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Delineating conservation units (CUs, e.g., evolutionarily significant units, ESUs, and management units, MUs) is critical to the recovery of declining species because CUs inform both listing status and management actions. Genomic data have strengths and limitations in informing CU delineation and related management questions in natural systems. We illustrate the value of using genomic data in combination with landscape, dispersal and occupancy data to inform CU delineation in Nevada populations of the Great Basin Distinct Population Segment of the Columbia spotted frog (Rana luteiventris). R. luteiventris occupies naturally fragmented aquatic habitats in this xeric region, but beaver removal, climate change and other factors have put many of these populations at high risk of extirpation without management intervention. We addressed three objectives: (i) assessing support for ESUs within Nevada; (ii) evaluating and revising, if warranted, the current delineation of MUs; and (iii) evaluating genetic diversity, effective population size, adaptive differentiation and functional connectivity to inform ongoing management actions. We found little support for ESUs within Nevada but did identify potential revisions to MUs based on unique landscape drivers of connectivity that distinguish these desert populations from those in the northern portion of the species range. Effective sizes were uniformly small, with low genetic diversity and weak signatures of adaptive differentiation. Our findings suggest that management actions, including translocations and genetic rescue, might be warranted. Our study illustrates how a carefully planned genetic study, designed to address priority management goals that include CU delineation, can provide multiple insights to inform conservation action.

Ni-catalyzed C-H functionalization reactions are becoming efficient routes to access a variety of functionalized arenes, yet the mechanisms of these catalytic C-C coupling reactions are not well understood. Here we report the catalytic and stoichiometric arylation reactions of a nickel(II) metallacycle. Treatment of this species with silver(I)-aryl complexes results in facile arylation, consistent with a redox transmetalation step. Additionally, treatment with electrophilic coupling partners generates C-C and C-S bonds. We anticipate that this redox transmetalation step may be relevant to other coupling reactions that employ silver salts as additives.

Ni-catalyzed C-H functionalization reactions are becoming efficient routes to access a variety of functionalized arenes, yet the mechanisms of these catalytic C-C coupling reactions are not well understood. Here we report the catalytic and stoichiometric arylation reactions of a nickel(II) metallacycle. Treatment of this species with silver(I)-aryl complexes results in facile arylation, consistent with a redox transmetalation step. Additionally, treatment with electrophilic coupling partners generates new C-C and C-S bonds. We anticipate that this redox transmetalation step may be relevant to other coupling reactions that employ silver salts as additives.

Background and Aims It has been documented that African Americans have been significantly affected by COVID-19 infection due to systemic societal factors, which may lead to increases in comorbid medical history and subsequently vulnerability to having higher viral loads as measured by the cycle threshold/number (CT/CN) values by reverse transcriptase polymerase chain reaction (RT-PCR). Differences in CT/CN values by ethnicity and comorbid medical history could play an important role in public health research, particularly in elucidating the reasons for differential public health outcomes by ethnicity, as viral loads are known to correlate with disease severity. However, there is a gap in the literature regarding CT/CN values by ethnicity and comorbid medical history. Therefore, this study seeks to address this literature gap and its important implication for public health research. Methods A retrospective review of all SARS-CoV-2 RT-PCR tests collected at the regional Veterans Administration Medical Center (VAMC) serving the Philadelphia area from March 17, 2020, to May 20, 2020, was performed to collect demographic information such as race, gender, and age. In addition, comorbid medical conditions, clinical course, and CT/CN values were obtained for the positive cases. Results There was a total of 1524 patients tested for SARS-CoV-2. A total of 713/1524 patients (46.8%) were African American. A total of 187/1524 patients (12%) had tested positive for SARS-CoV-2 from which 139/187 (74%) were African American. African American patients required more intensive unit care. Both African Americans and other ethnicities had similar rates of comorbid medical conditions. On comparison of the ethnic groups, there were lower viral loads in African Americans on admission, though the difference was not statistically significant. Conclusion African American Veterans tested positive at higher rates and require more ICU care, despite similar rates of comorbid illness and viral loads.

Background Exposure to high doses or a high cumulative dose of erythropoiesis-stimulating agents (ESAs) may contribute to cardiovascular events in patients with CKD and anemia. Whether using a low fixed ESA dose versus dosing based on a hemoglobin-based, titration-dose algorithm in such patients might reduce risks associated with high ESA doses and decrease the cumulative exposure-while reducing the need for red blood cell transfusions-is unknown. Methods In this phase-3, randomized trial involving 756 adults with stage-3 to -5 CKD and anemia, we evaluated incidence of red blood cell transfusions for participants randomized to receive darbepoetin given as a fixed dose (0.45 µg/kg every 4 weeks) versus administered according to a hemoglobin-based, titration-dose algorithm, for up to 2 years. Participants received transfusions as deemed necessary by the treating physician. Results There were 379 patients randomized to the fixed-dose group, and 377 to the titration-dose group. The percentage of participants transfused did not differ (24.1% and 24.4% for the fixed-dose and titration-dose group, respectively), with similar time to first transfusion. The titration-dose group achieved significantly higher median hemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl). The fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 µg) compared with the titration-dose group (53.6 µg median monthly dose). The FD and TD group received a median (Q1, Q3) cumulative dose per 4 weeks of darbepoetin of 30.9 (21.8, 40.0) µg and 53.6 (31.1, 89.9) µg, respectively; the median of the difference between treatment groups was -22.1 (95% CI, -26.1 to -18.1) µg. Conclusions These findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing.

