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• Certain comorbidities and socio-demographic characteristics increase the risk of a patient's hospitalization for community-acquired pneumonia (CAP). • How a patient's factors affect bacterial CAP prognosis during and after hospitalization is important in disease management. • Heart failure, stroke, diabetes, obesity, and COPD were associated with poor disease prognosis as measured by medical intensive care unit admission, higher length of hospital stay, in-hospital mortality, or readmission within one year with recurrent bacterial CAP. • Socio-demographic characteristics including age, sex, race, and admission source, were also associated with poor disease prognosis. How socio-demographic characteristics and comorbidities affect bacterial community-acquired pneumonia (CAP) prognosis during/after hospitalization is important in disease management. To identify predictors of medical intensive care unit (MICU) admission, length of hospital stay (LOS), in-hospital mortality, and bacterial CAP readmission in patients hospitalized with bacterial CAP. ICD-9/10 codes were used to query electronic medical records to identify a cohort of patients hospitalized for bacterial CAP at a tertiary hospital in Southeastern US between 01/01/2013–12/31/2019. Adjusted accelerated failure time and modified Poisson regression models were used to examine predictors of MICU admission, LOS, in-hospital mortality, and 1-year readmission. There were 1956 adults hospitalized with bacterial CAP. Median (interquartile range) LOS was 11 days (6–23), and there were 26 % (513) MICU admission, 14 % (266) in-hospital mortality, and 6 % (117) 1-year readmission with recurrent CAP. MICU admission was associated with heart failure (RR 1.38; 95 % CI 1.17–1.62) and obesity (RR 1.26; 95 % CI 1.04–1.52). Longer LOS was associated with heart failure (adjusted time ratio[TR] 1.27;95 %CI 1.12–1.43), stroke (TR 1.90;95 %CI 1.54,2.35), type 2 diabetes (TR 1.20;95 %CI 1.07–1.36), obesity (TR 1.50;95 %CI 1.31–1.72), Black race (TR 1.17;95 %CI 1.04–1.31), and males (TR 1.24;95 %CI 1.10–1.39). In-hospital mortality was associated with stroke (RR 1.45;95 %CI 1.03–2.04) and age ≥65 years (RR 1.34;95 %CI 1.06–1.68). 1-year readmission was associated with COPD (RR 1.55;95 %CI 1.05–2.27) and underweight BMI (RR 1.74;95 %CI 1.04–2.90). Comorbidities and socio-demographic characteristics have varying impacts on bacterial CAP in-hospital prognosis and readmission. More studies are warranted to confirm these findings to develop comprehensive care plans and inform public health interventions. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic joint infection (PJI) represents a devastating complication of total hip arthroplasty (THA) or total knee arthroplasty (TKA). Modifiable patient risk factors as well as various intraoperative and postoperative variables have been associated with risk of PJI. In 2011, our institution formulated a "bundle" to optimize patient outcomes after THA and TKA. The purpose of this report is to describe the "bundle" protocol we implemented for primary THA and TKA patients and to analyze its impact on rates of PJI and readmission.Methods: Our bundle protocol for primary THA and TKA patients is conceptually organized about 3 chronological periods of patient care: preoperative, intraoperative, and postoperative. The institutional total joint database and electronic medical record were reviewed to identify all primary THAs and TKAs performed in the 2 years before and following implementation of the bundle. Rates of PJI and readmission were then calculated.Results: Thirteen of 908 (1.43%) TKAs performed before the bundle became infected compared to only 1 of 890 (0.11%) TKAs performed after bundle implementation (P = .0016). Ten of 641 (1.56%) THAs performed before the bundle became infected, which was not statistically different from the 4 of 675 (0.59%) THAs performed after the bundle that became infected (P = .09).Conclusion: The bundle protocol we describe significantly reduced PJIs at our institution, which we attribute to patient selection, optimization of modifiable risk factors, and our perioperative protocol. We believe the bundle concept represents a systematic way to improve patient outcomes and increase value in total joint arthroplasty. [ABSTRACT FROM AUTHOR]

• Persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB) significantly increases mortality risk • There is a lack of data for the ideal management of persistent MRSAB • A combination of daptomycin plus ceftaroline (DAP/CPT) has been successfully used in persistent MRSAB • Switching to DAP/CPT after 1 week of persistent MRSAB did not lead to better outcomes This study aimed to evaluate both efficacy and safety of combination therapy with daptomycin plus ceftaroline (DAP/CPT) versus alternative therapy in the treatment of persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). This retrospective, single-centre study investigated adult patients who underwent a change in antibiotic therapy for persistent MRSAB. Daptomycin plus ceftaroline was compared with alternative therapy after initial treatment with vancomycin or DAP monotherapy was modified. The primary outcome was in-hospital mortality, and several secondary efficacy and safety outcomes were evaluated. A total of 68 patients with persistent MRSAB had initial therapy switched to DAP/CPT (n = 43) or alternative therapy (n = 25). In-hospital mortality was similar with DAP/CPT versus alternative therapy (16.3% vs. 16%; P = 1.0). On average, the total duration of bacteraemia was numerically 1 day less in patients switched to DAP/CPT (11.4 days vs. 12.5 days; P = 0.5). Daptomycin plus ceftaroline was de-escalated in 81% of patients after receiving combination therapy for an average of 12.5 days. Secondary outcomes, including rates of adverse events and emergence of antimicrobial resistance, were similar between the two groups. Switching to DAP/CPT after approximately 1 week of persistent MRSA bacteraemia may result in similar clinical outcomes when compared with alternative therapy. Rates of adverse events and emergence of antimicrobial resistance were low without a statistically significant difference observed between DAP/CPT and alternative therapy. These findings, as well as the impact of earlier switch or prolonged treatment with the combination, require further investigation. [ABSTRACT FROM AUTHOR]

Background: Range of motion (ROM) is important for functional outcome after total knee arthroplasty (TKA); however, some patients hesitate to maximize their ROM postoperatively. The Tampa Scale of Kinesiophobia (TSK) measures patients' fear of movement. The primary purpose of this investigation was to determine whether TSK scores correlated with decreased ROM after primary TKA. A secondary purpose was to determine whether biofeedback could increase ROM after TKA.Methods: Patients were recruited from the senior author's practice between June 2011 and March 2013. A clinical photograph was taken of each patient's knee in maximum passive flexion in the operating room immediately following closure. Patients were randomized to the control or photograph group before incision. A linear mixed model was implemented to determine whether the TSK score and viewing the photo correlated to ROM.Results: Seventy-nine patients were analyzed for correlation between the TSK score and the knee ROM. Sixty patients were analyzed for correlation between viewing the clinical photograph and the knee ROM. The linear mixed model demonstrated a significant negative correlation between the TSK score and both active (β = -0.47, P < .01) and passive (β = -0.66, P < .001) knee flexions. There was a trend toward decreased knee flexion among patients shown their clinical photograph.Conclusion: The TSK was developed as a tool to identify patients at risk for maladaptive responses to painful stimuli. Our data suggest that the TSK may help arthroplasty surgeons identify patients at risk for decreased ROM after TKA. Showing patients a clinical photograph failed to increase ROM after TKA. [ABSTRACT FROM AUTHOR]

This study sought to identify specific costs for 90-day readmissions following total hip arthroplasty in a bundled payment system. Hospital billing records revealed 139 readmissions (8.93%) in 1781 patients. Mean costs for surgical readmissions were greater (P=0.002) compared with medical reasons, but similar for Medicare/Medicaid and private payers (P=0.975). Costs for imaging, laboratory workup, medication and transfusions, and hospital cost correlated with increasing SOI (P<0.05). Patients transferred from outside hospitals or rehabilitation had higher hospital (P=0.006) and operating room costs (P=0.001) compared to patients admitted from ED or clinic. Hospitals that care for complex patients with Medicare/Medicaid may experience increased costs for unplanned 90-day readmissions highlighting considerations for payer mix. [ABSTRACT FROM AUTHOR]

Abstract: A bis-amide antagonist of Smoothened, a seven-transmembrane receptor in the Hedgehog signaling pathway, was discovered via high throughput screening. In vitro and in vivo experiments demonstrated that the bis-amide was susceptible to N-acyl transferase mediated amide scission. Several bioisosteric replacements of the labile amide that maintained in vitro potency were identified and shown to be metabolically stable in vitro and in vivo. [Copyright &y& Elsevier]

