A Randomized Study Comparing Closed-Incision Negative-Pressure Wound Therapy with Standard Care in Immediate Breast Reconstruction.

BACKGROUND: Breast cancer remains the most common nonskin cancer among women. Prophylactic methods for reducing surgical-site complications after immediate breast reconstruction (IBR) are crucial to prevent acellular dermal matrices or prosthesis exposure and loss. The authors assessed the impact of closed-incision negative-pressure wound therapy (ciNPWT) versus standard dressings (ST) after IBR on surgical-site complications, superficial skin temperature (SST), skin elasticity, and subjective scar quality, to determine the potential benefit of prophylactic ciNPWT application. METHODS: A multicenter randomized controlled study of 60 adult female patients was conducted between January of 2019 and July of 2021. All patients had oncologic indications for IBR using implants or expanders. RESULTS: Application of ciNPWT correlated with a significant decrease in surgical-site complications within 1 year of surgery (total, 40%; ST, 60%; ciNPWT, 20%; P = 0.003) and resulted in more elastic scar tissue as measured with a Cutometer (average coefficient of elasticity, 0.74; ST, 0.7; ciNPWT, 0.9; P < 0.001). The SST of each scar 1 week after surgery was significantly higher in the ciNPWT group (average SST, 31.5; ST SST, 31.2; ciNPWT SST, 32.3; P = 0.006). According to the Patient and Observer Scar Assessment Scale v2.0, subjective scar outcomes in both groups were comparable. CONCLUSIONS: This is the first randomized controlled study that demonstrated a significant decrease in surgical-site wound complications within 1 year of surgery in IBR patients receiving ciNPWT. A high probability of postoperative radiotherapy should be a relative indication for the use of ciNPWT. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Disseminated Juvenile Xanthogranuloma with a Novel MYH9-FLT3 Fusion Presenting as a Blueberry Muffin Rash in a Neonate.

Juvenile xanthogranuloma (JXG) is a benign proliferative histiocytic disorder of the dendritic cell phenotype. It mostly presents in the pediatric age group as a solitary skin lesion. We describe a rare case of an infant born with disseminated JXG who presented with a blueberry muffin rash at birth. A term infant was noted to have multiple petechiae, purple nodules, and macules (1 mm-2 cm in diameter) and hepatosplenomegaly, at the time of birth. Further investigations revealed thrombocytopenia and direct hyperbilirubinemia and a magnetic resonance imaging showed scattered tiny foci of restricted diffusion in multiple areas of the brain. Patient received multiple platelet transfusions in the first few weeks with gradual improvement in thrombocytopenia. Ultimately, a biopsy of one of the lesions revealed the diagnosis of disseminated JXG with notable atypical features. Somatic mutation analysis showed a novel MYH9-FLT3 fusion, but a bone marrow biopsy was negative. The lesions faded over time, relative to patient's growth and normal neurodevelopment was noted at 18 months of age. JXG should be considered in the differentials of blueberry muffin rash in an infant. Although, JXG is mostly a self-limited condition, congenital disseminated JXG may be associated with significant morbidity and mortality.

Post-Mastectomy Patients in an Urban Safety-Net Hospital: How Do Safety-Net Hospital Breast Reconstruction Rates Compare to National Breast Reconstruction Rates?

BACKGROUND: Breast reconstruction (BR) has documented psychological benefits following mastectomy. Yet, racial/ethnic minority groups have lower reported rates of BR. We sought to evaluate the rate, type, and outcome of BR in a racially and ethnically diverse population within a safety-net hospital system. METHODS: All patients who underwent mastectomy between October 2015 and July 2019 at Harbor-UCLA Medical Center were retrospectively examined. Rates and type of BR were analyzed according to patient characteristics (race/ethnicity, age, and body mass index), smoking status, cancer stage, and presence of diabetes mellitus. Breast reconstruction outcomes were also assessed. RESULTS: Of the 259 patients that underwent mastectomy, 87 (33.6%) received BR. Immediate BR was performed in 79 (30.5%) patients and delayed BR in 8 (3.1%). Of the 79 patients with immediate BR, 58 (73.4%) received implant-based BR and 21 (26.5%) autologous tissue. The BR failure rate was 10%, all implant-based. Increasing age and smoking negatively impacted BR rates. Black (P =.331) and Hispanic (P =.132) ethnicity were not independent predictors of decreased breast reconstruction. CONCLUSION: This study demonstrated that the rate, type, and quality of BR in this integrated safety-net hospital within a diverse population are comparable to national rates. When made available, historically underrepresented minority patients of Black and Hispanic ethnicity utilize BR.

