Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

Differences in intracortical responses following non-noxious and noxious stimulation in anaesthetized rats.

Cortical responses have been proposed as a source for the extraction of unique and non-subjective sensory information. The present study aimed to investigate if it is possible to distinguish between non-noxious and noxious cortical responses with two different types of anesthesia. Sixteen rats were randomly allocated to receive either Hypnorm/Dormicum (HD) or isoflurane (ISO) anesthesia. Each animal had a custom-made microelectrode array implanted in the primary somatosensory cortex to record the local field potentials and a cuff electrode implanted around the sciatic nerve to deliver electrical stimulations. Three stimulation intensities were applied: 1x movement threshold (MT) (i.e., non-noxious activation), 5x MT (low intensity noxious activation), and 10x MT (high intensity noxious activation). The evoked potentials were assessed by extracting three features: 1) the negative peak (NP), 2) the positive peak (PP), and 3) the peak-to-peak (PtP) amplitudes. Our results showed that it was possible to distinguish between three levels of stimulation intensities based on the NP, PP, and PtP features for the HD group, whereas it was only possible to make the same differentiation with the use of PP and PtP when applying ISO. This work is believed to contribute to a basic understanding of how the cortical responses change in the hyperacute phase of pain and which cortical features may be suitable as objective measures of nociception.

Molecular mechanism of hemolytic anemia in homozygous hemoglobin C disease. Electron microscopic study by the freeze-etching technique.

Erythrocytes from a patient with homozygous hemoglobin C disease were subjected to gradual osmotic dehydration by incubation in hypertonic saline. Serial observations of these cells before and after 4 and 12 hr incubation were carried out by means of interference, Soret absorption, polarization microscopy, and the electron microscope employing the freeze-etching technique. Light microscopic studies showed a progressive contraction of cellular contents into central masses which, after 12 hr dehydration, formed birefringent intracellular hemoglobin crystals in 50-75% of the cells. Electron microscopic study of freeze-etched replicas of these cells at 0, 4, and 12 hr of dehydration reveals progressive aggregation, alignment, and crystallization of hemoglobin molecules. Molecular aggregation found in C-C cells prior to osmotic dehydration was not seen in normal erythrocytes. Aggregation and packing varied from cell to cell. Reticulocytes showed a loosely packed aggregate mesh-work; older cells showed variation of molecular packing, which appeared tightest in cells corresponding to microspherocytes. With further loss of intracellular water, aggregates coalesced into patterns of tighter molecular packing with small regions of alignment, and, finally, crystallization occurred. Hemoglobin molecules measuring 70 A in diameter were readily identified within the period patterns of intracellular crystals. These findings suggest that the hemoglobin C molecules within C-C erythrocytes exist in an aggregated state. As the cell ages, intracellular water is lost and intermolecular distance decreases, hemoglobin C molecules polymerize into intracellular crystals. This pathological behavior of hemoglobin C is associated with a charge alteration conferred by the substitution of beta-6-lysine for glutamic acid on the external surface in the A-helix region of the beta-chain of the molecule, possibly increasing intermolecular attraction. Molecular aggregation accounts for the increased rigidity of C-C cells which leads to accelerated membrane and water loss with resultant microspherocyte formation. The microspherocyte, with highest intracellular hemoglobin concentration, rapidly undergoes intracellular crystallization, and is sequestered and destroyed by reticuloendothelial elements.

Antibodies against Crandell Rees feline kidney (CRFK) cell line antigens, alpha-enolase, and annexin A2 in vaccinated and CRFK hyperinoculated cats.

BACKGROUND: Cats inoculated with feline herpesvirus 1, calicivirus, and panleukopenia (FVRCP) vaccines grown on the Crandell Rees feline kidney (CRFK) cell line have been shown to develop anti-CRFK antibodies. The identities of common CRFK antigens are unknown. HYPOTHESIS: Cats inoculated with CRFK lysates and FVRCP vaccines will develop autoantibodies measurable by Western blot immunoassay. Antigens associated with these antibodies can be isolated for further study. ANIMALS: One CRFK hyperinoculated rabbit, 44 age-matched unvaccinated kittens purchased from a commercial vendor. METHODS: Commonly recognized CRFK antigens were identified by comparison of Western blot immunoassays using sera from a hyperinoculated rabbit and kittens inoculated with CRFK lysate or 1 of 4 commercially available FVRCP vaccines. Antigens were purified from CRFK lysates and sequenced. Antigen recognition was confirmed by Western blot immunoassay and indirect ELISA for 2 proteins using sera from CRFK and FVRCP inoculated kittens. RESULTS: CRFK antigens 47, 40, and 38 kD in size were identified. Protein isolation and sequencing identified 3 CRFK proteins as alpha-enolase, annexin A2, and macrophage capping protein (MCP). Sera from FVRCP and CRFK inoculated cats were confirmed to recognize annexin A2 and alpha-enolase by Western blot immunoassay and indirect ELISA. CONCLUSIONS AND CLINICAL RELEVANCE: This study validated the use of Western blot immunoassay for detection of antibodies against CRFK proteins and identified 3 CRFK antigens. In humans, alpha-enolase antibodies are nephritogenic; alpha-enolase and annexin A2 antibodies have been associated with autoimmune diseases. Further research will be necessary to determine the clinical relevance of these findings.

