Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Is the Rise of Medicare Advantage Impacting the Fidelity of Traditional Medicare Claims Data? Implications for Reporting of Long-Term Total Hip Arthroplasty Survivorship.

BACKGROUND: Arthroplasty registries often use traditional Medicare (TM) claims data to report long-term total hip arthroplasty (THA) survivorship. The purpose of this study was to determine whether the large number of patients leaving TM for Medicare Advantage (MA) has compromised the fidelity of TM data. METHODS: We identified 10,962 THAs in 9,333 Medicare-eligible patients who underwent primary THA from 2000 to 2020 at a single institution. Insurance type was analyzed, and 83% of patients had TM at the time of THA. Survivorship free from any revision or reoperation was calculated for patients who have TM. The same survivorship end points were recalculated with censoring performed when a patient transitioned to an MA plan after their primary THA to model the impact of losing patients from the TM dataset. Differences in survivorship were compared. The mean follow-up was 7 years. RESULTS: From 2000 to 2020, there was a decrease in TM insurance (93 to 73%) and a corresponding increase in MA insurance (0 to 19%) among THA patients. Following THA, 23% of TM patients switched to MA. For patients who had TM at the time of surgery, 15-year survivorship free from any reoperation or revision was 90% and 93%, respectively. When censoring patients upon transition from TM to MA, survivorship free from any reoperation became significantly higher (92 versus 90% at 15 years; hazard ratio = 1.16, P = .033), and there was a trend toward higher survivorship free from any revision (95 versus 93% at 15 years; hazard ratio = 1.16, P = .074). CONCLUSIONS: Approximately 1 in 4 patients left TM for MA after primary THA, effectively making them lost to follow-up within TM datasets. The mass exodus of patients out of TM appears to have led to a slight overestimation of survivorship free from any reoperation and trended toward overestimating survivorship free from any revision. If MA continues to grow, efforts to obtain MA data will become even more important.

Risk Factors for Peripheral Nerve Injury Following Revision Total Knee Arthroplasty in 132,960 Patients.

BACKGROUND: Peripheral nerve injury (PNI) following revision total knee arthroplasty (rTKA) is a potentially devastating injury for patients. This study assessed the frequency of and risk factors for postoperative PNI following rTKA. METHODS: Patients who underwent rTKA from 2003 to 2015 were identified using the National Inpatient Sample. Demographics, medical histories, surgical details, and complications were compared between patients who sustained a PNI and those who did not to identify risk factors for the development of PNI after rTKA. RESULTS: Overall, 132,960 patients who underwent rTKA were identified, and 737 (0.56%) sustained a postoperative PNI. After adjusting for confounders, patients with a history of a spine condition (adjusted odds ratio [aOR]: 1.7, 95%-confidence interval 1.2 to 2.4, P = .003) and postoperative anemia (aOR: 1.3, 95%-CI: 1.1 to 1.5, P = .004) had higher risk of PNI following rTKA. Intraoperative periprosthetic fracture (aOR: 1.3, 0.78 to 2.2, P = .308), rheumatoid arthritis (aOR: 1.0, 95%-CI: 0.68 to 1.6, P = .865), and history of knee dislocation (aOR: 1.1, 95%-CI: 0.85 to 1.5, P = .412), were not significantly associated with higher risk for PNI. CONCLUSIONS: This study found a 0.56% incidence of PNI following rTKA, and patients who had preexisting spine conditions or postoperative anemia were at an increased risk for this complication. Orthopedic surgeons may use the results of this study to appropriately counsel patients on the potential for a PNI following rTKA.

[Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageâ A lung cancer].

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

Multidisciplinary Treatment of Merkel Cell Carcinoma of the Extremities: Outcomes and Factors Associated with Poor Survival in Nodal Disease.

