Survival, disease progression and prognostic factors in elderly patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of 174 patients.

BACKGROUND: Advanced age at diagnosis is considered a poor prognostic factor in mycosis fungoides (MF) and Sézary syndrome (SS). OBJECTIVE: To evaluate the outcomes and prognostic factors in patients diagnosed at an advanced age (≥65 years) with MF/SS. METHODS: Survival, progression rates and various clinical and histopathological variables were studied in a group of 174 elderly patients diagnosed with MF/SS between 1992 and 2015 at a single referral cancer center in the United States. Kaplan-Meier estimates were used to determine survival and progression and Cox proportional hazards regression univariate and multivariate models were used to identify prognostic factors. RESULTS: Of 174 elderly patients, 76.4% were diagnosed with early-stage (clinical stages IA-IIA) and 23.6% with late-stage MF/SS (IIB-IV). Advanced age was associated with poor overall survival, but not with disease-specific survival (DSS) or progression-free survival (PFS). Gender, increasing clinical stage, T and B classifications, elevated lactate dehydrogenase (LDH) levels and development of large cell transformation (LCT) were significant predictors of poor survival or disease progression. Patients with early-stage MF and <10% total skin involvement (T1 classification) or patch-only disease (T1a/T2a) showed better PFS with no observed disease-specific mortality. Folliculotropic MF was associated with poor DSS in patients with early-stage disease. CONCLUSIONS: Older age at diagnosis of MF/SS does not predict worse disease-specific outcomes. Elderly patients with early-stage disease, specifically involving less than 10% of the skin surface with patches but without plaques or folliculotropism, have an excellent prognosis. However, the development of LCT is a strong prognostic indicator of poor survival in elderly patients with MF/SS.

Phase II study of idelalisib, a selective inhibitor of PI3Kδ, for relapsed/refractory classical Hodgkin lymphoma.

BACKGROUND: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment. We tested this hypothesis in a phase II study. PATIENTS AND METHODS: We enrolled 25 patients with relapsed/refractory HL with a median age of 42 years and who had previously received a median of five therapies including 18 (72%) with failed autologous stem cell transplant, 23 (92%) with failed brentuximab vedotin, and 11 (44%) with prior radiation therapy. Idelalisib was administered at 150 mg two times daily; an increase to 300 mg two times daily was permitted at the time of disease progression. RESULTS: The overall response rate to idelalisib therapy was 20% (95% confidence interval: 6.8%, 40.7%) with a median time to response of 2.0 months. Seventeen patients (68%) experienced reduction in target lesions with one complete remission and four partial remissions. The median duration of response was 8.4 months and median progression-free survival was 2.3 months. The most common grade ≥3 adverse event was elevation of alanine aminotransferase (two patients, 8%). Diarrhea/colitis was seen in three patients and was grade 1-2. There was one adverse event leading to death (hypoxia). CONCLUSIONS: Idelalisib was tolerable and had modest single-agent activity in heavily pretreated patients with HL. Rational combinations with other novel agents may improve response rate and duration of response. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov # NCT01393106.

A de novo splice site mutation in CASK causes FG syndrome-4 and congenital nystagmus.

Mutations in CASK cause X-linked intellectual disability, microcephaly with pontine and cerebellar hypoplasia, optic atrophy, nystagmus, feeding difficulties, GI hypomotility, and seizures. Here we present a patient with a de novo carboxyl-terminus splice site mutation in CASK (c.2521-2A>G) and clinical features of the rare FG syndrome-4 (FGS4). We provide further characterization of genotype-phenotype correlations in CASK mutations and the presentation of nystagmus and the FGS4 phenotype. There is considerable variability in clinical phenotype among patients with a CASK mutation, even among variants predicted to have similar functionality. Our patient presented with developmental delay, nystagmus, and severe gastrointestinal and gastroesophageal complications. From a cognitive and neuropsychological perspective, language skills and IQ are within normal range, although visual-motor, motor development, behavior, and working memory were impaired. The c.2521-2A>G splice mutation leads to skipping of exon 26 and a 9 base-pair deletion associated with a cryptic splice site, leading to a 28-AA and a 3-AA in-frame deletion, respectively (p.Ala841_Lys843del and p.Ala841_Glu868del). The predominant mutant transcripts contain an aberrant guanylate kinase domain and thus are predicted to degrade CASK's ability to interact with important neuronal and ocular development proteins, including FRMD7. Upregulation of CASK as well as dysregulation among a number of interactors is also evident by RNA-seq. This is the second CASK mutation known to us as cause of FGS4. © 2017 Wiley Periodicals, Inc.