RationaleA commonMUC5Bgene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis, but its role in the SARS-CoV-2 infection and disease severity is unclear.ObjectivesTo assess whether rs35705950-T confers differential risk for clinical outcomes associated with COVID-19 infection among participants in the Million Veteran Program (MVP) and COVID-19 Host Genetics Initiative (HGI).MethodsMVP participants were examined for an association between the incidence or severity of COVID-19 and the presence of aMUC5Brs35705950-T allele. Comorbidities and clinical events were extracted from the electronic health records (EHR). The analysis was performed within each ancestry group in the MVP, adjusting for sex, age, age2,and first twenty principal components followed by a trans-ethnic meta-analysis. We then pursued replication and performed a meta-analysis with the trans-ethnic summary statistics from the HGI. A phenome-wide association study (PheWAS) of the rs35705950-T was conducted to explore associated pathophysiologic conditions.Measurements and Main ResultsA COVID-19 severity scale was modified from the World Health Organization criteria, and phenotypes derived from the International Classification of Disease-9/10 were extracted from EHR. Presence of rs35705950-T was associated with fewer hospitalizations (Ncases=25353, Ncontrols=631,024; OR=0.86 [0.80-0.93], p=7.4 × 10−5) in trans-ethnic meta-analysis within MVP and joint meta-analyses with the HGI (N=1641311; OR=0.89 [0.85-0.93], p =1.9 × 10−6). Moreover, individuals of European Ancestry with at least one copy of rs35705950-T had fewer post-COVID-19 pneumonia events (OR=0.85 [0.76-0.96], p =0.008). PheWAS exclusively revealed pulmonary involvement.ConclusionsTheMUC5Bvariant rs35705950-T is protective in COVID-19 infection.

BACKGROUND: In 2006, the Centers for Disease Control and Prevention issued guidelines advocating routine HIV screening for all patients. However, false-positive results are a potential patient care threat for low-risk populations even with accurate screening assays. A reduction in HIV false-positive screening results can potentially be seen by switching from the third-generation to a more sensitive and specific fourth-generation screening assay. METHODS: We studied the impact on the false-positive screening rate of a change to a fourth-generation assay at a regional US Department of Veteran Affairs Medical Center. HIV screening tests performed by the laboratory from March 1, 2016 to February 28, 2017, prior to implementation of the new assay were compared with fourth-generation HIV screening tests performed from March 1, 2017 to February 28, 2018. RESULTS: Of 7,516 third-generation HIV screening tests reviewed, 52 were reactive on the screening assay; 24 were true positives, 28 were false positives. The following year 7,802 fourth-generation HIV screening tests were performed and 23 were reactive on the screening assay; 16 were true positives and 7 were false positives. The positive predictive value for the third-generation test was 46% and 70% for the fourth-generation test. CONCLUSIONS: There were fewer false-positive results with testing with the more specific fourth- vs third-generation assay (0.09% vs 0.37%, respectively), which was statistically significant (P = .002). This reduction in false-positive screening would reduce the laboratory workload and would save an estimated $3,875 yearly and reduce the adverse effects of false-positive screening results for patients.

ObjectiveWith the COVID-19 pandemic, there have been supply challenges necessitating that laboratories must prepare their own viral transport medium (VTM), which provides stability for clinical specimens for diagnostic viral testing.MethodsWithin a veteran affairs medical center clinical laboratory, VTM was prepared with a Hanks Balanced Salt Solution (HBSS) 500 mL bottle with phenol red, sterile heat-inactivated fetal bovine serum (FBS), gentamicin sulfate (50 mg/mL), and amphotericin B (250 μg/mL). An antimicrobial mixture was made of 50 mL each of amphotericin B and gentamicin sulfate. Ten mL of FBS and 2 mL of the antimicrobial mixture were mixed into the HBSS bottle, from which 3 mL aliquots were made. Sterility and efficacy check were assessed. These preparations were conducted at our VAMC’s clinical laboratory to assure adequate VTM supply during the COVID-19 shortage.ResultsThe VTM was successfully prepared in-house, supporting uninterrupted testing for the facility and other affiliated medical facilities/centers and community living centers.ConclusionThis quality assurance/improvement report represents the first published manuscript on feasible VTM preparation exclusively within a clinical microbiology laboratory during the COVID-19 pandemic.

