Quality of life in children with hydrocephalus treated with endoscopic third ventriculostomy.

OBJECTIVE: The objectives of this study were to determine the quality of life of a pediatric cohort with hydrocephalus treated by endoscopic third ventriculostomy (ETV), using the Hydrocephalus Outcome Questionnaire-Spanish version (HOQ-Sv), and study the clinical and radiological factors associated with a better or worse functional status. METHODS: This cross-sectional study was undertaken between September 2018 and December 2019. It comprised a series of 40 patients ranging from 5 to 18 years old with hydrocephalus treated by ETV. ETV was considered to be successful if there was no need for surgery for the treatment of hydrocephalus after a minimum follow-up of 6 months. The clinical variables included gender, age at hydrocephalus diagnosis, age at the time of ETV, age at completion of the questionnaire, etiology and type of hydrocephalus (communicating or not), prior shunt, repeat ETV, number of neurosurgical procedures, number of epileptic seizures, presenting signs, and follow-up duration until last office revision. The radiological variables were the Evans Index and the pre- and posttreatment frontooccipital horn ratio. An analysis was conducted of the association between all these variables and the various dimensions on the HOQ-Sv, completed by the parents of the patients via telephone or in the outpatient offices. RESULTS: The mean age of the children at ETV was 7 years (range 7-194 months), and on completing the questionnaire was 12 years (range 60-216 months). The mean HOQ scores were as follows: overall 0.82, physical domain 0.86, social-emotional (SE) domain 0.84, cognitive domain 0.75, and utility score 0.90. A history of epileptic crises was a predictive factor for a worse score overall and in the SE and cognitive domains. Factors related to a worse score in the physical domain were a previous shunt, the number of procedures, and the etiology and type of hydrocephalus. The mean follow-up duration from ETV to the last office visit was 5 years (64.5 months). No association was found between the degree of ventricular reduction and the quality of life. CONCLUSIONS: The factors related to a worse score in the different dimensions of the HOQ were a history of epileptic seizures, the number of procedures, communicating hydrocephalus, and having had a previous valve. No association was found between the reduction in ventricular size and the quality of life as measured on the HOQ-Sv.

Effects of music therapy as an adjunct to chest physiotherapy in children with cystic fibrosis: A randomized controlled trial.

Airway clearance therapy (ACT) is considered an important approach to improve airway clearance in children with cystic fibrosis (CF). Daily ACT administration requires substantial commitments of time and energy that complicate ACT and reduce its benefits. It is crucial to establish ACT as a positive routine. Music therapy (MT) is an aspect of integrative strategies to ameliorate the psycho-emotional consequences of chronic diseases, and a MT intervention could help children with CF between the ages of 2 and 17 develop a positive response. The aim of this randomized controlled trial was to evaluate the effects of specifically composed and recorded instrumental music as an adjunct to ACT. We compared the use of specifically composed music (Treated Group, TG), music that the patient liked (Placebo Group, PG), and no music (Control Group, CG) during the usual ACT routine in children with CF aged from 2 to 17. The primary outcomes, i.e., enjoyment and perception of time, were evaluated via validated questionnaires. The secondary outcome, i.e., efficiency, was evaluated in terms of avoided healthcare resources. Enjoyment increased after the use of the specifically composed music (children +0.9 units/parents +1.7 units; p<0.05) compared to enjoyment with no music (0 units) and familiar music (+0.5 units). Perception of time was 11.1 min (±3.9) less than the actual time in the TG (p<0.05), 3.9 min (±4.2) more than the actual time in the PG and unchanged in the CG. The potential cost saving related to respiratory exacerbations was €6,704.87, while the cost increased to €33,524.35 in the CG and to €13,409.74 in the PG. In conclusion, the specifically composed, played and compiled instrumental recorded music is an effective adjunct to ACT to establish a positive response and is an efficient option in terms of avoided costs. Trial registered as ISRCTN11161411. ISRCTN registry (www.isrctn.com).

Label-free, High-Resolution Optical Metabolic Imaging of Human Cervical Precancers Reveals Potential for Intraepithelial Neoplasia Diagnosis.

