Jeanes Hospital

OBJECTIVES: Given the extensive desmoplastic response associated with pancreatic adenocarcinoma, we hypothesized that the stromal protein fibroblast activation protein (FAP) would be highly expressed and associated with the presence of fibrosis and other clinical features. METHODS: Paraffin-embedded pancreatic adenocarcinomas that were resected with curative intent from 1992 to 2003 were used for this study. Fibroblast activation protein expression by immunohistochemical analysis was evaluated both by intensity (0-3+) and percentage. Fibrosis was estimated as a percentage of each tumor specimen. RESULTS: Ninety percent (63/70) of specimens demonstrated FAP expression. Expression was significantly more pronounced in tumor-associated myofibroblasts immediately adjacent to tumor than in surrounding tumor-associated myofibroblasts (P < 0.001). Lower FAP expression in adjacent tumor-associated myofibroblasts was associated with increased fibrosis (P = 0.02). Greater FAP expression in surrounding tumor-associated myofibroblasts was associated with an increased chance of having positive lymph nodes for all patients (P = 0.03) and a higher risk of tumor recurrence (P = 0.015) and death (P = 0.02) for patients who did not receive preoperative therapy. CONCLUSIONS: Fibroblast activation protein is highly expressed in pancreatic adenocarcinoma, with greatest expression immediately adjacent to tumor. Higher FAP expression is associated with worse clinical outcome. The investigation of FAP inhibitors as a therapeutic strategy against pancreatic cancer should be considered.

We examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m(2) or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graft-versus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P = .08) yet similar age-adjusted survival (38% vs 43%, P = .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P = .92) or relapse risk (P = .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus that belongs to the Coronaviridae family. SARS-CoV-2 is an enveloped spherical-shaped virus. The ribonucleic acid (RNA) is oriented in a 5'-3'direction which makes it a positive sense RNA virus, and the RNA can be read directly as a messenger RNA. The nonstructural protein 14 (nsp14) has proofreading activity which allows the rate of mutations to stay low. A change in the genetic sequence is called a mutation. Genomes that differ from each other in genetic sequence are called variants. Variants are the result of mutations but differ from each other by one or more mutations. When a phenotypic difference is demonstrated among the variants, they are called strains. Viruses constantly change in two different ways, antigenic drift and antigenic shift. SARS-CoV-2 genome is also prone to various mutations that led to antigenic drift resulting in escape from immune recognition. The Center of Disease Control and Prevention (CDC) updates the variant strains in the different classes. The classes are variant of interest, variant of concern and variant of high consequence. The current variants included in the variant of interest by the USA are: B.1.526, B.1.525, and P.2; and those included in the variant of concern by the USA are B.1.1.7, P.1, B.1.351, B.1.427, and B.1.429. The double and triple mutant variants first reported in India have resulted in a massive increase in the number of cases. Emerging variants not only result in increased transmissibility, morbidity and mortality, but also have the ability to evade detection by existing or currently available diagnostic tests, which can potentially delay the diagnosis and treatment, exhibit decreased susceptibility to treatment including antivirals, monoclonal antibodies and convalescent plasma, possess the ability to cause reinfection in previously infected and recovered individuals, and vaccine breakthrough cases in fully vaccinated individuals. Hence, continuation of precautionary measures, genomic surveillance and vaccination plays an important role in the prevention of spread, early identification of variants, prevention of mutations and viral replication, respectively.

In 20 patients with patellar "clunks" after posterior stabilized total knee arthroplasty, the average time to presentation was 10.7 months postarthroplasty. All patients demonstrated an audible and often painful "clunk" during extension. Fourteen procedures (11 arthroscopic debridements and three patellar component revisions) were performed in 12 patients. At reoperation, a suprapatellar fibrous nodule was seen to wedge into the intercondylar notch during flexion and dislodge during extension, generating the symptoms. The disorder resolved after nodule excision. Although four recurrences arose after arthroscopic debridements, none developed after arthrotomy and patellar button revision. Femoral component design, postsurgical inflammation, and altered extensor mechanics are potential etiologic agents of this complication.