Prognosis in HIV-infected patients with non-small cell lung cancer.

BACKGROUND: We conducted a population-based study to evaluate whether non-small cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV-uninfected patients. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC between 1996 and 2007. We used conditional probability function (CPF) analyses to compare survival by HIV status accounting for an increased risk of non-lung cancer death (competing risks) in HIV-infected patients. We used multivariable CPF regression to evaluate lung cancer prognosis by HIV status adjusted for confounders. RESULTS: Stage at presentation and use of stage-appropriate lung cancer treatment did not differ by HIV status. Median survival was 6 months (95% confidence interval (CI): 5-8 months) among HIV-infected NSCLC patients compared with 20 months (95% CI: 17-23 months) in patients without evidence of HIV. Multivariable CPF regression showed that HIV was associated with a greater risk of lung cancer-specific death after controlling for confounders and competing risks. CONCLUSION: NSCLC patients with HIV have a poorer prognosis than patients without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the setting of HIV.

The impact of gender on in-hospital outcomes after carotid endarterectomy or stenting.

AIM: We sought to better define the impact of sex on 'in-hospital outcomes' after carotid endarterectomy (CEA) or stenting (CAS). METHODS: Hospital discharge databases for all carotid interventions obtained from the New York State (NYS) Department of Health, Statewide Planning and Research Cooperative System between 2000 and 2009 (29,917 women, 39,771 men) were analysed. Mortality, stroke and composite event (stroke/death) were compared between procedures after matching of patients by propensity score. Acute myocardial infarction (AMI) was our secondary 'end' point. RESULTS: More than 90% of patients in both sexes were asymptomatic (27,439 women and 36,295 men). Compared to men, asymptomatic women experienced more strokes after CEA (women: 1.38%, men: 1.16%, P = 0.03) and higher AMI rates after both procedures (CEA; women: 0.75%, men: 0.51%, P = 0.0009, CAS; women: 0.96%, men: 0.28%, P = 0.01). Between procedures, symptomatic women undergoing CAS showed higher rates of mortality (CAS: 4.19%, CEA: 0.47%, P = 0.01) and combined (stroke/mortality) events (CAS: 12.09%, CEA: 6.05%, P = 0.02). In all other cohorts, no statistically significant difference was found between the procedures. CONCLUSIONS: Compared to CEA, CAS led to inferior in-hospital outcomes only in symptomatic women in the last decade in NYS. Men and asymptomatic women showed comparable outcomes after both procedures, whereas asymptomatic females were more prone to AMI after both interventions. These sex-associated differences should be taken into account for the treatment of carotid artery disease.

Process of care events in transplantation: effects on the cost of hospitalization.

Deviations in the processes of healthcare delivery that affect patient outcomes are recognized to have an impact on the cost of hospitalization. Whether deviations that do not affect patient outcome affects cost has not been studied. We have analyzed process of care (POC) events that were reported in a large transplantation service (n = 3,012) in 2005, delineating whether or not there was a health consequence of the event and assessing the impact on hospital resource utilization. Propensity score matching was used to adjust for patient differences. The rate of POC events varied by transplanted organ: from 10.8 per 1000 patient days (kidney) to 17.3 (liver). The probability of a POC event increased with severity of illness. The majority (81.5%) of the POC events had no apparent effect on patients' health (63.6% no effect and 17.9% unknown). POC events were associated with longer length of stay (LOS) and higher costs independent of whether there was a patient health impact. Multiple events during the same hospitalization were associated with the highest impact on LOS and cost. POC events in transplantation occur frequently, more often in sicker patients and, although the majority of POC events do not harm the patient, their effect on resource utilization is significant.

A patient with new Q waves: methods for decision making in the individual patient.

