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Objective: To describe the impact of empiric appropriate treatment and the risk factors associated with mortality in patients with bacteremia by E. coli, K. pneumoniae and P. mirabilis producing ESBL. Methods: Data were reviewed in an 8-year retrospective study, and 128 bacteremias were found: 80 caused by E. coli (62.5%), 28 by K. pneumoniae (21.9%) and 20 by P. mirabilis (18.6%). Results: The initial antibiotic treatment, administered within 72 h after the first positive blood culture, was appropriate with carbapenems or other antimicrobial agents with documented in vitro sensitivity in 53.8 and 16% of patients, respectively. The overall mortality 21 days after diagnosis was 17.2%, and it was 14.9 and 35.2% for patients adequately and inadequately treated, respectively. At univariate analysis the p value for mortality with and without appropriate treatment was 0.05, and significant differences were found only for previous positive blood cultures ( p = 0.004) and presence of septic shock at diagnosis ( p = 0.006). Conclusion: In this case series there was a high rate of initial appropriate empiric treatment, and only a marginal impact on mortality was found with regard to appropriate and inappropriate treatment. This report shows that the knowledge of ESBL-producing characteristics varies widely among the different case series for reasons that still have to be clarified. [ABSTRACT FROM AUTHOR]

Introduction: Effective pain management is vital in orthopaedic care, impacting postoperative recovery and patient well-being. This study aimed to discern national and regional pain prescription trends among orthopaedic surgeons through Medicare claims data, using geospatial analysis to ascertain opioid and nonopioid usage patterns across the United States., Methods: Physician-level Medicare prescription databases from 2016 to 2020 were filtered to orthopaedic surgeons, and medications were categorized into opioids, muscle relaxants, anticonvulsants, and NSAIDs. Patient demographics were extracted from a Medicare provider demographic data set, while county-level socioeconomic metrics were obtained primarily from the American Community Survey. Geospatial analysis was conducted using Geoda software, using Moran I statistic for cluster analysis of pain medication metrics. Statistical trends were analyzed using linear regression, Mann-Whitney U test, and multivariate logistic regression, focusing on prescribing rates and hotspot/coldspot identification., Results: Analysis encompassed 16,505 orthopaedic surgeons, documenting more than 396 million days of pain medication prescriptions: 57.42% NSAIDs, 28.57% opioids, 9.84% anticonvulsants, and 4.17% muscle relaxants. Annually, opioid prescriptions declined by 4.43% ( P < 0.01), while NSAIDs rose by 3.29% ( P < 0.01). Opioid prescriptions dropped by 210.73 days yearly per surgeon ( P < 0.005), whereas NSAIDs increased by 148.86 days ( P < 0.005). Opioid prescriptions were most prevalent in the West Coast and Northern Midwest regions, and NSAID prescriptions were most prevalent in the Northeast and South regions. Regression pinpointed spine as the highest and hand as the lowest predictor for pain prescriptions., Discussion: On average, orthopaedic surgeons markedly decreased both the percentage of patients receiving opioids and the duration of prescription. Simultaneously, the fraction of patients receiving NSAIDs dramatically increased, without change in the average duration of prescription. Opioid hotspots were located in the West Coast, Utah, Colorado, Arizona, Idaho, the Northern Midwest, Vermont, New Hampshire, and Maine. Future directions could include similar examinations using non-Medicare databases., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Background: The utilization of robotic knee arthroplasty (RKA) continues to increase across the United States. The aim of this geospatial analysis was to elucidate if RKA is distributed uniformly across the United States or if disparities exist in patient access., Methods: Publicly available provider-finding functions for 5 major manufacturers of RKA systems were used to obtain the practice locations of surgeons performing RKA along with their associated RKA system manufacturer. The average travel distance for each county to the nearest RKA surgeon was calculated and Moran's index clustering analysis was used to find hotspots and coldspots of RKA access. A logistic regression model was used to identify the predictive odds ratios between robotic hotspots and coldspots with county-level sociodemographic variables. Of the 34,216 currently practicing orthopedic surgeons in 2022, 2,571 have access to robotic assistance for knee arthroplasty., Results: Hotspots of increased travel time were predominantly in West South Central and West North Central census regions. Hotspots were significantly more rural and consisted of predominantly White populations, with lower median income and health insurance coverage., Conclusions: The results of the current study align with existing literature, demonstrating absolute geographic access disparities for rural and economically disadvantaged populations. Additionally, relative access disparities persist for minority populations and individuals with high comorbidity burdens residing in urban areas., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Monkeypox (MPOX) is a zoonotic disease that affects humans and other primates, resulting in a smallpox-like illness. It is caused by monkeypox virus (MPXV), which belongs to the Poxviridae family. Clinically manifested by a range of cutaneous and systemic findings, as well as variable disease severity phenotypes based on the genetic makeup of the virus, the cutaneous niche and respiratory mucosa are the epicenters of MPXV pathogenicity. Herein, we describe the ultrastructural features of MPXV infection in both human cultured cells and cutaneous clinical specimens collected during the 2022-2023 MPOX outbreak in New York City that were revealed through electron microscopy. We observed typical enveloped virions with brick-shaped morphologies that contained surface protrusions, consistent with the classic ultrastructural features of MPXV. In addition, we describe morpho-functional evidence that point to roles of distinct cellular organelles in viral assembly during clinical MPXV infection. Interestingly, in skin lesions, we found abundant melanosomes near viral assembly sites, particularly in the vicinity of mature virions, which provides further insight into virus-host interactions at the subcellular level that contribute to MPXV pathogenesis. These findings not only highlight the importance of electron microscopic studies for further investigation of this emerging pathogen but also in characterizing MPXV pathogenesis during human infection., (© 2023 Wiley Periodicals LLC.)

