Evaluating the Need for Preoperative MRI Before Primary Hip Arthroscopy in Patients 40 Years and Younger With Femoroacetabular Impingement Syndrome: A Multicenter Comparative Analysis.

Background: Routine hip magnetic resonance imaging (MRI) before arthroscopy for patients with femoroacetabular impingement syndrome (FAIS) offers questionable clinical benefit, delays surgery, and wastes resources. Purpose: To assess the clinical utility of preoperative hip MRI for patients aged ≤40 years who were undergoing primary hip arthroscopy and who had a history, physical examination findings, and radiographs concordant with FAIS. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 1391 patients (mean age, 25.8 years; 63% female; mean body mass index, 25.6) who underwent hip arthroscopy between August 2015 and December 2021 by 1 of 4 fellowship-trained hip surgeons from 4 referral centers. Inclusion criteria were FAIS, primary surgery, and age ≤40 years. Exclusion criteria were MRI contraindication, reattempt of nonoperative management, and concomitant periacetabular osteotomy. Patients were stratified into those who were evaluated with preoperative MRI versus those without MRI. Those without MRI received an MRI before surgery without deviation from the established surgical plan. All preoperative MRI scans were compared with the office evaluation and intraoperative findings to assess agreement. Time from office to arthroscopy and/or MRI was recorded. MRI costs were calculated. Results: Of the study patients, 322 were not evaluated with MRI and 1069 were. MRI did not alter surgical or interoperative plans. Both groups had MRI findings demonstrating anterosuperior labral tears treated intraoperatively (99.8% repair, 0.2% debridement, and 0% reconstruction). Compared with patients who were evaluated with MRI and waited 63.0 ± 34.6 days, patients who were not evaluated with MRI underwent surgery 6.5 ± 18.7 days after preoperative MRI. MRI delayed surgery by 24.0 ± 5.3 days and cost a mean $2262 per patient. Conclusion: Preoperative MRI did not alter indications for primary hip arthroscopy in patients aged ≤40 years with a history, physical examination findings, and radiographs concordant with FAIS. Rather, MRI delayed surgery and wasted resources. Routine hip MRI acquisition for the younger population with primary FAIS with a typical presentation should be challenged.

Meaningless Applications and Misguided Methodologies in Artificial Intelligence-Related Orthopaedic Research Propagates Hype Over Hope.

There exists great hope and hype in the literature surrounding applications of artificial intelligence (AI) to orthopaedic surgery. Between 2018 and 2021, a total of 178 AI-related articles were published in orthopaedics. However, for every 2 original research papers that apply AI to orthopaedics, a commentary or review is published (30.3%). AI-related research in orthopaedics frequently fails to provide use cases that offer the uninitiated an opportunity to appraise the importance of AI by studying meaningful questions, evaluating unknown hypotheses, or analyzing quality data. The hype perpetuates a feed-forward cycle that relegates AI to a meaningless buzzword by rewarding those with nascent understanding and rudimentary technical knowhow into committing several basic errors: (1) inappropriately conflating vernacular ("AI/machine learning"), (2) repackaging registry data, (3) prematurely releasing internally validated algorithms, (4) overstating the "black box phenomenon" by failing to provide weighted analysis, (5) claiming to evaluate AI rather than the data itself, and (6) withholding full model architecture code. Relevant AI-specific guidelines are forthcoming, but forced application of the original Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines designed for regression analyses is irrelevant and misleading. To safeguard meaningful use, AI-related research efforts in orthopaedics should be (1) directed toward administrative support over clinical evaluation and management, (2) require the use of the advanced model, and (3) answer a question that was previously unknown, unanswered, or unquantifiable.

Preoperative Magnetic Resonance Imaging Offers Questionable Clinical Utility, Delays Time to Hip Arthroscopy, and Lacks Cost-Effectiveness in Patients Aged ≤40 Years With Femoroacetabular Impingement Syndrome: A Retrospective 5-Year Analysis.