Merkel cell carcinoma (MCC) has a tendency for lymphatic spread and locoregional recurrence, although there is little data examining the risk factors for patients with lymph node-positive extremity lesions. The purpose of the current study was to examine the outcomes and risk factors associated with nodal metastasis in extremity MCC. We retrospectively reviewed the medical record of 120 patients with extremity MCC evaluated at our institution between 1994 and 2021. The mean age of this cohort was 71 years; 33% of patients were female; and 98% were Caucasian. Seventy-eight (65%) patients presented with localized disease. Thirty-seven (31%) patients had stage III disease, and five (4%) patients had stage IV disease. Treatment of primary lesions consisted primarily of margin-negative excision and adjuvant radiotherapy. Nodal metastases were most treated with adjuvant radiation or completion lymph node dissection. Five-year disease-specific survival in our series was 88% for patients with localized disease, 89% for stage IIIa disease, 40% for stage IIIb disease and 42% for stage IV. Factors associated with worse survival included immunosuppression and macroscopic nodal disease. In conclusion, extremity MCC has a low rate of local recurrence when treated with margin-negative excision and adjuvant radiation. However, treatment of nodal metastases remains a challenge with high rates of recurrence and mortality, particularly for patients who are immunosuppressed or who have macroscopic nodal disease.

[Regulation of colony-stimulating factor 1 receptor inhibitor pexidartinib on the senescence of mouse bone marrow-derived macrophages stimulated by lipopolysaccharide].

Objective: To investigate the effects of colony-stimulating factor 1 receptor (CSF-1R) inhibitor pexidartinib (PLX3397) on the senescence of bone marrow-derived macrophages (BMDM) stimulated by lipopolysaccharide (LPS). Methods: BMDM were isolated and cultured from femurs and tibiae of 10 male C57BL/6 mice aged 6-8 weeks (obtained from Laboratory Animal Center of Guizhou Medical University). They were divided into blank control group, LPS group (treated with 1 µg/ml LPS for 24 h) as well as low, medium and high concentration PLX3397 pretreatment groups (treated with 100, 500 and 1 000 nmol/L PLX3397 for 4 h respectively followed by 1 µg/ml LPS for 24 h). The corresponding markers of macrophages were detected by flow cytometry. Cell viability was detected by cell counting kit-8 and cellular senescence was detected by senescence-associated-ß-galactosidase (SA-ß-gal) staining. Meanwhile, protein expressions of cycle-dependent kinase inhibitor p16, p21 and CSF-1R were detected by Western blotting, and the expressions of p16 and p21 were detected by intracellular immunofluorescence. Real-time fluorescence quantitative PCR (RT-qPCR) was used to investigate the mRNA levels of senescence-associated secretory phenotype (SASP) genes including interleukin (IL), IL-1ß, chemokine-1/10 (CXCL-1/10), matrix metalloproteinase-8 (MMP-8), and transforming growth factor-ß (TGF-ß). Results: The rate of SA-ß-gal positive staining in medium and high concentration PLX3397 pretreatment groups [(39.33±4.93)% and (36.33±3.06)% respectively] were significantly downregulated compared with LPS group [(52.00±3.00)%] (P=0.020, P=0.005). The expression of CSF-1R protein in low, medium and high concentration PLX3397 pretreatment groups were (0.74±0.18, 0.61±0.07, 0.54±0.06), all of which were significantly lower than that in LPS group (1.16±0.08) (P=0.013, P=0.002, P<0.001). The expression levels of CSF-1R mRNA in low, medium and high concentration PLX3397 pretreatment groups (1.04±0.06, 0.90±0.05, 1.18±0.08) showed similar trend (2.90±0.25) (P<0.001). The average fluorescence intensity of p16 in all PLX3397 pretreatment groups were 49.76±3.65, 48.21±1.72, 47.99±1.26 respectively, which were significantly lower than that in LPS group (66.88±5.85) (P=0.001, P<0.001, P<0.001). The average fluorescence intensity of p21 in medium and high concentration PLX3397 pretreatment groups were (34.43±3.62, 30.13±0.86), significantly lower than that in LPS group (46.82±5.33) (P=0.043, P=0.007). The expression of p16 protein in low, medium and high concentration PLX3397 pretreatment groups (0.56±0.04, 0.55±0.04, 0.35±0.19) were significantly lower than that in LPS group (0.98±0.10) (P=0.003, P=0.002, P<0.001), as well the expression of p21 protein (0.69±0.20, 0.42±0.08, 0.26±0.14) (P=0.032, P=0.002, P<0.001). According to the results of RT-qPCR, the expressions of IL-6, IL-1ß, CXCL-1, CXCL-10 and MMP-8 in PLX3397 pretreatment groups were significantly lower than those in LPS group (P<0.001), while the expression of TGF-ß increased (P<0.001). Conclusions: LPS could induce the cell senescence, increase the secretion of SASP and aggravate local inflammation by activating the CSF-1R on the cell surface of bone marrow-derived macrophages. CSF-1R inhibitor PLX3397 might attenuate CSF-1R activation associated with LPS and inhibit the senescence of bone marrow-derived macrophages induced by LPS.

