Colorectal clinical pathways: a method of improving clinical outcome?

OBJECTIVE: Clinical pathways are intended to improve the quality of care. In March 2001, our unit implemented a pathway for patients undergoing major colorectal surgery. The aim of this study was to assess its impact on the quality of patient care. METHODS: We reviewed 204 patients managed using this pathway in 2001, and compared their outcomes with those of a control group of 204 patients who had undergone similar procedures the year before. The endpoints measured were postoperative morbidity, length of stay and readmission rates. RESULTS: Both groups were similar in terms of patient demographics, diagnosis, and nature of surgery performed. In the study group, 61% of patients underwent elective surgery compared with 62% in the control group. The incidence of postoperative morbidity in the study group was 20% compared with 33% in the control group (p = 0.003). The rate of readmission as a result of surgical complications was 6% in the study group versus 13% in the control group (p = 0.029). The average length of stay was 10.4 days in the study group and 12.1 days in the control group (p = 0.105). CONCLUSION: The introduction of a colorectal clinical pathway significantly improved the outcome of patients undergoing major colorectal surgery.     

Iron and a Man’s Reproductive Health: the Good,the Bad,and the Ugly

Purpose of Review

To discuss the physiologic and pathologic effects of iron on men’s reproductive health.

Recent Findings

Iron overload diseases are associated with hypogonadotropic hypogonadism, infertility, and sexual dysfunction in men. Recent findings have elucidated the roles by which iron may affect the male reproductive axis.

Summary

Iron is requisite for life. Iron can also catalyze the production of reactive oxygen species. To maintain balance, the human body tightly regulates dietary iron absorption. Severe iron overload disorders—e.g., hereditary hemochromatosis and β-thalassemia—occur when these regulatory mechanisms are deficient. While iron is necessary, the male reproductive system is particularly sensitive to iron overload. Hypogonadotropic hypogonadism, infertility, and sexual dysfunction commonly occur if excess iron from iron overload disorders is not removed. The average male in the USA consumes significantly more iron than needed to replace daily losses. How this degree of iron loading may affect one’s reproductive health remains less clear, but there is evidence it may have adverse effects.

     

β-adrenergic receptor antagonists and fracture risk: a meta-analysis of selectivity, gender, and site-specific effects

Summary

By meta-analysis, the risk of fracture was 15 % lower in patients treated with β-adrenergic blockers compared to controls independent of gender, fracture site, and dose. This might be attributable to β1-selective blockers.

Introduction

The aim of this study is to determine by meta-analysis whether β-adrenergic blockers (BBs) reduce fracture risk and whether the effect, if demonstrable, is dependent upon selectivity, dose, gender, or fracture site.

Methods

A literature search was performed in electronic databases MEDLINE, EMBASE, and reference sections of relevant articles to identify eligible studies. Adjusted estimates of fracture risk effect size (ES) were pooled across studies using fixed or random-effects (RE) meta-analysis as appropriate. Dose-related effects were evaluated using meta-regression. To explore the relative efficacy of β1-selective blockers in comparison to nonselective BBs, adjusted indirect comparison was performed.

Results

A total of 16 studies (7 cohort and 9 case–control studies), involving 1,644,570 subjects, were identified. The risk of any fracture was found to be significantly reduced in subjects receiving BBs as compared to control subjects (16 studies, RE pooled ES?=?0.86, 95 % CI 0.78–0.93; I²?=?87 %). In a sensitivity analysis limited to those studies deemed to be most robust, the BB effect to reduce fracture risk was sustained (four studies, pooled ES?=?0.79, 95 % CI 0.67–0.94; I²?=?96 %). The risk of a hip fracture was lower in both women and men receiving BBs (women: pooled ES?=?0.86, 95 % CI 0.80–0.91; I²?=?1 % and men: pooled ES?=?0.80, 95 % CI 0.71–0.90; I²?=?0 %). Similar risk reductions were found for clinical vertebral and forearm fractures, although statistical significance was not reached. The reduction in risk did not appear to be dose-related (test for a linear trend p value 0.150). Using adjusted indirect comparisons, it was estimated that β1-selective agents were significantly more effective than nonselective BBs in reducing the risk of any fracture (six studies, β1-selective blockers vs. nonselective BBs: RE pooled ES?=?0.82, 95 % CI?=?0.69–0.97).

Conclusions

The findings suggest that the risk of fracture is approximately 15 % lower in patients treated with BBs compared to controls independent of gender, fracture site, and dose. This risk reduction might be associated with the effects of β1-selective blockers.     

