Organometallic Pillarplexes That Bind DNA 4-Way Holliday Junctions and Forks.

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination, and repair) and are dynamic structures that adopt either open or closed conformations, the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core, an ideal structure to interact with open DNA junction cavities. Combining experimental studies and MD simulations, we show that an Au pillarplex can bind DNA 4-way (Holliday) junctions in their open form, a binding mode not accessed by synthetic agents before. Pillarplexes can bind 3-way junctions too, but their large size leads them to open up and expand that junction, disrupting the base pairing, which manifests in an increased hydrodynamic size and lower junction thermal stability. At high loading, they rearrange both 4-way and 3-way junctions into Y-shaped forks to increase the available junction-like binding sites. Isostructural Ag pillarplexes show similar DNA junction binding behavior but lower solution stability. This pillarplex binding contrasts with (but complements) that of metallo-supramolecular cylinders, which prefer 3-way junctions and can rearrange 4-way junctions into 3-way junction structures. The pillarplexes' ability to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures. In human cells, the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher-order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction binders into organometallic chemistry.

Patient-reported symptoms after minimally invasive hysterectomy and association with postoperative complications.

OBJECTIVE: To describe patient-reported postoperative symptoms and to evaluate the use of digital symptom tracking and alerts to detect postoperative complications. METHODS: We retrospectively reviewed patients who underwent a minimally invasive hysterectomy and enrolled in our Recovery Tracker program from 4/5/17-12/31/21. The Recovery Tracker is an at-home virtual tool used to track patient-reported postoperative symptoms for 10 days. Predefined thresholds for "red" and "yellow" alerts are based on symptom severity and timing. Data on patient demographics, surgery, and postoperative course were collected to evaluate the association of alerts with complications and compare outcomes of patients who did/did not enroll in the program. RESULTS: Of 2362 eligible patients, 1694 (71.7%) enrolled in the Recovery Tracker program. Pain was the most severe symptom, followed by fatigue. Eighty-seven patients experienced 102 complications (5.1% complication rate) and 32 experienced 39 grade ≥ 2 complications (1.9% severe complication rate). Excluding complications that occurred prior to Recovery Tracker use, 1673 patients experienced 28 grade ≥ 2 complications. Of 345 patients (20.6%) who triggered a red alert, 13 (3.8%) had a grade ≥ 2 complication. Of 1328 patients (79.4%) with no red alerts, 15 (1.13%) had a grade ≥ 2 complication. Relative risk of a grade ≥ 2 complication if a red alert was triggered was 3.25 (95% CI: 1.6-6.9, P = .002). Rate of severe complications was significantly higher among patients who did not use the tool (3.3% vs 1.9%; P = .04). CONCLUSIONS: The Recovery Tracker tool may assist in early identification of postoperative symptoms after minimally invasive hysterectomy.

A comparison of brief versus explicit descriptors for verbal rating scales: interrupted time series design.

BACKGROUND: Verbal rating scales (VRS) are widely used in patient-reported outcome (PRO) measures. At our institution, patients complete an online instrument using VRSs with a five-point brief response scale to assess symptoms as part of routine follow-up after ambulatory cancer surgery. We received feedback from patients that the brief VRS descriptors such as "mild" or "somewhat" were vague. We added explicit descriptors to our VRSs, for instance, "Mild: I can generally ignore my pain" for pain severity or "Somewhat: I can do some things okay, but most of my daily activities are harder because of fatigue" for fatigue interference. We then compared responses before and after this change was made. METHODS: The symptoms investigated were pain, fatigue and nausea. Our hypothesis was that the explicit descriptors would reduce overall variance. We therefore compared the coefficient of variation of scores and tested the association between symptoms scores and known predictors thereof. We also compared time to completion between questionnaires with and without the additional descriptors. RESULTS: A total of 17,500 patients undergoing 21,497 operations were assigned questionnaires in the period before the descriptors were added; allowing for a short transition period, 1,417 patients having 1436 operations were assigned questionnaires with the additional descriptors. Symptom scores were about 10% lower with the additional descriptors but the coefficient of variation was slightly higher. Moreover, the only statistically significant difference between groups for association with a known predictor favored the item without the additional language for nausea severity (p = 0.004). Total completion time was longer when the instrument included the additional descriptors, particularly the first and second time that the questionnaire was completed. CONCLUSIONS: Adding descriptors to a VRS of post-operative symptoms did not improve scale properties in patients undergoing ambulatory cancer surgery. We have removed the additional descriptors from our tool. We recommend further comparative psychometric research using data from PROs collected as part of routine clinical care.

