Serum Isoform [−2]proPSA Derivatives Significantly Improve Prediction of Prostate Cancer at Initial Biopsy in a Total PSA Range of 2–10 ng/ml: A Multicentric European Study

Background

Strategies to reduce prostate-specific antigen (PSA)–driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary.

Objective

To test the accuracy of serum isoform [−2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)—called index tests—in discriminating between patients with and without PCa.

Design, setting, and participants

This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2–10 ng/ml who were subjected to initial prostate biopsy for suspected PCa.

Outcome measurements and statistical analysis

The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis.

Results and limitations

Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p = 0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p < 0.001), %fPSA (0.14 vs 0.17; p < 0.001), %p2PSA (2.1 vs 1.6; p < 0.001), and PHI (48.2 vs 38; p < 0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p < 0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values.

Conclusions

In patients with a tPSA range of 2–10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.

Trial registration

The study is registered at http://www.controlled-trials.com, ref. ISRCTN04707454.     

Reflux-Associated Oxygen Desaturations: Usefulness in Diagnosing Reflux-Related Respiratory Symptoms

Background

Current diagnostic techniques establishing gastroesophageal reflux disease as the underlying cause in patients with respiratory symptoms are poor. Our aim was to provide additional support to our prior studies suggesting that the association between reflux events and oxygen desaturations may be a useful discriminatory test in patients presenting with primary respiratory symptoms suspected of having gastroesophageal reflux as the etiology.

Methods

Thirty-seven patients with respiratory symptoms, 26 with typical symptoms, and 40 control subjects underwent simultaneous 24-h impedance–pH and pulse oximetry monitoring. Eight patients returned for post-fundoplication studies.

Results

The median number (interquartile range) of distal reflux events associated with oxygen desaturation was greater in patients with respiratory symptoms (17 (9–23)) than those with typical symptoms (7 (4–11, p?<?0.001)) or control subjects (3 (2–6, p?<?0.001)). A similar relationship was found for the number of proximal reflux-associated desaturations. Repeat study in seven post-fundoplication patients showed marked improvement, with reflux-associated desaturations approaching those of control subjects in five patients; 20 (9–20) distal preoperative versus 3 (0–5, p?=?0.06) postoperative; similar results were identified proximally.

Conclusions

These data provide further proof that reflux-associated oxygen desaturations may discriminate patients presenting with primary respiratory symptoms as being due to reflux and may respond to antireflux surgery.     

MAASH Technique for Total Hip Arthroplasty: A Capsular Work

Background

Dislocation and leg length discrepancy are major complications following total hip arthroplasty (THA). Many surgical approaches for THA have been described, but none suggest a capsular incision that assures good exposure while maintaining adequate capsule integrity in closure.

Purposes

Modified anterolateral approach for stable hip (MAASH) is a modification of the classical Hardinge approach, but specifically preserves the anterior iliofemoral lateral ligament and pubofemoral ligament excising the “weak area” of the capsule, in the so called “internervous safe zone” and introducing the “box concept” for the anterior approach to the hip. This is the main difference of the MAASH approach. This technique can be used as a standard for all THA standard models, but we introduce new devices to make it easier.

Methods

From November 2007 to May 2012, data were collected for this observational retrospective consecutive case study. We report the results of 100 THA cases corresponding to the development curve of this new concept in THA technique.

Results

MAASH technique offers to hip surgeons, a reliable and reproducible THA anterolateral technique assuring accurate reconstruction of leg length and a low rate of dislocation. Only one dislocation and six major complications are reported, but most of them occurred at the early stages of technique development.

Conclusion

MAASH technique proposes a novel concept on working with the anterior capsule of the hip for the anterolateral approach in total hip arthroplasty, as well as for hemiarthroplasty in the elderly population with high dislocation risk factors. MAASH offers maximal stability and the ability to restore leg length accurately.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9332-1) contains supplementary material, which is available to authorized users.     

