Achieving enteral nutrition during the acute phase in critically ill children: Associations with patient characteristics and clinical outcome.

BACKGROUND & AIMS: In the absence of methodologically sound randomized controlled trials (RCTs), current recommendations for timing and amount of enteral nutrition (EN) in critically ill children are based on observational studies. These studies have associated achievement of a higher EN intake in critically ill children with improved outcome. Inherent to the observational design of these underlying studies, thorough insight in possible confounding factors to correct for is essential. We evaluated the associations between EN intake and 1) patient and daily clinical characteristics and 2) clinical outcomes adjusted for these patient and clinical characteristics during the first week of critical illness with a multivariable mixed model. METHODS: This secondary analysis of the multicentre PEPaNIC RCT investigated a subgroup of critically ill children with daily prospectively recorded gastrointestinal symptoms and EN intake during the first week with multivariable analyses using two-part mixed effect models, including multiple testing corrections using Holm's method. These models combined a mixed-effects logistic regression for the dichotomous outcome EN versus no EN, and a linear mixed-effects model for the patients who received any EN intake. EN intake per patient was expressed as mean daily EN as % of predicted resting energy expenditure (% of EN/REE). Model 1 included 40 fixed effect baseline patient characteristics, and daily parameters of illness severity, feeding, medication and gastrointestinal symptoms. Model 2 included these patient and daily variables as well as clinical outcomes. RESULTS: Complete data were available for 690 children. EN was provided in 503 (73%) patients with a start after a median of 2 (IQR 2-3) days and a median % of EN/REE of 38.8 (IQR 14.1-79.5) over the first week. Multivariable mixed model analyses including all patients showed that admission after gastrointestinal surgery (-49%EN/REE; p = 0.002), gastric feeding (-31% EN/REE; p < 0.001), treatment with inotropic agents (-22%EN/REE; p = 0.026) and large gastric residual volume (-64%EN/REE; p < 0.001) were independently associated with a low mean EN intake. In univariable analysis, low mean EN intake was associated with new acquired infections, hypoglycaemia, duration of PICU and hospital stay and duration of mechanical ventilation. However, after adjustment for confounders, these associations were no longer present, except for low EN and hypoglycaemia (-39%EN/REE; p = 0.018). CONCLUSIONS: Several patient and clinical characteristics during the first week of critical illness were associated with EN intake. No independent associations were found between EN intake and clinical outcomes such as mortality, new acquired infection and duration of stay. These data emphasize the necessity of adequate multivariable adjustment in nutritional support research and the need for future RCTs investigating optimal EN intake.

Sperm DNA damage measured by sperm chromatin structure assay in men with a history of undescended testes.

The aim of this study was to compare sperm DNA damage between men with a history of congenital undescended testis (UDT) and men with a history of acquired UDT. A long-term follow-up study of men with previous UDT was performed. Fifty men with congenital UDT who had undergone orchiopexy at childhood age, 49 men with acquired UDT after a 'wait-and-see'-protocol (e.g. awaiting spontaneous descent until puberty and perform an orchiopexy in case of non-decent), and 22 healthy proven fertile men were included. The DNA fragmentation index (DFI) using sperm chromatin structure assay (SCSA) was used to express the level of sperm DNA damage. Decreased fertility potential was considered if DFI was above 30%. Sperm DNA damage was not statistically different between cases of congenital and acquired UDT. DFI was significantly more often >30% in the complete group of men with congenital UDT (9/50; 18%) and in the subgroup with bilateral congenital UDT (3/7; 43%) in comparison with the controls (none) (p-value 0.049 and 0.01, respectively). Age at orchiopexy in congenital UDT had no statistical effect on DNA damage. In men with acquired UDT, DFI did not statistically differ between those having undergone orchiopexy and those experiencing spontaneous descent. This study supports the hypothesis that UDT is a spectrum representing both congenital UDT and acquired UDT. Sperm DNA damage at adult age is not influenced by age at orchiopexy in congenital UDT cases and by orchiopexy or spontaneous descent in acquired UDT cases.

Scrotal ultrasound findings in previously congenital and acquired unilateral undescended testes and their contralateral normally descended testis.