ObjectivesTo examine the temporal patterns of patient characteristics, treatments used and outcomes associated with COVID-19 in patients who were hospitalised for the disease between January and 15 November 2020.DesignObservational cohort study.SettingCOVID-19 subset of the Optum deidentified electronic health records, including more than 1.8 million patients from across the USA.ParticipantsThere were 51 510 hospitalised patients who met the COVID-19 definition, with 37 617 in the laboratory positive cohort and 13 893 in the clinical cohort.Primary and secondary outcome measuresIncident acute clinical outcomes, including in-hospital all-cause mortality.ResultsRespectively, 48% and 49% of the laboratory positive and clinical cohorts were women. The 50– 65 age group was the median age group for both cohorts. The use of antivirals and dexamethasone increased over time, fivefold and twofold, respectively, while the use of hydroxychloroquine declined by 98%. Among adult patients in the laboratory positive cohort, absolute age/sex standardised incidence proportion for in-hospital death changed by −0.036 per month (95% CI −0.042 to –0.031) from March to June 2020, but remained fairly flat from June to November, 2020 (0.001 (95% CI −0.001 to 0.003), 17.5% (660 deaths /3986 persons) in March and 10.2% (580/5137) in October); in the clinical cohort, the corresponding changes were −0.024 (95% CI −0.032 to –0.015) and 0.011 (95% CI 0.007 0.014), respectively (14.8% (175/1252) in March, 15.3% (189/1203) in October). Declines in the cumulative incidence of most acute clinical outcomes were observed in the laboratory positive cohort, but not for the clinical cohort.ConclusionThe incidence of adverse clinical outcomes remains high among COVID-19 patients with clinical diagnosis only. Patients with COVID-19 entering the hospital are at elevated risk of adverse outcomes.

BACKGROUND Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. METHODS We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients). Secondary end points included the incidences of nonvertebral and hip fracture at the time of the primary analysis. Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated. RESULTS Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% [127 of 2046 patients]) than in the alendronate-to-alendronate group (11.9% [243 of 2047 patients]) (P

Introduction/Objective Cardiac perforation is a life-threatening complication (~1% risk, with reported rates between 0.2% to 5%) of CA procedures. As cardiac perforation may lead to extensive bleeding, it would be reasonable for a medical center carrying out CA to be capable of arranging for a massive transfusion protocol and for surgical repair as required. However, there is sparse literature to guide a non-trauma medical center implementing a CA program on what the number of red blood cell (RBC) units for crossmatch should be for each case. Methods In interdisciplinary collaborative meetings, the CA program logistics were agreed to between the multiple clinical services. Given the case series on the amount of drained blood in complicated cases, there was agreement that three units of RBCs would be crossmatched for each case. Education was provided on the massive transfusion protocol and on blood bank procedures. As part of quality assurance/quality improvement, records were reviewed from the beginning of the CA program (10/1/2019) to 1/31/2019 to determine number of patient cases, crossmatched units, and transfused units for quality assurance purposes. Results A total of fifteen patients underwent CA procedures, for which three units were crossmatched for each patient. As there were no cardiac perforations with the cardiac ablation procedures so far, no units were transfused. The organized approach for ensuring adequate blood bank support and education led to the reassurance, alleviation of clinical anxiety, and building of a successful CA program. Education sessions completed with thorough understanding of blood bank procedures including the massive transfusion protocol, labeling of blood bank specimens, and on ordering of blood for crossmatch. Conclusion This study provides a reference that may provide helpful guidance to other blood banks on what the number of RBCs to be crossmatched prior to each CA procedure. Multidisciplinary collaborative meetings in advance are an essential component for ensuring adequate support for CA procedures or any new service that requires blood product support. Thorough education of clinical staff on blood bank procedures particularly the massive transfusion protocol is also recommended. This procedure for massive transfusion should be available to be referred to in real time.

Introduction/Objective Ordering pre-operative type and screen specimens before the day of surgery is very important to prevent delays in provision of blood products due to unexpected alloantibody findings, unexpected ABO discrepancies, or need for a repeat ABO-RH testing due to lack of historical testing. However, the important pre- operative type and screen was not always ordered prior to the day of surgery by the clinician. Due to this observation, after discussion and collaboration with the Blood Utilization Committee (BUC), an educational and mentoring intervention for the pre-operative clinicians was undertaken. Methods Education and mentoring of clinicians involved in the pre-operative clinics, surgical services, and new incoming physicians on an ongoing basis was undertaken through the BUC since March 2018. As part of quality assurance, to track the results of this widespread educational effort, the daily OR lists from January 2017 to December 2019 were examined with the medical record to determine if a pre-operative type and screen was ordered prior to the day of surgery. The established Maximum Surgery Blood order Schedule (MSBOS) for the facility was used to determine if a pre-operative type and screen would be indicated for the listed procedure. Results As we started reinforced pre type and screen should be ordered there has been significant increase in percent of compliance rate average from 76% (2017), 87% (2018), and 95.6% (2019). By the T-test, there was a statistically significant change in the monthly ordering rates (p-value < 0.05). The VAMC’s preferred threshold value of at least 95% with pre-operative type and screen prior to the day of procedure was achieved in the 2019 calendar year with no operating room delays. Conclusion Appropriately performing the pre-operative type and screen prior to the day of the elective surgical procedure would reduce the risk of delays due to unexpected findings or lack of a historical ABO-RH type. Educational interventions help tremendously in ensuring this critical patient care practice is followed. The value of collaborating and educating clinicians cannot be understated as it is both cheap, simple, and highly effective.