Quantifying neurological function in patients undergoing transcatheter aortic valve implantation.

Background: Transcatheter aortic valve implantation (TAVI) is a routine procedure that is often performed on older adults that are high-risk patients with severe aortic stenosis. Patients after TAVI may experience neurological complications. However, there is a lack of objective neurological testing available for patients undergoing cardiac surgery. Objective: This brief communication seeks to explore the use of robotic technology to quantify distinctive patterns of visuospatial, sensorimotor, and cognitive functioning in patients undergoing TAVI. Methods: Patients undergoing TAVI were recruited for this prospective observational study. Prior to their procedure, study participants performed four robotic reaching tasks using the Kinarm robotic system. Patients repeated the assessment three months after their TAVI procedure. Significant changes in overall task score and parameters were determined. Results: Ten patients were recruited and included in this brief report. In a simple reaching task, patients show significant improvement in performance post-TAVI. However, patients do not improve nor worsen in a complex reaching task after TAVI. Similarly, patients demonstrate impairments in both trail making tasks before and after their TAVI procedure. Conclusions: This study captures the variability in neurological functioning in older patients undergoing TAVI. Robotic technology and quantified assessment procedures can be extremely valuable for detecting perioperative neurological impairments in this patient population.

Novel Lipidomic Signature Associated With Metabolic Risk in Women With and Without Polycystic Ovary Syndrome.

CONTEXT: Dyslipidemia is a feature of polycystic ovary syndrome (PCOS) and may augment metabolic dysfunction in this population. OBJECTIVE: Using comprehensive lipidomic profiling and gold-standard metabolic measures, we examined whether distinct lipid biomarkers were associated with metabolic risk in women with and without PCOS. METHODS: Using preexisting data and biobanked samples from 76 women (n = 42 with PCOS), we profiled > 700 lipid species by mass spectrometry. Lipids were compared between women with and without PCOS and correlated with direct measures of adiposity (dual x-ray absorptiometry and computed tomography) and insulin sensitivity (hyperinsulinemic-euglycemic clamp), as well as fasting insulin, HbA1c, and hormonal parameters (luteinizing and follicle-stimulating hormones; total and free testosterone; sex hormone-binding globulin [SHBG]; and free androgen index [FAI]). Multivariable linear regression was used with correction for multiple testing. RESULTS: Despite finding no differences by PCOS status, lysophosphatidylinositol (LPI) species esterified with an 18:0 fatty acid were the strongest lipid species associated with all the metabolic risk factors measured in women with and without PCOS. Across the cohort, higher concentrations of LPI(18:0) and lower concentrations of lipids containing docosahexaenoic acid (DHA, 22:6) n-3 polyunsaturated fatty acids were associated with higher adiposity, insulin resistance, fasting insulin, HbA1c and FAI, and lower SHBG. CONCLUSION: Our data indicate that a distinct lipidomic signature comprising high LPI(18:0) and low DHA-containing lipids are associated with key metabolic risk factors that cluster in PCOS, independent of PCOS status. Prospective studies are needed to corroborate these findings in larger cohorts of women with varying PCOS phenotypes.