PURPOSE: To assess the clinical utility of preoperative magnetic resonance imaging (MRI) and quantify the delay in surgical care for patients aged ≤40 years undergoing primary hip arthroscopy with history, physical examination, and radiographs concordant with femoroacetabular impingement syndrome (FAIS). METHODS: From August 2015 to December 2020, 1,786 consecutive patients were reviewed from the practice of 1 fellowship-trained hip arthroscopist. Inclusion criteria were FAIS, primary surgery, and age ≤40 years. Exclusion criteria were MRI contraindication, reattempt of conservative management, or concomitant periacetabular osteotomy. After nonoperative treatment options were exhausted and a surgical plan was established, patients were stratified by those who presented with versus without MRI. Those without existing MRI received one, and any deviations from the surgical plan were noted. All preoperative MRIs were compared with office evaluation and intraoperative findings to assess agreement. Demographic data, Hip Disability and Osteoarthritis Outcome Score (HOOS)-Pain, and time from office to MRI or arthroscopy were recorded. RESULTS: Of the patients indicated by history, physical examination, and radiographs alone (70% female, body mass index 24.8 kg/m2, age 25.9 years), 198 patients presented without MRI and 934 with MRI. None of the 198 had surgical plans altered after MRI. Patients in both groups had MRI findings demonstrating anterosuperior labral tears that were visualized and repaired intraoperatively. Mean time from office to arthroscopy for patients without MRI versus those with was 107.0 ± 67 and 85.0 ± 53 days, respectively (P < .001). Time to MRI was 22.8 days. No difference between groups was observed among the 85% of patients who surpassed the HOOS-Pain minimal clinically important difference (MCID). CONCLUSION: Once indicated for surgery based on history, physical examination, and radiographs, preoperative MRI did not alter the surgical plan for patients aged ≤40 years with FAIS undergoing primary hip arthroscopy. Moreover, preoperative MRI delayed time to arthroscopy. The necessity of routine preoperative MRI in the young primary FAIS population should be challenged.

Development and progression of proteinuria in dogs treated with masitinib for neoplasia: 28 cases (2010-2019).

OBJECTIVES: To describe the incidence, severity and progression of proteinuria over the first 6 months of masitinib treatment in tumour-bearing dogs without pre-existing proteinuria. To describe the effect of treatment on urine protein:creatinine and renal parameters in patients with pre-existing proteinuria. MATERIALS AND METHODS: Records were reviewed from patients receiving masitinib for neoplasms between June 1, 2010, and May 5, 2019. Patients without pre-treatment and at least one urine protein:creatinine after ≥7 days treatment were excluded. Signalment, tumours and concurrent diseases, treatments, haematology, biochemistry and urinalysis results before, during and after treatment for up to 202 days were collected. Patient visits were grouped into six timepoints for analysis. RESULTS: Twenty-eight dogs were included. Eighteen percent of dogs non-proteinuric at baseline (four of 22) developed proteinuria during treatment, all within 1 month of treatment initiation. One dog developed hypoalbuminaemia, none developed oedema or ascites, azotaemia or were euthanased/died due to proteinuria. Masitinib was immediately discontinued in both dogs in which urine protein:creatinine greater than 2.0 was detected and in both, proteinuria improved. Six dogs with pre-treatment proteinuria were treated with masitinib, significant worsening of proteinuria did not occur. Neither azotaemia nor severe hypoalbuminaemia occurred. CLINICAL SIGNIFICANCE: Proteinuria, when it occurs, tends to develop within 1 month of masitinib commencement and may progress rapidly. Weekly proteinuria monitoring should be considered for the first month and a urine protein:creatinine greater than 0.5 should prompt reassessment within 1 week. Masitinib treatment can be considered in patients with pre-treatment proteinuria and does not inevitably cause worsening of proteinuria.

Predicting Inpatient Payments Prior to Lower Extremity Arthroplasty Using Deep Learning: Which Model Architecture Is Best?

BACKGROUND: Recent advances in machine learning have given rise to deep learning, which uses hierarchical layers to build models, offering the ability to advance value-based healthcare by better predicting patient outcomes and costs of a given treatment. The purpose of this study is to compare the performance of 2 common deep learning models, traditional multilayer perceptron (MLP), and the newer dense neural network (DenseNet), in predicting outcomes for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) as a foundation for future musculoskeletal studies seeking to utilize machine learning. METHODS: Using 295,605 patients undergoing primary THA and TKA from a New York State inpatient administrative database from 2009 to 2016, 2 neural network designs (MLP vs DenseNet) with different model regularization techniques (dropout, batch normalization, and DeCovLoss) were applied to compare model performance on predicting inpatient procedural cost using the area under the receiver operating characteristic curve (AUC). Models were implemented to identify high-cost surgical cases. RESULTS: DenseNet performed similarly to or better than MLP across the different regularization techniques in predicting procedural costs of THA and TKA. Applying regularization to DenseNet resulted in a significantly higher AUC as compared to DenseNet alone (0.813 vs 0.792, P = .011). When regularization methods were applied to MLP, the AUC was significantly lower than without regularization (0.621 vs 0.791, P = 1.1 × 10-15). When the optimal MLP and DenseNet models were compared in a head-to-head fashion, they performed similarly at cost prediction (P > .999). CONCLUSION: This study establishes that in predicting costs of lower extremity arthroplasty, DenseNet models improve in performance with regularization, whereas simple neural network models perform significantly worse without regularization. In light of the resource-intensive nature of creating and testing deep learning models for orthopedic surgery, particularly for value-centric procedures such as arthroplasty, this study establishes a set of key technical features that resulted in better prediction of inpatient surgical costs. We demonstrated that regularization is critically important for neural networks in arthroplasty cost prediction and that future studies should utilize these deep learning techniques to predict arthroplasty costs. LEVEL OF EVIDENCE: III.