Introduction Pancreatic cancer is the one of leading causes of cancer-related deaths, accounts for 7% of cancer related deaths, and generally is diagnosed at an advanced stage. The 5-year survival rate is about 62%. There are no current screening recommendations for pancreatic cancer, so primary diagnosis is of the utmost importance. EUS modality for FNA has revolutionized the ability for the early diagnosis and staging of cancers of the gastrointestinal tract as being safe, cost-effective, minimally invasive technology to assess the pancreas. To date, there is no study in English literature assessing the adequacy for diagnosis and ancillary studies on EUS-FNA of pancreatic mass lesions in veterans. The veteran patient population is a unique cohort with different risk factors and demographics. Methods As a part of quality assurance project, a search was conducted to identify all EUS of pancreatic lesions performed at our hospital from February 2, 2011, to March 3, 2019. We evaluated adequacy on the cell blocks and diagnostic accuracy of EUS-FNA among all pancreatic mass lesions. Results Out of the total 130 EUS-FNA pancreas cases, the diagnosis was established in 127 cases (97.6%). Three cases were insufficient and total 26 cases were diagnosed as atypia, suggesting repeat FNA for definitive diagnosis. A definitive diagnosis was made in 101 cases (77.7%). Four cases were suspicious for malignancy. Malignancy/severe dysplasia was diagnosed in total 45 cases, most being primary pancreatic adenocarcinoma (41) and four with other diagnoses. Conclusion EUS-FNA is highly successful for procuring adequate material on the cytology samples for pancreatic lesions. EUS-FNAs for pancreatic lesions have high sensitivity and specificity for diagnosing and directing early, appropriate clinical management in veterans. The percentage of primary pancreatic adenocarcinomas out of total tumors in this veteran population is high (91.1%).

Introduction Platelet products have a limited shelf life and are costly. Hence, it remains crucial to balance clinical usage and wastage in a tertiary hospital setting without a trauma center. Considering this, an innovative system model was established to reduce wastage: the CMCVAMC—starting October 2017—arranged to transfer the platelet unit to a nearby facility with a trauma center when product has a short expiration date and there is no anticipated need for the product. This is a cost-effective measure to reduce platelet wastage and ensure the appropriate blood product availability. Method QA/QI data were reviewed to determine the degree of platelet wastage both a year prior to the implementation of this platelet transfer to another facility and after the past implementation of this transfer to February 2019. The cost of each platelet product was determined from the blood supplier (American Red Cross). From these comparisons prior to and after implementation, a determination of reduction of product wastage and cost savings was made. Results Since the implementation of this platelet transfer, there have been no platelets expiring on the shelf. In contrast, from October 2016 to October 2017 prior to implementation of platelet transfer, platelet products were often wasted or expired. In contrast, from October 2017 to February 2019, there has been no wastage of platelets. Conclusion This is a highly effective model for a tertiary hospital without a trauma center to bring in house platelets without wastage of a costly product while maintaining appropriate availability of the product. This quality improvement system study demonstrates that the measure resulted in significant savings and this serves as a model for other similar facilities. This is an innovative, easy to implement, and cost-effective system model that can be used in other tertiary facilities without a trauma center.

Purpose In recent years, the use of red blood cell (RBC) transfusion for the treatment of chronic kidney disease (CKD)-related anemia has increased. We used the OptumInsight medical claims database to study the association between receiving a transfusion and hyperkalemia and heart failure events. Methods Persons 18–64 years of age with diagnosed stage 4 or 5 CKD (not requiring dialysis) between 2006 and 2010 were followed until their first hospitalization or emergency room visit with a diagnosis of hyperkalemia or heart failure, termination of insurance coverage, or death. We used a case-only design and conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CIs) describing associations between RBC transfusion and the risks of hyperkalemia or heart failure. We used single (1:1) and variable (1:m) self-control matching intervals, with adjustment for time-varying confounders. Results Seven thousand eight hundred twenty-nine individuals met our inclusion criteria; two-thirds were age 50 years or older; 43% were women and 51% had diabetes. Rates of hyperkalemia and heart failure were 7.9/100 person-years (95%CI: 7.3, 8.5) and 16.3/100 person-years (95%CI: 15.5, 17.2), respectively. RBC transfusion was associated with an increased risk of both hyperkalemia (single interval matched RR = 12.0, 95%CI: 1.3, 109; multiple interval matched RR = 6.1, 95%CI: 2.5, 15.1) and heart failure (single interval matched RR = 1.7, 95%CI: 0.3, 9.2; multiple interval matched RR = 3.8, 95%CI: 1.4, 10.3). Conclusion In patients with advanced CKD, RBC transfusion appears to be associated with an elevated risk of hyperkalemia and heart failure; further investigation into these risks is warranted. Copyright © 2015 John Wiley & Sons, Ltd.

Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naive patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. One-hundred sixteen pediatric ESA-naive subjects (aged 1–18 years) with CKD stages 3–5D and hemoglobin (Hb)

Standing before a meeting of the American Luncheon Club in London in 1916, the Chilean Minister to Great Britain, Agustin Edwards, offered his thoughts on Pan-Americanism. “I am an American,” he began, “a South American, and I have won my spurs as a businessman.”1 In this, Edwards targeted the commerce-minded men that were the majority of his listeners and granted authority to the statement that followed. Edwards spoke with more than the authority of a businessman. He was the founder of one of the most important newspapers in Chile (El Mercurio, Santiago edition), an alumnus of Chile’s National Congress, a former Chilean foreign minister, and a scion of one of the wealthiest and most influential families within Chile’s oligarchy. In sum, he was closely attuned to the attitudes of his government and the ruling elite in Chile. Within this context, Edwards made a bold claim: Argentina, Brazil, Chile (the so-called ABC nations) and the United States were called to be the “vanguard of Pan-Americanism.” This may have been merely an example of Edwards’ rhetorical exuberance (he also saddled the Americas with the epithet, “the reservoir of humanity”). Yet Edwards’s statement was a genuine reflection of Chile’s official foreign policy.

Ablative fractional photothermolysis (AFP) has been reported to be effective for changes in skin pigmentation and texture associated with photoaging.A prospective study for the treatment of photoaging using a fractionated ablative carbon dioxide laser in 10 subjects. Assessment of laser efficacy was made using two modalities: histologic examination of skin biopsies and blinded physician clinical photographic assessment. For the histologic portion of the study, patients were randomized to treatment with the device at settings of pulse durations of 500, 1,000, 1,500, and 1,800 μs. Depth of injury was assessed based on histologic evaluation of depth of thermal coagulation. For the clinical portion of the study, treatment was administered to the face using a carbon dioxide laser at settings of 30 W, 500-μm pitch (density of treatment equivalent to ablation of 25% of the skin), and variable pulse duration of 1,000 to 1,500 μs.The mean score for dyschromia had improved 47.5% (95% confidence interval (CI) = 44.1-50.9%), for skin texture 56.0% (95% CI = 51.9-60.1%), for skin laxity 56.0% (95% CI = 51.3-60.7%), for rhytides 52.5% (95% CI = 48.3-56.7%) and for overall cosmetic outcome 61.5% (95% CI = 56.4%,66.6%) 6 months after treatment. Histologic data revealed a proportional increase in depth of thermal coagulation at each pulse duration. The mean ablation depth was 283 μm for a pulse duration of 500 μs, 375 μm for 1,000 μs, 767 μm for 1,500 μs, and 1.05 mm for 1,800 μs.We present a histologic analysis documenting the correlation between longer pulse duration and ablation depth using an AFP device. We identified that pulse duration settings up to 1,800 μs could be used safely with an ablation depth up to 1.1 mm, correlating with injury into the deep reticular dermis.

Background Photodynamic therapy is an efficacious treatment modality for actinic keratoses and for superficial basal cell carcinoma (BCC) and squamous cell carcinoma. Only two prior case reports in the literature have used fluorescent diagnosis, with aminolevulinic acid, to define tumor margins. Methods Twenty patients with BCCs of the head, neck, and upper extremities were enrolled in this prospective trial. Methyl aminolevulinate (MAL) (Metvixia, Galderma Laboratories, LP, Fort Worth, TX) was applied overnight (mean of 13.3 hours) before fluorescence measurements of tumor size using a clinical Wood lamp examination. Results A total of 5 (25.0%) superficial and 15 (75.0%) nodular BCCs were included in this trial. The mean tumor sizes were 263.0 mm 2 (post-Mohs micrographic surgery [MMS] defect), 239.1 mm 2 (fluorescent examination of MAL under Wood lamp), and 65.8 mm 2 (clinical size). Using interclass correlation coefficients, a high degree of consistency and absolute agreement between post-MMS defect size and fluorescent examination size was identified (interclass correlation coefficient .962). This correlation was significantly higher than that between post-MMS defect size and clinical examination (.703) and that between fluorescent and clinical examination (.651). Limitations Although this study demonstrates the clinical feasibility of using MAL in conjunction with a Wood lamp examination to delineate tumor margins before MMS for superficial and nodular BCCs, future large-scale studies are needed. Conclusions The use of topical MAL as a photosensitizer in conjunction with a Wood lamp examination is a simple and inexpensive investigation that can be used before MMS to delineate the margins of ill-defined tumors.

BACKGROUND Biologic scaffolds have shown promise in patients unable to tolerate prolonged surgical closure or extensive wound care, but there has been little research in the field of Mohs micrographic surgery (MMS) on human cadaveric dermis in this capacity. OBJECTIVE To evaluate the utility of human cadaveric dermis as a means of decreasing operative time, minimizing postoperative wound care, and improving aesthetic outcomes in selected patients with deep surgical defects, including those with exposed bone. METHODS Fourteen patients (8 men, 6 women) with deep postoperative defects after MMS were treated with a cadaveric dermal allograft as part or all of their postoperative wound management. RESULTS Allograft placement was well tolerated, with high satisfaction levels relating to minimal postoperative wound care and aesthetic outcome. Significantly shorter operative times were noted in all patients than with primary closure or grafting. CONCLUSION In patients with significant comorbidities, inability to tolerate extended surgical repairs, or inability to perform extensive wound care, human cadaveric dermal allografts can decrease operative time and minimize wound care complexity while providing an excellent aesthetic outcome in many cases. Shorter healing times than expected were also noted in a number of patients. The authors have indicated no significant interest with commercial supporters.

