow areas of the genome and their use is often restricted to certain in vitro and in vivo models. Here, we show that Interclonal Genetic Variation (ICGV) can directly identify mutations genome-wide by comparing sequencing data of single-cell clones derived from the same source or organism. Upon ethyl methanesulfonate (EMS) exposure, ICGV detected greater levels of mutation in a dose- and time-dependent manner in E. coli. In addition, ICGV was also able to identify a ∼20-fold increase in somatic mutations in T-cell clones derived from an N-ethyl-N-nitrosourea (ENU)-treated rat vs. a vehicle-treated rat. These results demonstrate that the genetic differences of single-cell clones can be used for genome-wide mutation detection.

In vivo genotoxicity of furan in F344 rats at cancer bioassay doses.

Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 and 16mg/kg. Rats were killed 3h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity.

Mutagenicity of acrylamide and glycidamide in the testes of big blue mice.

Acrylamide (AA) is an industrial chemical, a by-product of fried starchy foods, and a mutagen and rodent carcinogen. It can also cause damage during spermatogenesis. In this study, we investigated whether AA and its metabolite glycidamide (GA) induce mutagenic effects in the germ cells of male mice. Male Big Blue transgenic mice were administered 1.4 or 7.0mM of AA or GA in the drinking water for up to 4 weeks. Testicular cII mutant frequency (MF) was determined 3 weeks after the last treatment, and the types of the mutations in the cII gene were analyzed by DNA sequencing. The testes cII MFs in mice treated with either the low or high exposure concentrations of AA and GA were increased significantly. There was no significant difference in the cII MFs between AA and GA at the low exposure concentration. The mutation spectra in mice treated with AA (1.4mM) or GA (both 1.4 and 7.0mM) differed significantly from those of controls, but there were no significant differences in mutation patterns between AA and GA treatments. Comparison of the mutation spectra between testes and livers showed that the spectra differed significantly between the two tissues following treatment with AA or GA, whereas the mutation spectra in the two tissues from control mice were similar. These results suggest that AA possesses mutagenic effects on testes by virtue of its metabolism to GA, possibly targeting spermatogonial stem cells, but possibly via different pathways when compared mutations in liver.

The genotoxicity of acrylamide and glycidamide in big blue rats.

Acrylamide (AA), a mutagen and rodent carcinogen, recently has been detected in fried and baked starchy foods, a finding that has prompted renewed interest in its potential for toxicity in humans. In the present study, we exposed Big Blue rats to the equivalent of approximately 5 and 10 mg/kg body weight/day of AA or its epoxide metabolite glycidamide (GA) via the drinking water, an AA treatment regimen comparable to those used to produce cancer in rats. After 2 months of dosing, the rats were euthanized and blood was taken for the micronucleus assay; spleens for the lymphocyte Hprt mutant assay; and liver, thyroid, bone marrow, testis (from males), and mammary gland (females) for the cII mutant assay. Neither AA nor GA increased the frequency of micronucleated reticulocytes. In contrast, both compounds produced small (approximately twofold to threefold above background) but significant increases in lymphocyte Hprt mutant frequency (MF, p < 0.05), with the increases having dose-related linear trends (p < 0.05 to p < 0.001). Neither compound increased the cII MF in testis, mammary gland (tumor target tissues), or liver (nontarget tissue), while both compounds induced weak positive increases in bone marrow (nontarget tissue) and thyroid (target tissue). Although the genotoxicity in tumor target tissue was weak, in combination with the responses in surrogate tissues, the results are consistent with AA being a gene mutagen in the rat via metabolism to GA.

Genotoxicity of acrylamide and its metabolite glycidamide administered in drinking water to male and female Big Blue mice.

The recent discovery of acrylamide (AA), a probable human carcinogen, in a variety of fried and baked starchy foods has drawn attention to its genotoxicity and carcinogenicity. Evidence suggests that glycidamide (GA), the epoxide metabolite of AA, is responsible for the genotoxic effects of AA. To investigate the in vivo genotoxicity of AA, groups of male and female Big Blue (BB) mice were administered 0, 100, or 500 mg/l of AA or equimolar doses of GA, in drinking water, for 3-4 weeks. Micronucleated reticulocytes (MN-RETs) were assessed in peripheral blood within 24 hr of the last treatment, and lymphocyte Hprt and liver cII mutagenesis assays were conducted 21 days following the last treatment. Further, the types of cII mutations induced by AA and GA in the liver were determined by sequence analysis. The frequency of MN-RETs was increased 1.7-3.3-fold in males treated with the high doses of AA and GA (P < or = 0.05; control frequency = 0.28%). Both doses of AA and GA produced increased lymphocyte Hprt mutant frequencies (MFs), with the high doses producing responses 16-25-fold higher than that of the respective control (P < or = 0.01; control MFs = 1.5 +/- 0.3 x 10(-6) and 2.2 +/- 0.5 x 10(-6) in females and males, respectively). Also, the high doses of AA and GA produced significant 2-2.5-fold increases in liver cII MFs (P < or = 0.05; control MFs = 26.5 +/- 3.1 x 10(-6) and 28.4 +/- 4.5 x 10(-6)). Molecular analysis of the mutants indicated that AA and GA produced similar mutation spectra and that these spectra were significantly different from that of control mutants (P < or = 0.001). The predominant types of mutations in the liver cII gene from AA- and GA-treated mice were G:C-->T:A transversions and -1/+1 frameshifts in a homopolymeric run of Gs. The results indicate that both AA and GA are genotoxic in mice. The MFs and types of mutations induced by AA and GA in the liver are consistent with AA exerting its genotoxicity in BB mice via metabolism to GA.