Risk factors analysis and establishment of predictive nomogram of extranodal B-cell lymphoma of mucosal-associated lymphoid tissue.

PURPOSE: The role of radiation therapy in mucosa-associated lymphoid tissue (MALT) lymphoma is poorly defined. The objective of this study was to explore the factors associated with the performance of radiotherapy and to assess its prognostic impact in patients with MALT lymphoma. PATIENTS AND METHODS: Patients with MALT lymphoma diagnosed between 1992 and 2017 were identified in the US Surveillance, Epidemiology, and End Results database (SEER). Factors associated with the delivery of radiotherapy were assessed by chi-square test. Overall survival (OS) and lymphoma-specific survival (LSS) were compared between patients with and without radiotherapy, using Cox proportional hazard regression models, in patients with early stage as well as those with advanced stage. RESULTS: Of the 10,344 patients identified with a diagnosis of MALT lymphoma, 33.6% had received radiotherapy; this rate was 38.9% for stage I/II patients and 12.0% for stage III/IV patients, respectively. Older patients and those who already received primary surgery or chemotherapy had a significantly lower rate of receiving radiotherapy, regardless of lymphoma stage. After univariate and multivariate analysis, radiotherapy was associated with improved OS and LSS in patients with stage I/II (HR=0.71 [0.65-0.78]) and (HR=0.66 [0.59-0.74]), respectively, but not in patients with stage III/IV (HR=1.01 [0.80-1.26]) and (HR=0.93 [0.67-1.29]). The nomogram built from the significant prognostic factors associated with overall survival of stage I/II patients had a good concordance (C-index=0.749±0.002). CONCLUSION: This cohort study shows that radiotherapy is significantly associated with a better prognosis in patients with early but not advanced MALT lymphoma. Prospective studies are needed to confirm the prognostic impact of radiotherapy in patients with MALT lymphoma.

Postoperative Complication and Reoperation Rates Following Resection of Soft Tissue vs. Bone Malignancies Based on Anatomic Location in the Inpatient Setting.

Introduction: Surgical excisions of upper and lower extremity malignancies are increasing annually, due in part to the rising incidence of sarcomas. The purpose of this study is to compare readmissions, reoperation rate, and complications following surgical excision of soft/connective tissue vs bone malignancies of the upper and lower extremities. Methods: The Nationwide Readmissions Database (NRD) was queried from 2016-2017 to conduct a retrospective analysis of 16,435 patients diagnosed with malignant neoplasms of the long bone (ULLB, n = 1,433) and soft tissue (ULST, n = 2,049) of the upper limb and malignant neoplasms of the long bone (LLLB, n = 5,422) and soft tissue (LLST, n = 7,531) of the lower limb. Patients who underwent surgical excision of their neoplasms were included. Binomial multivariate logistic regression was used to compare complications, nonelective readmission rates, and reoperation rates between the two groups at 30 and 90 days. Results: Average age of the ULST group was 61.88, with 36% female. Average age of the ULLB group was 44.97, with 41.90% female. Average age of the LLST group was 60.96, with 46.90% female. Average age of the LLLB group was 43.09, with 42.60% female. The ULST group had lower odds of readmission within 30 days (p=0.263), which became significant within 90 days of surgery (p=0.045). The LLST group had significantly higher odds of infection, reoperation within 30 to 90 days of the index surgery compared to the LLLB group (p < 0.0001). The LLST group had significantly lower odds of readmission within 30 (p=0.04) and 90 days (p=0.015) of the index surgery. Conclusion: Patients in the ULST group had significantly lower odds of 90-day readmission compared to the ULLB group. There were also significantly lower odds of 30- and 90-day readmission in the LLST group compared to the LLLB group. However, the LLST group had significantly higher odds of infection and reoperation within 30 and 90 days compared to the LLLB group.