BACKGROUND Management of lower extremity wounds after Mohs micrographic surgery can pose a challenge to the surgeon. Postoperative reactive edema and inflammation can lead to a painful and protracted healing course. Unna boots deliver zinc oxide to the wound bed and surrounding skin while providing compression and occlusion of the wound. OBJECTIVE To evaluate the utility of weekly Unna boot therapy in decreasing postoperative edema, inflammation, and morbidity; minimizing postoperative wound care; and improving the rate of wound healing in patients with lower leg surgical defects. METHODS Ten patients (6 men, 4 women) aged 72 to 91 with postoperative defects on the distal lower extremity were treated with weekly Unna boots until wounds had sufficiently granulated or re-epithelialized. RESULTS In all 10 patients, weekly Unna boot therapy was well tolerated, with high satisfaction levels relating to minimal postoperative wound care, rapid granulation, minimal pain, and excellent esthetic outcome of postoperative wounds. No infections or other complications were noted during the healing process. LIMITATIONS This was not a randomized, controlled trial. CONCLUSIONS In patients with postoperative wounds of the lower leg, weekly Unna boots significantly improve the healing process, decrease postoperative pain, and minimize wound care.

Lipomas are the most common benign tumor of the soft tissue, often presenting as soft, mobile subcutaneous masses. These lesions are often removed for cosmetic reasons, although they may be removed secondary to considerable discomfort or paresthesias. The large majority of lipomas appear as small, solitary lesions that are best removed by surgical excision. However, surgical removal of large (>10 cm) or multiple lesions may result in significant scarring. Tumescent local anesthesia and liposuction of larger lesions has been successful in a number of cases although this technique can be hindered by overly fibrous lesions. Laser lipolysis, performed alone or before liposuction, can further facilitate removal of these lesions. This technique is a minimally invasive and effective method of lipoma removal, resulting in an excellent cosmetic outcome. This report describes step-by-step removal of a large lipoma located on the back, as well as a review of currently employed techniques for minimally invasive treatment of lipomas.

Of the complications that can occur following tumescent liposuction, seroma formation is unusual. It is a common practice for seromas to be aspirated blindly with a needle and syringe. We present a case of seroma formation following liposuction, with a subsequent step-by-step technical description of ultrasound-guided drainage of the seroma. Utilization of ultrasound provides a safe, effective method for aspirating seromas, allowing for accurate visualization and delineation of the seroma margins, proper needle placement, and monitoring of progress. It is a simple and useful tool in postprocedural management of patients undergoing liposuction.

BACKGROUND Ablative fractional photothermolysis (AFP) has been reported to be effective in the treatment of photoaging. MATERIALS AND METHODS Treatment was administered using an AFP device and assessed photographically 3 months after treatment by a blinded physician. Ultrasound measurements evaluated skin thickness and subepidermal low echogenic band thickness (SLEB), the portion of the papillary dermis filled with solar elastosis. RESULTS Three months after treatment, the mean score improved 61.0% (95% confidence interval (CI)=56.8–65.2%) for dyschromia, 54.3% (95% CI=51.6–57.0%) for skin laxity, 51.5% (95% CI=49.6–53.4%) for rhytides, and 60.2%9 (95% CI=56.8–63.6%) for overall cosmetic outcome. Patients had a significant decrease in SLEB in all anatomic sites treated (0.078 cm at baseline, 0.038 cm at 3 months, 40.0% decrease) (p

Nephrogenic systemic fibrosis is a disabling progressive condition that is being reported with increased frequency in patients with kidney disease. Treatment is extremely limited and largely supportive. We report a case of severe nephrogenic systemic fibrosis in a dialysis patient exposed to multiple doses of gadolinium who improved clinically and histologically with treatment with imatinib.

In recent years, the use of red blood cell (RBC) transfusion for the treatment of chronic kidney disease (CKD)-related anemia has increased. We used the OptumInsight medical claims database to study the association between receiving a transfusion and hyperkalemia and heart failure events.Persons 18-64 years of age with diagnosed stage 4 or 5 CKD (not requiring dialysis) between 2006 and 2010 were followed until their first hospitalization or emergency room visit with a diagnosis of hyperkalemia or heart failure, termination of insurance coverage, or death. We used a case-only design and conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CIs) describing associations between RBC transfusion and the risks of hyperkalemia or heart failure. We used single (1:1) and variable (1:m) self-control matching intervals, with adjustment for time-varying confounders.Seven thousand eight hundred twenty-nine individuals met our inclusion criteria; two-thirds were age 50 years or older; 43% were women and 51% had diabetes. Rates of hyperkalemia and heart failure were 7.9/100 person-years (95%CI: 7.3, 8.5) and 16.3/100 person-years (95%CI: 15.5, 17.2), respectively. RBC transfusion was associated with an increased risk of both hyperkalemia (single interval matched RR = 12.0, 95%CI: 1.3, 109; multiple interval matched RR = 6.1, 95%CI: 2.5, 15.1) and heart failure (single interval matched RR = 1.7, 95%CI: 0.3, 9.2; multiple interval matched RR = 3.8, 95%CI: 1.4, 10.3).In patients with advanced CKD, RBC transfusion appears to be associated with an elevated risk of hyperkalemia and heart failure; further investigation into these risks is warranted.

