Acute Generalized Exanthematous Pustulosis Induced by Erlotinib (Tarceva) with Superimposed Staphylococcus aureus Skin Infection in a Pancreatic Cancer Patient: A Case Report

Acute generalized exanthematous pustulosis (AGEP) is a rare acute reaction that is drug induced in 90% of the cases and characterized by a widespread, sterile pustular rash. Erlotinib, a small-molecule EGFR tyrosine kinase inhibitor, has been approved by the FDA for patients with pancreatic cancer and non-small cell lung cancer. Skin rash is a well-known side effect related with all EGFR blocking agents. It has been suggested that rash could be used as a surrogate marker for response and possibly be associated with prolonged survival. We report a case of rare presentation of AGEP involving an adverse effect of erlotinib. The commonly reported adverse effects of erlotinib are mild skin eruptions. However, our case describes the rare presentation of AGEP induced by erlotinib. The estimated incidence rate of AGEP is approximately 1–5 cases per million/year.Key Words: Sterile pustular rash, Surrogate marker, Acute generalized exanthematous pustulosis, Epidermal growth factor receptor, Erlotinib     

阻塞D现象

患儿男性,11 d.因有明显的溶血转入本院.转院前在其他医院的实验室检查为:血红蛋白3.5 g/dl、网质细胞计数8.9%、白细胞计数26.5×109/L和血小板计数986×109/L.随后.在本院实验窜做了ABO和D定型、直接抗球蛋白试验(DAT)和抗体筛选试验.结果排除了新生儿溶血病(HDN).     

Surface-attached sulfonamide containing quaternary ammonium antimicrobials for textiles and plastics

With the risks associated with healthcare-associated infections and the rise of antibiotic resistant microorganisms, there is an important need to control the proliferation of these factors in hospitals, retirement homes and other institutions. This work explores the development and application of a novel class of sulfonamide-based quaternary ammonium antimicrobial coatings, anchored to commercially and clinically relevant material surfaces. Synthesized in high yields (60–97%), benzophenone-anchored antimicrobials were spray-coated and UV grafted onto plastic surfaces, while silane-anchored variants were adhered to select textiles via dip-coating. Surface modified samples were characterised by advancing contact angle, anionic dye staining, X-ray photoelectron spectroscopy and atomic force microscopy. After verifying coating quality through the above characterization methods, microbiological testing was performed on batch samples in conditions that simulate the natural inoculation of surfaces and objects (solid/air) and water containers (solid/liquid). Using the previously established Large Drop Inoculum (LDI) protocol at solid/air interfaces, all treated samples showed a full reduction (10⁵–10⁷ CFU) of viable Arthrobacter sp., S. aureus, and E. coli after 3 h of contact time. Additional testing of the walls of plastic LDPE vials treated with a UV-cured sulfonamide antimicrobial at a solid/liquid interface using the newly developed Large Reservoir Inoculum (LRI) protocol under static conditions revealed a complete kill (>10⁶ reduction) of Gram-positive Arthrobacter sp., and a partial kill (>10⁴ reduction) of Gram-negative E. coli within 24–48 h of contact.

A series of surface attached silane or benzophenone sulfonamide quaternary ammonium antimicrobials show potent efficacy at solid/air and solid/liquid interfaces.     

Leishmania donovani influenced cytokines and Toll‐like receptors expression among Sudanese visceral leishmaniasis patients

