Phase I clinical trials in 56 patients with thyroid cancer: the M. D. Anderson Cancer Center experience.

INTRODUCTION: Thyroid cancer is the most common endocrine malignancy. The outcomes of patients with relapsed thyroid cancer treated on early-phase clinical trials have not been systematically analyzed. PATIENTS AND METHODS: We reviewed the records of consecutive patients with metastatic thyroid cancer referred to the Phase I Clinical Trials Program from March 2006 to April 2008. Best response was assessed by Response Evaluation Criteria in Solid Tumors. RESULTS: Fifty-six patients were identified. The median age was 55 yr (range 35-79 yr). Of 49 patients evaluable for response, nine (18.4%) had a partial response, and 16 (32.7%) had stable disease for 6 months or longer. The median progression-free survival was 1.12 yr. With a median follow-up of 15.6 months, the 1-yr survival rate was 81%. In univariate analysis, factors predicting shorter survival were anaplastic histology (P = 0.0002) and albumin levels less than 3.5 g/dl (P = 0.05). Among 26 patients with tumor decreases, none died (median follow-up 1.3 yr), whereas 52% of patients with any tumor increase died by 1 yr (P = 0.0001). The median time to failure in our phase I clinical trials was 11.5 months vs. 4.1 months for the previous treatment (P = 0.04). CONCLUSION: Patients with advanced thyroid cancer treated on phase I clinical trials had high rates of partial response and prolonged stable disease. Time to failure was significantly longer on the first phase I trial compared with the prior conventional treatment. Patients with any tumor decrease had significantly longer survival than those with any tumor increase.

Clinical primary flexor tendon repair and rehabilitation: The Bern Experience

In this chapter we present our experience with treatment of zone 2 flexor tendon repair using a six-strand repair technique combined with postoperative place-and-hold exercise. The six-strand Lim/Tsai repair technique combined with place-and-hold exercises demonstrated better digital function compared to a two-strand repair without place-and-hold exercises. Range of motion in the Lim/Tsai repair group appeared to be increased without a higher rate of ruptures but with a shorter rehabilitation period. The fact that the two groups differed in both suture techniques and rehabilitation programs made it impossible to know whether the better results in the group of Lim/Tsai were due to the six-strand repair or the place-and-hold exercises or both. Despite the obvious benefit of early active mobilization, an active motion protocol may not always be possible to apply in a substantial number of patients due to concomitant injuries, the quality of the surgical repair or patient factors (swelling, pain, limited compliance). Since August 2006 a staged rehabilitation program (“stop and go”) was introduced within our unit using early active controlled flexion (green), place-and-hold (yellow), or passive flexion exercises (red) introduced by Kleinert-Duran. Our experience using the six-strand suture repair technique and “stop and go” is outlined.

The Freedom SOLO bovine pericardial stentless valve: Single-center experience, outcome and long-term durability

Abstract Objectives We report our institutional experience and long-term results with the Sorin Freedom SOLO bovine pericardial stentless bioprosthesis. Methods Between January 2005 and November 2009, 149 patients (mean age 73.6±8.7 years, 68 [45.6%] female) underwent isolated (n=75) or combined (n=74) aortic valve replacement (AVR) using the SOLO in our institution. Follow-up was 100% complete with an average follow-up time of 5.9±2.6 years (maximum 9.6 years) and a total of 885.3 patient years. Results Operative (30-day) mortality was 2.7% (1.3% for isolated AVR [n=1] and 4.0% for combined procedures [n=3]). All causes of death were not valve-related. Preoperative peak (mean) gradients of 74.2±23.0 mmHg (48.6 ± 16.3 mmHg) decreased to 15.6±5.4 (8.8±3.0) after AVR, and remained low for up to 9 years. The postoperative effective orifice area (EOA) was 1.6 ±0.57 cm2, 1.90±0.45 cm2, 2.12±0.48 cm2 and 2.20±0.66 cm2 for the valve sizes 21, 23, 25 and 27, respectively; with absence of severe prosthesis-patient-mismatch (PPM) and 0.7% (n=1) moderate PPM. During follow-up, Twenty-six patients experienced structural valve deterioration (SVD) and 14 patients underwent explantation. Kaplan-Meier estimates for freedom from death, explantation and SVD at 9 years averaged 0.57 [0.47‒0.66], 0.82 [0.69‒0.90] and 0.70 [0.57‒0.79], respectively. Conclusions The Freedom SOLO stentless aortic valve is safe to implant and shows excellent early and mid-term hemodynamic performance. However, SVD was observed in a substantial number of patients after only 5 ̶ 6 years and the need for explantation increased markedly, suggesting low durability.