Case study of the integration of electronic patient-reported outcomes as standard of care in a head and neck oncology practice: Obstacles and opportunities.

BACKGROUND: Patient-reported outcomes (PROs) allow for the direct measurement of functional and psychosocial effects related to treatment. However, technological barriers, survey fatigue, and clinician adoption have hindered the meaningful integration of PROs into clinical care. The objective of the authors was to develop an electronic PROs (ePROs) program that meets a range of clinical needs across a head and neck multidisciplinary disease management team. METHODS: The authors developed the ePROs module using literature review and stakeholder input in collaboration with health informatics. They designed an ePROs platform that was integrated as the standard of care for personalized survey delivery by diagnosis across the disease management team. Tableau software was used to create dashboards for data visualization and monitoring at the clinical enterprise, disease subsite, and patient levels. All patients who were treated for head and neck cancer were eligible for ePROs assessment as part of the standard of care. A descriptive analysis of ePROs program implementation is presented herein. RESULTS: The Head and Neck Service at Memorial Sloan Kettering Cancer Center has integrated ePROs into clinical care. Surveys are delivered via the patient portal at the time of diagnosis and longitudinally through care. From August 1, 2018, to February 1, 2020, a total of 4154 patients completed ePROs surveys. The average patient participation rate was 69%, with a median time for completion of 5 minutes. CONCLUSIONS: Integration of the head and neck ePROs program as part of clinical care is feasible and could be used to assess value and counsel patients in the future. Continued qualitative assessments of stakeholders and workflow will refine content and enhance the health informatics platform. LAY SUMMARY: Patients with head and neck cancer experience significant changes in their quality of life after treatment. Measuring and integrating patient-reported outcomes as a part of clinical care have been challenging given the multimodal treatment options, vast subsites, and unique domains affected. The authors present a case study of the successful integration of electronic patient-reported outcomes into a high-volume head and neck cancer practice.

Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication*.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel anti-viral agents.

Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding.

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.

Iridium Nanoparticles for Multichannel Luminescence Lifetime Imaging, Mapping Localization in Live Cancer Cells.

The development of long-lived luminescent nanoparticles for lifetime imaging is of wide interest as luminescence lifetime is environmentally sensitive detection independent of probe concentration. We report novel iridium-coated gold nanoparticles as probes for multiphoton lifetime imaging with characteristic long luminescent lifetimes based on iridium luminescence in the range of hundreds of nanoseconds and a short signal on the scale of picoseconds based on gold allowing multichannel detection. The tailor-made IrC6 complex forms stable, water-soluble gold nanoparticles (AuNPs) of 13, 25, and 100 nm, bearing 1400, 3200, and 22 000 IrC6 complexes per AuNP, respectively. The sensitivity of the iridium signal on the environment of the cell is evidenced with an observed variation of lifetimes. Clusters of iridium nanoparticles show lifetimes from 450 to 590 ns while lifetimes of 660 and 740 ns are an average of different points in the cytoplasm and nucleus. Independent luminescence lifetime studies of the nanoparticles in different media and under aggregation conditions postulate that the unusual long lifetimes observed can be attributed to interaction with proteins rather than nanoparticle aggregation. Total internal reflection fluorescence microscopy (TIRF), confocal microscopy studies and 3D luminescence lifetime stacks confirm the presence of bright, nonaggregated nanoparticles inside the cell. Inductively coupled plasma mass spectrometry (ICPMS) analysis further supports the presence of the nanoparticles in cells. The iridium-coated nanoparticles provide new nanoprobes for lifetime detection with dual channel monitoring. The combination of the sensitivity of the iridium signal to the cell environment together with the nanoscaffold to guide delivery offer opportunities for iridium nanoparticles for targeting and tracking in in vivo models.