Overview and Diagnostic Accuracy of Near Infrared Spectroscopy in Carotid Endarterectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: Carotid endarterectomy is recommended for the prevention of ischaemic stroke due to carotid stenosis. However, the risk of stroke after carotid endarterectomy has been estimated at 2% - 5%. Monitoring intra-operative cerebral oxygenation with near infrared spectroscopy (NIRS) has been assessed as a strategy to reduce intra- and post-operative complications. The aim was to summarise the diagnostic accuracy of NIRS to detect intra-operative ischaemic events, the values associated with ischaemic events, and the relative contribution of external carotid contamination to the NIRS signal in adults undergoing carotid endarterectomy. DATA SOURCES: EMBASE, MEDLINE, Cochrane Centre Register of Controlled Trials, and reference lists through May 2019 were searched. REVIEW METHODS: Non-randomised and randomised studies assessing NIRS as an intra-operative monitoring tool in carotid endarterectomy were included. Studies using NIRS as the reference were excluded. Risk of bias was assessed using the Newcastle Ottawa Scale, RoB-2, and QUADAS-2. RESULTS: Seventy-six studies were included (n = 8 480), under local (n = 1 864) or general (n = 6 582) anaesthesia. Seven studies were eligible for meta-analysis (n = 524). As a tool for identifying intra-operative ischaemia, specificity increased with more stringent NIRS thresholds, while there was unpredictable variation in sensitivity across studies. A Δ20% threshold under local anaesthesia resulted in pooled estimates for sensitivity and specificity of 70.5% (95% confidence interval, CI, 54.1 - 82.9) and 92.4% (95% CI 85.5 - 96.1) compared with awake neurological monitoring. These studies had low or unclear risk of bias. NIRS signal consistently dropped across clamping and recovered to pre-clamp values upon de-clamp in most studies, and larger decreases were observed in patients with ischaemic events. The contribution of extracranial signal to change in signal across clamp varied from 3% to 50%. CONCLUSION: NIRS has low sensitivity and high specificity to identify intra-operative ischaemia compared with awake monitoring. Extracranial signal contribution was highly variable. Ultimately, data from high quality studies are desperately needed to determine the utility of NIRS.

Cerebral oximetry and preventing neurological complication post-cardiac surgery: a systematic review.

OBJECTIVES: This systematic review aims to provide an up-to-date summary of the current literature examining the relationship between intraoperative regional cerebral oxygen saturation and neurological complications after cardiac surgery. METHODS: Observational and interventional studies investigating the link between regional cerebral oxygen saturation and postoperative delirium, cognitive dysfunction and stroke were included. After database searching and study screening, study characteristics and major findings were extracted. RESULTS: Twenty-seven studies were identified. Of the observational studies (n = 17), 8 reported that regional cerebral oxygen desaturations were significantly associated with neurological complications after cardiac surgery. Of the interventional studies (n = 10), 3 provided evidence for monitoring cerebral oximetry during cardiac surgery as a means of reducing incidence of postoperative cognitive dysfunction or stroke. There was significant heterogeneity in the tools and rigor used to diagnose neurological complications. CONCLUSIONS: Studies to date show an inconsistent relationship between regional cerebral oxygen saturation and neurological outcomes after cardiac surgery, and lack of clear benefit of targeting cerebral oximetry to minimize neurological complications. Standardized assessments, definitions of impairment and desaturation thresholds will help determine the benefits of cerebral oximetry monitoring during cardiac surgery.

Plastic Surgery and the Malpractice Industry.

SUMMARY: The current status of the plastic surgeon in the medical liability spectrum and ways to avoid litigation are explored by using pooled national data from the Medical Professional Liability Association, private information from Applied Medico-Legal Solutions RRG, and a detailed literature search. The medical liability system in the United States costs $55.6 billion, or 2.4 percent of total health care spending. Plastic surgery accounts for 3.31 percent of reported claims and 3.16 percent of paid claims. Total payments for plastic surgeons represent 1.75 percent of the total paid for all specialties. Malpractice awards are relatively light for plastic surgeons. Nevertheless, they still have a 15 percent chance per year of being sued. However, 93 percent of cases will close with a dismissal or a settlement, and only 7 percent will go to trial. Of these, the plastic surgeon will prevail in 79 percent. Most importantly, 75 percent of all cases will result in no payment. To minimize the chances of a lawsuit, plastic surgeons should maintain excellent communication with their patients and participate in shared decision-making. They should take a leadership role and buy in to the performance of perioperative checklists, embrace patient education, and actively participate in Maintenance of Certification. They should be transparent in their dealings with patients by preoperatively declaring their policies on revisions, refunds, complications, and payments. Plastic surgeons must maintain complete and accurate medical records and participate in hospital-based programs of prophylaxis. They should be aware that postoperative infection is the single costliest adverse outcome and proactively deal with it.

