Unexpected increase of the deuterium to hydrogen ratio in the Venus mesosphere.

This study analyzes H2O and HDO vertical profiles in the Venus mesosphere using Venus Express/Solar Occultation in the InfraRed data. The findings show increasing H2O and HDO volume mixing ratios with altitude, with the D/H ratio rising significantly from 0.025 at ~70 km to 0.24 at ~108 km. This indicates an increase from 162 to 1,519 times the Earth's ratio within 40 km. The study explores two hypotheses for these results: isotopic fractionation from photolysis of H2O over HDO or from phase change processes. The latter, involving condensation and evaporation of sulfuric acid aerosols, as suggested by previous authors [X. Zhang et al., Nat. Geosci. 3, 834-837 (2010)], aligns more closely with the rapid changes observed. Vertical transport computations for H2O, HDO, and aerosols show water vapor downwelling and aerosols upwelling. We propose a mechanism where aerosols form in the lower mesosphere due to temperatures below the water condensation threshold, leading to deuterium-enriched aerosols. These aerosols ascend, evaporate at higher temperatures, and release more HDO than H2O, which are then transported downward. Moreover, this cycle may explain the SO2 increase in the upper mesosphere observed above 80 km. The study highlights two crucial implications. First, altitude variation is critical to determining the Venus deuterium and hydrogen reservoirs. Second, the altitude-dependent increase of the D/H ratio affects H and D escape rates. The photolysis of H2O and HDO at higher altitudes releases more D, influencing long-term D/H evolution. These findings suggest that evolutionary models should incorporate altitude-dependent processes for accurate D/H fractionation predictions.

Use of the intradermal leishmanin test (Montenegro skin test) for feline visceral leishmaniosis: Detection of cellular immunity.

This study evaluated the humoral and cellular response in 100 cats living in an endemic area of visceral leishmaniosis (VL) using the Montenegro Skin Test (MST) and serological diagnosis and compared the MST with other diagnostic techniques. Sixty 60%, (60/100) cats were positive for MST and the diameter of positive skin reactions ranged from 5 to 9 mm. By serological methods, 74% (74/100) and 34% (34/100) had antibodies against Leishmania spp. by Immunofluorescence Antibody Test (IFAT) and Indirect Enzyme-Linked Immunosorbent Assay (ELISA), respectively. Comparing tests, the observed profiles were (1) IFAT (+)/MST (-) = 27 cats, (2) IFAT(-)/MST(+) = 13 cats, (3) IFAT(+)/MST(+) = 47 cats, (4) ELISA(+)/MST(-) = 12 cats, (5) ELISA(-)/MST(+) = 38 cats and (6) ELISA(+)/MST(+) = 22 cats. Through the combination of serological diagnosis and MST, a positivity frequency of 87% (87/100) by IFAT + MST and 72% (72/100) by ELISA + MST was identified in this cat population. Five cats (5%) were positive for Leishmania donovani complex DNA by molecular analysis, and two cats (2%) had Leishmania spp. amastigotes in lymph node smears. Therefore, the agreement between tests was classified as poor for all tests by Kappa index. The IFAT (+)/MST (+) response was the most frequent considering all cats (47%; 47/100); nonetheless, the most frequent immune expression in Polymerase Chain Reaction (PCR)-positive cats was the IFAT (+)/MST (-) profile (80%; 4/5). Five sick and PCR-positive cats, negative for Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV), that PCR sequencing matched 100% with L. donovani complex, all but one were MST negative. These results suggest that cats develop a significant cellular response against infection by parasites of the L. donovani complex, and most PCR and parasitological positive cats may be unable to develop a significant cellular response.

Implementing ICHOM standard set for cataract surgery at IPO-Porto (Portugal): clinical outcomes, quality of life and costs.