Evidence of surfactant inactivation by meconium has led to the use of exogenous surfactant therapy in the management of meconium aspiration syndrome (MAS). Liquid assisted ventilation has been shown to improve the cardiopulmonary function in lungs with high surface tension. We compared exogenous surfactant therapy with liquid assisted ventilation in the management of experimental acute meconium aspiration injury. Thirty-two newborn lambs were ventilated at peak inspiratory pressures of 13-16 cm H2O, positive end expiratory pressure of 3-4 cm H2O, fractional inspired oxygen concentration (FiO2) of 1.0, and a respiratory frequency range between 30 and 35 breaths/min. Baseline arterial blood gases, pulmonary function, and arterial blood pressure measurements were taken. All lambs were given 2-3 ml/kg of an unfiltered 25% meconium solution. Lambs were then randomized into either gas-ventilated meconium control, or one of three treatment groups: 1) surfactant; 2) partial liquid ventilation (PLV); or 3) total liquid ventilation (TLV) for 4 hours after meconium injury. All treated groups demonstrated a significant increase in arterial oxygenation (P < 0.05); surfactant and PLV-treated lambs demonstrated significantly decreased arterial PCO2 (P < 0.05). Compliance in all groups increased compared with injury values; compliance of the TLV group increased more than in all other treatment groups (P < 0.05). In addition, lung histology of the TLV group demonstrated clear, intact alveolar epithelium and homogeneously expanded alveoli, while no such improvement was evident in the other groups. These data suggest roles for both exogenous surfactant therapy and liquid assisted ventilation techniques in the management of MAS.

ONE of the recommended technics of vaccination against measles is to give a course of killed-measles-virus vaccine followed, after an interval of months, by a booster of live attenuated measles virus either accompanied or unaccompanied by gamma globulin.1 This technic is advocated as preventing the untoward reactions that may accompany the administration of the live virus even when gamma globulin is given coincidentally.In a certain number of these children, a local and, sometimes, general reaction may follow the final inoculation of the live-virus vaccine and may be severe enough to bring the child to the physician. This may occur . . .

Immunoperoxidase localization of prostatic tissue antigens has become useful in identifying the prostate as the origin of metastatic disease. Much research has been aimed at investigating the presence of these antigens in the adult prostate gland in benign and neoplastic states. Few studies have been done to determine the presence of these markers before puberty. We studied the prostate gland of 42 children of varying ages to determine the presence of these antigens at all age ranges to puberty. Sequential sections of the prostate were cut for prostate specific antigen, prostatic acid phosphatase, and hematoxylin and eosin staining. The degree of immunoperoxidase stain was graded from 0 to 4. The results showed that staining levels of prostate specific antigen and prostatic acid phosphatase were high at birth, decreased by age 6 months, reappeared by age 10 years and increased to puberty. Thus, the levels of prostate specific antigen and prostatic acid phosphatase appear to follow the testosterone levels, suggesting a hormonal dependence.

BACKGROUND: Symptoms related to carpal tunnel syndrome (CTS) represent common patient complaints for many primary care physicians. However, there is a surprising lack of guidelines on diagnosing occupational CTS readily accessible to primary care physicians. This article aims to fill part of that void by reviewing historical aspects of occupational CTS, leading up to more current epidemiologic studies of the association of CTS with occupational ergonomic risk factors. METHODS: The English medical literature was reviewed on the relationship between CTS and occupational ergonomic risk factors. Recent legislative initiatives are discussed. Guidelines of diagnosing and managing occupational CTS are outlined. RESULTS: Many studies are divided regarding whether CTS is associated with highly repetitive/forceful/vibration work. However, a subset of patients presenting with symptoms related to CTS probably has occupational CTS. These patients can be objectively diagnosed and successfully treated and are able to return to work. CONCLUSIONS: By being armed with knowledge regarding the background of CTS and by following simple diagnosis and treatment guidelines, the family practitioner should be able to manage many patients presenting with work-related CTS.

