Sepsis: Is There Room for Vasopressin?

Cardiovascular dysfunction contributes importantly to the high mortality of septic shock, which remains in excess of 50%. Non-survivors are characterized by an inadequate response to fluid resuscitation and catecholamine infusions. A number of recent reports suggest that vasopressin, a non-catecholamine vasopressor, may contribute usefully to the cardiovascular management of septic shock and other forms of vasodilatory shock. Here we review the clinical studies to date of vasopressin use in septic shock and other vasodilatory shock. We then review the known physiology of vasopressin to help understand why vasopressin may be beneficial in this setting. In general, humans having severe vasodilatory shock demonstrate low endogenous vasopressin blood concentration. Low-dose vasopressin infusion in this setting increases blood vasopressin concentration to that observed in hypotension of other causes, results in an increase in mean arterial pressure, and reduces the need for additional -adrenergic vasopressor infusions. Current studies in low numbers of patients suggest that low-dose vasopressin may increase urine output in this setting. Vasopressin infusion increases blood pressure by V1 receptor stimulation on vascular smooth muscle. This vasoconstrictor effect is less pronounced in the cerebral, coronary, and renal circulations. Diminished vasoconstriction in some regional circulations may be contributed to by nitric oxide-mediated vasodilation resulting from oxytocin receptor stimulation by low-dose vasopressin. Thus, low-dose vasopressin infusion may be a useful adjunct to fluid resuscitation and catecholamine infusion in severe septic shock and other forms of vasodilatory shock.     

Epilogue: How Will We Care for Patients with Early Arthritis?

This article draws conclusions about pinpointing the actual onset of disease and when interventions should start to occur. The identification of necessary biomarkers will be discussed. We will also examine the incremental consequences of delaying therapy, particularly for 'preclinical' disease. Medical economic analyses can help us balance benefits and avoid some adverse outcomes for patients. To conclude, we will discuss the new roles that need developing for primary care physicians and non-physican providers.     

Combination Therapy: Appropriate for Everyone?

The severity of asthma often varies throughout the course of the disease. At times the symptoms and underlying inflammation that are characteristic of asthma can worsen. Thus during an episode of viral-induced asthma or during a seasonal increase in asthma severity, a patient may be directed to increase his or her dosage of asthma controllers (i.e., inhaled corticosteroid) or add a long-acting bronchodilator (or other controller medications such as antileukotrienes) to manage symptoms, as recommended in guidelines published by the National Institutes of Health (NIH). Similarly, when symptoms are stable, decreasing dosages or discontinuing certain medications may be appropriate. The recent introduction of a combination product, of a long-acting bronchodilator formulated in the same dry powder device with an inhaled corticosteroid raises new challenges for the step care approach to asthma management recommended by the NIH in 1997. Although unquestionably more convenient for the patient, a combination formulation has the potential to decrease the flexibility required to successfully manage asthma over long periods. In addition, controversy exists regarding long-acting beta-agonists alone because their regular use may mask inflammation in the lung and decrease responsiveness to the bronchodilating effects of rescue medications (i.e., short-acting beta-agonists). The purpose of this article is to help physicians make informed therapeutic decisions for their patients with asthma. It focuses on the advantages and potential disadvantages of using combination products, which contain both an inhaled corticosteroid and a long-acting beta-agonist in the context of the NIH step care approach. Recent publications outlining the use of other add-on controller medications are also discussed.     

Local Therapy for Rectal Cancer: Still Controversial?

Purpose Many considerations, such as morbidity, sexual and urinary dysfunction, or risk of definitive stoma have led to the increased popularity of local therapy in the therapeutic strategy for rectal cancer. However, its role in curative intent is still controversial with oncologic long-term results lower than those obtained by radical surgery. Methods MEDLINE, EMBASE, LILACS, Abstract books, and reference lists from reviews were searched with English language publications to review the current status of evidence for local therapy in rectal cancer, looking especially at the oncologic results and patient selection. We have focused on the new strategies combining neoadjuvant and adjuvant treatment to explain their place in the management of rectal cancer. Results and Conclusions The key to potentially curative local treatment for rectal cancer is patient selection by identifying the best candidates with preoperative tumor staging and clinical and pathologic assessment of favorable features. Low-risk T1 is suitable for local excision alone. Limited data suggest that adjuvant chemoradiotherapy may be helpful in patients with unfavorable T1 and T2 lesions, achieving a local recurrence rate<20 percent. However, the efficacy of salvage surgery after local excision is uncertain.     

Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?

It is now evident that elevated circulating levels of triglycerides in the non-fasting state, a marker for triglyceride (TG)-rich remnant particles, are associated with increased risk of premature cardiovascular disease (CVD). Recent findings from basic and clinical studies have begun to elucidate the mechanisms that contribute to the atherogenicity of these apoB-containing particles. Here, we review current knowledge of the formation, intravascular remodelling and catabolism of TG-rich lipoproteins and highlight (i) the pivotal players involved in this process, including lipoprotein lipase, glycosylphosphatidylinositol HDL binding protein 1 (GPIHBP1), apolipoprotein (apo) C-II, apoC-III, angiopoietin-like protein (ANGPTL) 3, 4 and 8, apoA-V and cholesteryl ester transfer protein; (ii) key determinants of triglyceride (TG) levels and notably rates of production of very-low-density lipoprotein 1 (VLDL1) particles; and (iii) the mechanisms which underlie the atherogenicity of remnant particles. Finally, we emphasise the polygenic nature of moderate hypertriglyceridemia and briefly discuss modalities for its clinical management. Several new therapeutic strategies to attenuate hypertriglyceridemia have appeared recently, among which those targeted to apoC-III appear to hold considerable promise.     