The relationship between immune status as measured by stimulated ex-vivo tumour necrosis factor alpha levels and the acquisition of nosocomial infections in critically ill mechanically ventilated patients.

INTRODUCTION: Immunological dysfunction is common in critically ill patients but its clinical significance and the optimal method to measure it are unknown. The level of tumor necrosis factor alpha (TNF-α) after ex-vivo whole blood stimulation with lipopolysaccharide (LPS) has been proposed as a possible method to quantify immunological function. We hypothesized that in a cohort of critically ill patients, those with a lower post-stimulation TNF-α level would have increased rates of nosocomial infections (NIs) and worse clinical outcomes. METHODS: A secondary analysis of a phase 2 randomized, multi-centre, double-blinded placebo-controlled trial. As there was no difference between treatment and control arms in outcomes and NI rate, all the patients were analyzed as one cohort. On enrolment, day 4, 7, and weekly until day 28, whole blood was incubated with LPS ex-vivo and subsequent TNF-α level was measured. Patients were grouped in tertiles according to delta and peak TNF-α level. The primary outcome was the association between NIs and tertiles of TNF-α level post LPS stimulation; secondary outcomes included ICU and 90-day mortality, and ICU and hospital length of stay. RESULTS: Data was available for 201 patients. Neither the post LPS stimulation delta TNF-α group nor the peak TNF-α post-stimulation group were associated with the development of NIs or clinical outcomes. Patients in the highest tertile for post LPS stimulation delta TNF-α compared to the lowest tertile were younger [61.1 years ± 15.7 vs. 68.6 years ± 12.8 standard deviations (SD) in the lowest tertile], had lower acuity of illness (APACHE II 25.0 ± 9.7 vs. 26.7 ± 6.1) and had lower baseline TNF-α (9.9 pg/mL ± 19.0 vs. 31.0 pg/mL ± 68.5). When grouped according to peak post-stimulation TNF-α levels, patients in the highest tertile had higher serum TNF-α at baseline (21.3 pg/mL ± 66.7 compared to 6.5 pg/mL ± 9.0 in the lowest tertile). CONCLUSION: In this prospective multicenter study, ex-vivo stimulated TNF-α level was not associated with the occurrence of NIs or clinical outcomes. Further study is required to better ascertain whether TNF levels and ex-vivo stimulation can be used to characterize immune function in critical illness and if other assays might be better suited to this task.

Very high rate of false positive biochemical results when screening for pheochromocytoma in a large, undifferentiated population with variable indications for testing.

OBJECTIVE: Pheochromocytoma/Paraganglioma (PPGL) is a rare tumor with non-specific presentations overlapping common entities like anxiety, hypertension, acute illness and episodic "spells." Assessment of urine normetanephrine or metanephrine (UNM-UMN) in real-life, where PPGL is very rare and PPGL mimics extremely common, may show overlap in results with loss of specificity depending on the reference range. We determined the extent to which UNM-UMN are high in people undergoing screening for PPGL. DESIGN AND METHODS: Retrospective review of all UNM-UMN performed in a central lab serving Southern Alberta over 8 years. RESULTS: After excluding pediatric ages and patients with CKD, there were 12,572 unique patients with 14,383 measures of UNM-UMN. 85 patients (0.7%) had markedly high UNM-UMN compatible with likely PPGL. Depending on the age category (in decades), 10-22% of all UNM results were above the upper reference limit(URL), particularly between ages of 40-60. Less than 3% had elevations in both UNM and UMN. Of those with high UNM, 99% were less than 3-fold the URL. Based on the population data, a potential new reference range for UNM is suggested, which may be more appropriate to the types of patient who undergo this form of testing. CONCLUSIONS: There is an extraordinarily high prevalence of high UNM seen in real-life use of the test. However, the vast majority of high UNM are unlikely to be PPGL given the disease rarity and the massive number of tests ordered. This suggests the current laboratory URL may be too low (poor specificity) and/or the reference range may not be appropriate to the type of patient being screened for PPGL. Depending on the frequency of use of any screening test in a population, if the disease is rare and the specificity of the test is poor, a high rate of false positive results will be expected.

