Danbury Hospital

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery.

BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

BACKGROUND: Normal metabolism generates several volatile organic compounds (VOCs) that are excreted in the breath (e.g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so that their altered abundance in breath may provide biomarkers of lung cancer. METHODS: VOCs in 1.0 L alveolar breath were analyzed in 193 subjects with primary lung cancer and 211 controls with a negative chest CT. Subjects were randomly assigned to a training set or to a prediction set in a 2:1 split. A fuzzy logic model of breath biomarkers of lung cancer was constructed in the training set and then tested in subjects in the prediction set by generating their typicality scores for lung cancer. RESULTS: Mean typicality scores employing a 16 VOC model were significantly higher in lung cancer patients than in the control group (p<0.0001 in all TNM stages). The model predicted primary lung cancer with 84.6% sensitivity, 80.0% specificity, and 0.88 area under curve (AUC) of the receiver operating characteristic (ROC) curve. Predictive accuracy was similar in TNM stages 1 through 4, and was not affected by current or former tobacco smoking. The predictive model achieved near-maximal performance with six breath VOCs, and was progressively degraded by random classifiers. Predictions with fuzzy logic were consistently superior to multilinear analysis. If applied to a population with 2% prevalence of lung cancer, a screening breath test would have a negative predictive value of 0.985 and a positive predictive value of 0.163 (true positive rate =0.277, false positive rate =0.029). CONCLUSIONS: A two-minute breath test predicted lung cancer with accuracy comparable to screening CT of chest. The accuracy of the test was not affected by TNM stage of disease or tobacco smoking. Alterations in breath VOCs in lung cancer were consistent with a non-linear pathophysiologic process, such as an off-on switch controlling high-risk cytochrome p450 activity. Further research is needed to determine if detection of lung cancer with this test will reduce mortality.

BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable postoperative complication. Accurate risk prediction is an essential first step toward limiting serious, and sometimes fatal, postoperative VTE. We sought to develop and test a model to predict patients at high risk for postoperative VTE. STUDY DESIGN: Data from the Patient Safety in Surgery (PSS) Study were used to develop and test a predictive model of VTE using multiple logistic regression analyses. RESULTS: VTE occurred in 1,162 of 183,069 (0.63%) patients undergoing vascular and general surgical procedures. The 30-day mortality in patients who suffered a VTE was 11.19%. Fifteen variables independently associated with increased risk of VTE included patient factors (female gender, higher American Society of Anesthesiologists class, ventilator dependence, preoperative dyspnea, disseminated cancer, chemotherapy within 30 days, and > 4 U packed red blood cell transfusion in the 72 hours before operation), preoperative laboratory values (albumin < 3.5 mg/dL, bilirubin > 1.0 mg/dL, sodium > 145 mmol/L, and hematocrit < 38%), and operative characteristics (type of surgical procedure, emergency operation, work relative value units, and infected/contaminated wounds). These variables were used to develop a predictive model for postoperative VTE (c-index = 0.7647) and a risk score that can be used in the preoperative assessment of patients undergoing major operations. CONCLUSIONS: Venous thromboembolic events after noncardiac operations are relatively infrequent but highly lethal. Important multivariable risk factors for VTE in this setting were identified in the large PSS database. The risk-prediction scoring system, developed by using the logistic regression odds ratios, helps to identify patients at risk for postoperative VTE and to institute appropriate perioperative prophylactic measures.

The clinical relevance of histologic evidence of acute ascending intrauterine infection has been called into question by descriptions of "silent" chorioamnionitis. The described frequencies of silent chorioamnionitis in normal and abnormal pregnancies vary widely because of differences in the definition of a normal pregnancy, methods of placental examination, and pathologic criteria. Therefore, we examined placentas from 161 uncomplicated gestations for the presence and severity of acute inflammation in the amnion, chorion-decidua, chorionic plate, and umbilical cord using strict gross and microscopic protocols. Indicators of amniotic fluid infection, specifically umbilical cord inflammation, amnionitis, and inflammation within the chorionic plate were present in 0, 1.2, and 4% of the cases, respectively. Silent chorioamnionitis was rare. There was a statistical association between the presence of acute inflammation and the occurrence of labor at term. Methods of tissue sampling that included a more extensive examination of the site of membrane rupture resulted in an increased frequency of diagnosis of acute inflammation at the site of rupture in vaginal deliveries at term.