Partial meniscectomy is associated with increased risk of incident radiographic osteoarthritis and worsening cartilage damage in the following year.

OBJECTIVES: To assess whether partial meniscectomy is associated with increased risk of radiographic osteoarthritis (ROA) and worsening cartilage damage in the following year. METHODS: We studied 355 knees from the Osteoarthritis Initiative that developed ROA (Kellgren-Lawrence grade ≥ 2), which were matched with control knees. The MR images were assessed using the semi-quantitative MOAKS system. Conditional logistic regression was applied to estimate risk of incident ROA. Logistic regression was used to assess the risk of worsening cartilage damage in knees with partial meniscectomy that developed ROA. RESULTS: In the group with incident ROA, 4.4 % underwent partial meniscectomy during the year prior to the case-defining visit, compared with none of the knees that did not develop ROA. All (n = 31) knees that had partial meniscectomy and 58.9 % (n = 165) of the knees with prevalent meniscal damage developed ROA (OR = 2.51, 95 % CI [1.73, 3.64]). In knees that developed ROA, partial meniscectomy was associated with an increased risk of worsening cartilage damage (OR = 4.51, 95 % CI [1.53, 13.33]). CONCLUSIONS: The probability of having had partial meniscectomy was higher in knees that developed ROA. When looking only at knees that developed ROA, partial meniscectomy was associated with greater risk of worsening cartilage damage. KEY POINTS: • Partial meniscectomy is a controversial treatment option for degenerative meniscal tears. • Partial meniscectomy is strongly associated with incident osteoarthritis within 1 year. • Partial meniscectomy is associated with increased risk of worsening cartilage damage.

Testing a Positive Psychological Intervention for Osteoarthritis.

OBJECTIVE: Osteoarthritis is a leading cause of disability for which there is no cure. Psychosocial-oriented treatments are underexplored. We developed and tested an intervention to build positive psychological skills (e.g., gratitude) to reduce osteoarthritis symptom severity, including pain and functioning, and to improve psychosocial well-being in patients with knee or hip osteoarthritis. DESIGN: Two-arm randomized design with six-month follow-up. SETTING: An academic Veterans Affairs Medical Center. SUBJECTS: Patients aged 50 years or older with knee or hip osteoarthritis and pain ratings of 4 or higher. METHODS: Patients (N = 42) were randomized to a six-week program containing positive skill-building activities or neutral control activities tailored to the patient population. Adherence was assessed by telephone each week. We assessed osteoarthritis symptom severity (WOMAC Osteoarthritis Index) and measures of well-being (positive affect, negative affect, and life satisfaction) at baseline and by telephone one, three, and six months after the program ended. We used linear mixed models to examine changes over time. RESULTS: The majority (64%) of patients completed more than 80% of their weekly activities. Patients in the positive (vs neutral) program reported significantly more improvement over time in osteoarthritis symptom severity (P = 0.02, Cohen's d = 0.86), negative affect (P = 0.03, Cohen's d = 0.50), and life satisfaction (P = 0.02, Cohen's d = 0.36). CONCLUSIONS: The study successfully engaged patients with knee or hip osteoarthritis in a six-week intervention to build positive psychological skills. Improving osteoarthritis symptom severity and measures of psychosocial well-being, the intervention shows promise as a tool for chronic pain management.

Comparison of radiographic joint space width and magnetic resonance imaging for prediction of knee replacement: A longitudinal case-control study from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement. METHODS: Knees replaced between 36 and 60 months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI. Changes between the annual visit before replacement (T0) and 2 years before T0 (T-2) were compared using conditional logistic regression. RESULTS: One hundred and nineteen knees from 102 participants (55.5 % women; age 64.2 ± 8.7 [mean ± SD] years) were studied. Fixed-location JSW change at 22.5 % from medial to lateral differed more between replaced and control knees (case-control [cc] OR = 1.57; 95 % CI: 1.23-2.01) than minimum medial JSW change (ccOR = 1.38; 95 % CI: 1.11-1.71). Medial femorotibial cartilage loss displayed discrimination similar to minimum JSW, and central tibial cartilage loss similar to fixed-location JSW. Location-independent thinning and thickening scores were elevated prior to knee replacement. CONCLUSIONS: Discrimination of structural progression between knee pre-placement cases versus controls was stronger for fixed-location than minimum radiographic JSW. MRI displayed similar discrimination to radiography and suggested greater simultaneous cartilage thickening and loss prior to knee replacement. KEY POINTS: • Fixed-location JSW predicts surgical knee replacement more strongly than minimum JSW. • MRI predicts knee replacement with similar accuracy to radiographic JSW. • MRI reveals greater cartilage thinning and thickening prior to knee replacement.