BACKGROUND: This paper fills a gap in the applied research field, for a local context, by addressing the topics of describing cataract surgery' clinical outcomes; quality of life (QoL); and costs of the patients treated after the implementation of the ICHOM standard set. METHODS: This is a retrospective observational study using real-world data (RWD). We included all patients subjected to cataract surgery at the Portuguese Institute of oncology - Porto (IPO-Porto), Portugal, after 3 months follow up period completed between 5th June 2017 and 21st May 2018. The following inclusion criteria: corrected visual acuity of ≤ 6/10 or other significant visual disturbance due to lens opacity or the existence of a large anisometropia. A circuit was implemented based on the ICHOM standard for cataract, to measure clinical variables (e.g. visual acuity) and QoL (CATQUEST-9SF) before and after surgery, and cost of treatment. The results were explored by means of a paired-sample t-test, considering normality assumptions. RESULTS: Data refers to 268 patients (73 P25-P75:32-95 years old), regarding 374 eyes. The cataract surgery had a positive effect on visual acuity (p < 0.001), refraction (right and left cylinder; p < 0.001) and all QoL dimensions. The vast majority of patients, around 98%, reported improvements in QoL. Based on IPO-Porto administrative records, the direct cost of treating cataracts (per eye) is of 500€, representing a total cost of 187,000€ for the number of patients operated herein. CONCLUSION: This study reports the successful implementation of the ICHOM standard set for cataracts in a Portuguese institution and confirms that cataract surgery provides a rapid visual recovery, with excellent visual outcomes and minimal complications in most patients, while also having a positive impact on patients' quality of life.

Do Cohabitants Reliably Complete Questionnaires for Patients in a Terminal Cancer Stage when Assessing Quality of Life, Pain, Depression, and Anxiety?

BACKGROUND: Patients with bone metastases often are unable to complete quality of life (QoL) questionnaires, and cohabitants (such as spouses, domestic partners, offspring older than 18 years, or other people who live with the patient) could be a reliable alternative. However, the extent of reliability in this complicated patient population remains undefined, and the influence of the cohabitant's condition on their assessment of the patient's QoL is unknown. QUESTIONS/PURPOSES: (1) Do QoL scores, measured by the 5-level EuroQol-5D (EQ-5D-5L) version and the Patient-reported Outcomes Measurement Information System (PROMIS) version 1.0 in three domains (anxiety, pain interference, and depression), reported by patients differ markedly from scores as assessed by their cohabitants? (2) Do cohabitants' PROMIS-Depression scores correlate with differences in measured QoL results? METHODS: This cross-sectional study included patients and cohabitants older than 18 years of age. Patients included those with presence of histologically confirmed bone metastases (including lymphoma and multiple myeloma), and cohabitants must have been present at the clinic visit. Patients were eligible for inclusion in the study regardless of comorbidities, prognosis, prior surgery, or current treatment. Between June 1, 2016 and March 1, 2017 and between October 1, 2017 and February 26, 2018, all 96 eligible patients were approached, of whom 49% (47) met the selection criteria and were willing to participate. The included 47 patient-cohabitant pairs independently completed the EQ-5D-5L and the eight-item PROMIS for three domains (anxiety, pain, and depression) with respect to the patients' symptoms. The cohabitants also completed the four-item PROMIS-Depression survey with respect to their own symptoms. RESULTS: There were no clinically important differences between the scores of patients and their cohabitants for all questionnaires, and the agreement between patient and cohabitant scores was moderate to strong (Spearman correlation coefficients ranging from 0.52 to 0.72 on the four questionnaires; all p values < 0.05). However, despite the good agreement in QoL scores, an increased cohabitant's depression score was correlated with an overestimation of the patient's symptom burden for the anxiety and depression domains (weak Spearman correlation coefficient of 0.33 [95% confidence interval 0.08 to 0.58]; p = 0.01 and moderate Spearman correlation coefficient of 0.52 [95% CI 0.29 to 0.74]; p < 0.01, respectively). CONCLUSION: The present findings support that cohabitants might be reliable raters of the QoL of patients with bone metastases. However, if a patient's cohabitant has depression, the cohabitant may overestimate a patient's symptoms in emotional domains such as anxiety and depression, warranting further research that includes cohabitants with and without depression to elucidate the effect of depression on the level of agreement. For now, clinicians may want to reconsider using the cohabitant's judgement if depression is suspected. CLINICAL RELEVANCE: These findings suggest that a cohabitant's impressions of a patient's quality of life are, in most instances, accurate; this is potentially helpful in situations where the patient cannot weigh in. Future studies should employ longitudinal designs to see how or whether our findings change over time and with disease progression, and how specific interventions-like different chemotherapeutic regimens or surgery-may factor in.