Quantified pre-operative neurological dysfunction predicts outcome after coronary artery bypass surgery.

AIMS: Patients undergoing coronary artery bypass grafting (CABG) surgery may experience neurological impairment. We examined whether intraoperative regional cerebral oxygen saturation (rSO2) and neurological dysfunction prior to surgery, measured by robotic technology, are important predictors of post-operative performance following CABG surgery. METHODS: Adult patients undergoing CABG surgery were recruited for this single-center prospective observational study. Intraoperative rSO2 was captured using the FORESIGHT cerebral oximeter. Neurological assessment was performed pre-operatively and 3 months following surgery using robotic technology and a standardized pen-and-paper assessment. Linear regression models were generated to determine the predictive ability of both intraoperative rSO2 and pre-operative performance on post-operative neurological outcome. RESULTS: Forty patients had complete data available for analysis. Quantified pre-operative performance accounted for a significantly larger amount of variance in post-operative outcome compared to intraoperative rSO2. In particular, pre-operative scoring on a cognitive visuospatial task accounted for 82.2% of variance in post-operative performance (b = 0.937, t(37) = 12.98, p = 1.28e-5). DISCUSSION: Our results suggest that pre-operative performance is a stronger indicator of post-operative neurological outcome than intraoperative rSO2, and should be included as an important variable when elucidating the relationship between cerebral oxygen levels and post-operative neurological impairment. Rigorous neurological assessment prior to surgery can provide valuable information about each individual patient's path to recovery. CONCLUSION: Using robotic technology, quantified neurological impairment prior to CABG surgery may better predict post-operative neurological outcomes, compared to intraoperative rSO2 values.

Measurement of Muscle Mass and Sarcopenia Using Anthropometry, Bioelectrical Impedance, and Computed Tomography in Surgical Patients with Colorectal Malignancy: Comparison of Agreement Between Methods.

Background: Low skeletal muscle index (SMI) and sarcopenia adversely affect clinical outcomes in oncology patients. Study aims were to assess the agreement of bioelectrical impedance analysis (BIA), mid-arm muscle circumference (MAMC), and computed tomography (CT) at the third lumbar vertebra (L3), for the measurement of muscle mass and identification of sarcopenia, in patients with colorectal cancer (CRC).Method: A comparison study of low SMI and sarcopenia determined by BIA and MAMC, compared to CT. Sensitivity, specificity and area under the curve (AUC) were calculated.Results: CT scans were obtained for 100 participants. Low SMI was identified in 29%, 57%, and 20% of participants using CT at L3, BIA, and MAMC, respectively. For low muscle mass BIA showed 60% of participants were correctly classified (AUC 0.619, sensitivity 80%, specificity 52%, kappa 0.241, P = 0.009) and for MAMC, 73% of participants were correctly classified (AUC 0.625, sensitivity 38%, specificity 88%, kappa 0.286, P = 0.005). There were 14%, 31%, and 10% of participants identified as having sarcopenia from CT, BIA, and MAMC, respectively.Conclusions: Both BIA and MAMC show a poor level of agreement for measuring muscle mass compared to CT scans using L3 in patients with CRC.

The physiological determinants of near-infrared spectroscopy-derived regional cerebral oxygenation in critically ill adults.