Clinical experience with the freedom SOLO stentless aortic valve in 277 consecutive patients.

BACKGROUND The Sorin Freedom SOLO (FS) bovine pericardial stentless valve prosthesis is designed for supraannular, subcoronary implantation. We report our experience and results with 277 consecutively implanted FS bioprostheses. METHODS 277 patients (mean age, 74.2 ± 7.3 years; 139 (50.2%) female) underwent aortic valve replacement (AVR) with the FS stentless bioprosthesis. The hemodynamic performance was investigated with transthoracic echocardiography at discharge, 6 months later, and yearly thereafter. Follow-up was 100% complete, with an average observation time of 2.6 ± 1.7 years and a total of 697.3 patient-years. RESULTS The overall 30-day mortality was 4.3%. The mortalities for isolated AVR and combined procedures were 1.9% and 7.3%, respectively. No causes of death were valve-related. Preoperative peak (74.2 ± 23.0 mm Hg) and mean (48.6 ± 16.3 mm Hg) gradients decreased to 15.6 ± 5.4 mm Hg and 8.8 ± 3.0 mm Hg postoperatively and remained unchanged for as long as 5 years. The postoperative mean effective orifice area (EOA) for valve sizes 19, 21, 23, 25, and 27 were 1.49 ± 0.32 cm(2), 1.67 ± 0.40 cm(2), 1.92 ± 0.38 cm(2), 2.01 ± 0.42 cm(2), and 2.13 ± 0.36 cm(2), respectively. Severe prosthesis-patient mismach (PPM) was completely absent, and moderate PPM occurred in 17 patients (6.1%). In isolated AVR, 0.8% of patients with preoperative sinus rhythm required a permanent pacemaker before hospital discharge. There was 100% freedom from structural valve deterioration, 99.6 % freedom from endocarditis and reoperation, and 97.3% freedom from thromboembolism at 5 years. CONCLUSIONS The FS stentless aortic valve is safe to implant, and it shows excellent hemodynamic performance and early and midterm results. Owing to the favorable EOA, the valve appears particularly attractive for patients at risk for PPM.

Laparoscopic versus open end colostomy closure: a single-center experience

The aim of this study was to review our experience with laparoscopic end colostomy closure. A retrospective review of a prospectively entered database was performed. Proportions and continuous variables were compared using the Fisher's exact and the Mann-Whitney U tests, respectively. Within the study period, 53 patients underwent closure of end colostomies. The main reasons for the colonic resections were perforated diverticulitis (52.7%) and neoplasms (20.8%). In 28 patients (53%), laparoscopic closure (LC) was attempted. Demographics did not differ between the attempted LC and the primary open closure (OC) group. The conversion rate from an LC to an OC was 50 per cent (14 of 28), mostly as a result of adhesions (71.4%). Hospital length of stay (HLOS) was significantly longer for the OC than with the attempted LC group (15.4 ± 11.9 days vs 11.3 ± 8.5 days, P = 0.046). The overall complication rate was not different between the completed LC and the OC groups (43 vs 56%, P = 0.634). The majority of complications detected (91.1%) were minor and could be treated conservatively. The role of laparoscopy to close end colostomies is questionable, because the conversion rate is high. However, a shorter HLOS can be expected when laparoscopy is successful. To reduce morbidity resulting from prolonged operation times, it is crucial to convert early and pre-emptively if hostile adhesions are found.

