Application of sSPhos as a Chiral Ligand for Palladium-Catalyzed Asymmetric Allylic Alkylation.

Palladium-catalyzed asymmetric allylic alkylation is a versatile method for C-C bond formation. Many established classes of chiral ligands can perform allylic alkylation reactions enantioselectively, but identification of new ligand classes remains important for future development of the field. We demonstrate that enantiopure sSPhos, a bifunctional chiral monophosphine ligand, when used as its tetrabutyl ammonium salt, is a highly effective ligand for a benchmark Pd-catalyzed allylic alkylation reaction. We explore the scope and limitations and perform experiments to probe the origin of selectivity. In contrast with reactions previously explored using enantiopure sSPhos, it appears that steric bulk around the sulfonate group is responsible for the high enantioselectivity in this case, rather than attractive noncovalent interactions.

Medical Therapies for Heart Failure With Preserved Ejection Fraction.

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.

Heart failure with preserved ejection fraction. / Hjertesvikt med normal ejeksjonsfraksjon.

BACKGROUND: Approximately one half of all patients with heart failure have normal ejection fraction in the left ventricle, and heart failure is attributed to stiffness of the cardiac muscle. The most common cause is hypertension with ventricular hypertrophy. MATERIAL AND METHOD: Literature searches were conducted in PubMed. After we made our selection, a total of 15 articles on heart failure with normal ejection fraction were included. In addition, we included nine articles from our own literature archive. RESULTS: The diagnosis of heart failure with normal ejection fraction presupposes clinical findings consistent with heart failure and objective signs of diastolic dysfunction. The main objective sign is increased left ventricular filling pressure estimated by echocardiography. Ventricular hypertrophy and increased natriuretic peptides support the diagnosis. INTERPRETATION: Underlying conditions and symptoms are treated, and in general the same drugs are used as for heart failure with reduced ejection fraction.

Catalytic asymmetric synthesis of geminal-dicarboxylates.

Stereogenic acetals, spiroacetals and ketals are well-studied stereochemical features that bear two heteroatoms at a common carbon atom. These stereocenters are normally found in cyclic structures while linear (or acyclic) analogues bearing two heteroatoms are rare. Chiral geminal-dicarboxylates are illustrative, there is no current way to access this class of compounds while controlling the stereochemistry at the carbon center bound to two oxygen atoms. Here we report a rhodium-catalysed asymmetric carboxylation of ester-containing allylic bromides to form stereogenic carbon centers bearing two different carboxylates with high yields and enantioselectivities. The products, which are surprisingly stable to a variety of acidic and basic conditions, can be manipulated with no loss of enantiomeric purity as demonstrated by ring closing metathesis reactions to form chiral lactones, which have been extensively used as building blocks in asymmetric synthesis.

A systematic review of the relationship between glycemic control and necrobiosis lipoidica diabeticorum in patients with diabetes mellitus.

The association of specific skin disorders with diabetes mellitus (DM) has been well established. Current literature suggests that approximately 30-91% of patients with diabetes will experience at least one cutaneous manifestation of this systemic disease in their lifetime. To date, there are limited articles summarizing the link between necrobiosis lipoidica diabeticorum (NLD) prognosis and glycemic control in patients with diabetes. The objective of the study is to summarize and appraise the available evidence assessing the relationship between glycemic control and NLD. A literature search was conducted based on MEDLINE (1946-2015), EMBASE (1980-2015), Google Scholar, and PubMed for publications that described the results of diabetes control and NLD. Further studies were identified from bibliographies of all relevant studies, gray literature, and annual scientific assemblies. All studies investigating the relationship between DM (type 1 and type 2) management and NLD were included. Two reviewers independently extracted data including demographics, type of diabetes management measures (glucose, HbA1c, insulin), comorbidities, and outcome. A total of 622 studies were identified, and 10 studies met the inclusion and exclusion criteria: two case series and eight case reports. Of the 24 patients with NLD, 13 patients reported resolution of NLD after implementing various methods of glycemic control (diabetic diet consisting of 1600 kcal/day [1 patient], insulin regimen [3 patients], and pancreatic transplantation [9 patients]). Glycemic control may have a role in influencing the prognosis of necrobiosis lipoidica in patients with diabetes; however, there is currently insufficient evidence to support or refute this claim.

Lupus Miliaris Disseminatus Faciei With Isolated Axillary Involvement.