The Space Telescope Imaging Spectrograph (STIS) was successfully installed into the Hubble Space Telescope (HST) in 1997 February, during the second HST servicing mission, STS-82. STIS is a versatile spectrograph, covering the 115-1000 nm wavelength range in a variety of spectroscopic and imaging modes that take advantage of the angular resolution, unobstructed wavelength coverage, and dark sky offered by the HST. In the months since launch, a number of performance tests and calibrations have been carried out and are continuing. These tests demonstrate that the instrument is performing very well. We present here a synopsis of the results to date.

BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

BACKGROUND: The growing advances in DNA sequencing tools have made analyzing the human genome cheaper and faster. While such analyses are intended to identify complex variants, related to disease susceptibility and efficacy of drug responses, they have blurred the definitions of mutation and polymorphism. DISCUSSION: In the era of personal genomics, it is critical to establish clear guidelines regarding the use of a reference genome. Nowadays DNA variants are called as differences in comparison to a reference. In a sequencing project Single Nucleotide Polymorphisms (SNPs) and DNA mutations are defined as DNA variants detectable in >1 % or <1 % of the population, respectively. The alternative use of the two terms mutation or polymorphism for the same event (a difference as compared with a reference) can lead to problems of classification. These problems can impact the accuracy of the interpretation and the functional relationship between a disease state and a genomic sequence. We propose to solve this nomenclature dilemma by defining mutations as DNA variants obtained in a paired sequencing project including the germline DNA of the same individual as a reference. Moreover, the term mutation should be accompanied by a qualifying prefix indicating whether the mutation occurs only in somatic cells (somatic mutation) or also in the germline (germline mutation). We believe this distinction in definition will help avoid confusion among researchers and support the practice of sequencing the germline and somatic tissues in parallel to classify the DNA variants thus defined as mutations.

In this paper, the author's long history with somatosensation is overviewed with special emphasis on the creation of objective tests of sensibility. Objective testing is discussed using numerous examples from the author's experiences. The creation of the Semmes-Weinstein monofilaments is discussed. Tests employing the Semmes-Weinstein monofilaments, two-point discrimination, and point localization are discussed with reference to the fact that these tests reflect specific differences between the central and peripheral nervous systems. Towards that end, contrasts are made between the Semmes-Weinstein esthesiometer and both the two-point discrimination and the point-localization tests. A new enhancement of the original Semmes-Weinstein monofilament test, the Weinstein Enhanced Sensory Test (WEST), is introduced. Advantages of the WEST are discussed.

Idiopathic pulmonary haemosiderosis is a rare cause of diffuse alveolar haemorrhage of unknown aetiology. It occurs most frequently in children, has a variable natural history with repetitive episodes of diffuse alveolar haemorrhage, and has been reported to have a high mortality. Many patients develop iron deficiency anaemia secondary to deposition of haemosiderin iron in the alveoli. Examination of sputum and bronchoalveolar lavage fluid can disclose haemosiderin-laden alveolar macrophages (siderophages), and the lung biopsy shows numerous siderophages in the alveoli, without any evidence of pulmonary vasculitis, nonspecific/granulomatous inflammation, or deposition of immunoglobulins. Contrary to earlier reports, corticosteroids alone or in combination with other immunosuppressive agents may be effective for either exacerbations or maintenance therapy of idiopathic pulmonary haemosiderosis.