Blood transfusions increase the risk of venous thromboembolism following ventral hernia repair.

BACKGROUND: Blood transfusions can affect the clotting cascade, leading to a hypercoagulable state. The association of a venous thromboembolic (VTE) event and perioperative blood transfusion has been identified previously in surgical patients, but not after ventral hernia repair (VHR). The aim of this study was to evaluate the risk of VTE in VHR patients who receive a perioperative blood transfusion. METHODS: The American College of Surgeons National Surgery Quality Improvement Program was queried for open (n = 34,687) and laparoscopic (n = 11,544) VHRs that occurred from 2013 to 2015. Regression analyses were used to determine factors predictive of VTE within 30-day post-operatively, the impact of bleeding requiring blood transfusion, and the influence of surgical approach on VTE. RESULTS: Post-operative VTE occurred in 246 (0.5%) VHR patients. Among those patients, 53.0% occurred after discharge. Increased age, operative time, and comorbidities increased the risk of VTE (p < 0.05). Controlling for surgical approach, perioperative blood transfusion increased the risk of VTE 10.2-fold (p < 0.0001) in open and 12.2-fold in laparoscopic VHR (p < 0.0001). CONCLUSION: Perioperative blood transfusions are associated with an increased rate of VTE following VHR, more than 50% of which occur after discharge. This study highlights the importance of identifying quality initiatives for at risk patients, including adequate VTE screening and potential prophylaxis for those who receive perioperative blood transfusions.

Metastatic Malignant Thymoma to the Abdomen: A SEER Database Review and Assessment of Treatment Strategies.

BACKGROUND: Thymoma is a neoplasm occurring in 0.15 of 100,000 persons/year. Abdominal metastases are rare. We report the incidence of malignant thymoma (MT) and suggest imaging and treatment options for cases of abdominal metastasis. METHODS: A National Cancer Institute's Surveillance, Epidemiology and End Results database review was conducted to identify MT cases, followed by a literature review examining cases of metastases to the abdomen. Incidence rates were calculated, and symptoms, treatments, size and location of tumors, disease-free interval (DFI), and survival time were recorded. RESULTS: From 1973 to 2008, a total of 1,588 MT cases were identified (45.4 cases/year), which were extrapolated to 2,724 over 60 years. Incidence has risen from 17 cases in 1973 to 90 cases in 2008, with a larger incidence in males than females (0.23 vs. 0.17 per 100,000). There were 25 cases of abdominal metastasis (0.92%), 13 of which were asymptomatic. There was a wide variety of DFI and survival noted amongst the case reports. Multiple treatment modalities were used. CONCLUSIONS: The incidence of MT is on the rise with a male predominance. All patients should receive routine imaging to look for extrathoracic metastases as half will not have symptoms. All patients with abdominal metastases should be treated using a multimodal approach.

Use of accelerometry to investigate physical activity in dogs receiving chemotherapy.