Scarring Effects of Early Unemployment among Young Workers with Vocational Credentials in Switzerland

Background Using a unique, longitudinal survey that follows school-to-work transitions of pupils who participated in PISA 2000, this paper investigates adverse consequences, so-called scarring effects, of early unemployment among young adults who acquired vocational credentials in Switzerland. Methods As social, individual and contextual factors influence both early unemployment and later employment outcomes, taking into account endogeneity is of utmost importance when investigating scarring effects. In this regard we make use of nearest-neighbour propensity score matching and set up statistical control groups. Results Our results suggest that young adults who hold vocational credentials are more likely to be neither in employment nor in education, and to earn less and be more dissatisfied with their career progress later in work life than they would be, had they not experienced early unemployment. Conclusions We conclude that unemployment scarring also affects young adults with vocational credentials in a liberal labour market setting that otherwise allows for smooth school-to-work transitions. This finding runs counter to expectations that standardised vocational degrees, a liberal and flexible labour market structure, and predominantly short unemployment spells protect young skilled workers from scarring in case they happen to experience early career instability.

Fetal megacystis: experience of a single tertiary center in Switzerland over 20 years

OBJECTIVES Megacystis (MC) is rare and often associated with other structural and chromosomal anomalies. In euploid cases with early oligohydramnios, prognosis is poor mainly due to pulmonary hypoplasia and renal damage. We report our experience of the past 20 years. METHODS A retrospective review of cases with prenatally diagnosed MC was performed. Complete prenatal as well as postnatal medical records from 1989 to 2009 were reviewed focusing on diagnostic precision, fetal interventions [vesicocentesis (VC), vesicoamniotic shunt (VAS)], short- and long-term outcome, and potential prognostic factors. RESULTS 68 cases were included. Follow-up was available in 54 cases (9 girls and 45 boys including 3 cases with aneuploidy). We found 39 isolated MC at sonography (5 girls and 34 boys). 24 fetuses with isolated MC underwent VC and VAS at 19.6 ± 6.3 and 20 ± 4.9 weeks of gestation, respectively. Survival rate was higher in male than in female fetuses (51 vs. 33%). Renal problems occurred in 4/14 prenatally treated fetuses and in 1/10 when cases with prune belly syndrome (PBS) were excluded from the analysis. CONCLUSIONS Our study shows that a careful selection of cases with MC excluding fetuses with PBS and early treatment has still the potential to improve outcome.

Nerve Transfers for Persistent Traumatic Peroneal Nerve Palsy: The Inselspital Bern Experience

BACKGROUND Patients in whom conventional peroneal nerve repair surgery failed to reconstitute useful foot lift need to be evaluated for their suitability to undergo a concomitant tendon transfer procedure or nerve transfers. OBJECTIVE To report our first clinical experience with nerve transfers for persistent traumatic peroneal nerve palsy. METHODS Between 2007 and 2013, 8 patients were operated on for foot drop after unsuccessful nerve surgery. Six patients without fatty degeneration of the anterior tibial muscle and proximal lesion of the peroneal nerve were oriented for tibial to peroneal nerve transfer. In the other 2 cases where the anterior and lateral compartments were destructed, the anterior tibial muscle function was reconstructed with a neurotized lateral gastrocnemius transfer. For each patient, we graded postoperative results using the Bureau of Meteorology Research Centre scheme and the Ninkovic assessment scale. RESULTS Of the 6 patients who underwent nerve transfer of the anterior tibial muscle, 2 patients had excellent results, 1 patient had good results, 1 patient had fair results, and 2 patients had poor results. Of the 2 patients that underwent neurotized lateral gastrocnemius transfer, 1 patient achieved excellent results after tenolysis, whereas 1 patient achieved poor results. After the nerve transfer, 5 patients did not wear an ankle-foot orthosis. Four patients did not limp. Four patients were able to walk barefoot, navigate stairs, and participate in activities. CONCLUSION Early clinical results after tibial to peroneal nerve transfer and neurotized lateral gastrocnemius transfer appear mixed. The results of nerve transfer seem, on the whole, less reliable than the literature reports on tendon transfer. ABBREVIATIONS EMG, electromyographyNAP, nerve action potential.

European multicentre experience with the sutureless Perceval valve: clinical and haemodynamic outcomes up to 5 years in over 700 patients†.