Outcome of Multidisciplinary Treatment of Merkel Cell Carcinoma of the Hand and Wrist.

BACKGROUND/AIM: Skin cancers are the most common malignancy of the hand and wrist. Merkel cell carcinoma (MCC) is a rare, aggressive non-melanoma skin cancer arising from cutaneous neuroendocrine cells and is known for local and distant recurrence. The purpose of the current study was to examine the treatment outcome of patients with MCC of the hand and wrist. PATIENTS AND METHODS: We reviewed 25 patients (18 males:7 females) with MCC that occurred in the hand and wrist. The mean age at the time of biopsy of 71±11 years. RESULTS: Tumors were located on the hand (n=13), finger/thumb (n=9), and wrist (n=3). Local control included wide local excision (n=22). This included 21 non-amputation resections and one 5th digit ray amputation. Sentinel lymph node biopsy was performed in 21 patients with positive nodal disease in seven cases. Adjuvant radiotherapy was delivered to the primary site in 17 patients and additionally to the regional lymph node basin in six patients. Recurrence within five years was noted in 40% of patients (mean time to recurrence 18.4±20.6 months). Recurrence-free and disease-specific survival rates at 5-years were 54.8% and 67.6%. CONCLUSION: MCC is a rare cutaneous neuroendocrine carcinoma with a high propensity for regional nodal spread. Despite aggressive local treatment, adjuvant radiotherapy to the primary site and regional nodes, MCC of the hand and wrist has a high rate of recurrence and mortality within five years of diagnosis.

[Survival analysis of early-onset locally advanced rectal cancer: a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database].

Objective: To investigate the factors influencing tumor-specific survival of early-onset locally advanced rectal cancer. Methods: All-age patients with primary locally advanced rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2019) were included in this study. Early- and late-onset locally advanced rectal cancer was defined according to age of 50 years at diagnosis. Early-onset locally advanced rectal cancer was divided into five age groups for subgroup analyses. Age, sex, tumor-specific survival time and survival status of patients at diagnosis, pathological grade, TNM stage, perineural invasion, tumor deposits, tumor size, pretreatment CEA , radiotherapy, chemotherapy, and number of lymph node dissections were included. Progression-free survival (PFS) was analyzed and compared between patients with early- and late-onset rectal cancer. Results: A total of 5,048 patients with locally advanced rectal cancer were included in the study (aged 27-70 years): 1,290 (25.55%) patients with early-onset rectal cancer and 3,758 (74.45%) patients with late-onset rectal cancer. Patients with early-onset rectal cancer had a higher rate of perineural invasion (P<0.001), more positive lymph nodes dissected (P<0.001), higher positive lymph node ratios (P<0.001), and a higher proportion receiving preoperative radiotherapy (P=0.002). Patients with early-onset rectal cancer had slightly better short-term survival than those with late-onset rectal cancer (median (IQR ): 54 (33-83) vs 50 (31-79) months, χ2=5.192, P=0.023). Multivariate Cox regression for all patients with locally advanced rectal cancer showed that age (P=0.008), grade of tumor differentiation (P=0.002), pretreatment CEA (P=0.008), perineural invasion (P=0.021), positive number (P=0.004) and positive ratio (P=0.001) of dissected lymph nodes, and sequence of surgery and radiotherapy (P=0.005) influenced PFS. This suggests that the Cox regression results for all patients may not be applicable to patients with early-onset cancer. Cox analysis showed tumor differentiation grade (patients with low differentiation had a higher risk of death, P=0.027), TNM stage (stage III patients had a higher risk of death, P=0.025), T stage (higher risk of death in stage T4, P<0.001), pretreatment CEA (P=0.002), perineural invasion (P<0.001), tumor deposits (P=0.005), number of dissected lymph nodes (patients with removal of 12-20 lymph nodes had a lower risk of death, P<0.001), and positive number of dissected lymph nodes (P<0.001) were independent factors influencing PFS of patients with early-onset locally advanced rectal cancer. Conclusion: Patients with early-onset locally advanced rectal cancer were more likely to have adverse prognostic factors, but an adequate number of lymph node dissections (12-20) resulted in better survival outcomes.