We have employed noninvasive, external counting techniques for quantitation of I-131 F(ab')2 fragment of mouse monoclonal antibody localized in metastatic lesions and surrounding liver tissue in humans. This method utilizes counts from diametrically opposed views of tumor deposits and surrounding normal tissue. Corrections were made for patient attenuation, lesion size, and surrounding tissue activity. The validity of this method was evaluated using a fillable, tissue-equivalent organ-scanning phantom with organs and tumors of selected size. Less than 10% error was found in quantitation of various activities of I-131 in a 4-cm-diam lesion. Tumor activity ranged from 0.001% to 0.018% of administered dose per cm3 of tissue compared with 0.000 12% to 0.0023% per cm3 of liver. In addition, the vascular clearance of total I-131 and protein-bound I-131 was found to follow a two-compartment model with mean half lives of 3.8 and 21.4 h for total I-131 and 3.9 and 24.4 h for protein-bound I-131.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus causing a global pandemic. Coronaviruses are a large family of single-stranded ribonucleic acid (RNA) viruses. The virus has four essential structural proteins which include the spike (S) glycoprotein, matrix (M) protein, nucleocapsid (N) protein and small envelope (E) protein. Different technologies are being used for vaccine development to battle the pandemic. There are messenger ribonucleic acid (mRNA)-based vaccines, deoxyribonucleic acid (DNA) vaccines, inactivated viral vaccines, live attenuated vaccines, protein subunit-based vaccines, viral vector-based vaccines and virus-like particle-based vaccines. Vaccine development has five stages. In the clinical developmental stage, vaccine development can be sped up by combining phase 1 and 2. The vaccines can also be approved more swiftly on an emergent basis and released sooner for usage. The United States Food and Drug Administration (USFDA) has approved Pfizer-BioNTech, Moderna and Janssen coronavirus disease 2019 (COVID-19) vaccines for emergency use. There are other vaccines that have been approved around the world. The mRNA vaccines have been created using a novel technology and they contain a synthetically created RNA sequence of virus fragments encoding the S-protein which is injected. These vaccines have a relatively low cost of production and faster manufacturing time but can have comparatively lower immunogenicity and more than one dose of vaccine may be required. In the case of viral vector-based vaccines, genes encoding the SARS-CoV-2 S protein are isolated and following gene sequencings are introduced into the adenovirus vector. These vaccines have a relatively fast manufacturing time but the efficacy of the vaccine is variable based on the host's immune response to the viral vector. At the time of this paper, there were 81 vaccines in clinical development stage and 182 vaccines in preclinical development stage. Vaccines are an essential tool in our battle against COVID-19. Some of the COVID-19 vaccines have completed their phase III trials while many other potential vaccines are still in developmental stages. It used to take close to a decade for a vaccine to be developed and undergo rigorous testing until its production and availability to the public, but over the past year, we have seen multiple vaccines in different phases of testing against SARS-CoV-2 virus.

Objectives: The authors sought to validate a clinical decision rule that young adult (younger than 40 years) chest pain patients without known cardiac disease who had either no cardiac risk factors and/or a normal electrocardiogram (ECG) are at low risk (<1%) for acute coronary syndromes (ACS) and 30-day adverse cardiovascular (CV) events. Methods: A prospective cohort study of patients 24–39 years old who received an ECG for chest pain from July 1999 to March 2002 were included. Cocaine users were excluded. Data collection was structured at presentation, hospital course was followed daily, and 30-day follow-up was obtained by telephone. The main outcome was 30-day adverse CV events (death, acute myocardial infarction, percutaneous intervention, and coronary artery bypass graft). Descriptive statistics were used. Results: Of 4,492 visits for chest pain, 1,023 met criteria. Patients were most often female (61%) and African American (73%). Ninety-eight percent were available for 30-day follow-up. The overall risks of ACS and 30-day adverse CV events were 5.4% and 2.2%, respectively, in our entire cohort. For patients with no cardiac history and no cardiac risk factors, the risk of ACS and 30-day adverse CV events was 1.8%. The risk in patients with no cardiac history and a normal ECG was 1.3%. Patients with no cardiac history, no cardiac risk factors, and a normal ECG had a risk of 1.0%. A modified clinical decision rule found that in young adult patients without a known cardiac history, either no classic cardiac risk factors or a normal ECG, and initially normal cardiac marker studies, the risk of ACS was also extremely low (0.14%) and there were no adverse CV events at 30-day follow-up (95% confidence interval = 0.1% to 0.2%). Conclusions: A modified clinical decision rule described a group of patients with a 0.14% risk of ACS that was free from 30-day adverse CV events.

Complications of routine fiberoptic colonoscopy are infrequent and consist mainly of perforation and hemorrhage (1). Other complications, seldom considered because they occur even more infrequently, must be kept in mind to make a timely diagnosis. Splenic injury is uncommon after colonoscopy but still should be considered in the differential diagnosis of post-colonoscopy abdominal pain. We found 13 reported cases in the English language literature (1-10). Our patient represents the 14th case. Computed tomography (CT) was important in the diagnosis (20-21).

Collecting system duplication is marked by a variety of clinical syndromes. Bilateral and obstructed duplicated systems, particularly with asymmetric levels of duplication, are rare and typically due to ureteric bud development anomalies. The infrequency with which this condition exists makes it a formidable challenge for physicians and patients. To our knowledge, we present the first case report of bilateral obstruction of bilaterally duplicated collecting systems. In our case, a 52-year-old male complaining of low back pain, constipation, urinary urgency and hematuria was found to have bilateral obstructing stones as well as asymmetrical bilateral collecting system duplication. We discuss the natural history of this condition, its consequences and identification.