While metabolic changes are considered a cancer hallmark, their assessment has not been incorporated in the detection of early or precancers, when treatment is most effective. Here, we demonstrate that metabolic changes are detected in freshly excised human cervical precancerous tissues using label-free, non-destructive imaging of the entire epithelium. The images rely on two-photon excited fluorescence from two metabolic co-enzymes, NAD(P)H and FAD, and have micron-level resolution, enabling sensitive assessments of the redox ratio and mitochondrial fragmentation, which yield metrics of metabolic function and heterogeneity. Simultaneous characterization of morphological features, such as the depth-dependent variation of the nuclear:cytoplasmic ratio, is demonstrated. Multi-parametric analysis combining several metabolic metrics with morphological ones enhances significantly the diagnostic accuracy of identifying high-grade squamous intraepithelial lesions. Our results motivate the translation of such functional metabolic imaging to in vivo studies, which may enable improved identification of cervical lesions, and other precancers, at the bedside.

Impact of Early Reoperation on the Prognosis of Patients Operated on for Glioblastoma.

BACKGROUND: The prognosis for patients with glioblastoma depends particularly on the degree of tumor resection. Patients with tumor remnants in postsurgical magnetic resonance imaging (<72 hours) may benefit from early reoperation. We present our results concerning the impact on overall survival (OS) and progression-free survival (PFS) of reoperation in patients who have already undergone surgery for glioblastoma. METHODS: This study included all patients who had undergone surgery for glioblastoma with control magnetic resonance imaging, who received adjuvant therapy as per the Stupp protocol, with a minimum follow-up of 24 months. We recorded the number of complete resections, partial resections, and early reoperations. We determined the impact on OS and PFS of the early reoperations and the functional status. We considered complete resection when the volume of the residual tumor was 0 cm3. RESULTS: A total of 112 patients were diagnosed with glioblastoma between March 2014 and March 2017. The study included 58 patients who fulfilled all the inclusion criteria. Complete resection was achieved in 24 patients (41.4%) and partial resection in 34 (58.6%). Of these 34 patients, 11 (32.35%) underwent early reoperation. The final result was complete resection in 58.62% of the patients. In the patients who underwent reoperation, OS and PFS were 30.3 months and 16.6 months compared with 12.7 months and 6.75 months in those without reoperation (P = 0.013 and P = 0.012). The functional prognosis was similar between the 2 groups. CONCLUSIONS: Early reoperation in patients with residual tumor improved OS and PFS without increasing the number of complications compared with the patients who did not undergo reoperation.

Imaging mitochondrial dynamics in human skin reveals depth-dependent hypoxia and malignant potential for diagnosis.

Active changes in mitochondrial structure and organization facilitate cellular homeostasis. Because aberrant mitochondrial dynamics are implicated in a variety of human diseases, their assessment is potentially useful for diagnosis, therapy, and disease monitoring. Because current techniques for evaluating mitochondrial morphology are invasive or necessitate mitochondria-specific dyes, their clinical translation is limited. We report that mitochondrial dynamics can be monitored in vivo, within intact human skin by relying entirely on endogenous two-photon-excited fluorescence from the reduced metabolic coenzyme nicotinamide adenine dinucleotide (NADH). We established the sensitivity of this approach with in vivo, fast temporal studies of arterial occlusion-reperfusion, which revealed acute changes in the mitochondrial metabolism and dynamics of the lower human epidermal layers. In vitro hypoxic-reperfusion studies validated that the in vivo outcomes were a result of NADH fluorescence changes. To demonstrate the diagnostic potential of this approach, we evaluated healthy and cancerous human skin epithelia. Healthy tissues displayed consistent, depth-dependent morphological and mitochondrial organization patterns that varied with histological stratification and intraepithelial mitochondrial protein expression. In contrast, these consistent patterns were absent in cancerous skin lesions. We exploited these differences to successfully differentiate healthy from cancerous tissues using a predictive classification approach. Collectively, these results demonstrate that our label-free, automated, near real-time assessments of mitochondrial organization-relying solely on endogenous contrast-could be useful for accurate, noninvasive in vivo diagnosis.

Consistency and distribution of reflectance confocal microscopy features for diagnosis of cutaneous T cell lymphoma.

Reflectance confocal microscopy (RCM) represents a noninvasive imaging technique that has previously been used for characterization of mycosis fungoides (MF) in a pilot study. We aimed to test the applicability of RCM for diagnosis and differential diagnosis of MF in a clinical study. A total of 39 test sites of 15 patients with a biopsy-proven diagnosis of either MF, parapsoriasis, Sézary syndrome, or lymphomatoid papulosis were analyzed for presence and absence of RCM features of MF. Cochran and Chi(2) analysis were applied to test the concordance between investigators and the distribution of RCM features, respectively. For selected parameters, the Cochran analysis showed good concordance between investigators. Inter-observer reproducibility was highest for junctional atypical lymphocytes, architectural disarray, and spongiosis. Similarly, Chi(2) analysis demonstrated that selected features were present at particularly high frequency in individual skin diseases, with values ranging from 73% to 100% of all examined cases.