OBJECTIVES: To perform a preliminary study to assess whether single-agent palliative or adjuvant chemotherapy has an impact on objectively measured physical activity in dogs. METHODS: Fifteen dogs with neoplasia (treatment group) wore ActiGraph™ accelerometers for 5-day periods before, during and after receiving single-agent adjuvant or palliative chemotherapy. Mean 5-day total physical activity and time spent in three different intensities of activity (sedentary, light-moderate and vigorous) before, during and after receiving chemotherapy were compared to a group of 15 healthy dogs (control group). Results were also compared within the treatment group across time. RESULTS: Prior to chemotherapy, treated dogs tended to be less active than control dogs. Treatment group dogs were slightly more active at restaging than they were prior to treatment but had similar activity levels to control dogs. Marked effects of chemotherapy on physical activity were not detected. Physical activity was slightly lower in treated dogs during chemotherapy when compared to control dogs but there was a slight increase in physical activity of treated dogs during chemotherapy when compared with pretreatment recordings. There was little change in the mean 5-day total physical activity between treated dogs during chemotherapy and at restaging but a mild decrease in time spent sedentary and increase in time spent in light-moderate activity at this comparison of time points. CLINICAL SIGNIFICANCE: Single-agent adjuvant or palliative chemotherapy had minimal impact on physical activity levels in dogs with neoplasia.

Veterinarians' attitudes to chronic pain in dogs.

Veterinary surgeons in the UK were invited to complete an internet survey concerning their attitudes to chronic pain in dogs. UK veterinary surgeons numbering 215 completed surveys in full along with 48 worldwide specialists in anaesthesia and 37 worldwide specialists in oncology. Osteoarthritis, dental and aural disease, vertebral and spinal cord conditions, neoplasia and skin conditions were considered important causes of chronic pain in dogs. UK practitioners used significantly fewer classes of analgesic drugs regularly than either category of specialist. The major barriers to adequate treatment of chronic pain were reported as difficulties with pain assessment, expense of drugs, and difficulties with owner compliance. Illustrations of six common neoplastic conditions were used and scored for pain according to prior experience by practitioners. All six conditions were consistently described as involving some degree of pain with primary bone tumour and oral tumour, causing severe pain and moderate to severe pain, respectively. Years since graduation and specialist status affected the pain scores attributed to the conditions. There was a significant correlation between the pain score attributed to the illustrated condition, and the tendency to administer analgesia.

Nutrition education tools used in phenylketonuria: clinician, parent and patient perspectives from three international surveys.

BACKGROUND: Three international surveys were developed aiming to identify the current nutrition educational tools used in the management of phenylketonuria (PKU) and the perceived effectiveness of these tools by clinicians, parents and patients. METHODS: The first two surveys were distributed through the Metabolic Dietitians ListServe (pno-metabl@listserv.cc.emory.edu), and the third survey was distributed by international clinics and the National PKU Alliance website (www.npkua.org). A total of 888 responses (S1, n = 88; S2, n = 81; S3, n = 719) were collected from all three surveys. The surveys represent participants from 17 countries, in Europe; North America (USA and Canada); Mexico; Argentina; Turkey; Australia; and Africa (Tunisia). RESULTS: A consistent decline in 'parents as role models' as an educational tool was observed starting at age 10 years. Patients responded they feel their families are the most effective form of education, whereas handouts were selected as the least effective educational tool by patients. Parents responded they feel the most effective educational tool is one-on-one counselling. Patients and parents show a desirable trend in wanting to attend group clinic, even in centres where this type of educational tool is not offered. CONCLUSIONS: There was a discrepancy between clinicians and patient views regarding the perceived effectiveness of the nutrition education tools. Future research is needed surrounding the impact nutrition education may have on improved dietary compliance in patients with PKU.

A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane.

BACKGROUND: Trilostane is a recognized treatment for canine pituitary-dependent hyperadrenocorticism (PDH); however, its efficacy in dogs with adrenal-dependent hyperadrenocorticism (ADH) is unknown. OBJECTIVES: To examine factors that might influence survival in the medical management of ADH, with particular emphasis on treatment selection. ANIMALS: Thirty-seven animals referred to 4 centers over a period of 12 years that had been diagnosed with ADH and treated with either trilostane (22/37), mitotane (13/37), or both (2/37). METHODS: Retrospective analysis of clinical records. RESULTS: There was no statistically significant difference between the survival times of 13 dogs treated only with mitotane when compared with 22 dogs treated only with trilostane. The median survival time for animals treated with trilostane was 353 days (95% confidence interval [CI] 95-528 days), whereas it was 102 days (95% CI 43-277 days) for mitotane. Metastatic disease was detected in 8 of 37 dogs. There was a significantly lower probability of survival for dogs with metastatic disease when compared with those without metastatic disease (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The choice of medical treatment for ADH may not have a major effect on survival times. However, the presence of metastatic disease considerably decreases survival time regardless of the choice of medical treatment.

Detergent protease exposure and respiratory disease: case-referent analysis of a retrospective cohort.