Excitatory actions of GABA in developing chick vestibular afferents: Effects on resting electrical activity

The aim of this study was to characterize the effect of γ-aminobutyric acid (GABA) in the resting multiunit activity of the vestibular afferents during development using the isolated inner ear of embryonic and postnatal chickens (E15-E21 and P5). GABA (10⁻³ to 10⁻⁵ M; n = 133) and muscimol (10⁻³M) elicited an increase in the frequency of the basal discharge of the vestibular afferents. We found that GABA action was dose-dependent and inversely related to animal age. Thus, the largest effect was observed in embryonic ages such as E15 and E17 and decreases in E21 and P5. The GABA_A receptor antagonists, bicuculline (10⁻⁵M; n = 10) and picrotoxin (10⁻⁴M; n = 10), significantly decreased the excitatory action of GABA and muscimol (10⁻³M). Additionally, CNQX 10⁻⁶M, MCPG 10⁻⁵M and 7ClKyn 10⁻⁵M (n = 5) were co-applied by bath substitution (n = 5). Both the basal discharge and the GABA action significantly decreased in these experimental conditions. The chloride channel blocker 9-AC 0.5 mM produced an important reduction in the effect of GABA 10⁻³ (n = 5) and 10⁻⁴M (n = 5). Thus, our results suggest an excitatory role of GABA in the resting activity of the vestibular afferents that can be explained by changes in the gradient of concentration of Cl⁻ during development. We show for the first time that the magnitude of this GABA effect decreases at later stages of embryonic and early postnatal development. Taking into account the results with glutamatergic antagonists, we conclude that GABA has a presynaptic action but is not the neurotransmitter in the vestibular afferent synapses, although it could act as a facilitator of the spontaneous activity and may regulate glutamate release. Synapse 67:374–381, 2013. © 2013 Wiley Periodicals, Inc.     

Reliability and Validity of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Portuguese Version

This study examined the test–retest reliability, consensual, convergent and divergent validities, sensitivity, specificity, positive and negative predictive values, and accuracy of the Portuguese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Eighty-nine children/adolescents (65 psychiatric outpatients and 24 healthy controls) were interviewed with K-SADS-PL and completed measures of depressive and anxiety symptoms. The child’s parent/caretaker completed the Child Behavior Checklist. Good to excellent values were obtained for test–retest reliability and consensual validity. For the convergent validity, moderate correlations between the K-SADS-PL and the corresponding self-report measures were observed. Divergent validity was acceptable for the K-SADS-PL diagnoses. The lowest values of sensitivity, specificity, and accuracy of the K-SADS-PL were 88, 88, and 91, respectively. The Portuguese version of K-SADS-PL proved to be a valid and reliable assessment instrument for children and adolescents, and was sensitive, specific and accurate when diagnosing mood, anxiety, adjustment, and attention-deficit/hyperactivity disorders.

     

The Effects of Bariatric Surgery-Induced Weight Loss on Adipose Tissue in Morbidly Obese Women Depends on the Initial Metabolic Status

Background

Adipose tissue (AT) dysfunction in obesity is commonly linked to insulin resistance and promotes the development of metabolic disease. Bariatric surgery (BS) represents an effective strategy to reduce weight and to improve metabolic health in morbidly obese subjects. However, the mechanisms and pathways that are modified in AT in response to BS are not fully understood, and few information is still available as to whether these may vary depending on the metabolic status of obese subjects.

Methods

Abdominal subcutaneous adipose tissue (SAT) samples were obtained from morbidly obese women (n?=?18) before and 13.3?±?0.37 months after BS. Obese women were stratified into two groups: normoglycemic (NG; Glu?<?100 mg/dl, HbA1c <5.7 %) or insulin resistant (IR; Glu 100–126 mg/dl, HbA1c 5.7–6.4 %) (n?=?9/group). A multi-comparative proteomic analysis was employed to identify differentially regulated SAT proteins by BS and/or the degree of insulin sensitivity. Serum levels of metabolic, inflammatory, and anti-oxidant markers were also analyzed.

Results

Before surgery, NG and IR subjects exhibited differences in AT proteins related to inflammation, metabolic processes, the cytoskeleton, and mitochondria. BS caused comparable weight reductions and improved glucose homeostasis in both groups. However, BS caused dissimilar changes in metabolic enzymes, inflammatory markers, cytoskeletal components, mitochondrial proteins, and angiogenesis regulators in NG and IR women.

Conclusions

BS evokes significant molecular rearrangements indicative of improved AT function in morbidly obese women at either low or high metabolic risk, though selective adaptive changes in key cellular processes occur depending on the initial individual’s metabolic status.