Decision analysis, an analytic approach to making decisions when uncertainty is present, has its foundation in probability and utility theory. It provides insights into the trade-offs that are involved when a selection must be made among patient management strategies. In general, several broad steps are involved. The process begins by formulating the clinical problem as a well focused choice among a limited set of clinical etiologies. These strategies are then structured explicitly in a model that depicts the clinical events that may ensue from each option. By assigning probability values to each outcome, the weighted average outcome or expected utility can be calculated for each alternative strategy. The strategy with the highest expected utility is the optimal one. The methods of decision analysis offer a number of distinct advantages. These include: 1) providing a structure with which to simplify and focus clinical dilemmas; 2) providing a forum for discussing clinical reasoning; and 3) developing a consensus among groups of decision makers.

Diabetes care for Medicare beneficiaries. Attitudes and behaviors of primary care physicians.

OBJECTIVE: To obtain information related to primary care physician (PCP) attitudes, knowledge, and practice patterns, as well as perceptions about barriers to care and the use of materials to assist in the delivery of diabetes care for elderly patients in the office setting. RESEARCH DESIGN AND METHODS: A survey was mailed to a random sample (n = 900) of PCPs (internal medicine, family practice, and general practice physicians and endocrinologists) from the states of Alabama, Iowa, and Maryland who met selection criteria and provided diabetes care to > or = 25 Medicare beneficiaries during calendar year 1993. RESULTS: Respondents provided self-reported information regarding diabetes care for elderly patients. PCP respondents (n = 370) considered blood glucose control to be the most important treatment goal. Most respondents (92%) considered acceptable GHb values to be those < 8%. Blood pressure measurement and foot inspections for the detection of ulcers and infection were the most commonly reported routine procedures performed as part of an office visit. Laboratory tests reported to be frequently ordered included GHb, serum creatinine, and proteinuria tests. Patient nonadherence to the treatment regimen was reported to be the most common barrier to care. The majority of respondents reported using two treatment aids in caring for patients with diabetes. CONCLUSIONS: The results of this study provide some evidence that PCP self-reported attitudes, knowledge, and practice patterns in delivering diabetes care for elderly patients in the office setting more closely reflect current recommended practice than reported in previous physician surveys. Opportunities for improvement still exist.

Effect of stimulus orientation on the latency and amplitude of the VEP.

VEPs were recorded using 5.0 c/deg square wave gratings presented at vertical and oblique (45 deg) orientations and phase-alternated at two rates, 6 alternations/sec and 12 alternations/sec. In agreement with previous reports, VEP amplitude was smaller for obliquely oriented gratings than for vertically oriented gratings at both alternation rates. Unlike previous studies, however, the authors found that VEP latency was longer for obliquely oriented gratings at the slower (6/sec) alternation rate.

Comparison of pattern VEPs and preferential-looking behavior in 3-month-old infants.

Studies of visual acuity in human infants between 1 and 6 months of age using the visual-evoked potential (VEP) and forced-choice preferential looking (FPL) have shown that acuity is one to two octaves higher by VEP estimates than by FPL estimates. In an attempt to study these differences, the authors obtained both VEP and FPL data from 26 3-month-old infants. VEP data were obtained with gratings of 0.31, 0.62, 1.25 and 2.50 cycles/deg, which were counterphase alternated at 2 Hz. FPL data were obtained for stationary gratings using either the method of constant stimuli or a staircase procedure. Our study revealed three major findings: (1) recordable VEPs can be obtained for spatial patterns that are below threshold by behavioral measures; (2) the use of different scoring criteria that yields comparable VEP and FPL group mean acuities does not yield a significant correlation between VEP amplitude acuity and FPL acuity for individual infants, probably because of the inherent "noise" in each technique; and (3) when VEP latency rather than amplitude is used to estimate acuity, there is a significant correlation between electrophysiology and behavior.

Electrophysiological evidence for the oblique effect in human infants.

Visually-evoked potentials (VEPs) were recorded from infants between the ages of 2 and 11 months in response to 2.5 c/deg main axis and oblique square wave gratings. The oblique effect first appears at 3 months of age; some infants showed smaller VEP amplitude and/or longer VEP latency for obliquely oriented gratings. Regarding the age of onset of the oblique effect, VEP data from this study agree with the results obtained with preferential looking (PL) studies which have directly paired vertical and oblique gratings, but the current study found that fewer infants show an oblique effect by VEP than by PL.

Utility of the Arden grating test in glaucoma screening: high false-positive rate in normals over 50 years of age.