It has been reported that 50% to 80% of patients with Parkinson's disease have abnormal glucose tolerance which may be further exacerbated by levodopa therapy. Little is known about the impact of chronic hyperglycemia on the severity of the motor manifestations and the course of the disease as well as its impact on the efficacy of levodopa or other dopaminergic drugs. This issue, which has been largely ignored, is of clinical relevance since animal studies indicate that chronic hyperglycemia decreases striatal dopaminergic transmission and increases the sensitivity of postsynaptic dopamine receptors. In addition, evidence from experimental animal studies indicates that diabetic rats are resistant to the locomotor and behavioral effects of the dopamine agonist amphetamine. The resistance to the central effects of amphetamine is largely restored with chronic insulin therapy. In the present communication, I propose that in Parkinson's disease diabetes may exacerbate the severity of the motor disability and attenuate the therapeutic efficacy of levodopa or other dopaminergic agents as well as increase the risk of levodopa-induced motor dyskinesias. Thus, it is advocated that Parkinsonian patients should be routinely screened for evidence of glucose intolerance and that if found aggressive treatment of the hyperglycemia may improve the response to levodopa and potentially diminish the risk of levodopa-induced motor dyskinesias.

OBJECTIVE: We conducted a randomized, double blind clinical trial to determine the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee and cervical spine. METHODS: A controlled trial of 18 half-hour active or placebo treatments was conducted in 86 patients with OA of the knee and 81 patients with OA of the cervical spine, in which pain was evaluated using a 10 cm visual analog scale, activities of daily living using a series of questions (answered by the patient as never, sometimes, most of the time, or always), pain on passive motion (recorded as none, slight, moderate, or severe), and joint tenderness (recorded using a modified Ritchie scale). Global evaluations of improvement were made by the patient and examining physician. Evaluations were made at baseline, midway, end of treatment, and one month after completion of treatment. RESULTS: Matched pair t tests showed extremely significant changes from baseline for the treated patients in both knee and cervical spine studies at the end of treatment and the one month followup observations, whereas the changes in the placebo patients showed lesser degrees of significance at the end of treatment, and had lost significance for most variables at the one month followup. Means of the treated group of patients with OA of the knee showed greater improvement from baseline values than the placebo group by the end of treatment and at the one month followup observation. Using the 2-tailed t test, at the end of treatment the differences in the means of the 2 groups reached statistical significance for pain, pain on motion, and both the patient overall assessment and the physician global assessment. The means of the treated patients with OA of the cervical spine showed greater improvement from baseline than the placebo group for most variables at the end of treatment and one month followup observations; these differences reached statistical significance at one or more observation points for pain, pain on motion, and tenderness. CONCLUSION: PEMF has therapeutic benefit in painful OA of the knee or cervical spine.

The optical properties of n-type GaN are investigated for Si doping concentrations ranging from 5×1016 to 7×1018 cm−3. The photoluminescence linewidth of the near-band gap optical transition increases from 47 to 78 meV as the doping concentration is increased. The broadening is modeled in terms of potential fluctuations caused by the random distribution of donor impurities. Good agreement is found between experimental and theoretical results. The intensity of the near-band-gap transition increases monotonically as the doping concentration is increased indicating that nonradiative transitions dominate at a low doping density. The comparison of absorption, luminescence, reflectance, and photoreflectance measurements reveals the absence of a Stokes shift at room temperature demonstrating the intrinsic nature of the near-band edge transition.