BACKGROUND: Lupus miliaris disseminatus faciei (LMDF) is a chronic, granulomatous inflammatory disorder, commonly localized to the face. OBJECTIVE: To present an unusual manifestation of LMDF and review the literature. METHODS: We document a 41-year-old woman with LMDF with isolated axillary involvement. A literature review was conducted using Pubmed, Medline, Embase, and Google Scholar for similar cases using search terms lupus miliaris disseminatus faciei, LMDF, acne agminata, and acnitis. RESULTS: Extrafacial LMDF without concomitant facial involvement is rare; there has been only 1 other report of LMDF with exclusive axillary involvement to date. In addition, we report the successful use of doxycycline monohydrate combined with topical tacrolimus in the treatment of LMDF. CONCLUSION: Physicians should note that LMDF can occur in body sites other than the face and should be aware of the available treatment options to manage this condition.

A 13-Year Retrospective Study of Basal Cell Carcinoma in a Canadian Dermatology Practice: A Comparison Between Anatomical Location and Histopathologic Subtypes.

BACKGROUND: It is unknown whether the histologic subtypes of basal cell carcinoma (BCC) arise from a common progenitor cell or whether other factors play a role in their development. OBJECTIVE: To investigate the relationship between the different BCC histopathologic subtypes and anatomical distribution of BCCs in a Canadian dermatology practice. METHODS: The charts of all patients diagnosed with BCC between 1993 and 2005 from a single private dermatology practice in Vancouver, Canada, were reviewed. Descriptive data analysis was undertaken to look at the distribution of histologic subtypes based on age, gender, and anatomical location. RESULTS: Nodular BCCs accounted for 58% of all tumors. Sixty-six percent of these were situated on the head/neck (odds ratio [OR] = 3.0, 95% confidence interval [CI] = 2.1-4.3, P < .0001). Infiltrative (OR = 2.4, 95% CI = 1.5-4.1, P = .0003) and superficial BCCs were more common in women (OR = 3.7, 95% CI = 2.5-5.7, P < .0001), affected the trunk (OR = 3.2, 95% CI = 2.1-4.9, P < .0001), and appeared in younger individuals (OR = 1.8, 95% CI = 1.2-2.7, P = .004). CONCLUSION: Our results show a preference of distinct BCC subtypes for certain anatomical locations.

A review of the diagnosis and management of erythroderma (generalized red skin).

Erythroderma is a condition caused by several etiologies that result in red inflamed skin on 90% or more of the body surface. To optimize the diagnosis and management of the erythrodermic patient, healthcare professionals should be familiar with the underlying etiologies and treatment modalities. Patients with erythroderma require immediate attention as they may face a variety of medical complications. Early detection and effective management of these complications significantly reduce mortality and morbidity of this potential dermatologic emergency. This review highlights the underlying common diagnoses, assessment, and management of the patient with erythroderma.

Cancers mimicking fungal infections.

Primary and metastatic malignancies may occasionally mimic or coexist with cutaneous fungal infections. The authors report 3 cases of cancers that were initially presumed to be cutaneous fungal infections. Dermatologists should maintain a low threshold for skin biopsy in patients with persistent or refractory fungal infections.

Pretibial Myxedema: Case Presentation and Review of Treatment Options.

Pretibial myxedema (PM) is a rare autoimmune manifestation of Graves' disease, which commonly presents as diffuse, nonpitting edema of shins and less often as plaques, nodules, or elephantiasis lesions mimicking lymphedema. We present a 57-year-old woman with 12-month history of PM, which occurred a year after treatment of Graves' disease and improved with topical corticosteroids, support stockings, and intralesional steroid injections until recurrence with local erythema and woody edema. A literature review was undertaken of the evidence-based treatment modalities for symptomatic PM: although commonly asymptomatic and self-limited, severe cases of PM may be treated with topical corticosteroid, compressive therapy, and intralesional corticosteroid injections.

A review of the clinical variants and the management of psoriasis.

PURPOSE: To enhance the learner's competence with knowledge of the clinical variants and management of psoriasis. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Demonstrate knowledge of the types, symptoms, and diagnostic testing of psoriasis.2. Apply knowledge of psoriasis treatment to patient care scenarios. ABSTRACT: Psoriasis is an inflammatory skin condition that is associated with various comorbidities. To the wound care physician, the Koebner phenomenon is of importance, as any superficial trauma can induce psoriasis. Particularly, periwound and joints are particularly susceptible to flare-ups of this condition. This review highlights the epidemiology and treatment of psoriasis.