OBJECTIVES This report summarizes the 5-year clinical and haemodynamic data from three prospective, European multicentre trials with the Perceval sutureless aortic valve. METHODS From April 2007 to August 2012, 731 consecutive patients (mean age: 78.5 years; 68.1% females; mean logistic EuroSCORE 10.9%) underwent AVR with the Perceval valve in 25 European centres. Isolated AVR was performed in 498 (68.1%) patients. A minimally invasive approach was performed in 189 (25.9%) cases. The cumulative follow-up was 729 patients-years. RESULTS In isolated AVR, mean cross-clamp and cardiopulmonary bypass times were 30.8 and 50.8 min in full sternotomy, and 37.6 and 64.4 min in the minimally invasive approach, respectively. Early cardiac-related deaths occurred in 1.9%. Overall survival rates at 1 and 5 years were 92.1 and 74.7%, respectively. Major paravalvular leak occurred in 1.4% and 1% at early and late follow-up, respectively. Significant improvement in clinical status was observed postoperatively in the majority of patients. Mean and peak gradients decreased from 42.9 and 74.0 mmHg preoperatively, to 7.8 and 16 mmHg at the 3-year follow-up. LV mass decreased from 254.5 to 177.4 g at 3 years. CONCLUSIONS This European multicentre experience, with the largest cohort of patients with sutureless valves to date, shows excellent clinical and haemodynamic results that remain stable even up to the 5-year follow-up. Even in this elderly patient cohort with 40% octogenarians, both early and late mortality rates were very low. There were no valve migrations, structural valve degeneration or valve thrombosis in the follow-up. The sutureless technique is a promising alternative to biological aortic valve replacement.

Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer's Disease: From Early to Advanced Pathological Stages.

In addition to cognitive decline, individuals affected by Alzheimer's disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD.

Visual Acuity and Experience with Magnification Devices in Swiss Dental Practices

OBJECTIVES The aims of the present study in Swiss dental practices were 1) to provide an update on the prevalence of different magnification devices, 2) to examine the relationship between self-assessed and objectively measured visual acuity, and 3) to evaluate the visual performance of dentists in the individually optimized clinical situation of their respective practices. METHODS AND MATERIALS Sixty-nine dentists from 40 randomly selected private practices (n=20, <40 years; n=49, ≥40 years) participated in the study. A questionnaire was provided to evaluate the self-assessed near visual acuity and the experience with magnification devices. The objective near visual acuity was measured under standardized conditions on a negatoscope. The clinical situation, including the use of habitual optical aids, was evaluated with visual tests on a phantom head. RESULTS A total of 64% of the dentists owned a dental loupe: 45% Galilean loupes, 16% Keplerian loupes, and 3% single lens loupes. In total, 19% of the questioned dentists owned a microscope in addition to the loupes. The correlation between the self-assessed and the objective visual performance of the dentists was weak (Spearman rank correlation coefficient=0.25). In the habitual clinical situation, magnification devices (p=0.03) and the dentist's age (p=0.0012) had a significant influence on the visual performance. CONCLUSIONS Many dentists were not aware of their visual handicaps. Optical aids such as loupes or microscopes should be used early enough to compensate for individual or age-related visual deficiencies.

Single-center experience in the management of spontaneous isolated abdominal aortic dissection

OBJECTIVE This study aims to report the management of patients with spontaneous isolated dissection of the abdominal aorta (sIAAD). METHODS A cohort of 18 consecutive patients (12 male, mean age 58 years) with sIAAD was treated between 1990 and 2009. Dissection was asymptomatic in ten and symptomatic in eight patients. Retrospective data analysis from patient charts was performed. Follow-up included clinical examination, ultrasound, and/or CT-angiography. Mean follow-up was 54 months (range 1-211). RESULTS In total, eight out of 18 received invasive treatment. All asymptomatic patients initially underwent conservative treatment and surveillance. Spontaneous false lumen thrombosis occurred in four (40 %), and three patients showed relevant aneurysmatic progression and underwent elective invasive treatment (open n = 2, endovascular n = 1), representing a crossover rate of 30 %. Late mortality was 20 % (n = 2) in this group. In symptomatic patients, five underwent urgent treatment due to persistent abdominal or back pain (n = 4) or contained rupture (n = 1); one was treated for claudication. The remaining two patients presented with irreversible spinal cord ischemia and were treated conservatively. Three patients were treated by open surgery and three by endovascular interventions (two stentgrafts, one Palmaz XXL stent). Early and late morbidity and mortality was 0 % in this group. There were no reinterventions CONCLUSION: The majority of patients with sIADD require invasive treatment, with EVAR being the preferable treatment option today. In asymptomatic IADD, primary surveillance is justifiable, but close surveillance due to expansion is necessary.