BACKGROUND: Reliable, serial, noninvasive quantitative estimation of left ventricular ejection fraction is essential for selecting and timing therapeutic interventions in patients with heart disease. Equilibrium radionuclide angiography is widely used for this purpose but has well-recognized limitations. Advantages of echocardiography over equilibrium radionuclide angiography include assessment of wall motion, valvular pathology, and cardiac hemodynamics, in addition to portability, lack of radiation exposure, and substantially lower cost. However, conventional echocardiographic techniques are limited by geometric assumptions, image positioning errors, and use of subjective visual methods. To overcome these limitations, a three-dimensional echocardiographic method was developed. This study compares ejection fraction by three-dimensional echocardiography, quantitative two-dimensional echocardiography, and subjective two-dimensional echocardiographic visual estimation with that by equilibrium radionuclide angiography. METHODS AND RESULTS: Fifty-one unselected patients with suspected heart disease underwent left ventricular ejection fraction determination by equilibrium radionuclide angiography and three-dimensional echocardiography using an interactive line-of-intersection display and a new algorithm, ventricular surface reconstruction, for volume computation. In 44 patients, ejection fractions were also estimated visually by experienced observers from two-dimensional echocardiography and by quantitative two-dimensional echocardiography using an apical biplane summation-of-disks algorithm. An excellent correlation was obtained between three-dimensional echocardiography and equilibrium radionuclide angiography (r = .94 to .97, SEE = 3.64% to 5.35%; limits of agreement, 10.3% to 13.3%) without significant underestimation or overestimation. SEE values and limits of agreement were twofold to threefold lower than corresponding values for all two-dimensional echocardiographic techniques. In addition, interobserver variability was significantly lower for the three-dimensional echocardiographic method (10.2%) than for the apical biplane summation-of-disks method (26.1%) and subjective visual estimation (33.3%). CONCLUSIONS: Determination of ejection fraction by three-dimensional echocardiography yields results comparable to those obtained by equilibrium radionuclide angiography and is substantially superior to all two-dimensional echocardiographic methods. Therefore, three-dimensional echocardiography may be used for accurate serial quantification of left ventricular function as an alternative to equilibrium radionuclide angiography.

The measurement results for thin film barium strontium titanate (BST) based voltage tunable capacitors intended for RF applications are reported. At 9 V DC, BST capacitors fabricated using MOCVD (metalorganic chemical vapor deposition) method achieved 71% (3.4:1) tunability. The measured device quality factor (Q) for BST varactors is comparable with the device Q for commercially available varactor diodes of similar capacitance. The typical dielectric loss tangent was in the range 0.003-0.009 at VHF. Large signal measurement and modeling results for BST thin film capacitors are also presented.

OBJECTIVE: For many medical professionals dealing with patients with persistent pain following spine surgery, the term Failed back surgery syndrome (FBSS) as a diagnostic label is inadequate, misleading, and potentially troublesome. It misrepresents causation. Alternative terms have been suggested, but none has replaced FBSS. The International Association for the Study of Pain (IASP) published a revised classification of chronic pain, as part of the new International Classification of Diseases (ICD-11), which has been accepted by the World Health Organization (WHO). This includes the term Chronic pain after spinal surgery (CPSS), which is suggested as a replacement for FBSS. METHODS: This article provides arguments and rationale for a replacement definition. In order to propose a broadly applicable yet more precise and clinically informative term, an international group of experts was established. RESULTS: 14 candidate replacement terms were considered and ranked. The application of agreed criteria reduced this to a shortlist of four. A preferred option-Persistent spinal pain syndrome-was selected by a structured workshop and Delphi process. We provide rationale for using Persistent spinal pain syndrome and a schema for its incorporation into ICD-11. We propose the adoption of this term would strengthen the new ICD-11 classification. CONCLUSIONS: This project is important to those in the fields of pain management, spine surgery, and neuromodulation, as well as patients labeled with FBSS. Through a shift in perspective, it could facilitate the application of the new ICD-11 classification and allow clearer discussion among medical professionals, industry, funding organizations, academia, and the legal profession.