OBJECTIVES: To examine the relationship between protease exposure and respiratory disease in a cohort of detergent enzyme manufacturers. METHODS: Case-referent analysis of a cohort of employees working in a European detergent factory between 1989 and 2002. Cases with new lower or upper respiratory disease were ascertained by examination of occupational health records and matched to referents on date of first employment. Personal exposures to airborne detergent protease were estimated, using a job exposure matrix, from >12,000 measurements taken in the factory during the period of study. RESULTS: We found clear, monotonic relationships between estimated protease exposure and both lower and upper respiratory disease. After control for age, sex and smoking, the odds ratio of lower respiratory disease was significantly elevated (1.98, 95% CI 1.04 to 3.79) in those employees working in jobs in the highest quartile of protease exposure (geometric mean 7.9 ng x m(-3)). For employees with upper respiratory disease, the risk was significantly elevated at a lower level of estimated protease exposure (geometric mean 2.3 ng x m(-3)). CONCLUSIONS: These findings provide strong evidence of an association between detergent enzyme exposure and the development of respiratory disease in an occupational setting. Using the routinely collected information on specific sensitisation and the close attention to workplace exposures that are characteristic of this industry, it should be possible to derive meaningful occupational exposure standards for most detergent enzymes.

A novel solution for severe urinary incontinence in women with cystic fibrosis.

BACKGROUND: To explore whether Tension-free Vaginal Tape offers a solution for women with cystic fibrosis who suffer from severe stress incontinence. METHODS: Four adults with cystic fibrosis were formally assessed by gynaecological and urological specialists, prior to hospital admission for surgery. RESULTS: The procedure was tolerated well by all patients. In three, leakage ceased completely. The fourth patient experienced considerable improvement in symptoms. CONCLUSIONS: Tension-free Vaginal Tape is a safe, effective and worthwhile solution for stress incontinence in females with cystic fibrosis.

Evidence for new alleles in the protein kinase adenosine monophosphate-activated gamma(3)-subunit gene associated with low glycogen content in pig skeletal muscle and improved meat quality.

Several quantitative trait loci (QTL) affecting muscle glycogen content and related traits were mapped to pig chromosome 15 using a three-generation intercross between Berkshire x Yorkshire pigs. On the basis of the QTL location the PRKAG3 (protein kinase, AMP-activated, gamma(3)-subunit) gene was considered to be a good candidate for the observed effects. Differences in the PRKAG3 gene sequences of the founder animals of the intercross were analyzed. The RN(-) mutation previously reported was not present in the cross but three missense substitutions and a polymorphic short interspersed element (SINE) were identified. To confirm the hypothesis that at least one of these mutations was associated with differences in meat quality, >1800 animals from several unrelated commercial lines were genotyped for the candidate substitutions and an association study was performed. The results demonstrate the presence of new economically important alleles of the PRKAG3 gene affecting the glycogen content in the muscle and the resulting meat quality. Haplotype analysis was shown to resolve the effects of PRKAG3 more clearly than analysis of individual polymorphisms. Because of their prevalence in the more common commercial breeds, the potential implications for the pig industry and consumers are considerably greater than the original discovery of the RN(-) mutation. Furthermore, these results illustrate that additional alleles of genes involved in major mutations may play a significant role in quantitative trait variation.

Inhibition of store-operated Ca(2+) influx by acidic extracellular pH in cultured human microglia.

The effects of extracellular acidification on Ca(2+)-dependent signaling pathways in human microglia were investigated using Ca(2+)-sensitive fluorescence microscopy. Adenosine triphosphate (ATP) was used to elicit Ca(2+) responses primarily dependent on the depletion of intracellular endoplasmic reticulum (ER) stores, while platelet-activating factor (PAF) was used to elicit responses primarily dependent on store-operated channel (SOC) influx of Ca(2+). The duration of transient responses induced by ATP was not significantly different in standard physiological pH 7.4 (mean duration 30.2 +/- 2.5 s) or acidified pH 6.2 (mean duration 31.7 +/- 2.8 s) extracellular solutions. However, the time course of the PAF response at pH 7.4 was significantly reduced by 87% with external pH at 6.2. These results suggest that acidification of extracellular solutions inhibits SOC entry of Ca(2+) with little or no effect on depletion of ER stores. Changes of extracellular pH over the range from 8.6 to 6.2 during the development of a sustained SOC influx induced by PAF resulted in instantaneous modulation of SOC amplitude indicating a rapidly reversible effect of pH on this Ca(2+) pathway. Whole-cell patch clamp recordings showed external acidification blocked depolarization-activated outward K(+) current indicating cellular depolarization may be involved in the acid pH inhibition. Since SOC mediated influx of Ca(2+) is strongly modulated by membrane potential, the electrophysiological data suggest that acidification may act to inhibit SOC by cellular depolarization. These results suggest that acidification observed during cerebral ischemia may alter microglial responses and functions.

