Frequency of aquagenic palmoplantar keratoderma in cystic fibrosis: a new sign of cystic fibrosis?

BACKGROUND: Aquagenic palmoplantar keratoderma (APPK), also known as aquagenic wrinkling of the palms, is characterized by oedema of palms and/or soles, whitish papules, hyperwrinkling and sometimes pruritus or pain after water immersion. Its frequency in the general population is unknown. About 40 cases have been reported to date, including some among patients with cystic fibrosis (CF) or CF heterozygotes. OBJECTIVES: To determine the frequency of APPK among patients with CF. METHODS: Twenty-seven patients from the Centre of Competence on Cystic Fibrosis of Roscoff were examined by a dermatologist after immersion of the palms in water for 2-3 min. RESULTS: The frequency of APPK was 41% (11 of 27 patients). Some patients had not previously noticed the lesions. The frequency was higher among inpatients than outpatients. We suspect that occlusion (caused by the gloves worn by inpatients) can explain this difference. The number of patients included in this study is not sufficient to draw any conclusions concerning the type of CF mutation and its impact on the frequency of APPK. CONCLUSIONS: APPK is frequent among patients with CF and, thus, should be considered a sign of CF. APPK is underdiagnosed because physicians usually do not look for it. CF screening should be considered for any patient presenting with these symptoms, followed by genetic counselling if necessary.

Investigation of Stenotrophomonas maltophilia epidemiology in a French cystic fibrosis center.

BACKGROUND: Stenotrophomonas maltophilia is an emerging opportunistic pathogen. The increasing incidence is of particular concern in patients with cystic fibrosis (CF). Since 2012, the Western France has witnessed high annual prevalence of S. maltophilia colonization/infection. This retrospective cohort study investigated the epidemiology of S. maltophilia emergence in the CF center of Roscoff, Western France, a region of high prevalence of CF in Europe. METHODS: All CF patients with S. maltophilia isolated in respiratory samples between December 2013 and February 2017 were included. For each patient the colonization status with S. maltophilia was determined. The epidemiological and microbiological characteristics collected were compared between colonization statuses. RESULTS: S. maltophilia was isolated in 90 patients (42 males, 48 females). Mean age at first colonization was 24.4±13.5 years. Annual prevalence since 2013 was high (16-17.9%), but stable. This high prevalence is mainly due to a high rate of intermittent colonization. Only 2.8% of CF patients showed chronic colonization, with significantly more frequent co-colonization by methicillin-susceptible Staphylococcus aureus (P<0.0001) and Pseudomonas aeruginosa (P<0.05). During chronic colonization, S. maltophilia acquired resistance to cotrimoxazole and ß-lactams. Interestingly, there were cases of decolonization. CONCLUSION: This is the first epidemiological report of S. maltophilia in a French CF center. Prevalence was stable but above the national average. Most cases were intermittent; chronic colonization was rare.

A p53-dependent mouse spindle checkpoint.

Cell cycle checkpoints enhance genetic fidelity by causing arrest at specific stages of the cell cycle when previous events have not been completed. The tumor suppressor p53 has been implicated in a G1 checkpoint. To investigate whether p53 also participates in a mitotic checkpoint, cultured fibroblasts from p53-deficient mouse embryos were exposed to spindle inhibitors. The fibroblasts underwent multiple rounds of DNA synthesis without completing chromosome segregation, thus forming tetraploid and octaploid cells. Deficiency of p53 was also associated with the development of tetraploidy in vivo. These results suggest that murine p53 is a component of a spindle checkpoint that ensures the maintenance of diploidy.

Relations among maternal physical activity during pregnancy and child body composition.

OBJECTIVE: Physical activity (PA) during pregnancy is associated with lower neonatal fat mass, but associations with child body composition are mixed. The purpose of this study was to examine associations between trimester-specific pregnancy PA and child body composition at 4 years. METHODS: Participants of the Minnesota Infant Nutrition, Neurodevelopment, and Obesity Study were asked to recall participation in any moderate or vigorous PA in the first (T1), second (T2) and third (T3) trimesters at about 5 years postpartum. Child fat mass and fat-free mass were measured via air displacement plethysmography at 2 weeks, 3 months and 4 years of age. Multivariate linear regression was used for analyses. RESULTS: Of 51 possible participants, 37 recalled pregnancy PA. Any vigorous PA in T3 was associated with lower child fat mass at 4 years (adjß = -1.077, p < 0.05). CONCLUSION: Late pregnancy PA may have lasting benefits for child body composition. Replication of these findings is needed in a larger sample with prospective measures.

Do anthropometric measures accurately reflect body composition in preterm infants?