Microincision of sickled erythrocytes by a laser beam.

Increased mechanical fragility of the sickled red cell is thought to be important in the genesis of the hemolytic process in sickle-cell disease. Sickled cells were observed cinematographically after microincision by a ruby-laser beam. Distortion and charring invariably occurred at the site of injury, and with small injuries there was no further cell change. With larger injuries, variably rapid retraction of spicules occurred accompanied by sphering of the cell. In some cases, progressive loss of hemoglobin accompanied and followed the changes in shape; in others the sphered cell still contained hemoglobin. Regardless of the mecha nisms involved in these changes in vitro, the observations may be applicable to destruction of sickled cells in vivo. We suggest that the cells are subject to avulsion of rigid cellular processes as a result of mechanical injury incurred in normal circulation. Such injured cells may undergo either immediate hemolysis or trans formation into spherocytes which are subject to erythophagocytosis.

The hetero-oligomeric antigen receptor complex and its coupling to cytoplasmic effectors.

T-cell and B-cell antigen receptors are representative of a family of multisubunit receptors that utilize Src-family kinases as proximal cytoplasmic effectors in signal transduction. Recent studies have shown that distinct receptor subunits mediate ligand and effector interactions and demonstrate that physical interaction with effectors, and their activation, is a function of a 26 amino acid motif found in multiple receptor subunits. Further, receptor ligation induces tyrosine phosphorylation of this motif, and this initiates SH2-mediated association and activation of Src-family kinases and, apparently, ZAP70 kinases. Finally, this association triggers SH3-mediated binding of Lyn and Fyn to PI3-K, resulting in PI3-K activation. An integrated model of signal transduction is presented.

Effect of dioctyl sodium sulfosuccinate feeding on rat colorectal 1,2-dimethylhydrazine carcinogenesis.

The 1,2-dimethylhydrazine (DMH) rodent model for colorectal carcinogenesis was used to explore the effect of dietary dioctyl sodium sulfosuccinate (DSS) on carcinogenesis. Inbred male F344 rats were divided into two groups of 84 each and fed the following diets: ground chow and 5% corn oil (control group) and ground chow, 5% corn oil, and 1% DSS (experimental group). All rats received high-dose DMH base, 20 mg/kg/week sc for 20 weeks. Twenty rats per group were killed after 3, 4, 5, and 6 months. Duodenum, small intestine, colon, and rectum were dissected out. Each tumor was measured for size and location and evaluated histologically. The percentage of rats bearing tumors in the control and experimental groups did not differ significantly. In each rat there were fewer gastrointestinal tumors in the DSS-fed group of all histologic types combined, at all organ sites, at 5 and 6 months. This difference between the control and DSS-fed rats reached the level of statistical significance for tumors of the duodenum, colon, and rectum and for total gastrointestinal tumors at the 5th month.

Thermodynamic analysis of the stabilisation of pig heart mitochondrial malate dehydrogenase and maize leaf phosphoenolpyruvate carboxylase by different salts, amino acids and polyols.