Purpose Since the Centers for Medicare & Medicaid Services implemented the End-Stage Renal Disease Prospective Payment System, dialysis providers have increasingly focused on balancing resource utilization and quality outcomes for the treatment of anemia in patients undergoing peritoneal dialysis. Limited data exist regarding anemia management outcomes for these patients in US-based dialysis centers after the implementation of the new payment system. Methods This was a retrospective, observational, cohort study of stable PD patients with end-stage renal disease who received darbepoetin alfa for anemia management over a 15-month period (April 1, 2011–June 29, 2012). The medication was administered by staff in the home-training unit instead of being self-administered at home. The primary end point was mean quarterly hemoglobin (Hb) levels. Variability in Hb levels was assessed over the 5 quarters by using repeated measures ANOVA to test for differences in the observed mean SDs. Findings In the 139 adult patients on stable peritoneal dialysis and meeting the eligibility criteria, mean (SD) Hb level by quarter was 10.8 (1.2) g/dL in quarters 2 and 3 of 2011, 10.5 (1.1) g/dL in quarter 4 of 2011, and 10.4 (1.1) g/dL in quarters 1 and 2 of 2012. Hb levels were stable (mean SDs, 0.58–0.72) over the 5 quarters of the study. Patient compliance with attendance for all scheduled home training unit visits was 84%. Implications PD patients who underwent darbepoetin alfa administration and twice-monthly laboratory testing in the home-training unit had stable Hb levels. Despite more frequent center visits compared with a home-administered approach, patient compliance was high.

Background Most studies of HLA sensitization after red blood cell transfusion in transplant candidates were done before widespread use of leuko reduced blood and based on relatively insensitive, nonspecific antibody assays. We evaluated the effect of transfusion on the breadth and magnitude of HLA antibody formation using current, sensitive, HLA-specific immunoassays. Methods Serial HLA antibody data were merged with transfusion data from the US Renal Data System for 1324 patients on the kidney transplant wait list (2004-2010). Two study groups were identified: a matched cohort consisting of 89 patients who received transfusion and 251 patients who did not receive transfusion and a crossover cohort consisting of 69 patients. Changes in antibody levels and calculated panel-reactive antibody (CPRA) were compared using χ and Sign tests, respectively. Logistic regression was used to estimate the relative risk of antibody responses. Results Among the matched cohort, 20% of those who received transfusion compared to 3% of those who did not receive transfusion exhibited an antibody response (P=0.001), whereas in the crossover cohort, 19% exhibited a response in those who received transfusion compared to 1% of those who did not receive transfusion (P=0.0001). Moreover, 26.3% of those who received transfusion had increased CPRA compared to 5.8% of those who did not receive transfusion . These effects were greater in women and blacks compared to men and whites, respectively. Importantly, patients who received transfusion were at an increased risk of a potentially crossmatch positive response (odds ratio=9.6, 95% confidence interval=3.0-30.7). Conclusions Sensitization from transfusion can occur in up to 20% of transplant candidates, resulting in higher antibody levels and CPRA values that adversely impact access to transplantation. These results support transfusion avoidance whenever possible.

Transplant renal artery stenosis (TRAS) is an increasingly recognized complication of renal transplantation, with a reported incidence of between 1% and 23%. The clinical features include refractory hypertension, new-onset hypertension, allograft dysfunction, and the presence of a bruit over the graft. In this report, we describe the investigation and treatment of one such patient and review the current diagnostic approaches and therapy in this setting.

Background. Sensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods. Methods. Transfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ≥2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n= 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA). Results. In the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ≥10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ≥30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ≥3000 MFI threshold, cPRA significantly increased in both matched (P=0.01) and crossover (P=0.002) transfused patients. Conclusions. Among prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.

Background There is limited data available on the use of red blood cell (RBC) transfusions in younger chronic kidney disease patients not on dialysis (CKD-ND), for whom the consequences of developing antibodies to foreign antigens (allosensitization) may be particularly relevant. Methods We used the Ingenix medical claims database, comprising data on ∼40 million commercially insured US individuals, to identify annual (2002-08) cohorts of patients 18-64 years of age with newly diagnosed CKD. We followed each cohort for 1 year to estimate RBC transfusion rates and used Cox proportional hazards regression to identify patient characteristics associated with time to first transfusion. Results We identified 120 790 newly diagnosed CKD patients for the years 2002-08; 54% were 50-64 years of age. Overall, the transfusion rate was 2.64/100 person-years (PYs) (95% CI: 2.52-2.77). Rates were higher among those with diagnosed anemia [9.80/100 PYs (95% CI: 9.31-10.3)] and among those who progressed to end-stage renal disease (ESRD) [28.0/100 PYs (95% CI: 23.7-33.0)]. For those progressing to ESRD, transfusion rates more than doubled between 2002 and 2008. Of the factors evaluated, transfusion history and the presence of heart failure and diabetes were most strongly associated with a receipt of a transfusion. Conclusions RBC transfusions are relatively common and on the rise among younger CKD-ND patients who are anemic and progress to ESRD. Efforts to decrease the use of transfusions may be important for potential transplant candidates who progress to ESRD.

