Endometrial SUSD2+ Mesenchymal Stem/Stromal Cells in Tissue Engineering: Advances in Novel Cellular Constructs for Pelvic Organ Prolapse.

Cellular therapy is an emerging field in clinical and personalised medicine. Many adult mesenchymal stem/progenitor cells (MSC) or pluripotent derivatives are being assessed simultaneously in preclinical trials for their potential treatment applications in chronic and degenerative human diseases. Endometrial mesenchymal stem/progenitor cells (eMSC) have been identified as clonogenic cells that exist in unique perivascular niches within the uterine endometrium. Compared with MSC isolated from other tissue sources, such as bone marrow and adipose tissue, eMSC can be extracted through less invasive methods of tissue sampling, and they exhibit improvements in potency, proliferative capacity, and control of culture-induced differentiation. In this review, we summarize the potential cell therapy and tissue engineering applications of eMSC in pelvic organ prolapse (POP), emphasising their ability to exert angiogenic and strong immunomodulatory responses that improve tissue integration of novel surgical constructs for POP and promote vaginal tissue healing.

The modified International Society of Urological Pathology system improves concordance between biopsy and prostatectomy tumour grade.

OBJECTIVES: To assess the concordance between biopsy and radical prostatectomy (RP) specimens using the 2005 Gleason score (GS) and the International Society of Urological Pathology (ISUP) 2014/World Health Organization 2016 modified system, accounting for the introduction of transperineal biopsy and pre-biopsy multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: Between 2002 and 2019, we identified 2431 patients with paired biopsy and RP histopathology from a prospectively recorded and maintained prostate cancer database. Biopsy specimens were graded according to the 2005 GS or ISUP 2014 modified system, according to the year of diagnosis. Multivariable logistic regression analysis was conducted to retrospectively assess the impact of prostate-specific antigen (PSA), PSA density, age, pre-biopsy mpMRI, and biopsy method, on the rate of upgraded disease. The kappa coefficient was used to establish the degree of change in concordance between groups. RESULTS: Overall, 24% of patients had upgraded disease and 8% of patients had downgraded disease when using the modified ISUP 2014 criteria. Agreement in the updated ISUP 2014 cohort was 68%, compared with 55% in the 2005 GS group, which was validated by a kappa coefficient that was good (k = 0.5 ± 0.4) and poor (k = 0.3 ± 0.1), respectively. In multivariable models, a change in grading system independently improved overall disease concordance (P = 0.02), and there were no other co-segregated patient or pathological factors such as PSA, total number of cores, maximum cancer length, biopsy route or the use of mpMRI that impacted this finding. CONCLUSION: The 2014 ISUP modifed system improves overall concordance between biopsy and surgical specimens, and thus allows more accurate prognostication and management in high-grade disease, independent of more extensive prostate sampling and the use of mpMRI.

Future trends in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection: An in-depth review of newer antibiotics active against an enduring pathogen.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major public health problem. Vancomycin and teicoplanin have been in clinical use for several decades but their drawbacks are well described. In the last 10 years, several antibiotics have been made available for clinical use. Daptomycin and linezolid have been extensively used during this period. Other agents such as ceftaroline, ceftobiprole, dalbavancin, oritavancin, tedizolid and telavancin have been approved by regulatory agencies since 2009. Many others, such as the newer tetracyclines, fluoroquinolones, oxazolidinones and pleuromutilins, are in various stages of development. In addition, an ongoing multicentre trial is investigating the role of combination of vancomycin or daptomycin with ß-lactam antibiotics. This review discusses the role of the newer antibiotics, reflecting the views of the 6th MRSA Consensus Conference meeting of the International Society of Chemotherapy MRSA Working Group that took place in 2016.

The complex relationship between CD4 count, HIV viral load, trimethoprim-sulfamethoxazole prophylaxis, and skin-and-soft-tissue infection risk in patients with HIV: insights from a causal diagram and simulation study.

Skin and soft tissue infection (SSTIs) due to Staphylococcus aureus, particularly community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), are common in human immunodeficiency virus (HIV)-infected populations in the United States. Studies have differed as to the importance of epidemiological and immunological factors in this relationship, and have employed conflicting strategies for variable selection in multivariate analyses. Developments in causal inference methods in epidemiology have emerged in the last decade to clarify relationships between variables and identify appropriate variables to include in and exclude from multivariate analysis. In this paper, we develop a causal diagram to clarify the pathways linking CA-MRSA and HIV. We focus on the role played by trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, prescribed to many severely immunocompromised HIV patients and potentially protective against SSTIs, which both mediates and moderates the relationship between immunological parameters and SSTI risk. We demonstrate, using simulated data, that statistical models may yield biased results if they do not account for how HIV viral load may also be a marker of adherence to TMP-SMX prophylaxis. We conclude with a proposed causal model that includes both the epidemiological as well as immunological factors that may explain the increased risk of initial and recurrent SSTI risk in HIV-infected populations.