BACKGROUND: Recent literature suggests that neonatal adiposity is predictive of later metabolic health, while neonatal lean mass is predictive of later cognitive function amongst preterm infants. Anthropometric indices that accurately reflect neonatal body composition could improve clinical care and aid future research, but their validity has not been systematically tested in preterm infants. OBJECTIVE: To determine the weight/length indices that best reflect neonatal body composition in preterm infants. METHODS: Weight and length were measured, and body composition (fat-free mass (FFM), fat mass (FM) and percent body fat (%BF)) was assessed using air-displacement plethysmography within 72 h of birth in 218 preterm infants. The best weight/length proxy for FFM, FM and %BF were those with the highest proportion variance explained (R2 ) and lowest root mean square error (RMSE) in linear regression models. RESULTS: Among all of the weight/length indices tested, weight/length2 was the best proxy for %BF, but nonetheless exhibited very low variance explained (R2 = 0.27) and high prediction error (RMSE = 3.5% fat). Body weight unadjusted for length was strongly associated with FFM (R2 = 0.97). CONCLUSIONS: No weight/length index accurately reflected %BF. Weight/length indices are not appropriate for assessment of relative adiposity in preterm infants near birth. What's known on this subject: Compared with term infants, preterm infants have increased fat mass and diminished fat-free mass upon hospital discharge. Early adiposity predicts later metabolic health, while early lean mass is predictive of later neurodevelopmental outcomes. Optimal anthropometric proxies for preterm body composition at birth are not established. WHAT THIS STUDY ADDS: Weight is an adequate surrogate for lean mass at birth in preterm infants. There are no weight/length indices that accurately reflect neonatal adiposity at birth.

Evaluation of quantitative PCR for early diagnosis of Pseudomonas aeruginosa infection in cystic fibrosis: a prospective cohort study.

OBJECTIVES: Early detection of Pseudomonas aeruginosa lung positivity is a key element in cystic fibrosis (CF) management. PCR has increased the accuracy of detection of many microorganisms. Clinical relevance of P. aeruginosa quantitative PCR (qPCR) in this context is unclear. Our aim was to determine P. aeruginosa qPCR sensitivity and specificity, and to assess the possible time saved by qPCR in comparison with standard practice (culture). METHODS: A multicentre cohort study was conducted over a 3-year period in 96 patients with CF without chronic P. aeruginosa colonization. Sputum samples were collected at each visit. Conventional culture and two-step qPCR (oprL qPCR and gyrB/ecfX qPCR) were performed for 707 samples. The positivity criteria were based on the qPCR results, defined in a previous study as follow: oprL qPCR positivity alone if bacterial density was <730 CFU/mL or oprL qPCR combined with gyrB/ecfX qPCR if bacterial density was ≥730 CFU/mL. RESULTS: During follow up, 36 of the 96 patients with CF were diagnosed on culture as colonized with P. aeruginosa. This two-step qPCR displayed a sensitivity of 94.3% (95% CI 79.7%-98.6%), and a specificity of 86.3% (95% CI 83.4%-88.7%). It enabled P. aeruginosa acquisition to be diagnosed earlier in 20 patients, providing a median detection time gain of 8 months (interquartile range 3.7-17.6) for them. CONCLUSIONS: Implementing oprL and gyrB/ecfX qPCR in the management of patients with CF allowed earlier detection of first P. aeruginosa lung positivity than culture alone.

17p allelic deletions and p53 protein overexpression in Barrett's adenocarcinoma.

Barrett's esophagus is a condition in which the stratified squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium that predisposes to the development of esophageal adenocarcinoma. Allelic deletions of 17p and alterations of p53 including elevated p53 protein levels have been observed in many different tumors. To investigate the presence of 17p allelic deletions and p53 protein overexpression in Barrett's adenocarcinomas, we have combined the use of restriction fragment length polymorphism analysis, multiparameter flow cytometry, and DNA content cell sorting. The combined use of these methodologies permits the purification of aneuploid tumor cells for restriction fragment length polymorphism analysis of 17p allelic deletions and the evaluation of p53 protein expression by multiparameter flow cytometry in the same aneuploid tumor cell populations. We analyzed 15 aneuploid populations and one tetraploid populations from 13 Barrett's adenocarcinomas for 17p allelic deletions and p53 protein overexpression to determine whether both of these alterations are involved in carcinogenesis in Barrett's esophagus. Twelve of 13 tumors (92%) had 17p allelic deletions, and 8 of 13 tumors (62%) had p53 protein overexpression. Eight of the 12 tumors (67%) with 17p allelic deletions also had p53 protein overexpression. These data indicate that both 17p allelic deletions and p53 protein overexpression are frequently involved in carcinogenesis in Barrett's esophagus.