(1) Background: The objective of this in vitro study is to evaluate the marginal accuracy of crowns created by CAD/CAM. (2) Methods: A customized chrome-cobalt (Cr-Co) implant abutment simulating a maxillary right first molar was fixed in a hemi-maxillary stone model and scanned. In total, 27 crowns were fabricated, including 9 lithium disilicate crowns, 9 composite crowns, and 9 zirconia crowns. The measurements were determined by scanning electron microscopy. Descriptive analysis was performed using the mean and standard deviation, while the Kruskal-Wallis test was performed to determine whether the marginal discrepancies were significantly different between each group ( p < 0.05). (3) Results: The lowest marginal gap value was reported for zirconia (21.45 ± 12.58 µm), followed by composite (44.7 ± 24.96 µm) and lithium disilicate (62.28 ± 51.8 µm). The Kruskal-Wallis tests revealed a statistically significant difference ( p -value < 0.05) in the mean marginal gaps between different materials. (4) Conclusions: The proposed digital workflow can be a viable alternative for fixed prosthetic rehabilitations. The best performance in terms of marginal gap was achieved by zirconia crowns, but all three materials demonstrate marginal closure below the clinically accepted threshold value (120 µm). Clinical significance: although significant differences were reported, the investigated CAD/CAM materials showed clinically acceptable marginal gaps.

Monkeypox virus (MPXV) is a zoonotic orthopoxvirus within the Poxviridae family. MPXV is endemic to Central and West Africa. However, the world is currently witnessing an international outbreak with no clear epidemiological links to travel or animal exposure and with ever-increasing numbers of reported cases worldwide. Here, we evaluated and validated a new, sensitive, and specific real-time PCR-assay for MPXV diagnosis in humans and compare the performance of this novel assay against a Food & Drug Administration-cleared pan-Orthopox RT-PCR assay. We determined specificity, sensitivity, and analytic performance of the PKamp™ Monkeypox Virus RT-PCR assay targeting the viral F3L-gene. In addition, we further evaluated MPXV-PCR-positive specimens by viral culture, electron microscopy, and viral inactivation assays. The limit of detection was established at 7.2 genome copies/reaction, and MPXV was successfully identified in 20 clinical specimens with 100% correlation against the reference method with 100% sensitivity and specificity. Our results demonstrated the validity of this rapid, robust, and reliable RT-PCR assay for specific and accurate diagnosis of MPXV infection in human specimens collected both as dry swabs and in viral transport media. This assay has been approved by NYS Department of Health for clinical use., (© 2022 Wiley Periodicals LLC.)

