Bone Tissue Properties Measurement by Reference Point Indentation in Glucocorticoid‐Induced Osteoporosis

Glucocorticoids, widely used in inflammatory disorders, rapidly increase bone fragility and, therefore, fracture risk. However, common bone densitometry measurements are not sensitive enough to detect these changes. Moreover, densitometry only partially recognizes treatment‐induced fracture reductions in osteoporosis. Here, we tested whether the reference point indentation technique could detect bone tissue property changes early after glucocorticoid treatment initiation. After initial laboratory and bone density measurements, patients were allocated into groups receiving calcium + vitamin D (Ca+D) supplements or anti‐osteoporotic drugs (risedronate, denosumab, teriparatide). Reference point indentation was performed on the cortical bone layer of the tibia by a handheld device measuring bone material strength index (BMSi). Bone mineral density was measured by dual‐energy X‐ray absorptiometry (DXA). Although Ca+D‐treated patients exhibited substantial and significant deterioration, risedronate‐treated patients exhibited no significant change, and both denosumab‐ and teriparatide‐treated participants exhibited significantly improved BMSi 7 weeks after initial treatment compared with baseline; these trends remained stable for 20 weeks. In contrast, no densitometry changes were observed during this study period. In conclusion, our study is the first to our knowledge to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation after treatment with osteoporosis therapies in patients newly exposed to glucocorticoids. © 2015 American Society for Bone and Mineral Research.     

Graft rinse prior to reperfusion in liver transplantation: literature review and online survey within the Eurotransplant community

Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty‐four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community.     

Transperineal template‐guided mapping biopsy of the prostate

Accurate diagnosis of prostate cancer has eluded clinicians for decades. With our current understanding of prostate cancer, urologists should devise and confidently present the available treatment options – active surveillance/radical treatment/focal therapy to these patients. The diagnostic modalities used for prostate cancer have the dual problem of false negativity and overdiagnosis. Various modifications in the prostate biopsy techniques have increased the accuracy of cancer detection, but we are still far from an ideal diagnostic technique. Transperineal template‐guided mapping biopsy of the prostate is an exhaustive biopsy technique that has been improvised over the past decade, and has shown superior results to other available modalities. We have carried out a PubMed search on the available experiences on this diagnostic modality, and along with our own experiences, we present a brief review on transperineal template‐guided mapping biopsy of the prostate.     

Effectiveness,satisfaction and compliance with imiquimod in the treatment of external anogenital warts

This study aims to evaluate the effectiveness of imiquimod treatment of external anogenital warts and analyse its possible relationship with patient treatment satisfaction and compliance under conditions of routine clinical practice. An observational, prospective and multi-centre study was conducted in a cohort of 559 patients with external anogenital warts. Imiquimod 5% cream was administered three times a week until the end of treatment (complete wart clearance or up to a maximum of 16 weeks). Effectiveness and compliance were evaluated at four weeks and again at the end of treatment, when satisfaction was also assessed. Complete wart clearance was experienced by 66.6% of patients at the end of treatment and a 50% or greater reduction in total wart area occurred in 79.5%. Imiquimod was more effective in patients who were more satisfied and compliant with treatment. Under conditions of routine clinical practice, imiquimod is an effective treatment for external anogenital warts.     

Marcadores de daño miocárdico en la predicción del pronóstico a corto plazo de los pacientes con COVID-19

Introduction and objectivesCOVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19.MethodsWe included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT > 14 ng/L, the upper 99th percentile. Levels of NT-proBNP > 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV).ResultsCardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87).ConclusionsMyocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.     

The differential effects of the gonadotropin receptors on aromatase expression in primary cultures of immature rat granulosa cells are highly dependent on the density of receptors expressed and the activation of the inositol phosphate cascade

Signaling pathways mediating the divergent effects of FSH and LH on aromatase in immature rat granulosa cells were studied by infecting cells with increasing amounts of adenoviral vectors for the human LH receptor (hLHR) or FSH receptor (hFSHR). Increasing amounts of Ad-hLHR, used at a multiplicity of infection (MOI) of 20 or 200 viable viral particles/cell, increased human chorionic gonadotropin (hCG) binding and hCG-induced cAMP and Akt phosphorylation, but inositol phosphates only increased in response to hCG in cells infected with 200 MOI Ad-hLHR. In contrast, hCG increased aromatase expression in cells infected with 20, but not in cells infected with 200, MOI Ad-hLHR. Cells infected with 20 or 200 MOI Ad-hFSHR showed increased hFSH binding and hFSH-induced Akt phosphorylation, but the hFSH-induced cAMP response was unchanged relative to control cells. However, hFSH was able to stimulate the inositol phosphate cascade in the Ad-hFSHR-infected cells, and the hFSH induction of aromatase was abolished. We also found that activation of C kinase or expression of a constitutively active form of Galphaq inhibited the induction of aromatase by hFSH or 8Br-cAMP. We conclude that the differential effects of FSH and LH on aromatase in immature granulosa cells are highly dependent on gonadotropin receptor density and on the signaling pathways activated. We propose that aromatase is induced by common signals generated by activation of the FSHR and LHR (possibly cAMP and Akt) and that the activation of the inositol phosphate cascade in cells expressing a high density of LHR or FSHR antagonizes this induction.     

Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae at a Single Institution: Insights into Endemicity from Whole-Genome Sequencing

The global emergence of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) multilocus sequence type ST258 is widely recognized. Less is known about the molecular and epidemiological details of non-ST258 K. pneumoniae in the setting of an outbreak mediated by an endemic plasmid. We describe the interplay of bla_KPC plasmids and K. pneumoniae strains and their relationship to the location of acquisition in a U.S. health care institution. Whole-genome sequencing (WGS) analysis was applied to KPC-Kp clinical isolates collected from a single institution over 5 years following the introduction of bla_KPC in August 2007, as well as two plasmid transformants. KPC-Kp from 37 patients yielded 16 distinct sequence types (STs). Two novel conjugative bla_KPC plasmids (pKPC_UVA01 and pKPC_UVA02), carried by the hospital index case, accounted for the presence of bla_KPC in 21/37 (57%) subsequent cases. Thirteen (35%) isolates represented an emergent lineage, ST941, which contained pKPC_UVA01 in 5/13 (38%) and pKPC_UVA02 in 6/13 (46%) cases. Seven (19%) isolates were the epidemic KPC-Kp strain, ST258, mostly imported from elsewhere and not carrying pKPC_UVA01 or pKPC_UVA02. Using WGS-based analysis of clinical isolates and plasmid transformants, we demonstrate the unexpected dispersal of bla_KPC to many non-ST258 lineages in a hospital through spread of at least two novel bla_KPC plasmids. In contrast, ST258 KPC-Kp was imported into the institution on numerous occasions, with other bla_KPC plasmid vectors and without sustained transmission. Instead, a newly recognized KPC-Kp strain, ST941, became associated with both novel bla_KPC plasmids and spread locally, making it a future candidate for clinical persistence and dissemination.     

The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees

Polycystic kidney disease (PKD) is one of the most common life-threatening genetic diseases. Jared J. Grantham, M.D., has done more than any other individual to promote PKD research around the world. However, despite decades of investigation there is still no approved therapy for PKD in the United States. In May 2014, the University of Kansas Medical Center hosted a symposium in Kansas City honoring the occasion of Dr. Grantham''s retirement and invited all the awardees of the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease to participate in a forward-thinking and interactive forum focused on future directions and innovations in PKD research. This article summarizes the contributions of the 12 Kaplan awardees and their vision for the future of PKD research.