The Arden grating test was administered to 64 subjects between 6 and 82 years of age without ocular pathology, to 20 glaucoma patients, and to 21 ocular hypertensives. The results show an age effect, with significantly higher scores (lower sensitivity) in normal subjects over 50 years of age. In addition, there was no significant difference in performance between age-matched normals, glaucoma patients, and ocular hypertensives on the Arden gratings. The results show a high percentage of false-positives in older normal subjects. The Arden gratings should be used cautiously when one is testing patients over 50 years of age.

Infant VEP and preferential looking acuity measured with phase alternating gratings.

Previously, infants' grating acuity was found to be temporally tuned, but adults' grating acuity was not. In infants, acuity was higher for gratings phase alternating at 7.5 and 14 reversals/sec than for stationary gratings and gratings alternating at 2.5 or 23 reversals/sec. Also, when preferential looking (PL) and visually evoked potential (VEP) acuity were estimated with phase alternating gratings (14 reversals/sec), the acuity difference between the two techniques was smaller than that obtained when phase alternating gratings were used to estimate VEP acuity and stationary gratings were used to estimate PL acuity. In the present study, it was determined if PL grating acuity was tuned in older children and if the smaller difference between VEP and PL acuity found when infants were tested with phase alternating gratings was independent of temporal rate. Grating acuity in infants older than 2 yr was found to be not tuned, and the smaller difference between VEP and PL grating acuity in infants when both were measured with phase-alternating gratings was not rate dependent. VEP acuity and PL acuity for phase alternating gratings developed at different rates, converging to nearly equivalent levels by 12 mo of age.

Recording the contralateral PERG: effect of different electrodes.

A pattern electroretinogram (PERG) can be recorded when the eye wearing the electrode is occluded and the stimulus is viewed with the other eye. We find that this phenomenon occurs when an Arden gold foil electrode is used, but not when either an ERG-Jet lens or a scleral lens electrode is used. Therefore, a corneal-type electrode should be used in PERG recording situations where the fellow eye is not occluded.

The visual evoked potential in glaucoma and ocular hypertension: effects of check size, field size, and stimulation rate.

In order to determine the optimum stimulus conditions for the detection of optic nerve damage due to glaucoma and ocular hypertension, checkerboard pattern reversal visual evoked potentials (VEPs) were recorded from 20 glaucoma patients, 20 ocular hypertensive patients, and 20 age-matched normals. Two check sizes (12' and 48'), two field sizes (14 degrees and 28 degrees), and two alternation rates (1.9 and 7.5 alt/sec) were used. All subjects had visual acuities of 20/40 or better in each eye and equal pupils of 2 to 5 mm diameter. The largest number of VEP abnormalities were found with large checks (48') reversing at a fast rate (7.5 alt/sec). After correcting for the effects of age, visual acuity, and pupil size, 16 of 30 eyes with glaucomatous visual field defects had abnormally long VEP latencies under this condition (beyond the 99% confidence limit of the normal subjects). Nine of 40 ocular hypertensive eyes also had abnormally long latencies. Increased pattern VEP latency was significantly correlated with both the severity and location of visual field defects and the degree of cupping and pallor of the optic disc. VEP latency was not significantly related to intraocular pressure.

Hypoplastic left heart syndrome: valuing the survival.

OBJECTIVE: To examine the survival, developmental status, quality of life, and direct medical costs of children with hypoplastic left heart syndrome who have undergone stage I, II, and III reconstructive surgery. METHODS: A total of 106 children underwent staged repair for classic hypoplastic left heart syndrome between February 1990 and March 1999 (stage I: 106; stage II: 49; stage III: 25; 4 converted to heart transplantation). Survival was analyzed by the Kaplan-Meier method. In a cross-sectional study, parents assessed quality of life by completing the Infant/Toddler Child Health Questionnaire or Child Health Questionnaire Parent Format-28; they assessed developmental progress by completing the Ages and Stages Questionnaire. The ratio-of-costs-to-charges method was used to derive hospital costs, and payments were used to capture physician time and wholesale pricing for outpatient medications. RESULTS: Institutional 1-year and 5-year actuarial survivals were 58% and 54%. Birth weight, the need for preoperative inotropic drugs, and surgical experience were predictors of survival. Norwood I patients achieved fewer developmental benchmarks than those who survived to subsequent stages. Child Health Questionnaire Parent Format-28 mean summary scores for physical and psychosocial health were 48.5 +/- 6.3 and 42.8 +/- 9.9. The median inpatient costs for stage I, II, and III repairs were $51,000, $33,892, and $52,183, respectively. Monthly outpatient and readmission costs were less than 10% of total costs. CONCLUSION: A prospective, large-scale study of the comprehensive outcomes of staged repair and transplantation is needed. This study will need to address the longer-term developmental and quality-of-life outcomes, as well as the long-term cost effectiveness of these procedures.