Peritumoral clefting in basal cell carcinoma: correlation of in vivo reflectance confocal microscopy and routine histology.

BACKGROUND: Histopathologically, basal cell carcinoma (BCC) is characterized by basaloid tumor nodules of varying size showing peripheral palisading of cells and nuclei, and separation from surrounding stroma by optically empty appearing clefts. These are usually regarded as an artifact, occurring during routine tissue processing. Recently, reflectance confocal microscopy (RCM) has been applied for noninvasive, in vivo evaluation of BCC. Besides other features, small areas of low refractility separating tumor islands from the surrounding tissue can be observed in vivo, suggesting that the presence of amorphous material like mucin might be the causal factor for these clefts. METHODS: A total of 13 BCCs were studied by RCM and histopathological techniques. Staining was performed with Alcian blue for the detection of peritumoral mucin. Correlation between RCM images and histopathological samples was studied, and the diameter of hyporefractile areas on RCM as well as the thickness of peritumoral mucin was measured. RESULTS: Good correlation was seen between dark areas on RCM and thickness of peritumoral mucin with a mean diameter of 14 µm (RCM) and 11.44 µm (histopathology), respectively. Pearson correlation coefficient was 0.605 (p < 0.0001). CONCLUSIONS: Our results show that the peritumoral cleft-like spaces seen in BCC on histopathology exist in vivo, and correspond to the peritumoral mucin deposition.

Effects of a 1,450 nm diode laser on facial sebum excretion.

BACKGROUND AND OBJECTIVE: Laser therapy with a 1,450 nm diode laser is a clinically effective treatment for acne vulgaris, although the mechanism of action is unknown. To investigate this, we conducted a small, prospective, controlled clinical trial to assess this laser's effects on the facial sebum excretion rate (SER). MATERIALS AND METHODS: Fourteen healthy volunteers without active acne were enrolled in this study and received three laser treatments on test areas of the nose and forehead. Nine subjects completed the treatment regimen and were available for follow-up. SER was measured with Sebumeter prior to the first treatment, and at 1 week and 1 month after the third treatment. Photographs were taken and subjective assessment of skin oiliness and pore size determined by questionnaires at 1 month follow-up. RESULTS: No significant reduction in SER was observed comparing treated with control on all treatment sites (P>0.05) on the nose. Reduction in the absolute SER was observed for both test and control sites on the forehead, reaching significance on the treatment site (P = 0.04) and marginal significance on the control site (P = 0.08). CONCLUSION: While our study was designed to detect only large changes in SER, we conclude that three 1,450 nm laser treatment sessions did not cause marked changes in SER compared to the control (i.e., >44%). Thus, major destruction of sebaceous glands as a result of this treatment is unlikely. However, reduced sebum production was observed on both treatment and control sides at 1 month. Therefore alternative mechanisms should also be considered to explain the clinical efficacy of this treatment for acne vulgaris.

[Postoperative ureteral obstruction after endoscopic antireflux therapy]. / Reflujo vesicoureteral contralateral despues del tratamiento endoscópico del reflujo unilateral primario.

OBJECTIVES: To know the incidence of new contralateral VUR and its evolution in children with primary unilateral vesicoureteral reflux (VUR) managed with endoscopic treatment (ET). METHODS: During 7.5 years a total of 228 children with primary VUR underwent endoscopic implantation of bulking material, 90 of them (39.5%) have been unilateral. The inclusion criterion was: unilateral primary VUR managed with ET, without previously contralateral VUR. Collected data included: patient age, gender, indications for surgery, number of preoperative cystourethrograms, preoperative and new contralateral postoperative VUR grades, nephropathy in the ipsilateral or contralateral sides, type and volume of bulking material used, and VUR outcome. An update bibliographic review with methanalysis is also performed to compare results. RESULTS: Six children (6.7%) developed new contralateral VUR. Mean age was 3.3 years. Four patients were females and 2 males. The bulking material used was polydimethylsiloxane in one and Dextranomer/Non animal stabilished hyaluronic acid in 5. The initial grades of primary VUR were: II in 1 case, III in 3, and IV in 2. Four patients had previous history of bladder dysfunction. The new contralateral VUR was II in 5 and III in one. In 5 patients initial VUR persisted, always of lower grade than previously, and new contralateral VUR appeared. In one patient initial VUR disappeared and appeared in the contralateral side. Five patients were reinjected and VUR was cured, except one who is waiting for a new endoscopic procedure. One patient with grade II contralateral VUR is under observation. In the metanalysis performed nine issues have been found with an incidence of 8.2%. CONCLUSION: Contralateral VUR is a relatively frequent complication in unilateral primary VUR treated by endoscopic procedures (6.7%), but not enough as to perform bilateral endoscopic treatment in all unilateral VUR. Contralateral VUR etiology is not clear but bladder dysfunction can be an important factor.