Can structural joint damage measured with MR imaging be used to predict knee replacement in the following year?

PURPOSE: To assess whether magnetic resonance (MR) imaging-based cross-sectional measures of structural joint damage can be used to predict knee replacement during the following year. MATERIALS AND METHODS: Participants were drawn from the Osteoarthritis Initiative, a longitudinal observational study that includes 4796 participants who have knee osteoarthritis or are at risk. The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all participants. During the 5 years of follow-up, 199 knees underwent knee replacement and were matched with 199 control knees that did not undergo knee replacement. Knees were matched according to radiographic disease stage and patient sex and age. All knees that underwent knee replacement and had MR images available from the year before surgery were included. MR images were assessed for cartilage damage, bone marrow lesions, meniscal damage, meniscal extrusion, synovitis, and effusion prior to reported knee replacement. Conditional logistic regression was applied to assess the risk of knee replacement. Analyses were performed on a compartmental and knee level. RESULTS: Participants had a mean age ± standard deviation of 64.2 years ± 8.4 (range, 47-82 years) and were predominantly women (232 of 398 participants, 58.3%). Risk for knee replacement was significantly increased for knees that exhibited two or more subregions with severe cartilage loss (odds ratio [OR], 16.5; 95% confidence interval [CI]: 3.96, 68.76), more than two subregions with bone marrow lesions (OR, 4.00; 95% CI: 1.75, 9.16), medial meniscal maceration (OR, 1.84; 95% CI: 1.13, 2.99), effusion (OR, 4.75; 95% CI: 2.55, 8.85), or synovitis (OR, 2.17; 95% CI: 1.33, 3.56), but not extrusion (OR, 1.00; 95% CI: 0.60,1.67), when compared with knees that did not exhibit these features as the reference standard. CONCLUSION: Apart from meniscal extrusion, all features of tissue abnormalities at MR imaging were related to clinical prognosis and could be used to predict knee replacement in the following year.

Accessible Synthetic Probes for Staining Actin inside Platelets and Megakaryocytes by Employing Lifeact Peptide.

Lifeact is a 17-residue peptide that can be employed in cell microscopy as a probe for F-actin when fused to fluorescent proteins, but therefore is not suitable for all cell types. We have conjugated fluorescently labelled Lifeact to three different cell-penetrating systems (a myristoylated carrier (myr), the pH low insertion peptide (pHLIP) and the cationic peptide TAT) as a strategy to deliver Lifeact into cells and developed new tools for actin staining with improved synthetic accessibility and low toxicity, focusing on their suitability in platelets and megakaryocytes. Using confocal microscopy, we characterised the cell distribution of the new hybrids in fixed cells, and found that both myr- and pHLIP-Lifeact conjugates provide efficient actin staining upon cleavage of Lifeact from the carriers, without affecting cell spreading. This new approach could facilitate the design of new tools for actin visualisation.

Iron(II) supramolecular helicates condense plasmid DNA and inhibit vital DNA-related enzymatic activities.

The dinuclear iron(II) supramolecular helicates [Fe2 L3 ]Cl4 (L=C25 H20 N4 ) bind to DNA through noncovalent (i.e., hydrogen-bonding, electrostatic) interactions and exhibit antimicrobial and anticancer effects. In this study, we show that the helicates condense plasmid DNA with a much higher potency than conventional DNA-condensing agents. Notably, molecules of DNA in the presence of the M enantiomer of [Fe2 L3 ]Cl4 do not form intermolecular aggregates typically formed by other condensing agents, such as spermidine or spermine. The helicates inhibit the activity of several DNA-processing enzymes, such as RNA polymerase, DNA topoisomerase I, deoxyribonuclease I, and site-specific restriction endonucleases. However, the results also indicate that the DNA condensation induced by the helicates does not play a crucial role in these inhibition reactions. The mechanisms for the inhibitory effects of [Fe2 L3 ]Cl4 helicates on DNA-related enzymatic activities have been proposed.

