Citations

BACKGROUND Hidradenitis suppurativa is a progressive, recurrent inflammatory disease. Surgical management is potentially curative with limited efficacy data. OBJECTIVE To evaluate hidradenitis surgical patients. METHODS Retrospective review of outcomes of 590 consecutive surgically treated patients. RESULTS Most patients were white (91.0% [435/478]), men (337 [57.1%]), smokers (57.7% [297/515]) with Hurley Stage III disease (476 [80.7%]). Procedure types were excision (405 [68.6%]), unroofing (168 [28.5%]), and drainage (17 [2.9%]) treating disease of perianal/perineum (294 [49.8%]), axilla (124 [21.0%]), gluteal cleft (76 [12.9%]), inframammary (12 [2.0%]), and multiple surgical sites (84 [14.2%]). Postoperative complications occurred in 15 patients (2.5%) and one-fourth (144 [24.4%]) suffered postoperative recurrence, which necessitated reoperation in one-tenth (69 [11.7%]) of patients. Recurrence risk was increased by younger age (hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.7–0.9), multiple surgical sites (HR, 1.6; 95% CI, 1.1–2.5), and drainage-type procedures (HR, 3.5; 95% CI, 1.2–10.7). Operative location, disease severity, gender, and operative extent did not influence recurrence rate. CONCLUSION Excision and unroofing procedures were effective treatments with infrequent complications and low recurrence rates. Well-planned surgical treatment aiming to remove or unroof the area of intractable hidradenitis suppurativa was highly effective in the management of this challenging disease.

There is no consensus on whether patients with immunoglobulin light chain amyloidosis (AL) should receive induction therapy prior to an autologous stem cell transplant (ASCT). This study investigated the relationships between baseline bone marrow plasmacytosis (BMPC), cardiac staging, and pre‐transplant induction in AL patients. All patients who received ASCT for AL within 12 months of diagnosis were included. Patient characteristics and outcomes were abstracted. Univariate and multivariate modeling was performed. Among 415 AL patients, 35% had induction prior to ASCT. Post‐ASCT hematologic CR plus VGPR rates were significantly higher in those with baseline BMPC ≤ 10% compared to BMPC >10% (58% versus 40%, P = 0.0013). Significant risk factors for lack of attainment of CR included attenuated dose melphalan conditioning, baseline BMPC > 10%, no induction, and male gender. The 5‐year OS for the entire group was 65%. On multivariate analysis, risk factors for inferior OS included no induction therapy, advanced AL amyloid staging, BMPC > 10%, attenuated conditioning melphalan dose, and male gender. Patients with Mayo 2012 stage I–II patients with BMPC ≤ 10%, who comprised 56% of the ASCT population fared exceedingly well regardless of whether or not they received induction therapy with a 5‐year OS of 81 to 83%. Induction therapy pre‐ASCT may improve outcomes among AL patients due to a rapid reduction of toxic light chains or alternatively by elimination of less fit patients by “testing” their ability to tolerate chemotherapy. Prospective studies will be required to sort out these and other questions. Am. J. Hematol. 91:984–988, 2016. © 2016 Wiley Periodicals, Inc.

ABSTRACT Cellular senescence is a fundamental mechanism by which cells remain metabolically active yet cease dividing and undergo distinct phenotypic alterations, including upregulation of p16Ink4a, profound secretome changes, telomere shortening, and decondensation of pericentromeric satellite DNA. Because senescent cells accumulate in multiple tissues with aging, these cells and the dysfunctional factors they secrete, termed the senescence-associated secretory phenotype (SASP), are increasingly recognized as promising therapeutic targets to prevent age-related degenerative pathologies, including osteoporosis. However, the cell type(s) within the bone microenvironment that undergoes senescence with aging in vivo has remained poorly understood, largely because previous studies have focused on senescence in cultured cells. Thus in young (age 6 months) and old (age 24 months) mice, we measured senescence and SASP markers in vivo in highly enriched cell populations, all rapidly isolated from bone/marrow without in vitro culture. In both females and males, p16Ink4a expression by real-time quantitative polymerase chain reaction (rt-qPCR) was significantly higher with aging in B cells, T cells, myeloid cells, osteoblast progenitors, osteoblasts, and osteocytes. Further, in vivo quantification of senescence-associated distension of satellites (SADS), ie, large-scale unraveling of pericentromeric satellite DNA, revealed significantly more senescent osteocytes in old compared with young bone cortices (11% versus 2%, p < 0.001). In addition, primary osteocytes from old mice had sixfold more (p < 0.001) telomere dysfunction-induced foci (TIFs) than osteocytes from young mice. Corresponding with the age-associated accumulation of senescent osteocytes was significantly higher expression of multiple SASP markers in osteocytes from old versus young mice, several of which also showed dramatic age-associated upregulation in myeloid cells. These data show that with aging, a subset of cells of various lineages within the bone microenvironment become senescent, although senescent myeloid cells and senescent osteocytes predominantly develop the SASP. Given the critical roles of osteocytes in orchestrating bone remodeling, our findings suggest that senescent osteocytes and their SASP may contribute to age-related bone loss. © 2016 American Society for Bone and Mineral Research