As part of our investigations into the inactivation of pig heart mitochondrial malate dehydrogenase (phm-MDH) and maize leaf phosphoenolpyruvate carboxylase (ml-PEPC) in the presence of various cosolvents, the denaturation kinetics as a function of temperature have been determined based on Arrhenius plots derived from transition state theory analysis over the temperature range from 3.5 degrees C to 65 degrees C. The experimental data for phm-MDH were obtained in the presence of 1 M concentrations of various salts of monovalent and polyvalent anions, 1 M amino acids or 1 M sucrose and 6.1 M glycerol. Similarly, Arrhenius plot data were obtained for ml-PEPC in the presence of 2.5 M NaOAc and 0.8 M sodium glutamate. Distinct regimes of inactivation corresponding to high and low values of inactivation enthalpy were identified for the phm-MDH in the presence of all cosolvents and for the ml-PEPC in the presence of 2.5 M NaOAc, but not in the presence of 0.8 M sodium glutamate. A significant temperature-dependent effect dominated the inactivation of phm-MDH and ml-PEPC at elevated temperatures (e.g., > or = 45 degrees C), whilst the inactivation of these enzymes over a lower temperature range (< or = 25 degrees C) was dominated by temperature-independent phenomenon. The corresponding thermodynamic activation parameters (deltaG++, deltaH++ and deltaS++) associated with the transition state complexes involved in the inactivation of phm-MDH and ml-PEPC in the presence of the various cosolvents have been determined. The results indicate that the transition states associated with the inactivation of these two enzymes at elevated temperatures are characterised by large, positive enthalpic and entropic changes. In contrast, the inactivation process observed for phm-MDH at low temperatures in the presence of various cosolvents was marked by a large, negative entropic contribution and a small, positive enthalpic contribution. The results obtained in this study indicate that more than one mechanism of inactivation can occur with these two multimeric enzymes depending on the selected temperature range and the type of cosolvent. The relationship of these results to stabilisation models for phm-MDH and ml-PEPC in the presence of various cosolvents, as well as the application of Arrhenius plot data to extrapolate the long term solution stability of these enzymes at lower temperatures from the pseudo-first order rate constants of inactivation experimentally derived over a range of temperatures, are discussed.

Stability studies on pig heart mitochondrial malate dehydrogenase: the effect of salts and amino acids.

The effect of different salts and amino acids on the thermal stability and quaternary conformation of pig heart mitochondrial malate dehydrogenase (phm-MDH) in solution has been determined. The effectiveness of salts of anions in the stabilisation of phm-MDH followed the order: Citrate > SO(4)2- > or = Tartrate > Phosphate > F-, CH3COO- > Cl- > Br-. Anions above and including Cl- in this series were increasingly effective in stabilising phm-MDH with a rise in salt concentration from 0.05-2 M, whilst Br- was destabilising under similar conditions. The effect of potassium salts of acetate, chloride and bromide at a concentration of 1 M on the quaternary conformation of phm-MDH correlated also with the relative order of anion stabilisation above, with the anions higher in the series increasingly promoting the formation of the dimeric conformation of the enzyme. The cations of the corresponding salts had a relatively neutral (Cs+, K+, Na+, (CH3)4N+, NH4+) to a destabilising ((CH3)4N+, NH4+, Li+) effect on phm-MDH. Potassium ferrocyanide and potassium ferricyanide conferred complex, concentration dependent effects on the stability of phm-MDH, unlike the salts described above. Salts of amino acids were effective in the stabilisation of phm-MDH against temperature induced changes, following the order: NaGlutamatec = NaAspartate > NaGlycinate > lysine. HCl > arginine. HCl. The magnitudes and trends of the effects of these salts and amino acids on the stability and quaternary structure of phm-MDH were observed to correlate well with considerations based on the Hofmeister series of anions and solvophobic concepts as they apply to the influence of co-solvents at intermediate to higher concentrations. Other, more specific effects were also evident in the stabilisation and destabilisation of phm-MDH by low concentrations of the salts, as noted most particularly in the presence of potassium ferrocyanide and potassium ferricyanide.

Diagnostic studies in patients with sickle cell anemia and acute abdominal pain.

Twenty-eight patients with sickle cell disease who presented with acute abdominal pain were evaluated with clinical laboratory, ultrasound, and biliary scintigraphic studies to determine their predictive capabilities for differentiating veno-occlusive disease (sickle cell crisis) from acute biliary disease. Eleven patients were treated surgically and 17 medically. Gallstones were demonstrated in 25 (90%) of the patients studied by ultrasound, and biliary scans were abnormal in nine patients (32%). Abnormal laboratory and radiological studies (ultrasound, biliary scintigraphy) were not significantly different in the two groups and had a low positive predictive value for detection of acute biliary disease. Nevertheless, normal biliary scintigraphy had high negative predictive value in that, if normal, it gave assurance that the cystic duct was patent and unnecessary surgery could be obviated in this high-risk category of patients.

Hospital care by hospital-based and clinic-based faculty: a prospective, controlled trial.