Background: The United States accounts for the majority of prescription opioids consumed worldwide. Recent literature has focused on opioid prescribing patterns among orthopedic surgeons; however, public and patient expectations about postoperative opioid use remain understudied. Purpose : We sought to explore public perceptions of opioid use after elective orthopedic surgery. Methods : We posted a 32-question survey on Amazon Mechanical Turk (MTurk), an online platform with over 500,000 unique registered users that is a validated tool for collecting survey responses in medical research. The survey asked about attitudes regarding opioid use after elective orthopedic surgery and sociodemographic factors, as well as validated assessments of health literacy and patient engagement. Results : Of 727 respondents who completed surveys, nearly half (46%) said they would prefer nonopioid pain medication after elective orthopedic surgery, although 86% said they would expect to be prescribed opioids for 1 week to 1 month postoperatively. About half said they would expect to be prescribed extra opioid medication in case of unexpected pain following surgery, and 50% reported that they would save their pills to treat future pain. Approximately 63% said they would understand their surgeon's opioid weaning, but over ⅓ said weaning would lead to decreased satisfaction with their surgeon. Roughly ⅔ reported that pain control after surgery would directly affect their opinion of the surgeon. Conclusions : Our survey found that some members of the general public reported expectations regarding postoperative opioid prescribing that could lead to decreased patient satisfaction. These findings suggest the need for further research on the value of preoperative patient education in pain management, on patient expectations of pain control after elective surgery, and on the use of opioids following orthopedic surgery., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Carbapenemase-KPC producing Klebsiella pneumoniae (CP-Kp) infection represents a serious threat to solid organ transplant (SOT). All patients admitted between 1 May 2011 and 31 August 2014 undergoing SOT were included in the retrospective study. The primary outcomes included a description of the association of enteric colonization and invasive infections by CP- Kp with one-year mortality. Secondary outcomes were the study of risk factors for colonization and invasive infections by CP- Kp . Results: A total of 5.4% (45/828) of SOT recipients had at least one positive rectal swab for CP- Kp , with most (88.9%) occurring after transplantation. 4.5% (35/828) of patients developed a CP- Kp -related invasive infection, with 68.6% (24/35) being previously colonized. The 1-year mortality was 31.1% in patients with enteric colonization with CP-Kp and, it was 51.4% among patients with CP- Kp -related invasive infections. At univariate analysis, colonization, invasive infections, sepsis, severe sepsis, and septic shock were significantly associated with 1-year mortality. At multivariate analysis, only invasive infections and the combination of sepsis, severe sepsis, or septic shock were significantly associated with 1-year mortality, whereas gastrointestinal colonization was significantly associated with survival. In this population, the 1-year mortality was significantly associated with invasive infections; otherwise, gastrointestinal colonization was not associated with increased 1-year mortality.