The concept of optimizing health care by understanding and generating knowledge from previous evidence, ie, the Learning Health-care System (LHS), has gained momentum and now has national prominence. Meanwhile, the rapid adoption of electronic health records (EHRs) enables the data collection required to form the basis for facilitating LHS. A prerequisite for using EHR data within the LHS is an infrastructure that enables access to EHR data longitudinally for health-care analytics and real time for knowledge delivery. Additionally, significant clinical information is embedded in the free text, making natural language processing (NLP) an essential component in implementing an LHS. Herein, we share our institutional implementation of a big data-empowered clinical NLP infrastructure, which not only enables health-care analytics but also has real-time NLP processing capability. The infrastructure has been utilized for multiple institutional projects including the MayoExpertAdvisor, an individualized care recommendation solution for clinical care. We compared the advantages of big data over two other environments. Big data infrastructure significantly outperformed other infrastructure in terms of computing speed, demonstrating its value in making the LHS a possibility in the near future.

Background— Targeted postmortem genetic testing of the 4 major channelopathy-susceptibility genes ( KCNQ1 , KCNH2 , SCN5A , and RYR2 ) have yielded putative pathogenic mutations in ≤30% of autopsy-negative sudden unexplained death in the young (SUDY) cases with highest yields derived from the subset of exertion-related SUDY. Here, we evaluate the role of whole-exome sequencing in exertion-related SUDY cases. Methods and Results— From 1998 to 2010, 32 cases of exertion-related SUDY were referred by Medical Examiners for a cardiac channel molecular autopsy. A mutational analysis of the major long-QT syndrome–susceptibility genes ( KCNQ1 , KCNH2 , and SCN5A ) and catecholaminergic polymorphic ventricular tachycardia–susceptibility gene ( RYR2 ) identified a putative pathogenic mutation in 11 cases. Whole-exome sequencing was performed on the remaining 21 targeted gene–negative SUDY cases. After whole-exome sequencing, a gene-specific surveillance of all genes (N=100) implicated in sudden death was performed to identify putative pathogenic mutation(s). Three of these 21 decedents had a clinically actionable, pathogenic mutation (CALM2-F90L, CALM2-N98S, and PKP2-N634fs). Of the 18 remaining cases, 7 hosted at least 1 variant of unknown significance with a minor allele frequency <1:20 000. The overall yield of pathogenic mutations was higher among decedents aged 1 to 10 years (10/11, 91%) than those aged 11 to 19 years (4/21, 19%, P =0.0001). Conclusions— Molecular screening in this clinical scenario is appropriate with a pathogenic mutation detection rate of 44% using direct DNA sequencing followed by whole-exome sequencing. Only 5 of the 100 interrogated sudden death genes hosted actionable pathogenic mutations for more than one third of these exertion-related, autopsy-negative SUDY cases.

Fracture risk is significantly increased in both type 1 and type 2 diabetes, and individuals with diabetes experience worse fracture outcomes than normoglycemic individuals. Factors that increase fracture risk include lower bone mass in type 1 diabetes and compromised skeletal quality and strength despite preserved bone density in type 2 diabetes, as well as the effects of comorbidities such as diabetic macro- and microvascular complications. In this Perspective, we assess the developing scientific knowledge regarding the epidemiology and pathophysiology of skeletal fragility in patients with diabetes and the emerging data on the prediction, treatment, and outcomes of fractures in individuals with type 1 and type 2 diabetes.