Positive predictive value of an elevated cardiac troponin for type I myocardial infarction in ED patients based on the chief complaint.

BACKGROUND: Cardiac troponin testing is used to aid the diagnosis of myocardial infarction (MI) in the emergency department (ED) for patients who present with a range of symptoms. From a clinical perspective, the distinction between MI due to acute coronary artery thrombosis (type I MI) and other forms of direct and secondary myocardial injury (type II MI) is very important. However, the positive predictive value (PPV) of an elevated troponin for diagnosing type I MI, based on clinical history, has not been described. The objective of this study was to determine the PPV of an elevated troponin for type I MI based on the ED chief complaint. METHODS: We retrospectively reviewed the medical records of 1772 consecutive patients who had a troponin ordered in the ED at a tertiary care center over the period of March 1, 2013, to April 30, 2013. The chief complaint was based on official ED coding. For patients with a positive troponin, 2 authors independently reviewed the electronic medical record pertaining to the index encounter and subsequent hospitalization to adjudicate the cause. RESULTS: There was a significant association between the PPV of an elevated troponin for type I MI and the chief complaint. Patients with a chief complaint of chest pain were significantly more likely to have a type I MI compared to those without (PPV 84% vs 20%; Adjusted Odds Ratio (AOR), 14.31; P < .0001). There was also a significant association between the rate of type I MI and the chief complaint in all patients who had a troponin drawn. Patients with a chief complaint of chest pain were significantly more likely to have a type I MI compared to those without (PPV 9.8% vs 1.3%; AOR, 7.34; P < .0001). CONCLUSION: Applying information on the PPV of troponin for type I MI based on the clinical history could improve troponin utilization and clinical decision making.

Racial differences in treatment preferences among lupus patients: a two-site study.

OBJECTIVES: To identify the demographic, clinical and psychosocial characteristics associated with racial differences in willingness to receive cyclophosphamide (CYC) or participate in a research clinical trial (RCT) among patients with systemic lupus erythematosus (SLE). METHODS: Data from 163 African-American (AA) and 180 white (WH) SLE patients were evaluated. Structured interviews and chart reviews were conducted to determine treatment preferences in hypothetical situations and identify variables that may affect preferences. Logistic regression models were performed to evaluate the relationship between patient preferences and race, adjusted for patient characteristics. RESULTS: Among patients who had never received CYC (n=293), 62.9% AAs compared to 87.6% WHs were willing to receive the medication (p<0.001). This difference persisted (OR 0.37 [95% CI, 0.16-0.87]) after adjusting for socio-demographics, clinical characteristics, and perceptions about CYC and physicians. Income and higher perception of CYC effectiveness were other determinants of willingness to receive CYC. Among patients who had never participated in an RCT (n=326), 64.9% AAs compared to 84.3% WHs were willing to do so (p<0.001). This difference persisted (OR 0.41 [95% CI, 0.20-0.83]) after adjusting for socio-demographics, clinical context and patients' perceptions of physicians. SLE damage score, number of immunosuppressive medications and higher trust in physicians were also independently associated with willingness to participate in an RCT. CONCLUSIONS: Race remains an independent determinant of treatment preferences after adjustment for income, medications, medication efficacy expectations and trust in physicians. While some factors related to racial differences in preferences are relatively fixed, others that may alleviate these differences also exist, including medication beliefs and provider trust.

Willingness and access to joint replacement among African American patients with knee osteoarthritis: a randomized, controlled intervention.