BACKGROUND: The hospital length of stay decreases and clinical outcomes are maintained when teaching hospitals involve hospital-based attending physicians in comparison with traditional attending physicians. The attending physician's time commitment, including the number of hours per day and months per year, required to achieve this result is unknown. This study compared the clinical outcomes and cost of care for patients treated by hospital-based and clinic-based attending physicians devoting dramatically different amounts of time to supervising residents on the medical wards of a suburban county hospital. METHODS: Patients were alternately admitted to 2 groups of ward teams. Faculty who attended 10 months of the year supervised one group. The comparison group's attending physicians were on service for 2 months or less and maintained clinic responsibilities while on service. The cost of patient care was compared by means of the length of stay, total hospital costs, and costs for ancillary services. Hospital mortality and readmission rates compared clinical outcomes. RESULTS: There were 4456 patients hospitalized on the medical wards of a teaching service. No differences were detected in the length of stay (4.37 +/- 0.1 days for hospital-based and 4.39 +/- 0.1 days for clinic-based attending physicians). Hospital cost was observed to be similar (average cost, $5989 and $5977 per patient, respectively). The clinical outcomes were equivalent, with adjusted mortality rates for hospital-based attending physicians of 3.2% vs 3.9% for clinic-based attending physicians (P =.28). CONCLUSION: An increase of faculty time and involvement for supervision of resident-managed hospital care did not improve clinical outcomes or decrease costs during the 1-year study period.

Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge.

We describe an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel's cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intracranial tumors, but its incidence has been steadily increasing in some groups [1]. It usually arises in the periventricular cerebral white matter, and reports of lymphoma in extra-axial regions are rare [2]. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms.

Pulmonary complications of orthotopic liver transplantation.

Pulmonary complications following orthotopic liver transplantation (OLT) were prospectively evaluated in 18 individuals transplanted at the New England Deaconess Hospital. Of sixteen patients who survived the immediate postoperative period, 12 (75%) sustained a pulmonary complication. Of these complications, 64% were noninfectious--whereas 22% were infectious, and 14% probably infectious. Six of eight documented infections were caused by viruses of the herpes group. In four cases of viral pneumonitis other pulmonary pathogens were isolated (fungi-3, protozoan-1, bacteria-1). Unlike noninfectious complications, pulmonary infections were associated with a fatal outcome in five of six patients who died after OLT. Pulmonary complications are frequent and serious occurrences after OLT, and contribute to both the morbidity and mortality of this procedure. Compared with pulmonary complications seen after transplantation of other organs, OLT was associated with a higher proportion of noninfectious complications but a similar spectrum of pulmonary infections.

Myasthenia gravis presenting as isolated respiratory failure.

A patient with myasthenia gravis presenting as respiratory failure was unusual in his lack of peripheral neuromuscular involvement, negative results on many commonly used diagnostic tests, and lack of response to firstline therapeutic measures. Review of the pertinent literature revealed no previously described presentation of myasthenia gravis in this manner.

Abnormal airway function in individuals with the acquired immunodeficiency syndrome.

Pulmonary function test results of individuals with the acquired immunodeficiency syndrome (AIDS) were analyzed to determine the prevalence of abnormally low forced expiratory flow rates and bronchial hyperreactivity. Of 99 individuals with AIDS, a total of 44 (44 percent) had either low forced expiratory flow rates or a significant response to inhaled bronchodilator. Thirty-one (31 percent) individuals exhibited significant improvement in airflow rates after bronchodilator inhalation, while 33 (33 percent) had low flow rates. Twenty (20 percent) individuals had both low flow rates and a significant response to bronchodilator. In 83 percent of symptomatic individuals treated with bronchodilators there was clinical improvement. Thus, we conclude that abnormally low forced expiratory flow rate with or without bronchial hyperreactivity is a common and treatable complication of AIDS.

Analysis of induced sputum for the diagnosis of recurrent Pneumocystis carinii pneumonia.

We studied the sensitivity of ISA for diagnosis of second-episode PCP in AIDS patients. We induced sputum in 218 patients who had known or suspected AIDS and who had a presentation suggestive of PCP. All patients with negative sputum smear for PCP underwent BAL. Twenty-five patients were identified who had second-episode PCP at least 30 days after initial diagnosis. Chest roentgenographic infiltrate patterns for these 25 patients were blindly scored as normal, diffuse, upper lobe or focal non-upper lobe. The sensitivity of ISA was 72 percent for the first episode of PCP, 72 percent for the second episode of PCP, 72 percent for patients with second-episode PCP who had initial PCP detected by ISA and 71 percent for patients with second-episode PCP whose first episode of PCP was missed by ISA. Of the ten patients who were treated with AP, only one had a false-negative sputum analysis. A comparison of patients who had second-episode PCP diagnosed by ISA with those who had false-negative sputum analysis showed no difference in time to relapse, chest x-ray film pattern (all diffuse) or use of AP.