A practice-based culminating experience with Texas Children's Hospital: A hospital's journey to baby-friendly status

Breastfeeding and the use of human milk are widely accepted as the most complete form of nutrition for infants. Breastfeeding is shown to be associated with many positive health outcomes for both infants and mothers. Healthy People 2000 goals to increase breastfeeding rates in the early postpartum period to 75% fell short, with only 64% of mothers meeting this objective. Lack of support from healthcare providers, and unsupportive hospital policies and practices are noted as barriers to the initiation and duration of breastfeeding. The purpose of this study was to evaluate implementation of the BFHI Ten Steps to Successful Breastfeeding at Texas Children's Hospital. ^ The Baby-Friendly Hospital Initiative (BFHI) was developed in 1991 by the World Health Organization and the United Nations Children's Fund (UNICEF) to ensure that healthcare facilities offering maternity services adhere to the Ten Steps of Successful Breastfeeding and the International Code of Marketing of Breast-Milk Substitutes, and create legislation to protect the rights of breastfeeding women. The instrument used in this study was the BFHI 100 Assessment Tool created by Dr. Laura Haiek, Director of Public Health in Monteregie, Quebec, and her staff at Health and Social Services Agency of Quebec. The BFHI 100 tool utilizes 100 different indicators of compliance with BFHI through questionnaires administered to staff and administrators, pregnant and postpartum mothers, and an observer. ^ The study concluded that although there is much room for improvement in educating breastfeeding mothers, overall, the mothers interviewed were satisfied with their level of care in regards to breastfeeding support. Areas of improvement include staff training, as some nursing staff admitted to relying on the lactation consultants to provide most of the breastfeeding education for mothers. Only a small percentage of mothers interviewed reported that their baby “roomed-in” on average of 22 hours per day during their hospital stay. Staff encouragement of the rooming-in practice will help to increase the proportion of mothers who allow their babies to room-in. The current breastfeeding policy will also need to be revised and strengthened to be compliant with the Ten Steps. Ideally, Baby-Friendly practices will become the norm after staff are trained and policy revisions are made. Staff training and acceptance of breastfeeding as optimal nutrition for infants are the most critical factors that will ultimately drive change for the organization. ^

Health significance of chlorination byproducts in drinking water: The Houston experience: A continuation study

Background. Houston, Texas, once obtained all its drinking water from underground sources. However, in 1853, the city began supplementing its water from the surface source Lake Houston. This created differences in the exposure to disinfection byproducts (DBPs) in different parts of Houston. Trihalomethanes (THMs) are the most common DBP and are useful indicators of DBPs in treated drinking water. This study examines the relationship between THMs in chlorinated drinking water and the incidence of bladder cancer in Houston. ^ Methods. Individual bladder cancer deaths, from 1975 to 2004, were assigned to four surface water exposure areas in Houston utilizing census tracts—area A used groundwater the longest, area B used treated lake water the longest, area C used treated lake water the second longest, and area D used a combination of groundwater and treated lake water. Within each surface water exposure area mortality rates were calculated in 5 year intervals by four race-gender categories. Linear regression models were fitted to the bladder cancer mortality rates over the entire period of available data (1990–2004). ^ Results. A decrease in bladder cancer mortality was observed amongst white males in area B (p = 0.030), white females in area A (p = 0.008), non-white males in area D (p = 0.003), and non-white females in areas A and B (p = 0.002 & 0.001). Bladder cancer mortality differed by race-gender and time (p ≤ 0.001 & p ≤ 0.001), but not by surface water exposure area (p = 0.876). ^ Conclusion. The relationship between bladder cancer mortality and the four surface water exposure areas (signifying THM exposure) was insignificant. This result could be attributable to Houston controlling for THMs starting in the early 1980’s by using chloramine as a secondary disinfectant in the drinking water purification process.^