Implementation of Automated Pipeline for Resting-State fMRI Analysis with PACS Integration.

In recent years, the quantity and complexity of medical imaging acquisition and processing have increased tremendously. The explosion in volume and need for advanced imaging analysis have led to the creation of numerous software programs, which have begun to be incorporated into clinical practice for indications such as automated stroke assessment, brain tumor perfusion processing, and hippocampal volume analysis. Despite these advances, there remains a need for specialized, custom-built software for advanced algorithms and new areas of research that is not widely available or adequately integrated in these "out-of-the-box" solutions. The purpose of this paper is to describe the implementation of an image-processing pipeline that is versatile and simple to create, which allows for rapid prototyping of image analysis algorithms and subsequent testing in a clinical environment. This pipeline uses a combination of Orthanc server, custom MATLAB code, and publicly available FMRIB Software Library and RestNeuMap tools to automatically receive and analyze resting-state functional MRI data collected from a custom filter on the MR scanner output. The processed files are then sent directly to Picture Archiving and Communications System (PACS) without the need for user input. This initial experience can serve as a framework for those interested in simple implementation of an automated pipeline customized to clinical needs.

The Effect of Modifiable Risk Factors on Postoperative Complications in Lumbar Spine Fusions.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The impact of modifiable risk factors (MRFs) on complications, costs, and readmission rates at 30, 90, and 180-days following lumbar spine fusion. METHODS: Patients with lumbar spine fusions within the 2016-2017 Nationwide Readmissions Database (NRD). Patients were stratified by the following MRFs: Alcohol use, tobacco/nicotine use, nutritional malnourishment, dyslipidemia, and primary hypertension. Differences in complications, non-elective readmission rates, costs, and length of stay were compared between MRFs and the non-MRF group. Statistical analysis was conducted using Tukey multiple comparisons of means, 1-way ANOVA, Wald testing, unpaired Welch 2-sample t-tests, multivariate analysis, and predictive modeling. RESULTS: The final analysis included 297,579 lumbar fusion patients. At 30 and 90 days, patients with nutritional malnutrition, dyslipidemia, and primary hypertension had significantly greater readmission rates than patients without MRFs (all P<0.01). At 180-days, all MRFs had significantly greater readmission rates than the non-MRF group (all P<0.001). Dyslipidemia demonstrated significantly greater rates of myocardial infarction at 90 days compared to all groups (all P<0.02). Nutritional malnutrition was associated with a significantly greater mortality rate than primary hypertension, non-MRF, and tobacco/nicotine use at 90 days (P<0.001) and only tobacco/nicotine use at 180 days (P=0.007). Predictive modeling showed increases of 0.77%, 1.70%, and 2.44% risk of readmission at 30, 90, and 180-days respectively per additional MRF (all P<0.001). CONCLUSIONS: These findings highlight the negative impact each MRF has on patients following lumbar spinal fusion. Further longitudinal research is necessary to comprehensively characterize the effects of various MRFs on spine surgery outcomes.

The Rise of Medicare Advantage: Effects on Total Joint Arthroplasty Patient Care and Research.