Sickle cell disease and leg ulcers.

Sickle cell disease is a genetic disorder of hemoglobin synthesis leading to a deformation of the red blood cell. This disorder is associated with painful, slow-to-heal leg ulcers. This article discusses the wound bed preparation paradigm as a guide to the treatment of sickle cell-associated leg ulcers.

Demographic and tumor characteristics of patients diagnosed with nonmelanoma skin cancer: 13-year retrospective study.

BACKGROUND: The incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is increasing worldwide; however, this varies by region. To date, there are limited data about trends of nonmelanoma skin cancer (NMSC) in Canada. OBJECTIVE: To determine the demographic and tumor characteristic changes in patients diagnosed with BCC and SCC from 1993 to 2005 in a dermatology practice in Vancouver, British Columbia. METHOD: A retrospective chart review was conducted on patients with biopsy-confirmed NMSC between 1993 and 2005. Demographic and tumor characteristics were documented for the first two incident BCCs and SCCs per patient, and a descriptive data analysis was undertaken. RESULTS: A total of 1,177 NMSCs were identified from 885 patient charts. The number of BCCs increased from 1993 to 2003 and then decreased until 2005. BCCs and SCCs were generally diagnosed in older people (60+ years); however, an important group of younger patients (20-39 years) was also diagnosed with BCCs. BCCs and SCCs were most commonly seen on the head and neck, but the leg was a common location for SCC in women. CONCLUSION: NMSC is prevalent in British Columbia. These results highlight the fact that NMSC can affect individuals younger than 40 years old. Prevention strategies are warranted to reduce the burden of NMSC in British Columbia.

Toxic effects of skin-lightening products in Canadian immigrants.

BACKGROUND: The cultural practice of skin bleaching is highly prevalent in Africa. Most reported cases of toxic effects of skin-lightening products occur in this region. OBJECTIVE: To describe cases of misuse of over-the-counter (OTC) cosmetic skin-lightening products occurring in Canadian immigrants. METHODS: Two cases of Canadian immigrants with severe complications from OTC skin-bleaching agents were identified in a community-based dermatology practice in Toronto. The case histories were reviewed and analyzed. RESULTS: A 28-year-old African-Canadian woman developed extensive striae from long-term use of a topical cream containing clobetasol that she had purchased in a Caribbean health food store. A 55-year-old African-Canadian woman developed exogenous ochronosis from the use of a topical bleaching agent she had purchased in Ghana. CONCLUSION: Cosmetic skin lightening with unregulated topical products occurs in Canada. Dermatologists working in Canada need to be aware of this practice to provide appropriate directive care.

Assessment of left ventricular function in ST-elevation myocardial infarction by global longitudinal strain: a comparison with ejection fraction, infarct size, and wall motion score index measured by non-invasive imaging modalities.

AIMS: We aimed to compare two-dimensional global longitudinal strain (GS) with different non-invasive imaging modalities for the assessment of left ventricular function in an ST-elevation myocardial infarction population. METHODS AND RESULTS: GS was compared with ejection fraction (EF) determined by magnetic resonance imaging (MRI), standard echocardiography (echo), contrast echo, and electrocardiography-gated single-photon emission computed tomography (SPECT), as well as with MRI-determined relative infarct size and echo-determined wall motion score index (WMSI), in 163 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). The linear relation between GS and standard echo (r(2)= 0.43, P <0.001), contrast echo (r(2)= 0.38, P <0.001), and SPECT-determined EF (r(2)= 0.52, P <0.001) was almost identical as that between GS and the gold standard MRI-determined EF (r(2)= 0.47, P <0.001). GS was best associated with WMSI by echo (r(2)= 0.55, P <0.001), while the associations between GS and relative infarct size were weaker (r = 0.43, P <0.001). Receiver operator characteristics curves, used to analyse the ability of GS to discriminate low EF (≤ 40%) measured by the four different modalities, large myocardial infarction (MI ≥ 15.7%), and high WMSI (≥ 1.5), were significant for all. GS was shown to be the best predictor of low EF measured by MRI [area under the curve (AUC) 0.965], while the lowest AUC was found between GS and large MI (0.814). CONCLUSION: Global strain is associated well with EF measured by all modalities. Global strain was found to be the best predictor of low EF measured by the gold standard MRI. Since global strain is an inexpensive test, these data may be of health economic interest.