Baylor Scott & White - Central Texas Foundation

Ductular reaction (DR) is characterized by the proliferation of reactive bile ducts induced by liver injuries. DR is pathologically recognized as bile duct hyperplasia and is commonly observed in biliary disorders. It can also be identified in various liver disorders including nonalcoholic fatty liver disease. DR is associated with liver fibrosis and damage, and the extent of DR parallels to patient mortality. DR raises scientific interests because it is associated with transdifferentiation of liver cells and may play an important role in hepatic regeneration. The origin of active cells during DR can be cholangiocytes, hepatocytes, or hepatic progenitor cells, and associated signaling pathways could differ depending on the specific liver injury or animal models used in the study. Although further studies are needed to elucidate detailed mechanisms and the functional roles in liver diseases, DR can be a therapeutic target to inhibit liver fibrosis and to promote liver regeneration. This review summarizes previous studies of DR identified in patients and animal models as well as currently understood mechanisms of DR.

The COVID-19 pandemic presents clinicians a unique set of challenges in managing breast cancer (BC) patients. As hospital resources and staff become more limited during the COVID-19 pandemic, it becomes critically important to define which BC patients require more urgent care and which patients can wait for treatment until the pandemic is over. In this Special Communication, we use expert opinion of representatives from multiple cancer care organizations to categorize BC patients into priority levels (A, B, C) for urgency of care across all specialties. Additionally, we provide treatment recommendations for each of these patient scenarios. Priority A patients have conditions that are immediately life threatening or symptomatic requiring urgent treatment. Priority B patients have conditions that do not require immediate treatment but should start treatment before the pandemic is over. Priority C patients have conditions that can be safely deferred until the pandemic is over. The implementation of these recommendations for patient triage, which are based on the highest level available evidence, must be adapted to current availability of hospital resources and severity of the COVID-19 pandemic in each region of the country. Additionally, the risk of disease progression and worse outcomes for patients need to be weighed against the risk of patient and staff exposure to SARS CoV-2 (virus associated with the COVID-19 pandemic). Physicians should use these recommendations to prioritize care for their BC patients and adapt treatment recommendations to the local context at their hospital.

Upper abdominal surgery is associated with characteristic changes in pulmonary function which increase the risk of lower lobe atelectasis. Sixteen patients undergoing open cholecystectomy and 20 patients undergoing laparoscopie cholecystectomy were prospectively evaluated by pulmonary function tests (forced vital capacity [FVC], forced expiratory volume [FEV-1], and forced expiratory flow [FEF] 25% to 75%) before operation and on the morning after surgery to determine if the laparoscopie technique lessens the pulmonary risk. Fraction of the baseline pulmonary function was calculated by dividing the postoperative pulmonary function by the preoperative pulmonary function and multiplying by 100%. Postoperative FVC measured 52% of preoperative function for open cholecystectomy and 73% for laparoscopie cholecystectomy (p = 0.002). Postoperative FEV-1 measured 53% of baseline function for open cholecystectomy and 72% for laparoscopie cholecystectomy (p = 0.006). Postoperative FEF 25% to 75% measured 53% for open cholecystectomy and 81% for laparoscopie cholecystectomy (p = 0.07). It is concluded that laparoscopie cholecystectomy offers improved pulmonary function compared to the open technique.

STUDY DESIGN: Retrospective comparative study using prospectively collected data. OBJECTIVE: To compare the rate of infection with and without the use of vancomycin powder application during posterior cervical instrumentation. SUMMARY OF BACKGROUND DATA: Surgical site infections (SSI) are a significant source of morbidity in multilevel posterior-instrumented fusions for cervical spondylotic myelopathy (CSM). Local delivery of antibiotics has been associated with decreased rates of SSI in posterior-instrumented fusions, but no study has addressed the effects of these measures on a population composed of exclusively multilevel posterior cervical instrumentation performed with decompression for CSM. METHODS: All patients undergoing multilevel posterior decompression and instrumentation for CSM by a single surgeon from 2003-2011 were included. Post hoc analysis of prospectively collected data was analyzed comparing consecutive patients treated without the use of vancomycin powder with those treated after the initiation of vancomycin powder prophylaxis. Intervention cohort and controls were examined for differences in SSI rate, body mass index, neurological status, comorbidities, and complications. RESULTS: A total of 112 patients were included in the study. Intervention (n = 40) and control (n = 72) groups were statistically similar with regard to age, body mass index, comorbidities, estimated blood loss, and operative time. Univariate analysis showed a significant decrease in infection rate in the intervention group (0%) compared with the control group (15%) in this high-risk population (P = 0.007; power = 81%). No adverse events were noted in the intervention group associated with the use of vancomycin powder. CONCLUSION: The local application of vancomycin was associated with a significant reduction in the risk of SSI in multilevel posterior cervical-instrumented fusions for CSM. This study supports the growing body of evidence that vancomycin powder placed in the wound can reduce the incidence of postoperative wound infections, and is the first that addresses this specific population. LEVEL OF EVIDENCE: 2.