Identification of hospitalized patients with community-acquired infection in whom treatment guidelines do not apply: a validated model.

OBJECTIVES: To develop and validate a clinical model to identify patients admitted to hospital with community-acquired infection (CAI) caused by pathogens resistant to antimicrobials recommended in current CAI treatment guidelines. METHODS: International prospective cohort study of consecutive patients admitted with bacterial infection. Logistic regression was used to associate risk factors with infection by a resistant organism. The final model was validated in an independent cohort. RESULTS: There were 527 patients in the derivation and 89 in the validation cohort. Independent risk factors identified were: atherosclerosis with functional impairment (Karnofsky index <70) [adjusted OR (aOR) (95% CI) = 2.19 (1.41-3.40)]; previous invasive procedures [adjusted OR (95% CI) = 1.98 (1.28-3.05)]; previous colonization with an MDR organism (MDRO) [aOR (95% CI) = 2.67 (1.48-4.81)]; and previous antimicrobial therapy [aOR (95% CI) = 2.81 (1.81-4.38)]. The area under the receiver operating characteristics (AU-ROC) curve (95% CI) for the final model was 0.75 (0.70-0.79). For a predicted probability ≥22% the sensitivity of the model was 82%, with a negative predictive value of 85%. In the validation cohort the sensitivity of the model was 96%. Using this model, unnecessary broad-spectrum therapy would be recommended in 30% of cases whereas undertreatment would occur in only 6% of cases. CONCLUSIONS: For patients hospitalized with CAI and none of the following risk factors: atherosclerosis with functional impairment; previous invasive procedures; antimicrobial therapy; or MDRO colonization, CAI guidelines can safely be applied. Whereas, for those with some of these risk factors, particularly if more than one, alternative antimicrobial regimens should be considered.

Physical function and pain intensity in patients with metastatic bone disease.

BACKGROUND: Patient reported outcome data in bone metastatic disease are scarce and it would be useful to have normative data and understand what patients are at risk for poor function and more pain. OBJECTIVES: We aimed to assess what factors are independently associated with physical function and pain intensity in patients with bone metastasis. METHODS: We included data from 211 patients with bone metastasis who completed a survey (2014-2016) including the PROMIS Physical Function Cancer and PROMIS Pain Intensity questionnaires. RESULTS: Prostate (P < .001) and thyroid carcinoma (P = .007) were associated with better function and having other disabling conditions (P = 0.035) was associated with worse function. Prostate carcinoma (P = .001) and lymphoma (P = .007) were associated with less pain. There was a moderate correlation between pain and function (P < .001). Function was substantially worse as compared to a US reference population of patients with cancer (P < .001), whereas pain was slightly less compared to the US general population average (P < .001). CONCLUSIONS: Patients with bone metastasis have a poor physical function. Physical function and pain intensity depend on tumor histology, but also on potentially modifiable factors such as other disabling conditions. LEVEL OF EVIDENCE: Level III, prognostic study.

High Risk of Symptomatic Venous Thromboembolism After Surgery for Spine Metastatic Bone Lesions: A Retrospective Study.