Controlled utilization of induced sputum analysis in the diagnosis of Pneumocystis carinii pneumonia.

We investigated the outcome and potential cost savings of a system designed to limit physician access to induced sputum analysis (ISA) for the diagnosis of Pneumocystis carinii pneumonia (PCP). Four respiratory medicine physicians screened all requests for ISA to determine the pretest likelihood of PCP. Twenty-two of 102 requests for ISA over a 1-year period were denied due to a low clinical suspicion for PCP. Seven individuals had a definitive alternative diagnosis confirmed and the remaining 15 were empirically treated for a presumptive diagnosis. All individuals were followed for at least 60 days or until death. None of the 22 individuals developed PCP during the follow-up period. We estimate that this approach saved $27,474, avoided exposure of health care workers to Mycobacterium tuberculosis, and was educational for the referring physicians.

Pulmonary mucormycosis presenting as an endobronchial lesion.

A 56-year-old diabetic man presented with left upper lobe collapse and postobstructive pneumonitis. Fiberoptic bronchoscopy revealed an endobronchial mass obstructing the left mainstem bronchus. The lesion resembled a bronchial adenoma; however, cytologic and histologic examination revealed invasive mucormycosis. The patient was treated with intravenous amphotericin B followed by endoscopic laser surgery that relieved the obstruction.

The prevalence and response to therapy of Strongyloides stercoralis in patients with asthma from endemic areas.

STUDY OBJECTIVE: To evaluate the prevalence and response to therapy of Strongyloides stercoralis infection in immigrant patients with asthma from areas endemic for Strongyloides. DESIGN AND INTERVENTIONS: In all patients, we performed a complete history and physical examination, complete blood cell counts (CBC), S stercoralis serologic tests, spirometry, and evaluated three stool samples for ova and parasites. Patients treated for S stercoralis infection had follow-up CBC, spirometry, serologic tests, and at least three additional stool examinations to confirm eradication of the parasite. SETTING: Ambulatory and hospitalized patients who were referred to the respiratory medicine clinic of a general hospital for the evaluation and treatment of asthma. PATIENTS: Forty-five asthmatic adults, representing 12 endemic countries, ranging in age from 20 to 76 years, were prospectively evaluated. RESULTS: Six of 45 patients were infected with S stercoralis, which yielded a prevalence of 13 percent. The patients with asthma and S stercoralis infection had higher blood eosinophil counts (p = 0.006) and were younger (p = 0.006) compared with patients with only asthma. There was no difference in the duration of asthma, spirometry, or steroid use between the two groups. Patients with S stercoralis and asthma tended to be more recent immigrants (p = 0.05). Five of the six patients with S stercoralis agreed to be treated with thiabendazole but only four returned for follow-up evaluation. All four patients had eradication of S stercoralis infection confirmed by negative stool examinations and a decline in S stercoralis serology (160 +/- 25 percent vs 13 +/- 13 percent, p = 0.03). All four patients had a decline in total blood eosinophil counts (2,476 +/- 832 cells per cubic millimeter vs 551 +/- 138 cells per cubic millimeter, p = 0.03) without a clinical improvement in asthma. CONCLUSIONS: Our data suggest that patients with asthma from areas endemic for S stercoralis, who have elevated peripheral blood eosinophil counts, should be screened for S stercoralis infection. Successful eradication of S stercoralis, however, may not result in a clinical improvement of asthma.

Bronchoscopic and radiologic features of Kaposi's sarcoma involving the respiratory system.

In a group of 61 patients admitted to New England Deaconess Hospital, Boston, with a diagnosis of acquired immune deficiency syndrome (AIDS), 25 were found to have Kaposi's sarcoma involving the skin and mucous membranes. Of these 25 patients, eight had lesions involving the respiratory system. Radiographically, patients with Kaposi's sarcoma had hilar and mediastinal adenopathy with perihilar parenchymal infiltration which progressed to diffuse bilateral infiltrates over a period of months. This pattern and the tempo of its evolution were distinctly different from the diffuse infiltrates seen in patients with Pneumocystis carinii pneumonia. Bronchoscopy was performed in seven of the eight patients, revealing characteristic lesions of Kaposi's sarcoma in the airways. We propose that parenchymal pulmonary Kaposi's sarcoma can be strongly suspected in a patient with AIDS who has the following features: a characteristic radiologic pattern; endobronchial Kaposi's sarcoma at bronchoscopy; and no evidence of opportunistic infection. In this subset of patients, further diagnostic intervention such as open lung biopsy, a procedure with potential morbidity in these ill individuals, may be unnecessary.