Necrosis and glioblastoma: a friend or a foe? A review and a hypothesis

OBJECTIVE: Two main forms of cell death are encountered in biology: apoptosis (i.e., programmed cell death) and necrosis (i.e., accidental cell death). Because necrosis and apoptosis can lead to cell removal, one might intuit that they are both desirable in cancer treatment. However, in the setting of glioblastoma multiforme, a malignant brain tumor for which the presence of necrosis is an important diagnostic feature, clinical studies indicate that as the degree of necrosis advances, the patient's prognosis worsens. Despite the apparent importance of this form of cell death, the mechanism of development of necrosis in glioblastomas remains unelucidated. The purpose of this article is to try to resolve this dilemma by hypothesizing the mechanism of necrosis formation in these tumors. METHODS: On the basis of an extensive review of the literature, we present a hypothesis for the mechanism of necrosis formation in glioblastoma multiforme. RESULTS: One of the many possible pathways leading to necrosis formation may involve increased tumor cell secretion of tumor necrosis factor. Procoagulation and antiapoptotic mechanisms resulting from certain pathways could prevent the completion of tumor necrosis factor-induced apoptosis and could promote necrosis as the final mode of cell death. Such a hypothesis would explain the inverse correlation that exists between tumor necrosis and the survival of patients with glioblastomas, because the hypoxia that results from procoagulation selects for tumor cells that are more aggressive and more resistant to apoptosis-inducing therapies. CONCLUSION: A complete understanding of the series of events surrounding necrosis development in glioblastomas that is evidence-based is likely to provide targets for future therapies. On the basis of the potential mechanisms of development of necrosis described in this article, we postulate that effective therapies may have to be directed against the pathways that result in the formation of necrosis.     

Neurosurgery, "neurospine," and neuroscience: a vital synergy?

A fundamental dilemma that faces both neurosurgery in general and the subspecialty field of spine surgery is the question of whether those who trained in the former and now work in the latter should maintain their links with their origins and remain under the broader umbrella of neurosurgery, or whether they should develop their own organizational structure and identity separate from organized neurosurgery. This challenge raises many questions with respect to future potential for growth and development, professional identity, and collegiality. This paper is an edited version of an invited speech to the 2007 Annual Meeting of the Joint Section on Disorders of the Spine and Peripheral Nerves. It uses the concept of synergy to review relevant history and explore possible future options for neurosurgery, neurospine, and neuroscience. An example from medical politics is used to illustrate the importance of perspective in approaching these questions, and examples of current therapeutic cutting-edge endeavors highlight the need for team-based behavior that takes a broad view. The premise of the paper is that while individual and specialty aspirations need to be acknowledged, considered, and managed, the results from truly working together will be greater than the sum of the individual efforts-synergy.     

Repeat prostate biopsy: who,how and when?. a review

Urologists are frequently faced with the dilemma of treating a patient with a high index of suspicion of prostate cancer (PCa), but an initial set of negative biopsies. In this review, we evaluated the current knowledge on repeat prostate biopsies, focusing on when to perform them and in which patients, how many samples to take, where to direct the biopsies and what morbidity should be expected. We focussed on the available literature and the multicenter European Prostate Cancer Detection (EPCD) study. The EPCD study included 1051 men with a total PSA from 4 to 10 ng/ml who underwent a transrectal ultrasound (TRUS) guided sextant biopsy and a repeat biopsy in case of a negative initial biopsy. Most studies support that increasing the number of biopsy cores as compared to the sextant technique and improving prostate peripheral zone (PZ) sampling result in a significant improvement in the detection of prostate cancer without increase in morbidity or effects on quality of life. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. At least 10% of patients with negative sextant prostatic biopsy results in the EPCD study were diagnosed with PCa on repeat biopsy, percent free PSA and PSA density of the transition zone being the most accurate predictors. Despite differences in location (more apico-dorsal) and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy were similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Indications and ideal number of biopsy cores to take when repeating biopsies in patients who already underwent extensive biopsy protocols on the first biopsy remains to be determined.     

“The Infinite Maze” of breast cancer,signaling pathways and radioresistance

The parallel growth in our understanding of tumor biology and genetics might be the key to understanding local recurrence after optimal treatment is applied. Data suggest that genetic alterations and breast cancer molecular subtypes have an effect on radiotherapy efficacy and that the HER2, EGFR/PI3K/Akt signaling pathways play a pivotal role in modulation of post-irradiation survival. These pathways have been found to be involved in radiosensitivity and/or radioresistance, tumor cell proliferation, and hypoxia. Therefore, affecting the functional activity of key players combined with radiotherapy might be the future of breast irradiation.     

Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link?