BACKGROUND: Cancer and spinal surgery are both considered risk factors for venous thromboembolism (VTE). However, the risk of symptomatic VTE for patients undergoing surgery for spine metastases remains undefined. QUESTIONS/PURPOSES: The purposes of this study were to: (1) identify the proportion of patients who develop symptomatic VTE within 90-days of surgical treatment for spine metastases; (2) identify the factors associated with the development of symptomatic VTE among patients receiving surgery for spine metastases; (3) assess the association between the development of postoperative symptomatic VTE and 1-year survival among patients who underwent surgery for spine metastases; and (4) assess if chemoprophylaxis increases the risk of wound complications among patients who underwent surgery for spine metastases. METHODS: Between 2002 and 2014, 637 patients at two hospitals underwent spine surgery for metastases. We considered eligible for analysis adult patients whose procedures were to treat cervical, thoracic, or lumbar metastases (including lymphoma and multiple myeloma). At followup after 90 days and 1 year, respectively, 21 of 637 patients (3%) and 41 of 637 patients (6%) were lost to followup. In general, we used 40 mg of enoxaparin or 5000 IUs subcutaneous heparin every 12 hours. Patients on preoperative chemoprophylaxis continued their initial medication postoperatively. All chemoprophylaxis was started 48 hours after surgery and continued day to day but was discontinued if a bleeding complication developed. Low-molecular-weight heparin (including enoxaparin and dalteparin, in general dosages of respectively 40 mg and 5000 IUs daily) was the most commonly used chemoprophylaxis in 308 patients (48%). Subcutaneous heparin was injected into 127 patients (20%); aspirin was used for 92 patients (14%); and warfarin was administered in 21 patients (3.3%). No form of chemoprophylaxis was prescribed for 89 patients (14%). The primary outcome variable, VTE, was defined as any symptomatic pulmonary embolism (PE) or symptomatic deep venous thromboembolism (DVT) within 90 days of surgery as determined by chart review. The secondary outcome was defined as any documented wound complication within 90 days of surgery that might be attributable to chemoprophylaxis. Statistical analysis was performed using multivariable logistic and Cox regression and Kaplan-Meier. RESULTS: Overall, 72 of 637 patients (11%) had symptomatic VTE; 38 (6%) developed a PE-eight (1.3%) of which were fatal-and 40 (6%) a DVT. After controlling for relevant confounding variables such as age, the modified Charlson Comorbidity Index, visceral metastases, and chemoprophylaxis, longer duration of surgery was independently associated with an increased risk of symptomatic VTE (odds ratio 1.15 for each additional hour of surgery; 95% confidence interval [CI], 1.04-1.28; p = 0.009). After controlling for relevant confounding variables such as age, the modified Charlson Comorbidity Index, visceral metastases, and primary tumor type, patients with symptomatic VTE had a worse 1-year survival rate (VTE, 38%; 95% CI, 27-49 versus nonVTE, 47%; 95% CI, 42-51; p = 0.044). After controlling for relevant confounding variables, no association was found between wound complications and the use of chemoprophylaxis (odds ratio, 1.34; 95% CI, 0.62-2.90; p = 0.459). The overall proportion of patients who developed a wound complication was 10% (66 of 637), including 1.1% (seven of 637) spinal epidural hematomas. CONCLUSIONS: The risk of both symptomatic PE and fatal PE is high in this patient population, and those with symptomatic VTE were less likely to survive 1-year than those who did not, though this may reflect overall infirmity as much as anything else, because many of these patients did not die from VTE-related complications. Further study, such as randomized controlled trials with consistent postoperative VTE screening comparing different chemoprophylaxis regimens, are needed to identify better VTE prevention strategies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Prognostic role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with bone metastases.

BACKGROUND: Skeletal metastases are a common problem in patients with cancer, and surgical decision making depends on multiple factors including life expectancy. Identification of new prognostic factors can improve survival estimation and guide healthcare providers in surgical decision making. In this study, we aim to determine the prognostic value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with bone metastasis. METHODS: One thousand and twelve patients from two tertiary referral centers between 2002 and 2014 met the inclusion criteria. Bivariate and multivariate Cox regression analyses were performed to determine the association of NLR and PLR with survival. RESULTS: At 3 months, 84.0% of the patients with low NLR were alive versus 61.3% of the patients with a high NLR (p < 0.001), and 75.8% of the patients with a low PLR were alive versus 55.6% of the patients with a high PLR (p < 0.001). Both elevated NLR and elevated PLR were independently associated with worse survival (hazard ratio (HR): 1.311; 95% confidence interval (CI): 1.117-1.538; p = 0.001) and (HR: 1.358; 95% CI: 1.152-1.601; p < 0.001), respectively. CONCLUSION: This study showed both NLR and PLR to be independently associated with survival in patients who were treated for skeletal metastasis.