Diminished growth and lower adiposity in hyperglycemic very low birth weight neonates at 4 months corrected age.

OBJECTIVE: Characterize the relationship between neonatal hyperglycemia and growth and body composition at 4 months corrected age (CA) in very low birth weight (VLBW) preterm infants. STUDY DESIGN: A prospective study of VLBW appropriate-for-gestation infants (N=53). All blood glucose measurements in the first 14 days and nutritional intake and illness markers until discharge were recorded. Standard anthropometrics and body composition via air displacement plethysmography were measured near term CA and 4 months CA. Relationships between hyperglycemia and anthropometrics and body composition were examined using multivariate linear regression. RESULTS: Infants with >5 days of hyperglycemia were lighter (5345 vs 6455 g, P⩽0.001), shorter (57.9 vs 60.9 cm, P⩽0.01), had smaller occipital-frontal head circumference (39.4 vs 42.0 cm, P⩽0.05) and were leaner (percent body fat 15.0 vs 23.8, P⩽0.01) at 4 months CA than those who did not have hyperglycemia, including after correcting for nutritional and illness factors. CONCLUSIONS: Neonatal hyperglycemia in VLBW infants is associated with decreased body size and lower adiposity at 4 months CA independent of nutritional deficit, insulin use and illness. Downregulation of the growth hormone axis may be responsible. These changes may influence long-term growth and cognitive development.

Body composition at birth in preterm infants between 30 and 36 weeks gestation.

BACKGROUND: The American Academy of Pediatrics calls for aggressive management of preterm infants to achieve body composition approximating that of the healthy infant in utero. Air displacement plethysmography (ADP) has been validated for assessment of body composition in preterm infants and could be used to monitor their nutritional status during hospitalization. Comparative datasets on body composition at birth among healthy, live-born preterm infants are lacking. OBJECTIVE: The aim of this study is to provide the first descriptive fat mass (FM) and fat-free mass (FFM) data from healthy newborn preterm infants at birth as a proxy for healthy in utero body composition. METHODS: Body mass and volume were obtained using ADP within 72 h of birth in 98 singleton, appropriate-for-gestational-age preterm infants. FM and FFM were calculated using the Fomon equation. RESULTS: Measurement with ADP was feasible and well tolerated by infants as young as 30 weeks gestation and <72 h of age. FFM and FM increased linearly over the gestational age range period at rates of 171 and 46 g week(-1) , respectively. Mean values obtained by ADP by gestational week were similar to the previously published reference data from chemical analysis on stillbirths. CONCLUSIONS: Body composition assessment using ADP is feasible in newborn preterm infants and provides group estimates similar to that of the reference fetus. In the future, integrating body composition information into the nutritional management of preterm infants may help to identify new strategies to optimize growth and development in this vulnerable population.

Inactivation of p53 and the development of tetraploidy in the elastase-SV40 T antigen transgenic mouse pancreas.

Human pancreatic cancer develops in association with an acquired genomic instability, but the events that lead to instability are difficult to investigate because they occur sporadically and unpredictably. The elastase-SV40 T antigen transgenic mouse model of pancreatic adenocarcinoma reproducibly proceeds through a diploid --> tetraploid --> multiple aneuploid sequence of genetic abnormalities. We investigated the relationship between inactivation of p53 and development of tetraploidy in this model. Because T antigen inactivates p53 by forming a stable complex with it, we used multiparameter flow cytometry to assess p53 expression in pancreatic samples of transgenic and control mice between 8 and 24 days of age. On day 18, a cell cycle-specific inactivation of p53 developed between diploid G, and S phase and was associated with the appearance of a cycling tetraploid cell population that had p53 protein overexpression in both G1- and S-phase cells. Cytogenetic analysis of pancreatic samples confirmed the development of a tetraploid cell population. Inactivation of p53 in diploid cells of the transgenic pancreas is followed by the development of a tetraploid cell population. We have shown previously that this tetraploid intermediate is predisposed to progression to aneuploidy because it has abnormal mitotic poles. Therefore, our results suggest that inactivation of p53 by T antigen leads to formation of a tetraploid cell intermediate that is predisposed to chromosome segregation abnormalities and the development of multiple aneuploid cell populations.

Symptoms, laryngeal findings, and 24-hour pH monitoring in patients with suspected gastroesophago-pharyngeal reflux.