Abstract: Syntheses and SAR studies of 3,3-bisaryloxindole analogues provided potent mineralocorticoid receptor (MR) antagonists that were selective over other steroid nuclear hormone receptors. [Copyright &y& Elsevier]

The palladium(II) complex [PdCl{P(OC 6 H 4 NMe) 2 }{P(OC 6 H 4 NMe)OC 6 H 4 NHMe}] undergoes rapid interconversion between diastereomers by inversion of a displaced amine ligand. • A Pd(II) complex with a hydrophosphorane coordinated in both P(V) and P(III) forms. • A crystal structure of the Pd(II) complex was obtained. • The Pd(II) complex is comprised of 4 different diastereomers (each a pair of enantiomers), which are identified by 31P{1H} and 1H NMR. • At room temperature, there is rapid interconversion between pairs of diastereomers and the various possible mechanisms for this are investigated, using variable temperature 31P{1H} NMR and DFT studies. • The proposed mechanism of interconversion is the inversion of a dissociated amine ligand. [PdCl{P(OC 6 H 4 NMe) 2 }{P(OC 6 H 4 NMe)OC 6 H 4 NHMe}] was prepared by the reaction of LiP(OC 6 H 4 N(CH 3)) 2 with [PdCl 2 {P(OC 6 H 4 N(CH 3))(OC 6 H 4 NH(CH 3))}]. The expected four diastereomers of the complex are observed in the 31P{1H} and 1H NMR at −20 °C, however at room temperature there is fast exchange between pairs of diastereomers. The energetics of three possible mechanisms by which the diastereomers may be interconverting, are considered by DFT studies: displacement of the coordinated amine, followed by inversion at the nitrogen atom; displacement of the coordinated phosphoramidite, followed by inversion at the phosphorus atom; Berry pseudorotation at the coordinated phosphoranide. The inversion of a dissociated amine appears to be the most likely mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Sphingosine-1-phosphate (S1P) signaling plays a vital role in mitogenesis, cell migration and angiogenesis. Sphingosine kinases (SphKs) catalyze a key step in sphingomyelin metabolism that leads to the production of S1P. There are two isoforms of SphK and observations made with SphK deficient mice show the two isoforms can compensate for each other’s loss. Thus, inhibition of both isoforms is likely required to block SphK dependent angiogenesis. A structure based approach was used to design and synthesize a series of SphK inhibitors resulting in the identification of the first potent inhibitors of both isoforms of human SphK. Additionally, to our knowledge, this series of inhibitors contains the only sufficiently potent inhibitors of murine SphK1 with suitable physico-chemical properties to pharmacologically interrogate the role of SphK1 in rodent models and to reproduce the phenotype of SphK1 (−/−) mice. [Copyright &y& Elsevier]

Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH 1–34 ) can promote healing of Cox-2 -deficient fractures, we performed detailed in vivo analyses using a murine stabilized tibia fracture model. Periosteal progenitor cell proliferation as well as bony callus formation was markedly reduced in Cox-2 −/− mice at day 10 post-fracture. Remarkably, intermittent PTH 1–34 administration increased proliferation of periosteal progenitor cells, restored callus formation on day 7, and enhanced bone formation on days 10, 14 and 21 in Cox-2- deficient mice. PTH 1–34 also increased biomechanical torsional properties at days 10 or 14 in all genotypes, consistent with enhanced bony callus formation by radiologic examinations. To determine the effects of intermittent PTH 1–34 for callus remodeling, TRAP staining was performed. Intermittent PTH 1–34 treatment increased the number of TRAP positive cells per total callus area on day 21 in Cox-2 −/− fractures. Taken together, the present findings indicate that intermittent PTH 1–34 treatment could compensate for COX-2 deficiency and improve impaired fracture healing in Cox-2- deficient mice. [ABSTRACT FROM AUTHOR]

The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor β (TRβ) agonists is described. Compounds with >50× binding selectivity for TRβ over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo. [ABSTRACT FROM AUTHOR]