Conventional versus pigtail chest tube-are they similar for treatment of malignant pleural effusions?

INTRODUCTION: The optimal chest tube type and size for drainage and chemical pleurodesis of malignant pleural effusions remains controversial. This retrospective study was conducted to compare the efficacy of conventional versus pigtail chest tube in the treatment of malignant pleural effusions. METHODS: Patients submitted to chest tube drainage and slurry talc pleurodesis due to malignant pleural effusion in our pulmonology ward from 2012 to 2016 were eligible. According to the type of chest tube, they were divided into two groups: group I-conventional chest tube and group II-pigtail chest tube. Number of deaths, recurrence of malignant pleural effusion, and timelines associated with the procedures were reviewed and compared between groups. RESULTS: Out of the 61 included patients, 46 (75.4%) were included in group I and 15 (24.6%) in group II. Only one patient had pigtail chest tube obstruction, with posterior insertion of conventional chest tube. Death during hospital stay and up to 3 months, recurrence at 4 weeks, total duration of hospital stay, time from chest tube insertion to pleurodesis, and time from chest tube insertion to removal were not significantly different between the two groups (all p > 0.05). DISCUSSION: These findings suggest that pigtail chest tube can be an alternative on palliation, with no compromise in pleurodesis performance.

High Risk of Venous Thromboembolism After Surgery for Long Bone Metastases: A Retrospective Study of 682 Patients.

BACKGROUND: Previous studies have shown that venous thromboembolism (VTE) is a complication associated with neoplastic disease and major orthopaedic surgery. However, many potential risk factors remain undefined. QUESTIONS/PURPOSES: (1) What proportion of patients develop symptomatic VTE after surgery for long bone metastases? (2) What factors are associated with the development of symptomatic VTE among patients receiving surgery for long bone metastases? (3) Is there an association between the development of symptomatic VTE and 1-year survival among patients undergoing surgery for long bone metastases? (4) Does chemoprophylaxis increase the risk of wound complications among patients undergoing surgery for long bone metastases? METHODS: A retrospective study identified 682 patients undergoing surgical treatment of long bone metastases between 2002 and 2013 at the Massachusetts General Hospital and Brigham and Women's Hospital. We included patients 18 years of age or older who had a surgical procedure for impending or pathologic metastatic long bone fracture. We considered the humerus, radius, ulna, femur, tibia, and fibula as long bones; metastatic disease was defined as metastases from solid organs, multiple myeloma, or lymphoma. In general, we used 40 mg enoxaparin daily for lower extremity surgery and 325 mg aspirin daily for lower or upper extremity surgery. The primary outcome was a VTE defined as any symptomatic pulmonary embolism (PE) or symptomatic deep vein thrombosis (DVT; proximal and distal) within 90 days of surgery as determined by chart review. The tertiary outcome was defined as any documented wound complication that might be attributable to chemoprophylaxis within 90 days of surgery. At followup after 90 days and 1 year, respectively, 4% (25 of 682) and 8% (53 of 682) were lost to followup. Statistical analysis was performed using multivariable logistic and Cox regression and Kaplan-Meier. RESULTS: Overall, 6% (44 of 682) of patients had symptomatic VTE; 22 patients sustained a DVT, and 22 developed a PE. After controlling for relevant confounding variables, higher preoperative hemoglobin level was independently associated (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.60-0.93; p = 0.011) with decreased symptomatic VTE risk, the presence of symptomatic VTE was associated with a worse 1-year survival rate (VTE: 27% [95% CI, 14%-40%] and non-VTE: 39% [95% CI, 35%-43%]; p = 0.041), and no association was found between wound complications and the use of chemoprophylaxis (OR, 3.29; 95% CI, 0.43-25.17; p = 0.252). CONCLUSIONS: The risk of symptomatic 90-day VTE is high in patients undergoing surgery for long bone metastases. Further study would be needed to determine the VTE prevention strategy that best balances risks and benefits to address this complication. LEVEL OF EVIDENCE: Level III, therapeutic study.

Predicting pathological fracture in femoral metastases using a clinical CT scan based algorithm: A case-control study.

BACKGROUND: We assessed whether there was a difference in attenuation measurements (in Hounsfield units - HU) and geometric distribution of HU between femora with metastatic lesions that fracture, and metastatic lesions that did not fracture nor underwent prophylactic fixation. METHODS: Nine patients with femoral metastases who underwent CT and developed a pathological fracture were matched to controls. All femora were delineated in axial CT slices using a region of interest (ROI) tool; the HU within these ROIs were used to calculate: (1) the cumulative HU of the affected over the nonaffected side per slice and presented as a percentage, and (2) the cumulative HU accounting for geometric distribution (polar moment of HU). We repeated the analyses including cortical bone only (HU of 600 and above). RESULTS: CT-based calculations did not differ between patients with a lesion that fractured and those that did not fracture nor underwent prophylactic fixation when analyzing all tissue. However, when including cortical bone only, the pathological fracture group had a lower cumulative HU value compared to the no fracture and no fixation group for the weakest cross-sectional CT image (pathological fracture group, mean: 71, SD: 23 and no fracture and no prophylactic fixation group, mean: 85, SD: 18, p = 0.042) and the complete lesion analysis (pathological fracture group, mean: 78, SD: 21 and no fracture and no prophylactic fixation group, mean: 92, SD: 15, p = 0.032). CONCLUSION: The demonstrated CT-based algorithms can be useful for predicting pathological fractures in metastatic lesions.

Obstructive sleep apnoea in patients with fibrotic diffuse parenchymal lung disease-characterization and treatment compliance assessment.

INTRODUCTION: Recent studies have reported a high prevalence of obstructive sleep apnoea (OSA) among patients with diffuse parenchymal lung disease (DPLD), mainly idiopathic pulmonary fibrosis (IPF). Effective OSA treatment appears to have a positive impact on morbidity and mortality in these patients. However, poor compliance to positive airway pressure (PAP) treatment in fibrotic DPLD patients has been reported. The aims of our study were to characterize patients with fibrotic DPLD and OSA and to assess their compliance to PAP treatment. METHODS: Forty-nine patients with fibrotic DPLD underwent level III polysomnography. Auto-adjusting PAP (APAP) treatment was proposed for those patients with moderate-to-severe OSA and those with mild OSA with daytime sleepiness and/or cardiovascular disease. The APAP treatment compliance was assessed after 1 month of therapy. RESULTS: The distribution of the 49 fibrotic DPLD patients included was as follows: 21 with chronic hypersensitivity pneumonitis, 12 with IPF, 10 with connective-tissue associated DPLD, 4 with stage IV sarcoidosis, 1 with idiopathic pleuropulmonary fibroelastosis, and 1 with DPLD-associated vasculitis. Thirty-four (69.4%) of the patients presented with OSA; 22 had mild OSA, and 12 had moderate-to-severe OSA. APAP treatment was prescribed in 17 of the patients. After 1 month of therapy, all patients used APAP more than 70% of the nights for more than 4 h per night. CONCLUSION: We found a high prevalence of OSA among all of the patients with fibrotic DPLD (not only IPF). Despite certain difficulties, it was possible to achieve good APAP compliance in these patients.

The SORG nomogram accurately predicts 3- and 12-months survival for operable spine metastatic disease: External validation.

BACKGROUND AND OBJECTIVES: Externally validate the SORG12 nomogram and SORG classic algorithm at estimating survival in patients with spine metastatic disease, and compare predictive accuracy with other survival algorithms. METHODS: We received data from 100 patients who had surgery for spine metastatic disease at an external institution. Algorithms were accurate if the Area Under Curve (AUC) was >0.70, and we used Receiver Operating Characteristic (ROC) analysis to compare predictive accuracy with other algorithms. RESULTS: The SORG nomogram accurately estimated 3-months (AUC = 0.74) and 12-months survival (AUC = 0.78); it did not accurately estimate 1-month survival (AUC = 0.65). There was no difference in 1-month survival accuracy between the SORG nomogram and SORG classic algorithm (P = 0.162). The SORG nomogram was best at predicting 3-months survival, compared with the Tokuhashi score and SORG classic algorithm (P = 0.009). The SORG nomogram was best at predicting 12-months survival, compared with the Tomita score, Ghori score, Bauer modified score, Tokuhashi score, and SORG classic algorithm (P = 0.033). CONCLUSIONS: The SORG nomogram accurately estimated 3- and 12-months survival for operable spine metastatic disease, and is therefore, useful in clinical practice.

Factors associated with infection after reconstructive shoulder surgery for proximal humerus tumors.

BACKGROUND: The main reconstruction techniques for proximal humerus tumors include osteoarticular allografts (OAs), endoprostheses (EPs), or allograft prosthetic composites (APCs). A common complication is infection, and constructs involving the use of allografts are believed to be at a higher risk of infection. Literature comparing infection rates between different modalities of reconstruction is scarce and underpowered. The study purposes were (1) to determine and compare the prevalence of infection in patients who underwent reconstruction of the proximal humerus including OAs, EPs, and APCs; (2) to identify preoperative, perioperative, and postoperative predictors of infection that might be modifiable; and (3) to present our protocol of treatment in patients with superficial and deep infections. METHODS: We reviewed 150 patients of all ages with proximal humerus tumors treated by an OA, EP, or APC at 2 tertiary institutions. The prevalence of infection for each modality was calculated and compared between groups. We identified potential predictors of infection with stepwise backward multivariate Cox regression analysis. RESULTS: An infection developed in 19 patients (12%): 5 of 45 (11%) in the OA group, 12 of 85 (14%) in the EP group, and 2 of 20 (10%) in the APC group (P = .740). A lower preoperative hemoglobin blood level and low preoperative albumin blood level were independently associated with infection. CONCLUSIONS: We found similar infection rates compared with previously reported series. However, we did not identify a higher infection prevalence in constructs using allografts. Patients with a lower preoperative hemoglobin or albumin level are at higher risk of infection and should undergo optimization before surgery.

Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

BACKGROUND: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. OBJECTIVE: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. METHODS: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. RESULTS: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. CONCLUSIONS: In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

A comparison of questionnaires for assessing physical function in patients with lower extremity bone metastases.

OBJECTIVES: To assess, (i) the degree to which the: PROMIS Physical Function Cancer, PROMIS Neuro-QoL Mobility, Toronto Extremity Salvage Score (TESS), Lower Extremity Function Score (LEFS), and Musculoskeletal Tumor Society score (MSTS), measure physical function; (ii) differences in coverage and reliability; and (iii) difference in completion time. METHODS: One hundred of 115 (87%) patients with lower extremity metastases participated in this prospective study. We used exploratory factor analysis-correlating questionnaires with an underlying trait-to assess if questionnaires measure the same. Coverage was assessed by floor and ceiling effect and reliability by the standard error of measurement (SEM). Completion time was compared using the Friedman test. RESULTS: All questionnaires measured the same concept; demonstrated by high correlations (>0.7). Floor effect was absent, while ceiling effect was present in all, but highest for the PROMIS Neuro-QoL Mobility (7%). The SEM was below the threshold-indicating reliability-over a wide range of ability levels for the PROMIS-Physical Function, TESS, and LEFS. Completion time differed between questionnaires (P < 0.001) and was shortest for the PROMIS questionnaires. CONCLUSIONS: The PROMIS Physical Function is the most useful questionnaire. This is due to its reliability over a wide range of ability levels, validity, brevity, and good coverage. J. Surg. Oncol. 2016;114:691-696. © 2016 Wiley Periodicals, Inc.

Are perioperative allogeneic blood transfusions associated with 90-days infection after operative treatment for bone metastases?

BACKGROUND AND OBJECTIVES: We assessed whether allogeneic blood transfusions were associated with infection-within 90 days-after surgery for bone metastatic disease. Furthermore, we assessed other risk factors associated with infection. METHODS: We included 1,266 patients surgically treated for a bone metastasis at two hospitals between 2002 and 2013. Blood transfusions within 7 days before and after surgery were considered perioperative. RESULTS: We found no independent association between exposure to blood transfusion and infection (odds ratio [OR] 1.02, 95% confidence interval [CI]: 0.76-1.37, P = 0.889), nor a dose-response relationship (OR 1.02, 95%CI: 0.98-1.07, P = 0.245). Older age (OR 1.01, 95%CI: 1.00-1.02, P = 0.035), a higher modified Charlson comorbidity index (OR 1.13, 95%CI: 1.05-1.22, P = 0.002), surgery to the axial skeleton (OR 1.89, 95%CI: 1.42-2.51, P < 0.001), and previous radiotherapy (OR 1.45, 95%CI 1.07-1.96, P = 0.015) were independently associated with infection. CONCLUSIONS: There was no association between allogeneic blood transfusion and infection. We found other risk factors that should be taken into consideration when deciding to operate. J. Surg. Oncol. 2016;114:997-1003. © 2016 Wiley Periodicals, Inc.

Redislocation risk after an arthroscopic Bankart procedure in collision athletes: a systematic review.

BACKGROUND: The purpose of this review was to determine the redislocation risk for collision athletes after an arthroscopic Bankart repair and to compare the redislocation rate between collision athletes and noncollision athletes after an arthroscopic Bankart repair. METHODS: A PubMed and Embase query was performed, screening all relevant literature of arthroscopic Bankart procedures mentioning redislocation rates in collision athletes. Studies with a follow-up <2 years or lacking information on redislocation rates in collision athletes were excluded. We used the modified Coleman Methodology Score to assess the quality of included studies. Finally, the data in all the studies were combined and analyzed. RESULTS: There were 1012 studies screened on title and abstract, of which 111 studies were full-text screened, and finally 20 studies were included. Four studies reported on collision athletes only, whereas 16 compared collision with noncollision athletes. Fourteen studies reported increased redislocation rates for collision athletes in comparison to noncollision athletes (absolute risk difference varying from 0.4% to 28.6%), whereas 2 studies reported decreased rates (absolute risk differences of -6% and -2.4%). A combined analysis revealed that collision athletes have an increased absolute risk of 8.09 with 95% CI from 3.61 to 12.57% for development of postoperative instability in comparison to noncollision athletes (P = .001). CONCLUSION: Collision athletes have an increased risk for redislocation in comparison to noncollision athletes after an arthroscopic Bankart repair, although there were no differences in return to sport.

Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists.

Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl d-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i) a stereoselective cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic δ-oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson's disease). This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors.

Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis.

BACKGROUND: Nocardia species cause infections in both immunocompromised and otherwise immunocompetent patients, although the mechanisms defining susceptibility in the latter group are elusive. Anticytokine autoantibodies are an emerging cause of pathogen-specific susceptibility in previously healthy human immunodeficiency virus-uninfected adults, including anti-granulocyte macrophage colony-stimulating factor (GM-CSF) autoantibodies with cryptococcal meningitis. METHODS: Plasma from patients with disseminated/extrapulmonary nocardiosis and healthy controls was screened for anticytokine autoantibodies using a particle-based approach. Autoantibody function was assessed by intranuclear staining for GM-CSF-induced STAT5 phosphorylation in normal cells incubated with either patient or normal plasma. GM-CSF-mediated cellular activation by Nocardia was assessed by staining for intracellular cytokine production and intranuclear STAT5 phosphorylation. RESULTS: We identified neutralizing anti-GM-CSF autoantibodies in 5 of 7 patients studied with central nervous system nocardiosis and in no healthy controls (n = 14). GM-CSF production was induced by Nocardia in vitro, suggesting a causative role for anti-GM-CSF autoantibodies in Nocardia susceptibility and dissemination. CONCLUSIONS: In previously healthy adults with otherwise unexplained disseminated/extrapulmonary Nocardia infections, anti-GM-CSF autoantibodies should be considered. Their presence may suggest that these patients may be at risk for later development of pulmonary alveolar proteinosis or other opportunistic infections, and that patients may benefit from therapeutic GM-CSF administration.