Hypertension and hypertension-associated ESRD are epidemic in society. The mechanisms responsible for renal progression in mild to moderate hypertension and those groups most at risk need to be identified. Historic, epidemiologic, clinical, and experimental studies on the pathogenesis of hypertension and hypertension-associated renal disease are reviewed and an overview/hypothesis for the mechanisms involved in renal progression is presented. There is increasing evidence that hypertension may exist in one of two forms/stages. The first stage, most commonly observed in early or borderline hypertension, is characterized by salt-resistance, normal or only slightly decreased GFR, relatively normal or mild renal arteriolosclerosis, and normal renal autoregulation. This group is at minimal risk for renal progression. The second stage, characterized by salt-sensitivity, renal arteriolar disease, and blunted renal autoregulation, defines a group at highest risk for the development of microalbuminuria, albuminuria, and progressive renal disease. This second stage is more likely to be observed in blacks, in subjects with gout or hyperuricemia, with low level lead intoxication, or with severe obesity/metabolic syndrome. The two major mechanistic pathways for causing impaired autoregulation at mild to moderate elevations in BP appear to be hyperuricemia and/or low nephron number. Understanding the pathogenetic pathways mediating renal progression in hypertensive subjects should help identify those subjects at highest risk and may provide insights into new therapeutic maneuvers to slow or prevent progression.     

On rho, a marrow mediator, and estrogen: Their roles in bone strength and "mass" in human females, osteopenias, and osteoporoses—insights from a new paradigm

From existing evidence, this article argues that six assumptions could explain important estrogen effects on a woman's bone strength and "mass". T_h_e_ e_v_i_d_e_n_c_e_: Strains above a "modeling threshold" cause modeling to increase bone strength and "mass"; under lesser strains, modeling stays OFF. Remodeling by basic multicellular units (BMUs) turns bone over in small "packets," and "rho" signifies any difference in how much bone completed BMUs make and resorb. Where strains exceed a lower "remodeling threshold," rho approaches zero, so that remodeling conserves bone. When strains fall below this threshold, as in acute disuse, rho becomes negative, but only next to marrow, so remodeling removes bone only there. The bone lost during menopause also comes from bone next to marrow, so rho became more negative there too. Simultaneously, and in both cases, bone on periosteal and Haversian surfaces is conserved, meaning rho approaches zero there. T_h_e_ a_s_s_u_m_p_t_i_o_n_s_: (A) Estrogen lowers the threshold for BMU creations on all bone surfaces or envelopes, so loss of the hormone at menopause would increase those creations on all envelopes. (B) Estrogen and acute disuse have no direct effect on rho on any bone envelope. (C) Estrogen and acute disuse do affect some mediator(s) in marrow that can secondarily affect BMUs next to it. (D) That mediator has its own strain threshold, and estrogen lowers it. (E) Loss of estrogen raises that threshold, which causes the mediator to make rho more negative in BMUs next to marrow; that would increase bone loss only there, as would acute disuse, because it would reduce strains below that threshold. (F) Estrogen does not affect the modeling threshold, so it would have no direct effect on cortical bone modeling and outside bone diameter (but by affecting bone length, muscle strength, and physical activities, it might affect modeling indirectly). Those assumptions now have considerable support (although it does not yet amount to proof). The text discusses some of their implications for bone and osteoporosis research. Received: Oct. 1, 1997 / Accepted: Nov. 6, 1997     

Association of Chiari I malformation, mental retardation, speech delay, and epilepsy: a specific disorder?

OBJECTIVE: The Chiari I malformation is defined as tonsillar herniation of at least 3 to 5 mm below the foramen magnum. Although Chiari I malformation is considered to derive from a mesodermal disorder resulting in underdevelopment of the posterior fossa relative to its content, evidence for a possible heterogeneous etiology also has been reported. The aim of the present study is to elucidate the relationship between Chiari I malformation and mental retardation, speech delay, and epilepsy to consider a possible specific pathogenetic background. METHODS: Thirty-five patients with Chiari I malformations were identified by use of magnetic resonance imaging during a period between 1993 and 1999. The study consisted of nine patients (four boys and five girls) who were affected by mental retardation, speech delay, and epilepsy. All patients underwent electroencephalography and brain and cervical spine magnetic resonance imaging. RESULTS: All patients were mentally retarded with a mean intelligence quotient of 50. Seven patients had a positive history for speech delay, and five were epileptic. Electroencephalograms demonstrated abnormalities in seven patients. The mean tonsillar displacement was 10.1 mm. A thin corpus callosum and a wide cavum septum pellucidum were present in three patients. Neither hydromyelia nor scoliosis was observed. No correlation between the degree of the ectopia and clinical manifestation was noted. CONCLUSION: The association of Chiari I malformation with epilepsy, speech delay, and mental retardation may not be a mere incidental finding but may be a marker for a different pathogenetic background.