Leishmaniasis remains a serious health problem. The outcome of Leishmania infection depends on the early innate response. In this study, whole blood samples of 40 patients with visceral leishmaniasis (VL), 10 leishmanin skin test‐negative (LST?ve) controls and 10 leishmanin skin test‐positive (LST+ve) controls were stimulated by live L. donovani promastigotes. Also, THP1 human cell line was infected with L. donovani. The production of interleukin 10 (IL‐10), tumour necrosis factor alpha (TNF) and interferon gamma (IFNG) cytokines was measured, and the expression of Toll‐like receptors (TLR2, TLR4 and TLR9) was done in the blood samples and also in the THP1 cell line. IL‐10 was found to be higher in LST+ve controls compared with VL patients. TNF was moderately produced with no variation between patients, controls and THP1 cells. IFNG was higher in LST+ve controls also in THP1 cells. TLR4 and TLR9 were found to be highly expressed in patients with VL. L. donovani increases the expression of TLR4 and TLR9 in patients with VL and TLR2 in THP1 cells, suggesting a TLRs relation in induction of a mixed cytokine response. TLR9 was markedly recognized by L. donovani DNA.     

Sympathetic neural mechanisms in human hypertension

Compared with substantial clinical research on the renin-angiotensin-aldosterone system (RAAS), much less is known about the importance of the sympathetic nervous system as a therapeutic target to slow the initiation and progression of human hypertension. Using microelectrode recordings of sympathetic activity and radiotracer measurements of regional norepinephrine spillover in hypertensive patients, recent research has advanced several provocative findings with novel—but still largely potential—therapeutic implications for clinical hypertension. These include a stronger scientific rationale for using 1) combined α/β-blockers in the early phases of primary hypertension and obesity-related hypertension; 2) RAAS blockers as central sympatholytics in hypertension associated with chronic kidney disease; and 3) a higher dialysis dose—either nocturnal or short daily hemodialysis—to reduce uremic stimulation of a blood pressure-raising reflex arising in the failing kidneys. New outcomes trials are needed if we are to translate this largely theoretical body of research into clinical practice.     

Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug

The first oral direct renin inhibitor, aliskiren, recently received approval for the treatment of hypertension. This article addresses the premise, promise, and potential limitations of this new class of renin-angiotensin system inhibitor. Although aliskiren adds to a list of more than 100 drugs approved for the treatment of hypertension, its introduction into clinical medicine is of particular interest because of the novel mechanism of action: inhibition of renin’s catalytic activity, the most proximal and rate-limiting step in renin-angiotensin system activation. By producing more complete renin-angiotensin system inhibition than with existing agents, direct renin inhibitors may afford greater protection from hypertensive complications. Other potential advantages include additional blood pressure reduction when used in combination therapy, a placebo-like side-effect profile, avid renal concentration, and long duration of action. Potential limitations include modest levels of blood pressure reduction that are equivalent to but not greater than angiotensin receptor blockers, reduced gastrointestinal absorption with a high-fat meal, and large reactive increases in renin secretion—the functional importance of which is under intense investigation. The results of outcomes trials are eagerly awaited.     

Adherence to the American Diabetes Association standards of care among patients with type 2 diabetes in primary care in Saudi Arabia

Objectives:

To assess adherence to 11 American Diabetes Association (ADA) standards of diabetic care.

Methods:

We conducted this one-year historical prospective study between October 2010 and September 2011 on 450 adult type 2 diabetes patients in a primary care center in Saudi Arabia. We used the definitions of the 2010 ADA standards of diabetic care processes and targets.

Results:

Four-hundred and fifty medical files were valid. The adherence to ADA process standards of measurement of glycated hemoglobin (HbA1c) was 68.7%, 92.9% for blood pressure, and 80.2% for serum lipids. Screening was lowest for nephropathy (35.6%), and highest for diabetic foot (72%). Adherence to medications ranged between 82.2% for antiplatelets, and 92.4% for dyslipidemia. For outcome standards, 24.2% of the patients had an HbA1c <7%, and 32.2% had controlled blood pressure (<130/80 mm Hg); and 58.5% achieved targeted low-density lipoproteins (LDL). Only 7.2% had glycemic control in addition to controlled blood pressure and targeted LDL level. An increasing trend of patients achieving glycemic control (<7%) was shown throughout follow-up (p=0.003).