BACKGROUND: To maintain adequate oxygen delivery to tissue, resuscitation of critically ill patients is guided by assessing surrogate markers of perfusion. As there is no direct indicator of cerebral perfusion used in routine critical care, identifying an accurate strategy to monitor brain perfusion is paramount. Near-infrared spectroscopy (NIRS) is a non-invasive technique to quantify regional cerebral oxygenation (rSO2) that has been used for decades during cardiac surgery which has led to targeted algorithms to optimize rSO2 being developed. However, these targeted algorithms do not exist during critical care, as the physiological determinants of rSO2 during critical illness remain poorly understood. MATERIALS AND METHODS: This prospective observational study was an exploratory analysis of a nested cohort of patients within the CONFOCAL study ( NCT02344043 ) who received high-fidelity vital sign monitoring. Adult patients (≥ 18 years) admitted < 24 h to a medical/surgical intensive care unit were eligible if they had shock and/or required mechanical ventilation. Patients underwent rSO2 monitoring with the FORESIGHT oximeter for 24 h, vital signs were concurrently recorded, and clinically ordered arterial blood gas samples and hemoglobin concentration were also documented. Simultaneous multiple linear regression was performed using all available predictors, followed by model selection using the corrected Akaike information criterion (AICc). RESULTS: Our simultaneous multivariate model included age, heart rate, arterial oxygen saturation, mean arterial pressure, pH, partial pressure of oxygen, partial pressure of carbon dioxide (PaCO2), and hemoglobin concentration. This model accounted for a significant proportion of variance in rSO2 (R2 = 0.58, p < 0.01) and was significantly associated with PaCO2 (p < 0.05) and hemoglobin concentration (p < 0.01). Our selected regression model using AICc accounted for a significant proportion of variance in rSO2 (R2 = 0.54, p < 0.01) and was significantly related to age (p < 0.05), PaCO2 (p < 0.01), hemoglobin (p < 0.01), and heart rate (p < 0.05). CONCLUSIONS: Known and established physiological determinants of oxygen delivery accounted for a significant proportion of the rSO2 signal, which provides evidence that NIRS is a viable modality to assess cerebral oxygenation in critically ill adults. Further elucidation of the determinants of rSO2 has the potential to develop a NIRS-guided resuscitation algorithm during critical illness. TRIAL REGISTRATION: This trial is registered on clinicaltrials.gov (Identifier: NCT02344043 ), retrospectively registered January 8, 2015.

Higher order genomic organization and epigenetic control maintain cellular identity and prevent breast cancer.

Cells establish and sustain structural and functional integrity of the genome to support cellular identity and prevent malignant transformation. In this review, we present a strategic overview of epigenetic regulatory mechanisms including histone modifications and higher order chromatin organization (HCO) that are perturbed in breast cancer onset and progression. Implications for dysfunctions that occur in hormone regulation, cell cycle control, and mitotic bookmarking in breast cancer are considered, with an emphasis on epithelial-to-mesenchymal transition and cancer stem cell activities. The architectural organization of regulatory machinery is addressed within the contexts of translating cancer-compromised genomic organization to advances in breast cancer risk assessment, diagnosis, prognosis, and identification of novel therapeutic targets with high specificity and minimal off target effects.

Septal dysembryoplastic neuroepithelial tumor: a comprehensive clinical, imaging, histopathologic, and molecular analysis.

BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed "DNET-like neoplasms of the septum pellucidum." Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series. METHODS: We collected 20 of these tumors for a comprehensive study of their clinical, radiological, and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n = 22) were also reviewed for comparative purposes. RESULTS: The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum/septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). Septal DNET showed a high frequency (~80%) of mutations of platelet derived growth factor receptor A (PDGFRA), and alterations in fibroblast growth factor receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group. CONCLUSIONS: Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity.

Selective Loss of Levator Ani and Leg Muscle Volumes in Men Undergoing Androgen Deprivation Therapy.