Placental examination was carried out in 128 consecutive cases of idiopathic intrauterine growth retardation (IUGR) at term and the findings were compared with those of 179 gestational age-matched cases with normal growth. Mean pregnancy weight and mean maternal weight gain during pregnancy of IUGR cases were both significantly lower than for non-IUGR cases. There was a higher frequency of a history of previous growth-retarded infants between IUGR cases (18 of 128, or 14%) compared with non-IUGR cases (7 of 179, or 3.9%). The studied placental lesions were placental infarction, chronic villitis, hemorrhagic endovasculitis, and placental vascular thromboses. One or more of these lesions were present in 71 of 128 (55%) of IUGR cases, and 58/179 (32%) of non-IUGR cases. Thirty-eight of 72 (53%) cases with chronic villitis were IUGR (30% of all IUGR cases). Thirty-one of 49 cases (63%) with placental infarction were IUGR cases (24% of all IUGR cases). Nineteen of 32 cases (59%) with hemorrhagic endovasculitis were IUGR cases (15% of all IUGR cases). Twelve of 17 cases (71% with placental vascular thromboses were IUGR (9% of all IUGR cases). Relationships of all placental lesions to IUGR were independent of each other. IUGR infants more frequently had multiple types of lesions in their placentas. Chronic villitis and hemorrhagic endovasculitis tended to occur in the same placentas. There were no significant relationships between maternal characteristics and placental lesions, except for an association between low pregravid weight and increased incidence of placental infarction. Decreased birth length was associated only with placental infarction (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PURPOSE: Because in vitro studies suggest that low levels of electromagnetic fields may modify cancer cell growth, we hypothesized that systemic delivery of a combination of tumor-specific frequencies may have a therapeutic effect. We undertook this study to identify tumor-specific frequencies and test the feasibility of administering such frequencies to patients with advanced cancer. PATIENTS AND METHODS: We examined patients with various types of cancer using a noninvasive biofeedback method to identify tumor-specific frequencies. We offered compassionate treatment to some patients with advanced cancer and limited therapeutic options. RESULTS: We examined a total of 163 patients with a diagnosis of cancer and identified a total of 1524 frequencies ranging from 0.1 Hz to 114 kHz. Most frequencies (57-92%) were specific for a single tumor type. Compassionate treatment with tumor-specific frequencies was offered to 28 patients. Three patients experienced grade 1 fatigue during or immediately after treatment. There were no NCI grade 2, 3 or 4 toxicities. Thirteen patients were evaluable for response. One patient with hormone-refractory breast cancer metastatic to the adrenal gland and bones had a complete response lasting 11 months. One patient with hormone-refractory breast cancer metastatic to liver and bones had a partial response lasting 13.5 months. Four patients had stable disease lasting for +34.1 months (thyroid cancer metastatic to lung), 5.1 months (non-small cell lung cancer), 4.1 months (pancreatic cancer metastatic to liver) and 4.0 months (leiomyosarcoma metastatic to liver). CONCLUSION: Cancer-related frequencies appear to be tumor-specific and treatment with tumor-specific frequencies is feasible, well tolerated and may have biological efficacy in patients with advanced cancer. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT00805337.

Thalidomide enhances rituximab-mediated, antibody-dependent, cell-mediated cytotoxicity. We therefore conducted a phase 2 study using thalidomide and rituximab in symptomatic Waldenstrom macroglobulinemia (WM) patients naive to either agent. Intended therapy consisted of daily thalidomide (200 mg for 2 weeks, then 400 mg for 50 weeks) and rituximab (375 mg/m(2) per week) dosed on weeks 2 to 5 and 13 to 16. Twenty-five patients were enrolled, 20 of whom were untreated. Responses were complete response (n = 1), partial response (n = 15), and major response (n = 2), for overall and major response rate of 72% and 64%, respectively, on an intent-to-treat basis. Median serum IgM decreased from 3670 to 1590 mg/dL (P < .001), whereas median hematocrit rose from 33.0% to 37.6% (P = .004) at best response. Median time to progression for responders was 38 months. Peripheral neuropathy to thalidomide was the most common adverse event. Among 11 patients experiencing grade 2 or greater neuropathy, 10 resolved to grade 1 or less at a median of 6.7 months. Thalidomide in combination with rituximab is active and produces long-term responses in WM. Lower doses of thalidomide (ie, <or= 200 mg/day) should be considered given the high frequency of treatment-related neuropathy in this patient population. This trial is registered at www.clinicaltrials.gov as #NCT00142116.