Gene Therapy for Restenosis: Progress or Frustration?

No systemic pharmacological treatment has been shown to convincingly reduce the incidence of restenosis after angioplasty in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates post-angioplasty and following stent-implementation shown in dozens of clinical trials has encouraged the development of new technological approaches as treatment. Gene therapy has the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation. Mechanical methods of preventing restenosis, such as sophisticated local drug delivery strategies and biodegradable stents using new materials in combination with gene therapy, may be of use to maximize safety and efficiency.     

Nighttime Blood Pressure: A Target for Therapy?

Ambulatory blood pressure (BP) monitoring is increasingly used in the evaluation of hypertensive patients. The ability to monitor BP throughout the day and night allows the detection of abnormal nocturnal BP patterns, the most common being a “nondipping” pattern, which is associated with increased cardiovascular risk; its correction appears to have a positive impact on cardiovascular outcome. Antihypertensive treatment should be individually adjusted to control BP during both daytime and nighttime. However, drug-induced lowering of nocturnal BP, if excessive, could amplify the morning BP surge in patients with daytime BP elevation, increasing the risk of developing a cardiovascular event. Ambulatory BP monitoring therefore represents a unique tool to establish the most appropriate antihypertensive drug regimen for the individual patient.     

Cardiovascular Disease Progression: A Target for Therapy?

Clinical research aimed at preventing cardiovascular disease has focused on the effect of interventions to reduce risk factors on the incidence of future morbid events. Disease progression, which likely serves as a necessary prerequisite for morbid events, has not served as a target for therapy. The Rasmussen Center at the University of Minnesota has, for the past 18 years, been performing a noninvasive cardiovascular evaluation in individuals with no history of cardiovascular disease. The studies, performed in 1 hour in one room, provide a comprehensive noninvasive assessment of the severity of functional and structural abnormalities in the small arteries, the large arteries and the left ventricle, the target organs for most cardiovascular morbid events. Preliminary follow-up data have revealed a striking relationship between the Disease Score, which represents the sum of the abnormal tests, and the risk of future morbid events. In order to develop strategies to prolong cardiovascular disease-free life expectancy, studies in early stages of disease aimed at slowing disease progression should be encouraged.     

INTERMACS and MedaMACS: How Will They Guide Future Therapy?

The INTERMACS registry has played a central role in the evolving field of device therapy for advanced heart failure (HF). This nationwide, prospective registry of approved assist devices has defined the boundaries of mechanical support, tracked the evolution from pulsatile to continuous flow, developed new profiles for advanced HF, and standardized adverse event definitions. INTERMACS has guided current therapy and in the future will do so aided by new insights from MedaMACS, a parallel registry of medically-managed ambulatory patients with advanced HF. Together INTERMACS and MedaMACS will leverage the power of observation research to guide patient-centered decisions about mechanical circulatory support.     

Therapy for recurrent acute pericarditis: a rheumatological solution?

OBJECTIVE: To assess the efficacy of a multidrug protocol in recurrent acute pericarditis. We tried also to assess the specific role of colchicine. METHODS:We studied 58 patients (34 males) in the largest monocentric observational study. All patients received prolonged courses of non-steroidal anti-inflammatory drugs; generally we do not start a corticosteroid in recurrent acute pericarditis, but if a steroid had already been started, we planned a very slow tapering; if necessary azathioprine, hydroxychloroquine, and other immunosuppressive drugs were used; 44 patients (27 males, 61.4%) were treated also with colchicine and 14 patients (7 males, 50%) were not given this drug. RESULTS: After starting our protocol recurrences dropped from 0.48 to 0.03 attacks/patient/month (p < 0.00001) within 12 months and remained at the same level till the end of the follow-up (mean 8.1 years) in the whole cohort. In the 44 patients treated with colchicine recurrences dropped from 0.54 to 0.03 attacks/patient/month (p < 0.00001) within 12 months, and in 14 patients not given colchicine recurrences decreased from 0.31 to 0.06 attacks/patient/month (p = 0.002). In patients treated with colchicine the decrease was significantly higher (0.51) than in patients not taking this drug (0.25) (p = 0.006). Colchicine was discontinued by 16.3% of patients because of side effects. CONCLUSION: A multidrug protocol including non-steroidal anti-inflammatory drugs at high dosage, slow tapering of corticosteroid, colchicine, reassurance and close clinical monitoring is very effective in recurrent pericarditis; this improvement is more dramatic in colchicine treated patients, but also patients who do not tolerate it can achieve good control of the disease.     

How Can Psoriatic Arthritis Be Diagnosed Early?

Psoriatic arthritis (PsA) is an inflammatory arthritis that usually develops after the onset of cutaneous psoriasis. Early diagnosis of PsA may lead to less joint damage and better long-term outcomes. Identifying inflammatory arthritis in individuals with psoriasis is the key to early diagnosis of PsA. Screening strategies targeted at individuals with psoriasis, as well as family members of patients with PsA will result in early identification of PsA. This article describes the various strategies that could be employed to identify inflammatory arthritis in patients with psoriasis so that appropriate referral to a rheumatologist for early diagnosis of PsA may be made.