Incidence of surgical site infection following mastectomy with and without immediate reconstruction using private insurer claims data

OBJECTIVE: The National Healthcare Safety Network classifies breast operations as clean procedures with an expected 1–2% surgical site infection (SSI) incidence. We assessed differences in SSI incidence following mastectomy with and without immediate reconstruction in a large, geographically diverse population. DESIGN: Retrospective cohort study. PATIENTS: Commercially-insured women aged 18–64 years with ICD-9-CM procedure or CPT-4 codes for mastectomy from 1/1/2004–12/31/2011. METHODS: Incident SSIs within 180 days after surgery were identified by ICD-9-CM diagnosis codes. The incidence of SSI after mastectomy +/− immediate reconstruction was compared by the chi-square test. RESULTS: From 2004–2011, 18,696 mastectomy procedures among 18,085 women were identified, with immediate reconstruction in 10,836 (58%) procedures. The 180-day incidence of SSI following mastectomy with or without reconstruction was 8.1% (1,520/18,696). Forty-nine percent of SSIs were identified within 30 days post-mastectomy, 24.5% between 31–60 days, 10.5% between 61–90 days, and 15.7% between 91–180 days. The incidence of SSI was 5.0% (395/7,860) after mastectomy-only, 10.3% (848/8,217) after mastectomy plus implant, 10.7% (207/1,942) after mastectomy plus flap, and 10.3% (70/677) after mastectomy plus flap and implant (p<0.001). The SSI risk was higher after bilateral compared with unilateral mastectomy with (11.4% vs. 9.4%, p=0.001) and without (6.1% vs. 4.7%, p=0.021) immediate reconstruction. CONCLUSIONS: SSI incidence was two-fold higher after mastectomy with immediate reconstruction than after mastectomy alone. Only 49% of SSIs were coded within 30 days after operation. Our results suggest stratification by procedure type will facilitate comparison of SSI rates after breast operations between facilities

Assessing an online patient decision aid about upper extremity reconstructive surgery for cervical spinal cord injury: Pilot testing knowledge, decisional conflict, and acceptability

UNLABELLED: HIGHLIGHTS: People with cervical spinal cord injury prioritize gaining upper extremity function after injury, but few individuals receive information about treatment options.A newly created patient decision aid (PtDA) provides information about recovery after spinal cord injury and the role of traditional tendon and newer nerve transfer surgery to improve upper extremity upper extremity function.The PtDA improved knowledge and decreased decisional conflict in this pilot study.Future work should focus on studying dissemination and implementation of the ptDA into clinical practice

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

Living with cervical spinal cord injury during the COVID-19 pandemic: A qualitative study

OBJECTIVE: To understand how COVID-19 has affected the daily lives of people living with cervical spinal cord injury (SCI). DESIGN: Cross sectional qualitative study. SETTING: Academic medical center in the Midwestern United States. PARTICIPANTS: Ten community-dwelling individuals (8 men, 2 women), average 11.6 years post-mid-cervical level SCI (N=10). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Semistructured interviews were completed by phone. The research team used thematic analysis and inductive strategies to analyze the data in this exploratory investigation. RESULTS: People with cervical SCI living in the United States during the spring of 2020 experienced changes to their daily lives. Participants described how interactions with caregivers for activities of daily living were complicated by fear about contracting and/or transmitting COVID-19. The pandemic limited this population\u27s access to medical care and adversely affected their mental and physical health. Telemedicine was seen as a helpful alternative to in-person visits. Some participants felt that their previous life-altering experience (SCI) better prepared them to cope with the pandemic and roll with things. CONCLUSIONS: Learning about how people with SCI cope, persevere, and survive to overcome adversity during the pandemic should inform future research to support those with SCI. Improving telemedicine and rewarding and recognizing caregivers for their role in maintaining health are important first steps. We must continue to be creative about improving our health care systems and access for people with disabilities, particularly during this and future public health crises

Predictors of digital amputation in diabetic patients with surgically treated finger infections

BACKGROUND: Diabetes is a well-established risk factor for severe digital infection, and patients are more likely to require digital amputation for adequate source control. This study aims to identify factors predictive of digital amputation compared with preservation in patients with diabetes who present with surgically treated finger infections. METHODS: Current Procedural Terminology (CPT) and International Classification of Diseases Versions 9 and 10 (ICD-9/10) databases from a single academic medical center were queried to identify patients with type 1 or type 2 diabetes mellitus who underwent surgical treatment in the operating room for treatment of a digital infection from 2010 to 2020. Electronic medical records were reviewed to obtain historical and acute clinical variables at the time of hospital presentation. Bivariate and multivariable regression were used to identify factors associated with amputation. RESULTS: In total, 145 patients (61 digital amputation, 84 digital preservation) met inclusion criteria for this retrospective cohort study. Mean hospital stay was 6 days, and the average patient underwent 2 operations. Multivariable analysis revealed that the presence of osteomyelitis, ipsilateral upper extremity dialysis fistula, end-stage renal disease, and vascular disease each had significant independent predictive value for amputation rather than digital preservation. CONCLUSIONS: Digital amputation is common in the setting of diabetic finger infection. The 4 variables found to independently predict the outcome of amputation can be understood as factors which decrease the likelihood of successful digital salvage and increase the potential consequence of ongoing uncontrolled infection. Further study should focus on clinical factors affecting surgical decision making and how the treatment rendered affects patient outcomes

New Phase Diagram for Black Holes and Strings on Cylinders

We introduce a novel type of phase diagram for black holes and black strings on cylinders. The phase diagram involves a new asymptotic quantity called the relative binding energy. We plot the uniform string and the non-uniform string solutions in this new phase diagram using data of Wiseman. Intersection rules for branches of solutions in the phase diagram are deduced from a new Smarr formula that we derive.Comment: 19 pages, 6 figures, v2: typos corrected, v3: refs. added, comment on bounds on the relative binding energy n added in end of section

Mesenchymal Stromal Cells Engage Complement and Complement Receptor Bearing Innate Effector Cells to Modulate Immune Responses

Infusion of human third-party mesenchymal stromal cells (MSCs) appears to be a promising therapy for acute graft-versus-host disease (aGvHD). To date, little is known about how MSCs interact with the body's innate immune system after clinical infusion. This study shows, that exposure of MSCs to blood type ABO-matched human blood activates the complement system, which triggers complement-mediated lymphoid and myeloid effector cell activation in blood. We found deposition of complement component C3-derived fragments iC3b and C3dg on MSCs and fluid-phase generation of the chemotactic anaphylatoxins C3a and C5a. MSCs bound low amounts of immunoglobulins and lacked expression of complement regulatory proteins MCP (CD46) and DAF (CD55), but were protected from complement lysis via expression of protectin (CD59). Cell-surface-opsonization and anaphylatoxin-formation triggered complement receptor 3 (CD11b/CD18)-mediated effector cell activation in blood. The complement-activating properties of individual MSCs were furthermore correlated with their potency to inhibit PBMC-proliferation in vitro, and both effector cell activation and the immunosuppressive effect could be blocked either by using complement inhibitor Compstatin or by depletion of CD14/CD11b-high myeloid effector cells from mixed lymphocyte reactions. Our study demonstrates for the first time a major role of the complement system in governing the immunomodulatory activity of MSCs and elucidates how complement activation mediates the interaction with other immune cells

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes