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Objectives To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and Methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk‐calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m‐R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN 3 , and ILNM ratio were associated with higher recurrence rate. The 2‐year OS rates were lower for patients with high (>37%) and intermediate (19–37%) compared to low (<19%) 24m‐R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment ( P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts ( P > 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

Abstract Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. We report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers from 2005 through 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients &lt;5 vs ≥5 years of age at the time of HCT (94% vs 66%; overall P = .0008). OS was excellent regardless of donor type, even in cord blood recipients (90%). Conditioning intensity did not affect OS, but was associated with donor T-cell and myeloid engraftment after HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism &lt;50% early after HCT. In addition, higher platelet counts were observed among recipients who achieved full (&gt;95%) vs low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005, compared with prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution after either myeloablative or busulfan-containing reduced intensity conditioning. (This trial was registered at www.clinicaltrials.gov as #NCT02064933.)

AbstractBackgroundPulseless ventricular tachycardia/ventricular fibrillation (VT/VF) is the initial rhythm in a third of in‐hospital cardiac arrest patients. Mechanical circulatory support (MCS) device use remains poorly understood in this population.MethodsWe conducted an observational analysis of temporal trends in the utilization of MCS in VT/VF IHCA between January 2008 and December 2014 utilizing the Nationwide Inpatient Sample (NIS) database. Using multivariable analysis, we assessed factors associated with MCS use and survival to discharge.ResultsAmong 151,628 hospitalizations with VT/VF IHCA, 14,981 (9.9%) received MCS. Intra‐aortic balloon pump (IABP) was the most commonly used MCS (9.1%). From 2008 to 2014, there was significant increase in the utilization of MCS (8.7–11%; ptrend < 0.0001). On multivariable analysis, there was 12‐fold increase and three‐fold increase in the utilization of PVAD and ECMO respectively; however, there was no significant change in the use of IABP. Over the seven‐year sample period, there was significant increase in the overall survival to hospital discharge (35.4–43.5%; ptrend < 0.0001). Survival to hospital discharge increased in both MCS and non‐MCS groups.ConclusionThere was significant increase in utilization of MCS after VT/VF IHCA during the study period. IABP was the most commonly utilized MCS. The survival to hospital discharge increased in the overall study population including both MCS and non‐MCS groups. Future studies are needed to identify patient population most likely to benefit from the use of MCS after VT/VF IHCA.

OBJECTIVE Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. RESEARCH DESIGN AND METHODS Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. RESULTS The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1–3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1–3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1–3 INT groups (P = 0.024) and was similar to that for the CONV group. CONCLUSIONS For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.

Objective This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence‐based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). Methods A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi‐step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. Results The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease‐modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low‐ or moderate‐quality evidence. Conclusion This guideline should help decision‐making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high‐quality direct randomized controlled trial data.

ObjectiveThis collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence‐based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA).MethodsA panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi‐step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences.ResultsThe guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease‐modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low‐ or moderate‐quality evidence.ConclusionThis guideline should help decision‐making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high‐quality direct randomized controlled trial data.

Aortoiliac occlusive disease is a subset of peripheral arterial disease involving an atheromatous occlusion of the infrarenal aorta, common iliac arteries, or both. The disease, as it is known today, was described by the French surgeon René Leriche as a thrombotic occlusion of the end of the aorta. Leriche successfully linked the anatomic location of the occlusion with a unique triad of symptoms, including claudication, impotence, and decreased peripheral pulses. The anatomical location of the atheromatous lesions also has a direct influence on classification of the disease, as well as choice of treatment modality. Considering its impact on diagnosis and treatment, we aimed to provide a detailed understanding of the anatomical structures involved in aortoiliac occlusive disease. Familiarity with these structures will aid the physician in interpretation of radiologic images and surgical planning. Clin. Anat. 27:1264–1274, 2014. © 2014 Wiley Periodicals, Inc.

Abstract Extracellular cyclophilins have been well described as chemotactic factors for various leukocyte subsets. This chemotactic capacity is dependent upon interaction of cyclophilins with the cell surface signaling receptor CD147. Elevated levels of extracellular cyclophilins have been documented in several inflammatory diseases. We propose that extracellular cyclophilins, via interaction with CD147, may contribute to the recruitment of leukocytes from the periphery into tissues during inflammatory responses. In this study, we examined whether extracellular cyclophilin-CD147 interactions might influence leukocyte recruitment in the inflammatory disease allergic asthma. Using a mouse model of asthmatic inflammation, we show that 1) extracellular cyclophilins are elevated in the airways of asthmatic mice; 2) mouse eosinophils and CD4+ T cells express CD147, which is up-regulated on CD4+ T cells upon activation; 3) cyclophilins induce CD147-dependent chemotaxis of activated CD4+ T cells in vitro; 4) in vivo treatment with anti-CD147 mAb significantly reduces (by up to 50%) the accumulation of eosinophils and effector/memory CD4+ T lymphocytes, as well as Ag-specific Th2 cytokine secretion, in lung tissues; and 5) anti-CD147 treatment significantly reduces airway epithelial mucin production and bronchial hyperreactivity to methacholine challenge. These findings provide a novel mechanism whereby asthmatic lung inflammation may be reduced by targeting cyclophilin-CD147 interactions.