OBJECTIVES: To investigate the laryngeal signs and symptoms associated with gastroesophago-pharyngeal reflux (GEPR). STUDY DESIGN: A prospective controlled study. METHODS: Nineteen healthy control subjects and 43 patients, 26 with posterior laryngitis (PL) and 17 with a normal larynx and suspected GEPR, were examined using videolaryngoscopy and 24-hour ambulatory dual-probe pH monitoring. RESULTS: Pharyngeal acid reflux occurred in 18 (69%) patients with PL, in 9 (53%) patients with a normal larynx, and in 5 (26%) healthy control subjects. Multiple-comparison procedure showed that pharyngeal reflux was significantly more prevalent in patients with PL than in the healthy control subjects (P < .05). The laryngoscopic findings in patients with pharyngeal reflux varied from normal mucosa to thickening or edema of the posterior wall of the glottis, which was the most frequent finding in the PL group. Erythema was uncommon; it was found only in patients with verified pharyngeal reflux. There was no difference in symptom profile between the patients with PL and patients with a normal larynx or patients with or without pharyngeal reflux. CONCLUSIONS: Pharyngeal reflux is significantly more prevalent in patients with posterior laryngitis than in healthy control subjects. Moreover, a certain degree of pharyngeal reflux appears to be a normal phenomenon. The most common laryngeal finding in patients with posterior laryngitis is thickening or edema of the posterior wall of the glottis. GEPR does not yield specific laryngeal symptoms. Thus, it is unreliable to base the reflux diagnosis on symptoms alone.

Comparison of laparoscopic and open Nissen fundoplication 2 years after operation. A prospective randomized trial.

BACKGROUND: Laparoscopic operation has replaced the conventional open procedure in the treatment of gastroesophageal reflux disease (GERD) in spite of the fact that long-term results based on controlled clinical trials have been lacking. The objective of this study was to compare outcome, quality of life, and patient satisfaction after laparoscopic and open Nissen fundoplication in a community hospital setting with a 2-year follow-up. METHODS: Forty-two patients with GERD were randomized to either laparoscopic (LNF) or open (ONF) Nissen fundoplication. Outcome evaluation included reflux symptoms, gastrointestinal quality of life (GIQLI), and upper GI endoscopy. RESULTS: Esophagitis was cured among all patients in the LNF group and in 90% of the ONF group. There were two patients (10%) in both groups who had medicine-dependent recurrent reflux together with significant worsening in the GIQLI scores. One patient in the LNF group has been reoperated due to a suture granuloma in the left epigastric port. Two patients in the LNF group needed esophageal dilatation due to persistent dysphagia. GIQLI scores (scale, 0-144) were equally normalized in both groups. Overall, 90% in the LNF and 100% in the ONF group were either satisfied or very satisfied with the operation. There was only one patient (LNF) who would not choose to have the operation again. CONCLUSIONS: Laparoscopic and open Nissen fundoplication seem to be equally effective methods for improving reflux symptoms and quality of life, resulting in a high rate of satisfaction among patients with an intermediate follow-up period of 2 years.

Is a dissection balloon beneficial in totally extraperitoneal endoscopic hernioplasty (TEP)? A randomized prospective multicenter study.

BACKGROUND: Laparoscopic hernioplasty has been criticized because of its technical complexity and increased costs. Disposable dissection balloons can be used to facilitate the creation of the initial working space in totally extraperitoneal endoscopic hernioplasty (TEP), but their use adds to the cost of the operation. METHODS: A total of 322 men with unilateral, primary, or recurrent inguinal hernias were randomized to undergo TEP with or without a dissection balloon. RESULTS: In the group with the balloon, three of 161 patients (2.5%) required conversion to transabdominal preperitoneal hernioplasty (TAPP), or open herniorraphy, whereas 17 of 161 patients (10.6%) were converted to TAPP or open herniorraphy in the group without the balloon (p = 0.002). The mean operation time was 55 min in the group with the balloon and 63 min in the group without the balloon (p = 0.004). There was no difference between them in postoperative morbidity, and there were no major complications in either group. The recurrence rate was 3.1% in the group with the balloon and 3.7 % in the group without the balloon (p = 0.8). CONCLUSION: The use of a dissection balloon in TEP reduces the conversion rate and may be especially beneficial early in the learning curve.

Is a dissection balloon beneficial in bilateral, totally extraperitoneal, endoscopic hernioplasty? A randomized, prospective, multicenter study.