Volume-outcome relationships in cardiovascular operations: New York State, 1990-1995.

BACKGROUND: It has been known for nearly 20 years that, in cardiovascular operations, a significant inverse relationship exists between clinical outcomes and the volume of procedures performed. Interestingly, this relationship persists 2 decades after it was recognized. OBJECTIVE: The purpose of this study was to examine the relationship between hospital volume and in-hospital deaths in 3 cardiovascular procedures: coronary artery bypass grafting, elective repair of abdominal aortic aneurysms, and repair of congenital cardiac defects. METHODS: The database includes all patients who were hospitalized in New York State during the years 1990 to 1995. Using standard logistic regression techniques, we analyzed the relationship between hospital volume and outcome. RESULTS: No correlation exists between hospital volume and in-hospital deaths in coronary artery bypass grafting. Statewide, 31 hospitals performed 97,137 operations over the 6-year period (overall mortality rate, 2. 75%). By contrast, most of the hospitals statewide (195 of 230 hospitals) performed 9847 elective abdominal aortic aneurysm repairs with an overall mortality rate of 5.5%. In abdominal aortic aneurysm operations, a significant inverse relationship between hospital volume and in-hospital deaths was determined. Sixteen hospitals performed 7199 repairs for congenital cardiac defects. A significant inverse relationship (which was most pronounced for neonates) was found between volume and death. CONCLUSIONS: The importance of these findings lies in the rather striking difference between the volume-outcome relationship found for operations for abdominal aortic aneurysms and congenital cardiac defects and the lack of such a relationship for coronary artery bypass grafting. This observation may be largely explained by the quality improvement program in New York State for bypass operations since 1989. If so, these results have important implications for expanding the scope of quality improvement efforts in New York State.

Contrast sensitivity in diabetics with and without background retinopathy.

Contrast sensitivity measurements were obtained from 64 patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus who had normal Snellen acuity and minimal or no visible diabetic retinopathy. Contrast thresholds were determined for stationary gratings at six spatial frequencies, ranging from 0.5 to 22.8 cycles/degree (c/deg), and for 1.0-c/deg gratings phase-alternated at 15 Hz. Data from each group of diabetic patients were compared with data from age-matched normal subjects. We found that (1) patients with IDDM and no retinopathy had normal contrast sensitivity, (2) patients with NIDDM and no retinopathy had abnormal contrast sensitivity at only one spatial frequency (22.8 c/deg), and (3) patients with NIDDM and background retinopathy had abnormal contrast sensitivity at all spatial frequencies tested. We also found a dissociation of Snellen acuity and contrast sensitivity, indicating that contrast sensitivity can be used as an early index of changes in the retina not demonstrated by measurements of visual acuity.

The cost of long-term LVAD implantation.

BACKGROUND: With increasing use of left ventricular assist devices (LVAD) worldwide, the economics of LVAD implantation have become an important focus of concern. Although these devices have high unit costs, they are the only hope for survival for a large group of terminally ill patients and are likely to have an expansion in indications for use. METHODS: We calculated the costs associated with long-term LVAD implantation. We used the ratio of cost-to-charges method to calculate hospital costs per resource category, market prices for drugs and device, and payments for physician services. RESULTS: Based on our experience with "bridge-to-transplantation" patients, we estimated average first-year costs to be $222,460 including professional fees and $192,154 excluding professional fees. The latter figure is comparable to average first-year costs for cardiac transplantation, which is $176,605 without professional fees at our institution. CONCLUSIONS: The costs of LVAD therapy will change after the first year of implantation, and device reliability and longevity will be important factors in determining these costs. Should the costs of LVAD therapy continue to track those of cardiac transplantation, devices will be cost-effective only if they offer similar efficacy to cardiac transplantation.