BACKGROUND: Early in the 20th century, thyroid surgery was performed using local anesthetic techniques. When general anesthesia became safer, surgeons started performing thyroidectomy exclusively under general anesthesia. However, recent descriptions of thyroidectomy under local anesthesia claim similar results to thyroidectomy under general anesthesia. Surgery conducted under local anesthesia can result in early discharge, ie, a hospital stay of less than 8 hours. HYPOTHESIS: Thyroidectomy can be performed under local anesthesia with monitored anesthesia care (MAC) with results similar to general anesthesia in an outpatient or inpatient surgery setting. DESIGN: A prospective randomized study comparing local anesthesia with MAC vs general anesthesia in adult patients undergoing thyroidectomy in a potential outpatient setting, defined as same-day discharge. Patients were excluded if they were not able to receive local or general anesthesia. In addition, we performed an outcome evaluation of the use of local anesthesia with MAC for thyroidectomy and the use of outpatient surgery for thyroidectomy. We compared 58 consecutive thyroidectomies performed prior to the study with 58 consecutive thyroidectomies performed after the study. SETTING: A 486-bed university-affiliated hospital. RESULTS: Fifty-eight patients undergoing thyroidectomy received random assignment: 29 to local anesthesia with MAC and 29 to general anesthesia under study protocol. Fifty-one surgical procedures (88%) were completed as outpatient surgery. No significant differences were found between the 2 study groups in demographics, postoperative adverse symptoms, complications, hospital admission, or patient satisfaction. Patients in the general anesthesia group spent, on average, more time postoperatively than patients in the group that received local anesthesia with MAC in the outpatient surgery center until same-day discharge (P = .02). When compared before the study, we found a significant increase after the randomized study in the use of local anesthesia with MAC (P<.001) and outpatient thyroidectomies (P<.001). CONCLUSIONS: Thyroidectomy can be performed in the studied patient population under either general anesthesia or local anesthesia with MAC, expecting similar operative results, clinical results, and patient satisfaction. In addition, local anesthesia with MAC can reduce the postoperative time spent in an outpatient surgery setting with potential health care cost savings.

Cigarette smoking contributes to the development of cancer, and pathogenesis of other diseases. Many chemicals have been identified in cigarettes that have potent biological properties. Nicotine is especially known for its role in addiction and plays a role in other physiological effects of smoking and tobacco use. Recent studies have provided compelling evidence that, in addition to promoting cancer, nicotine also plays a pathogenic role in systems, such as the lung, kidney, heart, and liver. In many organ systems, nicotine modulates fibrosis by altering the functions of fibroblasts. Understanding the processes modulated by nicotine holds therapeutic potential and may guide future clinical and research decisions. This review discusses the role of nicotine in the general fibrogenic process that governs fibrosis and fibrosis-related diseases, focusing on the cellular mechanisms that have implications in multiple organ systems. Potential research directions for the management of nicotine-induced fibrosis, and potential clinical considerations with regard to nicotine-replacement therapy (NRT) are presented.

Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam (IV LEV), a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of IV LEV and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

AIMS: This prospective, multicenter post-approval study evaluated the success rate of sacral neuromodulation (SNM) with the InterStim® System at 12-months. Subjects with bothersome symptoms of overactive bladder (OAB) including urinary urge incontinence (UI) or urgency-frequency (UF), who failed at least one anticholinergic medication and had at least one not tried were included. METHODS: Subjects with successful test stimulation received an SNM implant. Therapeutic success (≥50% improvement in average leaks/day or voids/day or a return to normal voiding frequency [<8 voids/day]) and quality of life through 12 months were evaluated for implanted subjects. RESULTS: Of the 340 subjects that went through test stimulation, 272 were implanted with SNM. Of these, 91% were female, mean age was 57, UI subjects had 3.1 ± 2.7 leaks/day, UF subjects had 12.6 ± 4.5 voids/day. The analysis which includes all implanted subjects with diary data at baseline and 12 months showed an OAB therapeutic success rate of 85% at 12 months. UI subjects had a mean reduction of 2.2 ± 2.7 leaks/day; UF subjects had a mean reduction of 5.1 ± 4.1 voids/day (both P < 0.0001). Subjects showed significant improvement from baseline in all measures of ICIQ-OABqol (all P < 0.0001). 80% of subjects reported improved changes in their urinary symptom interference at 12 months. Device-related adverse events occurred in 16% (56/340) of subjects during test stimulation and 30% (82/272) of subjects post-implant. CONCLUSIONS: This multicenter study shows SNM is safe and effective and results in improved outcomes through 12 months in subjects with OAB symptoms, without requiring failure of all medications.