Conclusions:

We found suboptimal adherence with many ADA standards of diabetic care among patients with type 2 diabetes treated at a primary care center in Saudi Arabia. The achievement of outcome standards, either singly or combined, is lower than the adherence rates. However, the figures show improvement in adherence during the follow-up period.Diabetes mellitus is a chronic disease that can cause devastating secondary complications, reducing the quality and length of life as well as increasing medical costs for the patient and society.1-3 Saudi Arabia has one of the highest diabetes prevalence rates worldwide. The International Diabetes Federation estimates that 8.3% of the world’s adult population (20-79 years) have diabetes, with Saudi Arabia one of the top countries affected (20%).4 Additionally, a national study estimated the overall prevalence of diabetes in Saudis aged 30-70 years at 23.7% (26.7% in women, and 21.5% in men).5Diabetes care is a complex process requiring ongoing patient self-management, education, and support to prevent acute complications, and to reduce the risk of long-term complications.6 Compelling evidence from clinical trials shows that intensive glycemic control effectively delays the onset and slows the progression of diabetic complications, such as nephropathy, retinopathy, and neuropathy.7-9 Likewise, substantial evidence shows that control of associated risk factors such as hypertension and dyslipidemia is protective against undesirable outcomes in patients with diabetes.10-14 The American Diabetes Association (ADA) put together a set of diabetic care standards that are annually revised.15 However, despite the availability of convincing evidence and clear guidelines, many studies throughout the world reported suboptimal adherence to diabetic care standards.16-19 Only a few studies have examined the quality of diabetic care among Saudi patients in a primary care setting,20 outpatient clinics of internal medicine,21,22 and specialized diabetic care centers.23 These studies covered one or more of the screening, diagnostic, and therapeutic components of the ADA standards of diabetic care. However, the extent to which these standards are met at primary care settings was not comprehensively studied. Moreover, the degree to which multiple ADA processes and outcomes are simultaneously achieved was also not studied. Therefore, we aimed to assess the adherence of primary care patients to 11 ADA standards of diabetic care including glycemic control, blood pressure control, and lipid management, singly and combined.     

Weight loss independently predicts urinary albumin excretion normalization in morbidly obese type 2 diabetic patients undergoing bariatric surgery

Background

Despite obesity being closely associated with two common risk factors for albuminuria, namely type 2 diabetes mellitus (T2DM) and hypertension, information on the impact of weight loss on albumin excretion rate in morbidly obese (MO) subjects is scarce.

Objective

To evaluate the independent contribution of weight loss following bariatric surgery (BS) to the improvement of the albumin-to-creatinine ratio (ACR) in MO subjects with T2DM.

Subjects and methods

Observational prospective study, including consecutive (n = 255) patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG) of whom 37.6 % (n = 96) presented with T2DM. Stepwise logistic regression analysis was used to assess the contribution of T2DM-related, hypertension-related, and weight loss-related variables, and type of surgery to normalization of ACR (<30 mg/g) at 12 and 24 months follow-up.

Results

In T2DM subjects, baseline ACR was 85.7 ± 171 mg/g with ACR ≥30 mg/g being present in 45.7 % of the cohort. At 12 months, the ACR significantly decreased in T2DM subjects (42.2 ± 142.8 mg/g; p < 0.005) with no further reduction at 24 months after surgery (44.4 ± 227.7; p = 0.862). Among T2DM subjects with ACR ≥30 mg/g at baseline, the ACR became <30 mg/g in 58.5 % and 76.9 % at 12 and 24 months, respectively (p < 0.001 relative to baseline). Body mass index (BMI) change from baseline was the only independent predictor of ACR normalization at 12 months [Exp(B) 1.373, 95 % confidence interval 1.075–1.703; p < 0.05]. None of the evaluated variables appeared as an independent predictor of ACR normalization at 24 months.

Conclusions

Our data suggest that, in MO subjects with T2DM, interventions aiming at slowing the progression of nephropathy should not only focus on optimization of glucose and blood pressure control but also include effective weight loss strategies.