Elderly patients with traumatic brain injury (TBI) have greater mortality and poorer outcomes than younger individuals. The extent to which old age alters long-term recovery and chronic microglial activation after TBI is unknown, and evidence for therapeutic efficacy in aged mice is sorely lacking. The present study sought to identify potential inflammatory mechanisms underlying age-related outcomes late after TBI. Controlled cortical impact was used to induce moderate TBI in young and old male C57BL/6 mice. At 12 weeks post-injury, aged mice exhibited higher mortality, poorer functional outcomes, larger lesion volumes, and increased microglial activation. Transcriptomic analysis identified age- and TBI-specific gene changes consistent with a disease-associated microglial signature in the chronically injured brain, including those involved with complement, phagocytosis, and autophagy pathways. Dysregulation of phagocytic and autophagic function in microglia was accompanied by increased neuroinflammation in old mice. As proof-of-principle that these pathways have functional importance, we administered an autophagic enhancer, trehalose, in drinking water continuously for 8 weeks after TBI. Old mice treated with trehalose showed enhanced functional recovery and reduced microglial activation late after TBI compared to the sucrose control group. Our data indicate that microglia undergo chronic changes in autophagic regulation with both normal aging and TBI that are associated with poorer functional outcome. Enhancing autophagy may therefore be a promising clinical therapeutic strategy for TBI, especially in older patients.

We performed a multicenter retrospective analysis across 10 US academic medical centers (2010 - 2018) to evaluate current treatment patterns and outcomes in patients age ≥60 with classical Hodgkin lymphoma (cHL). Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 14% had ECOG performance status (PS) 2-4, and 12% had documented loss of ≥1 activity of daily living (ADLs). Medical comorbidities were assessed by the Cumulative Illness Rating Scale - Geriatric (CIRS-G), where n=44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; HR 2.13, p=0.007) and overall survival (OS; HR=2.52, P=0.02). Most patients (n=203, 83%) received conventional chemotherapy regimens, including ABVD (56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P=0.0007) and OS (HR 0.31, p=0.0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, p=0.63; OS HR 0.73, p=0.55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28 vs 12%, p=0.016) or documented geriatric syndrome (28 vs 13%, p=0.02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, p=0.02) and higher mortality from causes other than disease or treatment in those with high CIRS-G or geriatric syndromes. These data suggest conventional chemotherapy regimens be considered standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.

Background Dupuytren contracture (DC) is a common disorder characterized by progressive fibrosis of palmar fascia. This study analyzed cost trends of 3 common treatments for DC: fasciotomy, fasciectomy, and collagenase injection (CI)/cord manipulation. Methods The Vizient Clinical Data/Resource Manager electronic database was reviewed for all procedures for the treatment of DC at participating hospitals in the United States (US) from October 1, 2015, to September 1, 2019. Cases were placed into 1 of 3 categories: (1) CI, (2) needle fasciotomy (NF), and (3) open fasciectomy (OF). Total and direct costs were averaged for each procedure and compared nationally and regionally. Temporal trends and specific market share were analyzed. One-tailed t test and Pearson correlation analysis was performed (P < 0.05 and r > 0.9 or r < −0.9 was considered significant). Results A total of 22,974 total cases were identified. A total of 16,966 OF, 3962 NF, and 2046 CI were performed. There was a nearly a 4-fold increase in number of procedures to treat DC from 2015 to 2018. Market share percentage of each procedure stayed relatively similar over time. However, market share percentage differed between procedures. Needle fasciotomy had the lowest market share percentage approximately 7%. Collagenase injection had the highest average cost at US $4453.66 and was significantly higher than OF at US $3394.90 and NF at US $2010.75. Cost and distribution of procedures were further analyzed by geographic regions. In 2018, 32% of procedures performed were in the Northeastern US, 29% in the Midwestern US, 23% in the Southern US, and 16% in the Western US. Total number of Dupuytren procedures increased more than 300% in all regions across the US from 2015 to 2018. In every region, NF was the lowest cost intervention. Cost of OF and CI varied between regions and was often the most expensive intervention. Conclusions Treatment of DCs with NF seems to be the least costly treatment option. Needle fasciotomy seems to be the least commonly performed procedure. Regional data show variations in the cost of OF and CI. However, OF has the majority market share nationally and regionally. Although the cost of these procedures seems to vary regionally, the type of procedures being performed seem to be similar across regions.

There is a paucity of large‐scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly‐diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60–88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale‐Geriatrics (CIRS‐G) score was 6 (range, 0–27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high‐dose methotrexate (HD‐MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R‐MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58‐month median follow‐up, median progression‐free survival (PFS) and overall survival (OS) were 17 months (95% CI 13–22 months) and 43 months (95% CI 31–56 months), respectively. Three‐year PFS and OS were highest with MTR (55% and 74%, respectively). With single‐agent methotrexate ± rituximab, 3‐year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS‐G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3‐year PFS was 65% versus 45% without maintenance (p = 0.02), with 3‐year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD‐MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.

Introduction Hand surgery fellowships accept applicants from 3 different residencies: general surgery, orthopedic surgery, and plastic surgery. Although all of these specialties culminate into a board-certified hand surgeon, each specialty receives drastically different training in residency, which can have effects on which procedures these surgeons feel comfortable performing in their own practices. This study aims to compare practice patterns and complication rates among hand surgeons by residency training. Methods The National Surgical Quality Improvement Program database was queried between the years of 2014 and 2018 for all Current Procedural Terminology codes pertaining to upper-extremity surgical procedures performed below the elbow. Procedures not performed by a general, orthopedic, or plastic surgeon were excluded, as well as polytraumas. Procedures were then stratified by anatomic region, tissue type, and primary specialty of the attending surgeon. Data collected included the number of each procedure, patient complexity, and complications. Statistical analysis consisted of a t test for continuous variables, χ 2 analysis for categorical variables, and linear regression analysis to compare complications rates between specialties. Results A total of 76,980 unique cases were included in our analysis: 4979 (6.4%) at the elbow, 43,680 (56.7%) at the forearm/wrist, 23,284 (30.2%) at the hand, 1421 (1.8%) flaps/grafts, 285 (0.4%) vascular, and 3331 (4.3%) neurological. Orthopedics performed most (79.5%) of the procedures, whereas plastic surgeons and general surgeons performed 17.3% and 3.1%, respectively. There were also significant differences by anatomic location/type of procedure, with orthopedic surgeons performing 99.2% of procedures at the elbow but only 67.7% of procedures at the hand. Linear regression analysis showed general surgeons had the lowest complication rates. Conclusions Our data show significant differences in the number of upper-extremity surgeries performed by surgeons from each specialty at different anatomic locations. This could be due to differences in training during residency or proportionately more orthopedic surgeons being “full-time” hand surgeons. These data could affect hiring patterns in hospitals seeking hand surgeons depending on the variety of pathology encountered at that particular institution.