Clinical applicability of in vivo reflectance confocal microscopy for the diagnosis of actinic keratoses.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) has been used for evaluation of the morphologic features of nonmelanoma skin cancer. The application of RCM for diagnosis of basal cell carcinoma has been reported; however, the evaluation of actinic keratoses (AKs) has only been the subject of preliminary studies. STUDY GOAL: The goal of this study was to evaluate the applicability of RCM in the diagnosis of AK in correlation with routine histology. MATERIALS AND METHODS: Forty-four Caucasians with a minimum of one AK participated in this study. Evaluation consisted of clinical examination, RCM, and routine histology, including a total of 46 AKs in the final analysis. Ten normal skin sites served as controls. RCM features of AK included parakeratosis, architectural disarray, and keratinocyte pleomorphism. Following blinded evaluations, sensitivity/specificity, kappa analysis, and Spearman's correlation were performed on all parameters. RESULTS: Sensitivity/specificity values of RCM features ranged from 80% to 98.6%. The presence of architectural disarray and cellular pleomorphism appeared to be the best predictor of AK. CONCLUSION: In summary, RCM may be a promising technology for the noninvasive detection of AK and as adjunct tool to clinical diagnosis and monitoring. However, the preliminary nature of this study warrants further investigations.

Prognostic value of serum angiogenic activity in colorectal cancer patients.

Angiogenesis, resulting from an imbalance between angiogenic activator factors and inhibitors, is required for tumour growth and metastasis. The determination of the circulating concentration of all angiogenic factors (activators and inhibitors) is not feasible at present. We have evaluated diagnostic and prognostic values of the measurement of serum angiogenic activity in colorectal carcinoma (CRC) patients. Serum proliferative activity (PA) on human umbilical vein endothelial cells (HUVEC) in vitro, and serum vascular endothelial growth factor (VEGF) levels were determined by ELISA in 53 patients with primary CRC, 16 subjects with non-neoplastic gastrointestinal disease (SC) and 34 healthy individuals. Data were compared with clinical outcome of the patients. Although serum from CRC patients significantly increased the PA of HUVEC, compared to culture control (HUVEC in medium + 10% foetal bovine serum (FBS); P < 0.001); our results indicate that serum PA in CRC patients was similar to that of SC or healthy individuals. There was no correlation between serum PA and circulating VEGF concentrations. Surgery produced a decrease of PA at 8 hrs after tumour resection in CRC patients compared to pre-surgery values (186 +/- 47 versus 213 +/- 41, P < 0.001). However, an increase in serum VEGF values was observed after surgery (280 [176-450] versus 251 [160-357] pg/ml, P = 0.004). Patients with lower PA values after surgery showed a worse outcome that those with higher PA values. Therefore, this study does not support a diagnostic value for serum angiogenic activity measured by proliferative activity on HUVEC but suggests it could have a prognostic value in CRC patients.

Long-pulsed neodymium:yttrium-aluminum-garnet laser treatment for port-wine stains.

OBJECTIVE: Laser treatment of port-wine stain (PWS) might be improved using a deeply penetrating wavelength. METHODS: PWSs in 17 patients were treated 3 times with a 595-nm pulsed dye laser (PDL) and a 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Fluences of 1.0, 0.8, and 0.6 times the minimum purpura dose (MPD) were used for Nd:YAG laser. Posttreatment biopsy specimens were taken. Blind assessment and quantitative analysis of PWS clearing were performed from digital photographs. RESULTS: MPD for Nd:YAG laser varied widely, from 40 to 250 J/cm 2 . Purpura lasted longer after PDL. Treatment achieved similar 50% to 75% clearing with both PDL and Nd:YAG laser at 1 MPD. Nd:YAG caused greater perivascular and epidermal injury. Scarring occurred in the only patient treated with a Nd:YAG fluence greater than 1 MPD. Patients preferred Nd:YAG laser because of their faster recovery. CONCLUSION: Nd:YAG laser used at MPD is as effective as PDL for treating PWS. Nd:YAG laser fluences higher than MPD may cause scarring.

Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study.

BACKGROUND: The current standard diagnostic procedure for basal cell carcinoma (BCC) is histologic examination after invasive biopsy. Reflectance-mode confocal microscopy (RCM) offers noninvasive high-resolution imaging of human skin in vivo. OBJECTIVE: The objective of this study was to explore the sensitivity and specificity of RCM for diagnosis of BCC. METHODS: This was a retrospective study of RCM images from 4 institutions of 152 skin lesions representing a variety of benign and malignant diagnoses. These 152 lesions were examined clinically, with biopsies recorded for all the 83 BCCs detected. Based on a previous study, a set of 5 histologically correlated confocal imaging criteria for diagnosing BCC was established, eg, the presence of elongated monomorphic nuclei. Blinded retrospective analysis of the images from the 152 lesions was carried out by a single novice reviewer to determine the sensitivity and specificity of these 5 RCM criteria for diagnosing BCC. The accuracy of combining the probability of BCC based on examination of clinical photographs with the predicted probability of BCC based on confocal criteria was also evaluated. RESULTS: The presence of two or more criteria is 100% sensitive for the diagnosis of BCC, and with 4 or more RCM criteria present the specificity was 95.7% and sensitivity was 82.9%. These results were found to have little variability across study sites and across BCC subtypes. The combination of RCM with photography-based predictions of clinical probability of BCC significantly improved the accuracy for noninvasive diagnosis of BCC. CONCLUSION: RCM offers a sensitive and specific tool for the noninvasive diagnosis of BCC in vivo.

Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin.

BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin. RESULTS: A significant decrease in erythema was found in PL-treated skin (P < .01). Histologically, PL-treated biopsy specimens showed less sunburn cells (P < .05), cyclobutane pyrimidine dimers (P < .001), proliferating epidermal cells (P < .001), and dermal mast cell infiltration (P < .05). A trend toward Langerhans cell preservation was seen. CONCLUSION: Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiation.

Reflectance confocal microscopy may differentiate acute allergic and irritant contact dermatitis in vivo.

BACKGROUND: Acute irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) may be difficult to distinguish by clinical or histologic assessment. Reflectance confocal microscopy (RCM) enables real-time, high-resolution skin imaging in vivo. OBJECTIVE: We sought to image, characterize, and distinguish acute ACD and ICD in vivo. METHODS: Volunteers with ACD were patch tested with an allergen and the irritant, sodium lauryl sulfate. RCM imaging and transepidermal water loss measurements were performed at 24 and 72 hours. Biopsy specimens were correlated with RCM images. RESULTS: Spongiosis, epidermal inflammatory cell infiltrate, and vesicle formation were observed in ACD and ICD. Compared with ACD, ICD showed greater disruption of the stratum corneum, and more parakeratosis. There was a significantly greater increase in transepidermal water loss for ICD compared with ACD. CONCLUSION: RCM is a promising tool for dynamic, noninvasive assessment and may help to differentiate acute ACD and sodium lauryl sulfate-induced ICD.

Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin.

BACKGROUND: The use of psoralen-UVA (PUVA) in patients of skin phototype I to II is limited by side effects of acute phototoxicity and possible long-term carcinogenesis. OBJECTIVE: We sought to assess oral Polypodium leucotomos (PL) extract in decreasing PUVA-induced phototoxicity of human skin on a clinical and histologic level. METHODS: A total of 10 healthy patients with skin phototypes II to III were exposed to PUVA alone (using 0.6 mg/kg oral 8-methoxypsoralen) and to PUVA with 7.5 mg/kg of oral PL. RESULTS: Clinically, phototoxicity was always lower in PL-treated skin after 48 to 72 hours (P<.005), and pigmentation was also reduced 4 months later. Histologically, PL-treated skin showed a significant numeric reduction of sunburn cells (P=.05), preservation of Langerhans cells (P< or =.01), decrease of tryptase-positive mast cell infiltration (P<.05), and decrease of vasodilation (P< or =.01). No differences were found in Ki-67+ proliferating cells. CONCLUSIONS: PL is an effective chemophotoprotector against PUVA-induced skin phototoxicity and leads to substantial benefits of skin protection against damaging effects of PUVA as evidenced by histology.