The aim of this study was to report on different anomalies found by physical examination and scrotal ultrasound in men with previously unilateral congenital undescended testes (UDT; N = 50), acquired UDT (N = 49), their contralateral normally descended testis (CNDT) and control testes (N = 53). Acquired UDT significantly more often had a testicular volume being <15 mL than congenital UDT (88% vs. 68%). In the congenital group, significant differences were found between UDT and CNDT for soft consistency (UDT 36% vs. CNDT 14%), epididymal diameter (UDT 7.6 mm vs. CNDT 8.9 mm), testicular volume (UDT 9.8 mL vs. CNDT 13.8 mL), and inhomogeneous parenchyma (UDT 38% vs. CNDT 14%). In the acquired group, significant differences were found between UDT and CNDT for epididymal diameter (UDT 7.5 mm vs. CNDT 8 mm), testicular volume (UDT 9.3 mL vs. CNDT 14.1 mL), testicular volume <15 mL (UDT 88% vs. CNDT 59%), and inhomogeneous parenchyma (UDT 27% vs. CNDT 6%). The following parameters of congenital UDT, acquired UDT, congenital CNDT, and/or acquired CNDT significantly differed compared with controls: soft testicular consistency (congenital UDT 36%, acquired UDT 20%, congenital CNDT 14%, acquired CNDT 12% vs. controls 0%), epididymal diameter (congenital UDT 7.6 mm, acquired UDT 7.5 mm, acquired CNDT 8 mm vs. controls 9.2 mm), testicular volume (congenital UDT 9.8 mL, acquired UDT 9.3 mL, congenital CNDT 13.8 mL, acquired CNDT 14.1 mL vs. control testes 15.8 mL), testicular volume <15 mL (congenital UDT 68%, acquired UDT 88%, congenital CNDT 66% vs. controls 43%), inhomogeneous parenchyma (congenital UDT 38%, acquired UDT 27%, congenital CNDT 14% vs. controls 0%), and testicular microlithiasis (congenital CNDT 24% vs. control testes 8%). Few differences between congenital and acquired unilateral UDT and congenital and acquired CNDT support the hypothesis of a spectrum of maldescended testes containing congenital and acquired UDT instead of them being two different entities. The CNDT also has anomalies albeit less severe than the UDT, indicating that in unilateral UDT both testes are affected.

Acquired undescended testes and fertility potential: is orchiopexy at diagnosis better than awaiting spontaneous descent?

The aim of this study was to evaluate testicular function in men with previous acquired undescended testis (UDT) in whom orchiopexy was performed at diagnosis compared with a similar group of men in whom spontaneous descent was awaited until puberty. Secondly, we examined the influence of age at orchiopexy on fertility parameters in adult life. A total of 169 men of the 'orchiopexy at diagnosis' group and 207 men of the 'wait and see' protocol group were invited for participation. All participants underwent an andrological evaluation, including medical history, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Results were compared for men in whom orchiopexy was performed at diagnoses with men in whom spontaneous descent was awaited until puberty followed by orchiopexy in case of non-descent. In the 'orchiopexy at diagnosis' group, 63 men of whom 14 with bilateral UDT, and in the 'wait and see' protocol group, 65 men of whom 15 with bilateral UDT were included. For unilateral UDT Inhibin B was found to be significantly lower and median progressive motility was higher in men with orchiopexy at diagnosis. For bilateral UDT, semen concentration and progressive motility showed a trend toward a favorable outcome for orchiopexy at diagnosis. Age at orchiopexy being under or above 10 years of age had no significant influence on the fertility potential. The outcome of physical examination, scrotal ultrasound, endocrine function, and semen analysis indicates a compromised fertility potential in men with previous acquired UDT. None of the protocols proved to be superior. For bilateral UDT, a trend toward favorable outcome of orchiopexy at diagnosis was seen. Furthermore, age at orchiopexy did not have an influence on fertility parameters. Therefore, in our opinion a 'conservative policy' is warranted for unilateral UDT, especially because over 50% of acquired UDT descend spontaneously.

Fertility potential in men with a history of congenital undescended testes: a long-term follow-up study.