SUMMARY: Laparoscopic hernioplasty has been criticized because of its technical complexity and increased costs. Disposable dissection balloons can be used to gain the initial working space in totally extraperitoneal endoscopic (TEP) hernioplasty, but this increases its cost. Forty-four men with bilateral, primary or recurrent inguinal hernias were randomized to undergo TEP with or without dissection balloon. There were two conversions to transabdominal preperitoneal hernioplasty, or open herniorrhaphy, in the group with balloon and four in the group without balloon. There was no difference in the postoperative morbidity or operation time between the two groups, and there were no major complications in either group. The recurrence rate was 4.3% in the group with the balloon and 7.1% in the group without the balloon. There were no statistically significant differences between the groups. Although our study population is too small to detect small differences between the groups, it seems that the use of a dissection balloon is not beneficial in a bilateral TEP.

Orthodontic treatment standards in a public group practice in Sweden.

The aim was to assess the orthodontic treatment service provided by 6 orthodontists in a group practice in Malmö. One hundred cases were randomly selected from the model store. The Index of Complexity, Outcome and Need (ICON) was used to assess the need, complexity of the problem, outcome, the degree of improvement and whether the completed case was acceptable or not. The reliability of the examiner using the ICON was assessed using Root Mean Square. Logistic regression analysis was employed to explore the variables related to acceptability of the finish and duration of treatment. The younger the patient at the start of treatment the lower initial ICON score, with short treatment duration were associated with an acceptable finish. Three out of 100 cases were deemed as not requiring orthodontic treatment and 36 cases were classified as very difficult to treat. Nevertheless, 71 cases out of the 100 exhibited acceptable finishes with 27 indicating substantial or great improvement. 6 cases finished treatment with ICON scores greater than 43 indicating need for orthodontic treatment. The treatment on average took 22 months. An objective appraisal of the quality of orthodontic care in a group practice in Malmö has been undertaken. Seventy-one cases were completed with acceptable occlusions. The Index of Complexity, Outcome and Need appears to be a valuable tool to assess the multiple facets of orthodontic provision.

[Simulator training in medicine and health care. A new pedagogic model for good patient safety]. / Simulatorträning inom medicinsk verksamhet. Ny pedagogisk modell för god patientsäkerhet.

Advanced simulation within medicine and health care is a rapidly growing field. Simulator based training can be applied in minimal invasive surgery, in endoscopic procedures as well as in anaesthesia and critical care management. At Huddinge University Hospital a center for advanced simulation of both endoscopic surgery and anaesthesia/critical care management is currently being set up. The objective is to focus on improved medical and health care training and thus improving patient safety by reducing medical errors.

Outpatient laparoscopic cholecystectomy. A prospective study with 100 consecutive patients.

One hundred patients with cholelithiasis were included in a prospective consecutive follow-up study to evaluate laparoscopic cholecystectomy in a day surgical setting. The median operating time was 70 min. In 96% of the patients, it was possible to perform peroperative cholangiography. The median time off work was 7 days and the median time to full recovery was 14 days. Five patients were admitted due to weakness/nausea. Six patients were admitted due to conversion to open surgery or choledocholithiasis. Eighty-nine patients were treated in ambulatory surgery. We conclude that laparoscopic outpatient cholecystectomy can be performed safely with a low unplanned admission rate.

Neonatal hyperglycemia and diminished long-term growth in very low birth weight preterm infants.

OBJECTIVE: To investigate the association between early hyperglycemia and growth and development from hospital discharge to 2 years corrected age (CA) in very low birth weight (VLBW) infants. STUDY DESIGN: Blood glucose levels during the first 14 days after birth, weight, length and occipital-frontal circumference (OFC) at birth, hospital discharge and 4, 12 and 24 months CA, Bayley developmental scores at 12 and 24 months CA, and information on multiple clinical variables were recorded on VLBW preterm infants (N=80). The relationships between hyperglycemia, growth and developmental scores were determined using linear mixed effects regression. RESULT: Hyperglycemia was a strong predictor of poor rate of increase in weight, length and OFC until 24 months CA. Hyperglycemia was not associated with lower scores on the Bayley scales. CONCLUSION: Neonatal hyperglycemia was associated with poor physical growth until at least 2 years CA in this cohort of VLBW preterm infants.

[Physical activity and exercise training for patients with cystic fibrosis]. / Activité physique et réentraînement à l'effort du patient atteint de mucoviscidose.

In France patients with cystic fibrosis benefit from a multidisciplinary follow-up in Cystic Fibrosis Centres. In this follow-up, despite the numerous therapeutic benefits of exercise in this disease, little emphasis is placed on the promotion of physical activity. The aim of this article is to improve this aspect of management, giving advice from a working group of experts, based on the medical literature and clinical experience. These proposals include quantification of physical activity, evaluation of exercise, training and rehabilitation programs and finally, modification of behaviour to include physical activity in the overall cystic fibrosis treatment strategy. It is intended to set up multicentre studies to evaluate the impact of these proposals.