Predictors of skin and soft tissue infections in HIV-infected outpatients in the community-associated methicillin-resistant Staphylococcus aureus era.

Skin and soft tissue infections (SSTIs) are common in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) among human immunodeficiency virus (HIV)-infected patients, but the risk factors are not well defined. We sought to elucidate the risk factors for SSTI occurrence in an HIV cohort. This investigation was a retrospective, single-center cohort study, carried out during the period 2005-2009. In this cohort of 511 HIV-infected individuals, 133 SSTIs occurred in 87 individuals over 1,228.6 person-years of follow-up, for an incidence of 108 SSTIs/1,000 person-years [95 % confidence interval (CI) 87-135]. The incidence declined significantly over time (p < 0.01). In a multivariable Cox regression, diabetes [hazard ratio (HR) 2.01; 95 % CI 1.04-3.89], psoriasis (HR 5.77; 95 % CI 1.86-17.9), lymphedema (HR 6.84; 95 % CI 2.59-18.1), intravenous catheter presence (HR 3.38; 95 % CI 1.00-11.5), and HIV viral load greater than 1,000 copies/mL (HR 2.13; 95 % CI 1.33-3.41) were most strongly associated with development of the first SSTI. Trends toward an association between SSTI risk and Medicaid insurance (HR 1.67; 95 % CI 0.98-2.83) and sexually transmitted disease during follow-up (HR 1.66; 0.99-2.78) were present. CD4+ count and trimethoprim-sulfamethoxazole use were not associated with SSTI risk. HIV-infected individuals are at high risk for SSTIs. In a primarily urban, African-American cohort, we found that a number of immunologic and demographic factors were associated with SSTI risk.

Prior infections are associated with increased mortality from subsequent blood-stream infections among patients with hematological malignancies.

Many patients who are evaluated and treated for sepsis have histories of recent infections. The prognostic implications of surviving an infectious process are not well understood. We undertook this study to determine the clinical impact of prior infections among patients with hematological malignancies, a population at high risk for developing and dying from sepsis. The medical records of 203 patients with hematological malignancies and blood-stream infections admitted over a 3-year period to an urban teaching hospital were retrospectively reviewed. The 30-day mortality after blood-stream infection in these high-risk patients was 24 %. There were 46 patients (23 %) who had inpatient infections in the 90 days prior to the index blood-stream infection. History of recent infection portended worse prognosis from blood-stream infection under multivariable analysis [odds ratio (OR) 2.60, p = 0.04, 95 % confidence interval (CI) 1.04-6.47]. There were 86 patients (42 %) who had subsequent infections in the first 90 days after the index blood-stream infection. Patients with subsequent infections had greater mortality during days 91-365 than patients without subsequent infections [hazard ratio (HR) 1.97, p = 0.02, 95 % CI 1.13-3.44]. Recent infections prognosticate worse outcomes from subsequent blood-stream infections for this high-risk population. Further research into the clinical and biochemical reasons for this observation may lead to targets for intervention, and, ultimately, improvements in long-term mortality from sepsis.

The economic burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).

The economic impact of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) remains unclear. We developed an economic simulation model to quantify the costs associated with CA-MRSA infection from the societal and third-party payer perspectives. A single CA-MRSA case costs third-party payers $2277-$3200 and society $7070-$20 489, depending on patient age. In the United States (US), CA-MRSA imposes an annual burden of $478 million to 2.2 billion on third-party payers and $1.4-13.8 billion on society, depending on the CA-MRSA definitions and incidences. The US jail system and Army may be experiencing annual total costs of $7-11 million ($6-10 million direct medical costs) and $15-36 million ($14-32 million direct costs), respectively. Hospitalization rates and mortality are important cost drivers. CA-MRSA confers a substantial economic burden on third-party payers and society, with CA-MRSA-attributable productivity losses being major contributors to the total societal economic burden. Although decreasing transmission and infection incidence would decrease costs, even if transmission were to continue at present levels, early identification and appropriate treatment of CA-MRSA infections before they progress could save considerable costs.