BACKGROUND: Medicare Advantage (MA) plans are popular among Medicare-eligible patients, but little is known about MA in lower-extremity total joint arthroplasty (TJA). The purpose of this study was to describe trends in MA utilization and analyze differences in patient characteristics and postoperative outcomes between patients undergoing primary TJA using traditional Medicare (TM) or MA plans. METHODS: Patients ≥65 years of age who underwent primary total knee or total hip arthroplasty were identified using the Premier Healthcare Database. Patients were categorized into TM and MA cohorts. Data from 2004 to 2020 were used to describe trends in insurance coverage. Data from 2015 to 2020 were used to identify differences in patient characteristics and postoperative complications using ICD-10 codes. Multivariate analyses were performed using 2015 to 2020 data to account for potential confounders. RESULTS: From 2004 to 2020, the proportion of patients with MA increased from 7.9% to 34.4%, while those with TM decreased from 83.7% to 54.0%. Of the 697,317 patients who underwent primary elective TJA from 2015 to 2020, 471,439 (67.6%) had TM coverage and 225,878 (32.4%) had MA coverage. The cohorts were similar in terms of age and sex. However, a higher proportion of Black patients (8.29% compared with 4.62%; p < 0.001) and a lower proportion of White patients (84.0% compared with 89.2%; p < 0.001) were enrolled in MA compared with TM. After controlling for confounders, patients with MA had higher odds of surgical site infection (adjusted odds ratio [aOR]: 1.15; 95% confidence interval [CI]: 1.04 to 1.47; p = 0.031), periprosthetic joint infection (aOR: 1.10; 95% CI: 1.03 to 1.18; p = 0.006), stroke (aOR: 1.15; 95% CI: 1.02 to 1.31; p = 0.026), and acute kidney injury (aOR: 1.08; 95% CI: 1.04 to 1.11; p < 0.001), but lower odds of urinary tract infection (aOR: 0.94; 95% CI: 0.90 to 0.98; p = 0.003). CONCLUSIONS: From 2004 to 2020, the number of patients utilizing MA increased markedly such that 1 in 3 were covered by MA in 2020. From 2015 to 2020, patients who were non-White were more likely to have MA than TM, and the MA group had a higher rate of several postoperative complications compared with the TM group. As TM claims data inform health-care policy and clinical decisions, this change portends future challenges, including limitations in arthroplasty registry research, an increase in the administrative burden of surgeons, and a potential worsening of social disparities in health care.

Merkel cell carcinoma of unknown primary: Clinical presentation and outcomes.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion. METHODS: We reviewed 415 patients with biopsy-proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease-free survival, and overall survival. RESULTS: Patients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence-free survival was 59.3% at 5 years. Disease-specific survival was 63.3% at 5 years. CONCLUSION: Patients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

Tumor lysis syndrome following ifosfamide monotherapy in metastatic osteosarcoma: a case report and review of the literature.

BACKGROUND: Tumor lysis syndrome is an oncologic emergency that involves multiple metabolic abnormalities and clinical symptoms such as acute renal failure, cardiac arrhythmias, seizures, and multiorgan failure, and may be fatal if not promptly recognized. Tumor lysis syndrome occurs most often in patients with hematologic malignancies, and relatively few cases have been described in patients with sarcoma. CASE PRESENTATION: A 64-year-old male of Asian heritage presented to his primary care physician with a right lower-extremity mass and was ultimately diagnosed with widely metastatic osteosarcoma. He was treated with one cycle of cisplatin and doxorubicin that was complicated by hypervolemia and hypoxic respiratory failure. Given concerns for volume overload, therapy was changed to single-agent, dose-reduced ifosfamide. After receiving one dose of ifosfamide 1 g/m2 (1.8 g total) intravenously over 1 hour, the patient developed renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and lactic acidosis. The patient ultimately died from severe electrolyte abnormalities associated with tumor lysis syndrome. CONCLUSION: This is the first instance of tumor lysis syndrome described in a patient with osteosarcoma undergoing ifosfamide monotherapy. Clinicians must be vigilant in identifying tumor lysis syndrome regardless of the malignancy type or chemotherapy regimen in order to prevent potentially fatal complications.