OBJECTIVE: African American patients are significantly less likely to undergo knee replacement for the management of knee osteoarthritis (OA). Racial difference in preference (willingness) has emerged as a key factor. This study was undertaken to examine the efficacy of a patient-centered educational intervention on patient willingness and the likelihood of receiving a referral to an orthopedic clinic. METHODS: A total of 639 African American patients with moderate-to-severe knee OA from 3 Veterans Affairs primary care clinics were enrolled in a randomized, controlled trial with a 2 × 2 factorial design. Patients were shown a knee OA decision-aid video with or without brief counseling. The main outcome measures were change in patient willingness and receipt of a referral to an orthopedic clinic. Also assessed were whether patients discussed knee pain with their primary care provider or saw an orthopedic surgeon within 12 months of the intervention. RESULTS: At baseline, 67% of the participants were definitely/probably willing to consider knee replacement, with no difference among the groups. The intervention increased patient willingness (75%) in all groups at 1 month. For those who received the decision aid intervention alone, the gains were sustained for up to 3 months. By 12 months postintervention, patients who received any intervention were more likely to report engaging their provider in a discussion about knee pain (92% versus 85%), to receive a referral to an orthopedic surgeon (18% versus 13%), and for those with a referral, to attend an orthopedic consult (61% versus 50%). CONCLUSION: An educational intervention significantly increased the willingness of African American patients to consider knee replacement. It also improved the likelihood of patient-provider discussion about knee pain and access to surgical evaluation.

An obese body habitus does not preclude a minimally invasive partial nephrectomy.

INTRODUCTION: Partial nephrectomy (PN) via open or minimally invasive (MI) techniques is the referent standard for managing renal cell carcinoma (RCC) whenever possible. Outcomes of MIPN in the obese patient population are incompletely defined. We investigate the feasibility of MIPN in obesity class I-III patients via comparison of surgical outcomes to those with a lower body mass index (BMI). MATERIALS AND METHODS: The electronic medical records of 184 consecutive patients undergoing MIPN via laparoscopic (n = 109) or robotic (n = 75) techniques were reviewed. Patients were classified into the following patient cohorts stratified by BMI: 1) BMI < 30; 2) BMI 30-35 - obesity class I; 3) BMI 35-40 - obesity class II; 4) BMI > 40 - obesity class III. The association between obesity class and perioperative and pathologic outcomes was determined. RESULTS: Ninety-five men and 89 women with a median age of 55 years, BMI of 31, tumor size of 2.9 cm, and RENAL nephrometry score of 6 were included. Median operative time was 218 minutes, ischemia duration was 23.5 minutes, estimated blood loss (EBL) was 150 cc, and length of stay was 3.0 days. Of the 184 patients, 71 (39%) were non-obese, 58 (32%) had class I obesity, 33 (18%) patients had class II obesity, and 22 (12%) had class III obesity. Compared to patients with a BMI < 30, neither an obese body habitus nor the degree of obesity was associated with any adverse perioperative or pathologic outcomes. In a multivariate model querying variables associated with complications, only a RENAL nephrometry ≥ 8 (HR 5.1, 95% CI 2.4-7.9, p < 0.001) was significant. CONCLUSION: An increase in obesity classification was not associated with adverse outcomes following MIPN. Increasing nephrometry score was the sole variable associated with perioperative complications. The presence of an obese body habitus alone should not preclude offering appropriate patients a MIPN.

New England journal of medicine article evaluating the usefulness of meniscectomy is flawed.

A controversial article was recently published in the New England Journal of Medicine titled "Arthroscopic Partial Meniscectomy Versus Sham Surgery for a Degenerative Meniscal Tear" by Sihvonen et al. We believe that readers of this article should be careful about making sweeping generalizations regarding the study findings given several methodologic flaws inherent in the population studied. There are significant concerns regarding the generalizability of these data. The actual study sample group is exceedingly small as compared with the normal volume of meniscal surgery the authors are reported to routinely perform. The authors' definition of a sham procedure must be revisited. The authors' final conclusion that "arthroscopic partial meniscectomy is of no value" is simply not what the study found. We share the concerns that several other leading authorities have recently expressed about the societal implications of this work. Arthroscopic partial meniscectomy has revolutionized the way we are able to treat symptomatic meniscal pathology. However, this procedure, like all surgical procedures, must be properly indicated to truly benefit our patients.