Objectives: Tenofovir DF (TDF) remains one of the preferred backbone agents for naïve HIV patients starting antiretroviral treatment (ART). The impact of TDF on renal function and metabolic parameters may vary by anchor agent. We investigated the impact of TDF in combination with 3 different integrase inhibitors on tubular and glomerular function, and metabolic parameters in ART-naïve patients. Methods: Sixty patients with normal renal function were randomised (20 per arm) to TDF/emtricitabine (FTC) plus either raltegravir (RAL) (400 mg b.d.), dolutegravir (DTG) or elvitegravir/cobicistat (EVG/c) for 48 weeks. Results: 57 patients completed the study. Significant increases in RBP/creatinine ratio at week 24 were seen in all arms [RAL +4.7 μg/mmol (CI 0.43 to 8.98, p  = 0.032); DTG +4.96 μg/mmol (CI 0.77 to 9.15, p  = 0.021); EVG/c +6.95 μg/mmol (CI 2.53 to 11.36, p  = 0.002)], although this was not sustained to week 48 in the RAL arm. Similar changes across the arms were observed for urinary α1microglobulin (RAL +6.20 mg/L, p  = 0.030; DTG +6.30 mg/L, p  = 0.025; EVG/c +8.15 mg/L, p  = 0.003). Urinary β2microglobulin significantly increased at week 24 with DTG and EVG/c but remained unchanged in the RAL arm. Glomerular filtration measured with CKD-EPI creatinine-cystatin C increased significantly in the RAL arm at week 24 through 48 but declined modestly in other two arms. Total and LDL cholesterol decreased in the RAL arm, but increased in the EVG/c arm, with no significant changes in the DTG arm. Weight increased significantly from baseline with DTG but not RAL or EVG/c. Conclusion: INSTIs in combination with TDF/FTC impact differently on tubular microproteinuria, eGFR, metabolic markers and weight. Use of TDF/FTC with RAL had the least tubular effects and the most favorable metabolic profile.

The demand for revision total joint arthroplasties (rTJAs) is expected to increase as the age of the population continues to rise. Accurate cost data regarding hospital expenses for differing age groups are needed to deliver optimal care within value-based healthcare (VBHC) models. The aim of this study was to compare the total in-hospital costs by decadal groups following rTJA and to determine the primary drivers of the costs for these procedures. Time-driven activity-based costing (TDABC) was used to capture granular hospital costs. A total of 551 rTJAs were included in the study, with 294 sexagenarians, 198 septuagenarians, and 59 octogenarians and older. Sexagenarians had a lower ASA classification (2.3 vs. 2.4 and 2.7; p < 0.0001) and were more often privately insured (66.7% vs. 24.2% and 33.9%; p < 0.0001) as compared to septuagenarians and octogenarians and older, respectively. Sexagenarians were discharged to home at a higher rate (85.3% vs. 68.3% and 34.3%; p < 0.0001), experienced a longer operating room (OR) time (199.8 min vs. 189.7 min and 172.3 min; p = 0.0195), and had a differing overall hospital length of stay (2.8 days vs. 2.7 days and 3.6 days; p = 0.0086) compared to septuagenarians and octogenarians and older, respectively. Sexagenarians had 7% and 23% less expensive personnel costs from post-anesthesia care unit (PACU) to discharge ( p < 0.0001), and 1% and 24% more expensive implant costs ( p = 0.077) compared to septuagenarians and octogenarians and older, respectively. Sexagenarians had a lower total in-hospital cost for rTJAs by 0.9% compared to septuagenarians but 12% more expensive total in-hospital costs compared to octogenarians and older ( p = 0.185). Multivariate linear regression showed that the implant cost (0.88389; p < 0.0001), OR time (0.12140; p < 0.0001), personnel cost from PACU through to discharge (0.11472; p = 0.0007), and rTHAs (-0.03058; p < 0.0001) to be the strongest associations with overall costs. Focusing on the implant costs and OR times to reduce costs for all age groups for rTJAs is important to provide cost-effective VBHC.

Disease due to pulmonary Aspergillus infection remains a significant unmet need, particularly in immunocompromised patients, patients in critical care and those with underlying chronic lung diseases. To date, treatment using inhaled antifungal agents has been limited to repurposing available systemic medicines. PC945 is a novel triazole antifungal agent, a potent inhibitor of CYP51, purpose-designed to be administered via inhalation for high local lung concentrations and limited systemic exposure. In preclinical testing, PC945 is potent versus Aspergillus spp. and Candida spp. and showed two remarkable properties in preclinical studies, in vitro and in vivo. The antifungal effects against Aspergillus fumigatus accumulate on repeat dosing and improved efficacy has been demonstrated when PC945 is dosed in combination with systemic anti-fungal agents of multiple classes. Resistance to PC945 has been induced in Aspergillus fumigatus in vitro, resulting in a strain which remained susceptible to other antifungal triazoles. In healthy volunteers and asthmatics, nebulised PC945 was well tolerated, with limited systemic exposure and an apparently long lung residency time. In two lung transplant patients, PC945 treated an invasive pulmonary Aspergillus infection that had been unresponsive to multiple antifungal agents (systemic ± inhaled) without systemic side effects or detected drug-drug interactions.