The impact of frailty on postoperative complications in geriatric patients undergoing multi-level lumbar fusion surgery.

STUDY DESIGN: Retrospective Cohort Study. PURPOSE: This study evaluates the impact of patient frailty status on postoperative complications in those undergoing multi-level lumbar fusion surgery. METHODS: The Nationwide Readmission Database (NRD) was retrospectively queried between 2016 and 2017 for patients receiving multi-level lumbar fusion surgery. Demographics, frailty status, and relevant complications were queried at index admission and readmission intervals. Primary outcome measures included perioperative complications and 30-, 90-, and 180-day complication and readmission rates. Perioperative complications of interest were infection, urinary tract infection (UTI), and posthemorrhagic anemia. Secondary outcome measures included inpatient length of stay (LOS), adjusted all-payer costs, and discharge disposition. Nearest-neighbor propensity score matching for demographics was implemented to identify non-frail patients with similar diagnoses and procedures. Subgroup analysis of minimally invasive surgery (MIS) versus open surgery within frail and non-frail cohorts was conducted to evaluate differences in surgical and medical complication rates. The analysis used nonparametric Mann-Whitney U testing and odds ratios. RESULTS: Frail patients encountered higher rates perioperative complications including posthemorrhagic anemia (OR: 1.73, 95%CI 1.50-2.00, p < 0.0001), infection (OR: 2.94, 95%CI 2.04-4.36, p < 0.0001), UTI (OR: 2.57, 95%CI 2.04-3.26, p < 0.0001), and higher rates of non-routine discharge (OR: 2.07, 95%CI 1.80-2.38, p < 0.0001). Frail patients had significantly greater LOS and total all-payer inpatient costs compared to non-frail patients (p < 0.0001). Frailty was associated with significantly higher rates of 90- (OR: 1.43, 95%CI 1.18-1.74, p = 0.0003) and 180-day (OR: 1.28, 95%CI 1.03-1.60, p = 0.02) readmissions along with higher rates of wound dehiscence (OR: 2.21, 95%CI 1.17-4.44, p = 0.02) at 90 days. Subgroup analysis revealed that frail patients were at significantly higher risk for surgical complications with open surgery (16%) compared to MIS (0%, p < 0.0001). No significant differences were found between surgical approaches with respect to medical complications in both cohorts, nor surgical complications in non-frail patients. CONCLUSIONS: Frailty was associated with higher odds of all perioperative complications, LOS, and all-payer costs following multi-level lumbar fusion. Frail patients had significantly higher rates of 90 and 180-day readmission and higher rates of wound disruption at 90-days. On subgroup analysis, MIS was associated with significantly reduced rates of surgical complications specifically in frail patients. Our results suggest frailty status to be an important predictor of perioperative complications and long-term readmissions in geriatric patients receiving multi-level lumbar fusions. Frail patients should undergo surgery utilizing minimally invasive techniques to minimize risk of surgical complications. Future studies should explore the utility of implementing frailty in risk stratification assessments for patients undergoing spine surgery.

Midterm Survivorship of Robotic-Assisted Lateral Unicompartmental Knee Arthroplasty.