Levodopa is the most effective agent to alleviate motor dysfunction in Parkinson's disease but its long-term use is associated with the development of dyskinesias. Although the pathogenic processes behind the development of levodopa-induced dyskinesias are still being elucidated, it appears that chronic administration of this short-lived agent results in nonphysiologic pulsatile stimulation of striatal neurons and abnormal firing patterns in the basal ganglia. Dyskinesias have been associated with decreased quality of life, and a number of methodologies to evaluate severity of dyskinesias are now available. Strategies to avoid, reduce, or eliminate dyskinesias include providing more continuous dopaminergic stimulation, administering an antidyskinetic agent, and surgery. Several new compounds that may provide an antidyskinetic effect are also under investigation.

Since the end of World War II, the gen-eral public and the scientific community have shown increased interest in the common ophthalmologic condition var-iously known as amblyopia, amblyopia ex anopsia, and &amp;quot;lazy eye. &amp;quot; The child with a patch over one eye has become a common sight, the subject has developed into a fa-vorite research target for neurophysiolo-gists and neuroanatomists (1), and ex-citing new insights have been gained into the underlying disease process (2-6). Re-search progress has been uneven, how-ever. Amblyopia has not attracted much attention from trained epidemiologists, and fundamental epidemiologic questions remain unanswered. The term &amp;quot;amblyopia &amp;quot; simply means dimness of vision and is used for any non-specific loss of visual acuity. Formal def-initions in the literature reflect this gen-erality (7, 8). The term is also used to de-note a specific clinical entity that is easy to illustrate but hard to define. Except where otherwise noted, we will use the term to mean low vision that occurs in infants or young children who have ex-

Experimental methods are commonly used for patient-specific IMRT delivery verification. There are a variety of IMRT QA techniques which have been proposed and clinically used with a common understanding that not one single method can detect all possible errors. The aim of this work was to compare the efficiency and effectiveness of independent dose calculation followed by machine log file analysis to conventional measurement-based methods in detecting errors in IMRT delivery. Sixteen IMRT treatment plans (5 head-and-neck, 3 rectum, 3 breast, and 5 prostate plans) created with a commercial treatment planning system (TPS) were recalculated on a QA phantom. All treatment plans underwent ion chamber (IC) and 2D diode array measurements. The same set of plans was also recomputed with another commercial treatment planning system and the two sets of calculations were compared. The deviations between dosimetric measurements and independent dose calculation were evaluated. The comparisons included evaluations of DVHs and point doses calculated by the two TPS systems. Machine log files were captured during pretreatment composite point dose measurements and analyzed to verify data transfer and performance of the delivery machine. Average deviation between IC measurements and point dose calculations with the two TPSs for head-and-neck plans were 1.2 ± 1.3% and 1.4 ± 1.6%, respectively. For 2D diode array measurements, the mean gamma value with 3% dose difference and 3 mm distance-to-agreement was within 1.5% for 13 of 16 plans. The mean 3D dose differences calculated from two TPSs were within 3% for head-and-neck cases and within 2% for other plans. The machine log file analysis showed that the gantry angle, jaw position, collimator angle, and MUs were consistent as planned, and maximal MLC position error was less than 0.5 mm. The independent dose calculation followed by the machine log analysis takes an average 47 ± 6 minutes, while the experimental approach (using IC and 2D diode array measurements) takes an average about 2 hours in our clinic. Independent dose calculation followed by machine log file analysis can be a reliable tool to verify IMRT treatments. Additionally, independent dose calculations have the potential to identify several problems (heterogeneity calculations, data corruptions, system failures) with the primary TPS, which generally are not identifiable with a measurement-based approach. Additionally, machine log file analysis can identify many problems (gantry, collimator, jaw setting) which also may not be detected with a measurement-based approach. Machine log file analysis could also detect performance problems for individual MLC leaves which could be masked in the analysis of a measured fluence.