Heyward, Vivian H.; Kotarski, Mark MEd, Certified Exercise Specialist Author Information

Ytterbium-DTPA was evaluated as a potential intravascular contrast agent. Ytterbium-DTPA was synthesized from ytterbium oxide and diethylene triamine penta-acetic acid (DTPA). CT scans of increasing concentrations of ytterbium and iodine showed that at 125 kVp, ytterbium was denser than an equal concentration of iodine. The LD50 of intravenous ytterbium-DTPA was 10 mM/kg (1.73 g ytterbium/kg) in rats. In enhanced CT scans and pulmonary angiography in dogs, ytterbium was visibly denser than iodine, and CT Hounsfield units showed greater enhancement of the aorta and inferior vena cava with ytterbium. The animals showed no sign of acute or delayed toxicity. Ytterbium-DTPA deserves further evaluation as a contrast agent for high kVp techniques.

In Brief Can your facility meet the changing expectations of healthcare insurers and consumers? Can your facility meet the changing expectations of healthcare insurers and consumers?

BACKGROUND: RhD variants have altered D epitopes and/or decreased antigen copies per red cell. Individuals carrying these variants may test antigen negative, weakly positive, or positive by serology, and may or may not be at risk of alloimmunisation after exposure. There have been recommendations to perform RHD genotyping of patients, pregnant women and females of childbearing potential with serological weak D phenotype, to guide prophylactic use of Rh immune globulin (RhIG), and better conserve D-negative blood products. The purpose of this study was to evaluate the performance of a set of empirical criteria to identify such patients. MATERIALS AND METHODS: A two-method strategy of gel testing (GT) and tube testing (TT) was used for Rh typing of patients with no historical blood type in the present institution. A monoclonal-polyclonal blend anti-D was used for Rh typing by TT at immediate spin. Three empirical criteria were used to identify candidates for genotyping: C1: discrepancy between the two test methods and a GT reaction strength >2+ stronger than TT; C2: weak serological reaction, defined as reaction strength ≤2+ regardless of testing method if both GT and TT were performed or reaction strength ≤2+ if only GT was performed, or reaction strength ≤1+ if only TT was performed; C3: presence of anti-D in D-positive patients with no history of RhIG use in the preceding 3 months and in whom alloanti-D is suspected. RESULTS: Overall, 50 patients, ranging from newly born to 93 years old, were identified. Genomic testing confirmed D variants in 49/50 cases with a positive predictive value of 98%. DISCUSSION: This two-method strategy is a powerful screening tool for identifying candidates for RHD genotyping. This strategy meets the current requirements of two blood type determinations/two specimens in pre-transfusion testing while simultaneously identifying candidates for RHD genotyping with a minimal increase in work load and cost.

PURPOSE/OBJECTIVES: To explore positive and negative aspects of the experiences of informal caregivers of patients with cancer and patients with other chronic medical conditions, to compare the reactions of caregivers of patients with cancer and patients with other chronic medical conditions, and to study the association of caregiver reactions with demographic factors. . DESIGN: Descriptive, correlational. . SETTING: A comprehensive cancer center and a community hospital, both in Philadelphia, PA. . SAMPLE: 111 informal caregivers. . METHODS: A survey that could be completed either in paper format or electronically was administered. . MAIN RESEARCH VARIABLES: Self-esteem, impact on schedule, impact on finances, impact on health, lack of family support, positive aspects of caregiving. . FINDINGS: For caregivers, offering emotional and psychological support was most challenging, whereas providing transportation was least challenging. Caregivers reported high self-esteem and moderately positive aspects of caregiving. Caregivers of patients with cancer identified more positive aspects of caregiving. Differences in the caregiving experience based on demographic factors (e.g., gender, race, ethnicity) were found. . CONCLUSIONS: Caregivers reported positive and negative aspects of caregiving. Reactions of informal caregivers to the caregiving experience vary more based on individual demographic factors than on the diagnosis of the patient. Differences exist in the caregiving experience based on race and ethnicity. . IMPLICATIONS FOR NURSING: Nurses need to be aware that positive and negative reactions to the caregiving experience exist. Assessment and care planning should include consideration for individual factors, such as gender, race, and ethnicity.

Collaboration between nurses and speech language pathologists is vital to the screening and management of dysphagia in acute care settings. This article examines each discipline's role in caring for patients with dysphagia.

Abstract Sixty knees in 46 patients with rheumatoid arthritis (RA), Stages II and III, and severe to moderate synovitis were synovectomized and debrided, and observed for an average of 2.8 years. Improvement was noted in 73% of the knees. This figure diminished with longer followup due to recurrence of disease, development of valgus and varus deformities and involvement of hips. The results of knee surgery did not correlate with severity of disease. Some reduction in walking ability occurred as a result of progression of RA in joints other than the operated one(s).