BACKGROUND: Lateral unicompartmental knee arthroplasty (UKA) is a popular alternative to total knee arthroplasty (TKA) for patients with isolated lateral compartment osteoarthritis. Few studies have investigated outcomes following robotic-assisted lateral UKA. The purpose of this study is to evaluate mid-term survivorship and patient-reported outcomes of robotic-assisted lateral UKA. METHODS: A retrospective case series was conducted on all robotic-assisted lateral UKAs performed by a single surgeon between 2013 and 2019. Patient demographics, surgical variables, and Kozinn and Scott criteria were collected. Implant survivorship was estimated using the Kaplan-Meier method with all-cause reoperation and conversion to TKA as endpoints. Participating patients were assessed for patient satisfaction and the Forgotten Joint Score-12. Correlations between patient demographics and patient outcome scores were investigated. RESULTS: In total, 120 lateral UKAs were identified, 84 of which met inclusion criteria, with a mean follow-up of 4.0 years (range 2.0-7.0). Five-year survivorship was 92.9% (95% confidence interval [CI] 84.5-96.7) with all-cause reoperation as the endpoint, and 100% (95% CI 95.0-100) with conversion to TKA as the endpoint. One patient was converted to TKA after the 5-year mark, resulting in a 6-year survival for conversion to TKA of 88.9% (95% CI 44.9-98.5). Average Forgotten Joint Score-12 score was 82.7/100, and patient satisfaction 4.7/5. Mean coronal plane correction was 2.5° ± 1.9° toward the mechanical axis. Neither final postoperative alignment nor failure to meet classic Kozinn and Scott criteria for UKA resulted in differences in patient-reported outcomes. CONCLUSION: The current study demonstrates high mid-term survivorship and excellent patient-reported outcomes with robotic-assisted lateral UKA. Robotic-assisted lateral UKA is a viable treatment option for isolated lateral compartment arthritis even in patients who do not meet classic indications.

Genetic associated complications of type 2 diabetes mellitus.

According to the International Diabetes Federation, the number of adults (age of 20-79) being diagnosed with diabetes mellitus (DM) have increased from 285 million in year 2009 to 463 million in year 2019 which comprises of 95% type 2 DM patient (T2DM). Research have claimed that genetic predisposition could be one of the factors causing T2DM complications. In addition, T2DM complications cause an incremental risk to mortality. Therefore, this article aims to discuss some complications of T2DM in and their genetic association. The complications that are discussed in this article are diabetic nephropathy, diabetes induced cardiovascular disease, diabetic neuropathy, diabetic foot ulcer (DFU) and Alzheimer's disease (AD). According to the information obtained, genes associated with diabetic nephropathy (DN) are gene GABRR1 and ELMO1 that cause injury to glomerular. Replication of genes FRMD3, CARS and MYO16/IRS2 shown to have link with DN. The increase of gene THBS2, NGAL, PIP, TRAF6 polymorphism, ICAM-1 encoded for rs5498 polymorphism and C667T increase susceptibility towards DN in T2DM patient. Genes associated with cardiovascular diseases are adiponectin gene (ACRP30) and apolipoprotein E (APOE) polymorphism gene with ξ2 allele. Haptoglobin (Hp) 1-1 genotype and mitochondria superoxide dismutase 2 (SOD2) plays a role in cardiovascular events. As for genes related to diabetic neuropathy, janus kinase (JAK), mutation of SCN9A and TRPA1 gene and destruction of miRNA contribute to pathogenesis of diabetic neuropathy among T2DM patients. Expression of cytokine IL-6, IL-10, miR-146a are found to cause diabetic neuropathy. Besides, A1a16Va1 gene polymorphism, an oxidative stress influence was found as one of the gene factors. Diabetic retinopathy (DR) is believed to have association with monocyte chemoattractant protein-1 (MCP-1) and insulin-like growth factor 1 (IGF1). Over-expression of gene ENPP1, IL-6 pro-inflammatory cytokine, ARHGAP22's protein rs3844492 polymorphism and TLR4 heterozygous genotype are contributing to significant pathophysiological process causing DR, while research found increases level of UCP1 gene protects retina cells from oxidative stress. DFU is manifested by slowing in re-epithelialization of keratinocyte, persistence wound inflammation and healing impairment. Re-epithelialization disturbance was caused by E2F3 gene, reduction of Tacl gene encoded substance P causing persistence inflammation while expression of MMp-9 polymorphism contributes to healing impairment. A decrease in HIF-1a gene expression leads to increased risk of pathogenesis, while downregulation of TLR2 increases severity of wound in DFU patients. SNPs alleles has been shown to have significant association between the genetic dispositions of T2DM and AD. The progression of AD can be due to the change in DNA methylation of CLOCK gene, followed with worsening of AD by APOE4 gene due to dyslipidemia condition in T2DM patients. Insulin resistance is also a factor that contributes to pathogenesis of AD.