Bloodstream infections caused by non-albicans Candida species are increasing and echinocandins have been extensively used especially in patients with hemodynamic instability, previous antifungal treatment and hospital risk factors for intrinsic or acquired resistance to azoles. Candida glabrata resistance to echinocandins is reported and is generally associated with previous use of echinocandins; FKS gene mutations have been associated with a worse outcome. We report the case of a 65-year-old woman who developed candidemia and endocarditis by C. glabrata with a newly acquired FKS mutation 24 months after successful treatment of infective endocarditis by C. glabrata with a double dosage of anidulafungin (200 mg daily) followed by oral voriconazole. Driven by high echinocandin MICs the strain taken by intraoperative cultures was further analyzed in a referral microbiology laboratory, confirming the new onset of point mutation S633P of the FKS2 gene.

Background: There is limited literature available about educational satisfaction and fellowship selection among orthopaedic surgery residents. The purpose of this study was to identify factors that influence resident subspecialty career choice, fellowship selection, and satisfaction with orthopaedic training programs., Methods: A self-report survey was electronically administered to orthopaedic surgery residents at 44 academic centers in the United States and Canada. Basic demographic information and level of satisfaction with a number of factors (surgical independence, mentorship opportunities, etc.) were evaluated using a 5-point Likert scale ranging from "excellent" to "poor." Summary statistics and group differences for discrete variables were compared with use of a chi-square test., Results: Of the 283 respondents, 77% rated residency program satisfaction as "very good" or "excellent," and 93% said they would choose the same training program again. Decreased surgical independence (p < 0.01), poor faculty reputation (p < 0.01), reduced volume and variety of cases (p < 0.01), inadequate mentorship (p < 0.01), and reduced educational opportunities (p < 0.01) were associated with low satisfaction. Surgical variety and job opportunities were the top 2 factors contributing to subspecialty choice. Sports medicine and joints were the most popular career choices; case volume, surgical variety, and program reputation were the top factors contributing to fellowship program selection., Conclusions: In order to achieve resident satisfaction, orthopaedic training programs should strive to improve resident surgical independence, surgical case variety, mentorship programs, faculty reputation, and educational opportunities. Important factors for fellowship program selection include case volume, surgical variety, and overall program reputation.

Medial scapular winging is often due to dysfunction of the serratus anterior muscle as a result of injury to the long thoracic nerve. Impairment of the serratus anterior muscle may cause uncoordinated scapulohumeral rhythm during shoulder elevation and subsequent subscapular or shoulder pain, subacromial impingement, and glenohumeral joint instability. Although long thoracic nerve injury typically resolves in 12 to 18 months after a physical therapy regimen, surgical intervention is indicated in patients who fail conservative management. Both direct and indirect pectoralis major tendon transfer techniques have been described in the literature as surgical options for these patients. Indirect transfer of the pectoralis major and augmentation with either allograft or autograft has been shown to successfully restore scapular functioning and glenohumeral stability. We describe a technique that uses hamstring autograft to augment a pectoralis major transfer with the sternal head to correct medial scapular winging due to dysfunction of the long thoracic nerve and serratus anterior muscle atrophy.