Effectiveness and economic impact of screening for colorectal cancer by mass fecal occult blood testing.

OBJECTIVES: Fecal occult blood testing has been shown to reduce mortality from colorectal cancer in large randomized, controlled trials conducted in the United States, Denmark, and the United Kingdom, and mathematical simulation modeling found it to be cost-effective relative to other health care services. Before making a concerted effort to implement mass fecal occult blood testing based on this evidence alone, however, we considered it prudent to critically re-evaluate the effectiveness and economic impact of screening in the US population as a whole. METHODS: To assess the effectiveness of screening, we projected published outcomes from each of the three large randomized controlled trials of fecal occult blood testing to the US population, as if each clinical trial had been done in the population as a whole. We then determined the resource costs of detection and treatment that would be associated with the outcomes predicted from each trial. RESULTS: More than 1 million colorectal cancers could be expected to arise over 10 yr in the cohort of US residents eligible to enter a screening program in 1997, and trial outcomes indicate that > or = 60% of these cancers would be fatal. If the 60-67% compliance rate of the population-based randomized controlled trials were achieved, a fecal occult blood testing program would detect 30% of known colorectal cancers and save 100,000 lives over 10 yr. Screening would incur total costs of $3-4 billion over 10 yr, or $2,500 per life-year saved. CONCLUSIONS: Mass fecal occult blood testing is cost-effective, and, although not inexpensive, many would consider the total cost acceptable. Even with a concerted effort to achieve compliance, however, the effectiveness of fecal occult blood testing would be limited to saving the lives of < or = 15% of those who otherwise would die from their cancer in the first 10 yr after beginning mass screening. The limitations of fecal occult blood testing suggest the need to further evaluate the role of endoscopy in screening, and to develop more effective, noninvasive screening tools.

Anion channels modulate store-operated calcium influx in human microglia.

Recent work from this laboratory has demonstrated that purinergic-mediated depolarization of human microglia inhibited a store-operated pathway for entry of Ca2+. We have used Fura-2 spectrofluorometry to investigate the effects on store-operated Ca2+ influx induced by replacement of NaCl with Na-gluconate in extracellular solutions. Three separate procedures were used to activate store-operated channels. Platelet activating factor (PAF) was used to generate a sustained influx of Ca2+ in standard physiological saline solution (PSS). The magnitude of this response was depressed by 70% after replacement of PSS with low Cl- PSS. A second procedure used ATP, initially applied in Ca2+-free PSS solution to deplete intracellular stores. The subsequent perfusion of PSS solution containing Ca2+ resulted in a large and sustained entry of Ca2+, which was inhibited by 75% with low Cl- PSS. The SERCA inhibitor cyclopiazonic acid (CPA) was used to directly deplete stores in zero-Ca2+ PSS. Following the introduction of PSS containing Ca2+, a maintained stores-operated influx of Ca2+ was evident which was inhibited by 77% in the presence of the low Cl- PSS. Ca2+ influx was linearly reduced with cell depolarization in elevated K+ (7.5 to 35 mM) suggesting that changes in external Cl- were manifest as altered electrical driving force for Ca2+ entry. However, 50 mM external KCl effectively eliminated divalent entry which may indicate inactivation of this pathway with high magnitudes of depolarization. Patch clamp studies showed low Cl-PSS to cause depolarizing shifts in both holding currents and reversal potentials of currents activated with voltage ramps. The results demonstrate that Cl- channels play an important role in regulating store-operated entry of Ca2+ in human microglia.

Colorectal cancer screening.

Colorectal cancer is an important problem in the United States, with over 130,000 new cases and 55,000 deaths each year. There is now strong evidence that screening for colorectal cancer with fecal occult blood testing can decrease mortality, and additional evidence that removing benign adenomas can decrease cancer incidence. Evidence-based screening guidelines depend on colorectal cancer risk. Individuals at higher risk because of a personal or family history deserve more intensive screening than asymptomatic individuals over age 50.