PURPOSE: This study explored the impact of personal digital assistant (PDA) features, users' perceptions, and other factors that may have hindered PDA acceptability and usability as technology advances in e-health diabetes self-management. STUDY DESIGN AND RESULTS: An ongoing study on PDA usage is set within the context of the advancements of Web 2.0 for type 2 diabetes mellitus (T2DM) self-management e-interventions. Advancements in technology as it relates to the future of T2DM mobile applications are discussed as possible deterrents of PDA acceptability and usability. CONCLUSIONS: This case study illustrates the importance of addressing factors that may impede the adoption of electronic devices intended for sustained health behavior change. Recognizing the importance of individual perception within the context of rapid technological advancements is imperative for designing future health interventions. Incorporating electronic devices that individuals are more inclined to utilize, such as smartphones, as the platform for health interventions is a promising strategy to improve acceptability and usability, allowing researchers to more accurately assess the health benefits of self-management programs.

We have performed cytogenetic studies on five renal oncocytic neoplasms (three grade 2 tumors and two grade 1 tumors) identified histologically by light microscopy. One grade 1 tumor failed to produce mitotic cells. The other four tumors exhibited both normal and abnormal cell lines. Numerical abnormalities were found in both the single grade 1 and two of the grade 2 tumors whereas structural abnormalities were limited to grade 2 tumors. Aneuploidy of chromosome 12 was observed in both grade 1 and 2 tumors. Grade 2 tumors showed more extensive numerical change than the grade 1 tumors. Abnormalities of chromosome 3 characteristic of renal cell carcinoma were not found in any tumor in this series. A combination of C-banding and HaeIII endonuclease banding was used to identify an ambiguous marker. In our four cases and in the cases previously reported, loss of a sex chromosome, abnormalities of chromosomes 1 and 22, and trisomy 12 are findings most often observed in renal oncocytoma.

Knowledge of how the immune system recognizes and attempts to control cancer growth and development has improved dramatically. The advent of immunotherapies for cancer has resulted in robust clinical responses and confirmed that the immune system can significantly inhibit tumor progression. Until recently, metastatic melanoma was a disease with limited treatment options and a poor prognosis. CD137 (also known as 4-1BB) a member of the tumor necrosis factor (TNF) receptor superfamily, is an activation-induced T cell costimulator molecule. Growing evidence indicates that anti-CD137 monoclonal antibodies possess strong antitumor properties, the result of their powerful capability to activate CD8+ T cells, to produce interferon (IFN)-γ, and to induce cytolytic markers. Combination therapy of anti-CD137 with other anticancer agents, such as radiation, has robust tumor-regressing abilities against nonimmunogenic or poorly immunogenic tumors. Of importance, targeting CD137 eliminates established tumors, and the fact that anti-CD137 therapy acts in concert with other anticancer agents and/or radiation therapy to eradicate nonimmunogenic and weakly immunogenic tumors is an additional benefit. Currently, BMS-663513, a humanized anti-CD137 antibody, is in clinical trials in patients with solid tumors, including melanoma, renal carcinoma, ovarian cancer, and B-cell malignancies. In this review, we discuss the basis of the therapeutic potential of targeting CD137 in cancer treatment, focusing in particular, on BMS-663513 as an immune costimulatory monoclonal antibody for melanoma immunotherapy.

Laparoscopic appendectomy is the widely accepted treatment for acute appendicitis. This approach offers the potential of less pain, shorter hospital stay, and quicker return to activities. Traditionally, patients are hospitalized for 24 hours after laparoscopic appendectomy. This practice can be questioned due to the good results of other outpatient laparoscopic surgery. A retrospective review of 119 patients undergoing laparoscopic appendectomy for uncomplicated acute appendicitis was undertaken from January through September 2009; outpatient and inpatient laparoscopic appendectomies were compared. Patients were selected for outpatient management based upon physician discretion and their clinical course in operation and recovery rooms. Forty-two patients were dismissed on the day of surgery and 77 were admitted for 1 to 5 days postoperatively. No significant differences in age, gender, and preoperative comorbidities between outpatient and inpatient groups were found. Postoperative complications occurred in 2.4 per cent of outpatients and 11.7 per cent of inpatients (P = 0.16). Complications included superficial wound infections, urinary retention, urinary tract infection, intra-abdominal bleeding, pneumonia, and infected hematoma. Based upon this study, outpatient laparoscopic appendectomy can be performed safely in selected patients. This study provides the background for the present prospective protocol for routine outpatient laparoscopic appendectomy at our institution.