Men with a history of congenital undescended testes (UDT) have an increased risk of fertility problems. Despite no definitive proof, current guidelines recommend early surgical intervention because this may have a positive effect on future fertility potential by preventing degenerative changes of the testes in early life. Also surgical intervention facilitates observability of the testes in view of possible malignancy. We evaluated testicular function in adult men with previous UDT treated at different ages before puberty. A long-term follow-up study of men with previous UDT was performed. Andrological evaluation included medical history taking, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Findings were compared with those of a control group of men with normal testicular descent. The influence of age at orchiopexy on future fertility parameters was evaluated in a multivariate regression analysis. 62 men were included of whom seven had had bilateral UDT. Twenty-four patients had had their orchiopexy before the age of 24 months of whom eight men had it before 12 months of age. Forty-eight men had had unsuccessful luteinizing-hormone-releasing-hormone (LHRH) nasal spray treatment during childhood, whereas 14 of 24 men operated before 24 months of age had not received LHRH treatment before orchiopexy. Fertility potential in men with a history of UDT is compromised in comparison with controls. We could not detect any influence of age at orchiopexy on fertility parameters. However, the number of patients operated before the age of 12 months is limited. This study does not support the assumption that early orchiopexy results in better fertility potential.

Surgical findings in acquired undescended testis: an explanation for pubertal descent or non-descent?

AIM: Surgical findings were studied to find an explanation for the phenomenon that some acquired undescended testes (UDT) descend spontaneously whereas others need orchiopexy. METHODS: In patients with acquired UDT spontaneous descent was awaited until at least Tanner stage P2G2. Orchiopexy was performed when a stable scrotal position had not been achieved by the end of follow-up. RESULTS: Orchiopexy was needed in 57 of 132 cases (43%). In cases requiring orchiopexy, the difference in testis volume compared to the contralateral healthy testis was significantly larger than for spontaneously descended testes. 41 (72%) undescended testes were found in the superficial inguinal pouch; 16 (28%) at the external annulus. 26 of the 41 testes in the superficial inguinal pouch position (63%) could be manipulated preoperatively into a non-stable scrotal position; 15 could only reach the scrotal entrance prior to surgery. None of the 16 testes located at the external annulus could reach a scrotal position. Inguinal exploration in most cases revealed a fibrous string or a partially open processus vaginalis. CONCLUSION: The mobility of acquired UDT located within the external annulus is limited. It is mainly the fibrous string and the partially open processus vaginalis that prevent normal elongation of the spermatic cord with growth. These testes are unlikely to descend spontaneously. Acquired UDT lying in the superficial inguinal pouch can often be pushed down well below the scrotal entrance. We speculate that under normal hormonal stimulation at puberty, some of these growing testes may overcome the strength of the fibrous string in the spermatic cord and descend again spontaneously.

The ignis fatuus of reduction and unification: back to the rough ground.

Given the enormous variety of possible intertheoretical relations, the proliferation of definitions of reduction, supervenience, emergence, unification, and so on, as well as the fact that empirical studies have provided support for almost any metaphysical option or, alternatively, have shown rather conclusively that empirically the case is inconclusive, I suggest a moratorium on the use of words such as "reduction," "supervenience," and "unification" and to go back to the rough ground and give perspicuous renderings of the practice of chemistry. What is needed are very detailed case studies and further discussions about them, instead of bickering about whether chemistry can be reduced to physics, supervenes on it, can be unified with it, and similar "metaphysical" concerns.

Are there nontrivial constraints on colour categorization?

In this target article the following hypotheses are discussed: (1) Colour is autonomous: a perceptuolinguistic and behavioural universal. (2) It is completely described by three independent attributes: hue, brightness, and saturation: (3) Phenomenologically and psychophysically there are four unique hues: red, green, blue, and yellow; (4) The unique hues are underpinned by two opponent psychophysical and/or neuronal channels: red/green, blue/yellow. The relevant literature is reviewed. We conclude: (i) Psychophysics and neurophysiology fail to set nontrivial constraints on colour categorization. (ii) Linguistic evidence provides no grounds for the universality of basic colour categories. (iii) Neither the opponent hues red/green, blue/yellow nor hue, brightness, and saturation are intrinsic to a universal concept of colour. (iv) Colour is not autonomous.