Background: We investigated the pharmacokinetics (PK) of atazanavir/cobicistat and darunavir/cobicistat once daily over 72 h following drug intake cessation in plasma, saliva and urine., Methods: Healthy volunteers received a fixed-dose combination of 300/150 mg of atazanavir/cobicistat once daily for 10 days, followed by a 10 day washout period and then a fixed-dose combination of 800/150 mg of darunavir/cobicistat once daily for 10 days. Full PK profiles were assessed for each phase for 72 h following day 10 and parameters determined to the last measurable concentration in plasma, saliva and urine by non-compartmental methods., Results: Sixteen subjects completed the study. Geometric mean (GM) terminal elimination half-life values to 72 h of atazanavir and darunavir were 6.77 and 6.35 h, respectively. All subjects had atazanavir concentrations above the suggested minimum effective concentration of 150 ng/mL 24 h post-dose and 14/16 subjects had concentrations higher than this target at 30 h post-dose (GM of 759 and 407 ng/mL, respectively). Thirteen out of 16 subjects had darunavir concentrations higher than the target of 550 ng/mL at 24 h post-dose and 5/16 subjects had concentrations higher than the target at 30 h post-dose (GM of 1033 and 382 ng/mL, respectively). Cobicistat half-life to 72 h was 4.21 h with atazanavir and 3.62 h with darunavir. GM values 24 h after the observed dose ( C 24 ) for atazanavir and darunavir were 141 and 43 ng/mL, respectively, in saliva and 24857 and 11878 ng/mL, respectively, in urine. Concentration decay in saliva/urine mirrored plasma concentrations for both drugs., Conclusions: Different concentration decay patterns were seen for atazanavir and darunavir, which may be partially explained by cobicistat half-life (longer with atazanavir than darunavir). For the first time, we also measured drug PK forgiveness in saliva and urine, which represent easier markers of adherence., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In infectious and inflammatory diseases, pharmacogenetics affects treatment efficacy and toxicity. Moreover, recent studies suggest its important role in predicting the clinical outcome of sepsis. Our aim was to investigate the influence of single nucleotide polymorphisms (SNPs) in genes which we supposed to be involved in linezolid elimination upon sepsis outcome. Fourteen ICU-admitted patients in therapy with intravenous linezolid (600mg q12h) were enrolled and classified into three groups: group 0 for sepsis, 1 for severe sepsis and 2 for septic shock. Genotyping for SNPs in MDR1 3435 rs1045642 C>T, 2677 rs2032582 G>T and 1236 rs1128503 C>T, MRP2 -24 rs717620 G>A and 1249 rs2273697 G>A, MRP4 *879 rs1059751 T>C and 3348 rs1751034 T>C, BCRP1 421 rs2231142 C>A and 1194+928 rs13120400 T>C, -127 rs4149170 G>A and OCT1 480 rs683369 C>G genes was done using real-time PCR allelic discrimination assay. The Mann-Whitney statistical test was used to analyse variables. MDR1 2677 (p= 0.012), MRP2 1249 (p= 0.038), MRP4 *879 (p= 0.032) and 3348 SNPs significantly influenced the sepsis score. Our study, despite its limited sample size, could be decisive for early sepsis prediction and may improve the management of critically ill patients.

Background: Hepatocellular carcinoma (HCC) is increasingly prevalent in people living with HIV. Systemic inflammation is a prognostic factor requiring validation in HIV-associated HCC., Aims: Using a multi-centre database of consecutive HCC cases, we investigated the prognostic role of a panel of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), using univariate and multivariate survival analyses., Results: Fifty-nine patients with HIV-associated HCC secondary to hepatitis C (69%) or B virus infection (32%) were identified. The median survival was 22 months. A raised NLR independently predicted patients' survival and was correlated with advanced Barcelona Clinic Liver Cancer stage (p = 0.003) and poor performance status (p < 0.001) but not with HIV RNA or CD4 counts., Conclusion: Systemic inflammation, as measured by NLR, is a prognostic determinant associated with adverse pathological features of malignancy, but not coexisting HIV infection, suggesting a tumour-promoting role of the innate immune response that warrants further investigation in mechanistic studies., (© 2017 S. Karger AG, Basel.)