We evaluated the cycle threshold (CT) values of 1,160 influenza A positive and 806 influenza B positive specimens from two seasons of the US Flu VE Network to identify factors associated with CT values. Low CT values (high genomic load) were associated with shorter intervals between illness onset and specimen collection, young age (ages 3-8 years old), and self-rated illness severity for both influenza A and B. Low CT values were also associated with reported fever/feverishness and age ≥65 years for influenza A.

Persistent hiccups have been reported to occur occasionally during rehabilitation hospitalizations. Hiccups can interfere with patient participation and progress, and this can lengthen and complicate the rehabilitation hospitalization. Chlorpromazine, the only Food and Drug Administration-approved agent specifically indicated for hiccups, is often chosen as a first-line treatment. However, chlorpromazine does not always provide favorable results. The intent of this paper is to (1) review hiccups and implications of persistent hiccups in the rehabilitation setting, (2) provide additional evidence that chlorpromazine is often not the best treatment choice for hiccups in rehabilitative patients, (3) report the effectiveness and favorable tolerability of modest doses of gabapentin in a small case series of three patients, and (4) review potentially effective treatment approaches for hiccups.

In the past 30 years, the incidence of esophageal adenocarcinoma (EAC) has increased more rapidly than any other cancer in the United States. The prevalence of obesity and diabetes mellitus has drastically increased as well. We explored the potential association between obesity, diabetes mellitus, and EAC. By means of retrospective interrogation of an administrative database from fiscal year 2005-2009, we identified two cohorts. The cancer cohort was defined as patients with adenocarcinoma of the distal esophagus or gastric cardia. The comparison cohort contained patients with gastroesophageal reflux disorder (GERD; diagnosis coupled with a procedure code for fundoplication). Patient data, including demographic measures, diagnoses of obesity, diabetes mellitus, dyslipidemia, alcohol abuse, and nicotine dependence were examined. A logistic regression model identified risk factors for development of EAC. The sample included 2,836 patients identified as having either EAC (1,704) or fundoplication with GERD (1,132). Although slightly higher percentages of the benign cohort were obese, the cancer cohort had more diabetics (30.8% vs. 14.8%; chi-square = 94.5; P < 0.0001). In a logistic regression analysis adjusting for comorbidity and lifestyle factors, diagnosis of diabetes mellitus was significantly associated with esophageal cancer as opposed to GERD without cancer (OR = 2.2; 95% confidence interval [CI] 1.7-2.8). Nicotine dependence was also identified as a risk factor (OR = 1.7; 95% CI 1.4-2.0). We identified a potential association between diabetes mellitus and adenocarcinoma of the esophagus or gastric cardia. This association appears to be independent of obesity. Additionally, nicotine dependence was identified as a risk factor for EAC.

Abstract Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD following trauma is heritable, but robust common variants have yet to be identified by genome-wide association studies (GWAS). We have collected a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls. We first demonstrate significant genetic correlations across 60 PTSD cohorts to evaluate the comparability of these phenotypically heterogeneous studies. In this largest GWAS meta-analysis of PTSD to date we identify a total of 6 genome-wide significant loci, 4 in European and 2 in African-ancestry analyses. Follow-up analyses incorporated local ancestry and sex-specific effects, and functional studies. Along with other novel genes, a non-coding RNA (ncRNA) and a Parkinson’s Disease gene, PARK2 , were associated with PTSD. Consistent with previous reports, SNP-based heritability estimates for PTSD range between 10-20%. Despite a significant shared liability between PTSD and major depressive disorder, we show evidence that some of our loci may be specific to PTSD. These results demonstrate the role of genetic variation contributing to the biology of differential risk for PTSD and the necessity of expanding GWAS beyond European ancestry.

Cryptococci react positively with various histochemical stains, including the Fontana-Masson (FM), which stains the cell wall, and mucin stains, such as alcian blue and mucicarmine, which stain the capsule. Combinations of the FM stain with both the alcian blue and mucicarmine stains were performed on paraffin-embedded tissue specimens that were obtained from 15 patients who had culture-proved cryptococcosis. Combined FM-mucicarmine and FM-alcian blue stains were compared with other individual fungal stains. The FM stain, followed by either the mucicarmine or alcian blue stain, distinctively demonstrated both the cell wall and capsule of most organisms. More organisms were recognized in the combined stains than with either stain done individually. No interference between the stains was noted. Combining the FM stain with either of these two mucin stains appears to be helpful for identifying cryptococci.