Between March 1981 and November 1992, 100 heart-lung transplantations were performed at our institution. We report on the renal function in the 67 patients who survived a minimum of 6 months posttransplantation, and who were aged more than 10 years at the time of transplant. Renal function was determined by serial measurement of serum creatinine. Mean serum creatinine increased from 0.96 ± 0.03 mg/dL at baseline to 1.55 ± 0.07 mg/dL at 6 months posttransplantation, to 1.88 ± 0.11 mg/dL at the end of follow-up (mean follow-up, 50.0 months; range, 6 to 140 months). The decline in renal function was biphasic, with a rapid decrease in the first 6 months, followed by a much slower decline. Three patients developed end-stage renal failure. This compares with 14 of 416 cardiac transplant recipients at Stanford who developed end-stage renal failure over the same period. We conclude that in our large series at a single center the incidence of renal impairment and end-stage renal failure is low and similar between heart-lung and heart transplant patients.

Background Transfusion patterns are not well characterized in non-dialysis (ND) chronic kidney disease (CKD) patients. This study describes the proportion of patients transfused, units of blood transfused and trigger-hemoglobin (Hb) levels for transfusions in severe anemic, ND-CKD patients in routine practice. Methods A retrospective cohort study of electronic medical record data from the Henry Ford Health System identified 374 adult, ND-CKD patients with severe anemia (Hb < 10 g/dL and subsequent use of erythropoiesis-stimulating agents [ESA] therapy, blood transfusions, or a second Hb < 10 g/dL) between January 2004 and June 2008. Exclusions included those with prior diagnoses of cancer, renal or liver transplant, end-stage renal disease, acute bleeding, trauma, sickle cell disease, or aplastic anemia. A gap of ≥ 1 days between units of blood transfused was counted as a separate transfusion. Results At least 1 transfusion (mean of 2 units; range, 1-4) was administered to 20% (75/374) of ND-CKD patients with mean (± SD) follow-up of 459 (± 427) days. The mean (± SD) Hb level closest and prior to a transfusion was 8.8 (± 1.5) g/dL. Patients who were hospitalized in the 6 months prior to their first anemia diagnosis were 6.3 times more likely to receive a blood transfusion than patients who were not hospitalized (p < 0.0001). Patients with peripheral vascular disease (PVD) were twice as likely to have a transfusion as patients without PVD (p = 0.04). Conclusions Transfusions were prevalent and the trigger hemoglobin concentration was approximately 9 g/dL among ND-CKD patients with anemia. To reduce the transfusion burden, clinicians should consider other anemia treatments including ESA therapy.

Of the complications that can occur following tumescent liposuction, seroma formation is unusual. It is a common practice for seromas to be aspirated blindly with a needle and syringe. We present a case of seroma formation following liposuction, with a subsequent step-by-step technical description of ultrasound-guided drainage of the seroma. Utilization of ultrasound provides a safe, effective method for aspirating seromas, allowing for accurate visualization and delineation of the seroma margins, proper needle placement, and monitoring of progress. It is a simple and useful tool in postprocedural management of patients undergoing liposuction.

Epoetin alfa (EPO) and darbepoetin alfa are erythropoiesis-stimulating agents (ESAs) used to treat anemia in patients with chronic kidney disease. EPO and darbepoetin alfa have a non-proportional dose conversion relationship across the dosing spectrum. However, reports comparing the dose relationship between the two ESAs do not adjust for the non-proportional dose relationship or for population differences. Because drug cost is directly related to dosage, appropriate methods to assess the dose relationship between the two ESAs are important to understand the economic implications of converting patient populations from one ESA treatment to another.To describe dose conversion methods that take into account the non-proportional dose relationship between EPO and darbepoetin alfa, and calculate the dose conversion ratio (DCR) between the two ESAs in a hospital-based dialysis patient population.This was a retrospective observational study where longitudinal data from medical charts were collected for chronic hemodialysis patients being treated at hospital-based dialysis centers. Mean maintenance DCRs were calculated at the population level for hemodialysis patients converted from EPO to darbepoetin alfa treatment and subsequently maintained on darbepoetin alfa. Two methods were used to determine the DCRs: a regression-based method using ordinary least squares regression, and ratio-based method using an arithmetic mean.The estimated population mean maintenance DCR for the population in this analysis was 320:1 (Units EPO:µg darbepoetin alfa) using the regression-based method, and 350:1 using the ratio-based method. Sensitivity analysis yielded DCRs ranging from 311 to 333:1.The two methods in estimating the DCR presented here provide payers with an empirical way of comparing ESA utilization for pharmacoeconomic evaluation. DCR results may vary according to patient characteristics; however, mean DCRs of greater than 300:1 were obtained in this analysis. Exclusion of other patient-related factors that may influence ESA dose is a possible limitation of the study.