CONTEXT: Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT have demonstrated that the levator ani is exquisitely androgen sensitive. OBJECTIVE: To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved and ADT is associated with a selective loss in leg muscle volume. DESIGN: Prospective longitudinal case-control study. SETTING: Tertiary referral hospital. PARTICIPANTS: Thirty-four men newly beginning ADT and 29 age-matched controls with PCa. MAIN OUTCOME MEASURES: The muscle volumes in liters of the levator ani and primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf). RESULTS: Compared with controls, during a 12-month period, men receiving ADT experienced a mean reduction in total testosterone from 14.1 to 0.4 nmol/L and demonstrated greater decreases in levator ani [mean adjusted difference (MAD), -0.005 L; 95% CI, -0.007 to -0.002; P = 0.002; -16% of initial median value], gluteus maximus (MAD, -0.032 L; 95% CI, -0.063 to -0.002; P = 0.017; -5% of initial median value), iliopsoas (MAD, -0.005 L; 95% CI, -0.001 to 0.000; P = 0.013; -5% of initial median value), and quadriceps (MAD, -0.050 L; 95% CI, -0.088 to -0.012; P = 0.031; -3% of initial median value). No substantial differences were observed in the gluteus medius and calf muscles. CONCLUSIONS: The androgen responsiveness of the levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases the volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor, will improve clinical outcomes.

Relationship Between Near-Infrared Spectroscopy-Derived Cerebral Oxygenation and Delirium in Critically Ill Patients: A Systematic Review.

BACKGROUND: A common neurological complication of critical illness is delirium, defined as an acute change in level of consciousness, with impaired attention and disorganized thinking. Patients with delirium have increased risk of long-term cognitive dysfunction and mortality. The cause is unknown, which limits our ability to design therapeutic interventions. In patients undergoing surgery, low regional cerebral oxygenation (rSO2), as measured by near-infrared spectroscopy (NIRS), is associated with postoperative neurological dysfunction (eg delirium and long-term cognitive impairment). However, the relationship between NIRS-derived rSO2 and neurological outcomes in critically ill patients is unclear. The objective of this study was to assess the utilization of NIRS-derived rSO2 in critically ill patients outside the operating theater. We aimed to examine the relationship between rSO2 and neurological outcomes as well as to report rSO2 values in this population. METHODS: The following databases were searched from inception to August 14, 2017: Ovid MedLine, Embase, Cochrane Library, and Web of Science. RESULTS: Of 1410 articles identified by the search strategy, 8 were ultimately selected for final review. Most (7 of 8) were published since 2014. These studies included a total of 213 patients primarily with shock or respiratory failure. A variety of devices were used to measure rSO2, including INVOS and FORESIGHT. The duration of recording varied from 5 minutes to 72 hours. Four of the 8 studies reported on neurological outcomes. In all 4 studies, rSO2 was lower in critically ill patients who were delirious compared to controls, but this was only statistically significant in 2 of the studies. The heterogeneity in devices and duration of recording precluded meta-analysis. CONCLUSIONS: There is limited literature describing rSO2 in critically ill patients outside the operating room. Although there may be a slight signal of an association between low rSO2 and delirium, more study is needed to explore this relationship.

Evaluation of Staphylococcus aureus eradication therapy in orthopaedic surgery.

PURPOSE: Despite WHO recommendations, there is currently no national screening and eradication policy for the detection of methicillin-sensitive Staphylococcus aureus (MSSA) in the UK prior to elective orthopaedic surgery. This study aimed to evaluate the effectiveness of current standard methicillin-resistant S. aureus (MRSA) eradication therapies in the context of S. aureus (both MRSA and MSSA) decolonization in an elective orthopaedic population. METHODOLOGY: A total of 100 patients awaiting joint replacement surgery who were positive for S. aureus on PCR nasal screening underwent the current standard MRSA pre-operative decolonization regimen for 5 days. Prior to commencement of the eradication therapy, swabs of the anterior nares, throat and perineum were taken for culture. Further culture swabs were taken at 48-96 h following treatment, at hospital admission for surgery and at hospital discharge. Following the completion of treatment, patients were asked to provide feedback on their experience using Likert rating scales. The primary outcome of this study was S. aureus clearance 48-96 h following eradication treatment.Results/Key Findings. Clearance of S. aureus 48-96 h following treatment was 94 % anterior nares, 66 % throat and 88 % groin. Mean completion with nasal mupirocin was 98 %. There was no statistically significant recolonization effect between the end of the eradication treatment period and the day of surgery (P>0.05) at a median time of 10 days. CONCLUSION: Current MRSA decolonisation regimens are well tolerated and effective for MSSA decolonization for the anterior nares and groin. The decolonization effect is preserved for at least 10 days following treatment.

Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed.

OBJECTIVES: Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization's recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients. METHODS: Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery. RESULTS: The prevalence of MSSA nasal colonization was found to be between 22.4% to 35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p = 0.005), failing to identify its presence in approximately one-third of patients undergoing joint arthroplasty surgery. CONCLUSION: Modelling these results to national surveillance data, it was estimated that approximately 5000 to 8000 S. aureus surgical site infections could be prevented, and approximately $140 million to $950 million (approximately £110 million to £760 million) saved in treatment costs annually in the United States and United Kingdom combined, by using alternative diagnostic methods to direct culture in preoperative S. aureus screening and eradication programmes.Cite this article: S. T. J. Tsang, M. P. McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh, I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed. Bone Joint Res 2018;7:79-84. DOI: 10.1302/2046-3758.71.BJR-2017-0175.R1.

Low-Molecular-Weight Thiols and Thioredoxins Are Important Players in Hg(II) Resistance in Thermus thermophilus HB27.

Mercury (Hg), one of the most toxic and widely distributed heavy metals, has a high affinity for thiol groups. Thiol groups reduce and sequester Hg. Therefore, low-molecular-weight (LMW) and protein thiols may be important cell components used in Hg resistance. To date, the role of low-molecular-weight thiols in Hg detoxification remains understudied. The mercury resistance (mer) operon of Thermus thermophilus suggests an evolutionary link between Hg(II) resistance and low-molecular-weight thiol metabolism. The mer operon encodes an enzyme involved in methionine biosynthesis, Oah. Challenge with Hg(II) resulted in increased expression of genes involved in the biosynthesis of multiple low-molecular-weight thiols (cysteine, homocysteine, and bacillithiol), as well as the thioredoxin system. Phenotypic analysis of gene replacement mutants indicated that Oah contributes to Hg resistance under sulfur-limiting conditions, and strains lacking bacillithiol and/or thioredoxins are more sensitive to Hg(II) than the wild type. Growth in the presence of either a thiol-oxidizing agent or a thiol-alkylating agent increased sensitivity to Hg(II). Furthermore, exposure to 3 µM Hg(II) consumed all intracellular reduced bacillithiol and cysteine. Database searches indicate that oah2 is present in all Thermus sp. mer operons. The presence of a thiol-related gene was also detected in some alphaproteobacterial mer operons, in which a glutathione reductase gene was present, supporting the role of thiols in Hg(II) detoxification. These results have led to a working model in which LMW thiols act as Hg(II)-buffering agents while Hg is reduced by MerA.IMPORTANCE The survival of microorganisms in the presence of toxic metals is central to life's sustainability. The affinity of thiol groups for toxic heavy metals drives microbe-metal interactions and modulates metal toxicity. Mercury detoxification (mer) genes likely originated early in microbial evolution in geothermal environments. Little is known about how mer systems interact with cellular thiol systems. Thermus spp. possess a simple mer operon in which a low-molecular-weight thiol biosynthesis gene is present, along with merR and merA In this study, we present experimental evidence for the role of thiol systems in mercury resistance. Our data suggest that, in T. thermophilus, thiolated compounds may function side by side with mer genes to detoxify mercury. Thus, thiol systems function in consort with mer-mediated resistance to mercury, suggesting exciting new questions for future research.