Management of ventriculomegaly in pediatric patients with syndromic craniosynostosis: a single center experience.

INTRODUCTION: Management of ventriculomegaly in pediatric patients with syndromic craniosynostosis (SC) requires understanding the underlying mechanisms that cause increased intracranial pressure (ICP) and the role of cerebrospinal fluid (CSF) in cranial vault expansion in order to select the best treatment option for each individual patient. METHODS: A total of 33 pediatric patients with SC requiring craniofacial surgery were retrospectively evaluated. Cases of nonsyndromic craniosynostosis and shunt-induced craniosynostosis were excluded. Six syndrome-based categories were distinguished: Crouzon syndrome, Pfeiffer syndrome, Apert syndrome, cloverleaf skull syndrome, and others (Muenke syndrome, Sensenbrenner syndrome, unclassified). All of the patients were treated surgically for their cranial deformity between 2010 and 2016. The presence of ventriculomegaly and ventriculoperitoneal (VP) shunt requirement with its impact in cranial vault expansion were analyzed. Clinical and neuroimaging studies covering the time from presentation through the follow-up period were revised. The mean postoperative follow-up was 6 years and 3 months. A systematic review of the literature was conducted through a PubMed search. RESULTS: Of the total of 33 patients with SC, 18 (54.5%) developed ventriculomegaly and 13 (39.4%) required ventriculoperitoneal (VP) shunt placement. Six patients (18.2%) required shunt placement previous to craniofacial surgery. Seven patients (21.2%) required a shunt after craniofacial surgery. Seven fixed pressure ventriculoperitoneal shunts and six programmable valves were placed as first choice. All patients improved their clinical symptoms after shunt placement. Aesthetic results seemed to be better in patients with programmable shunts. CONCLUSIONS: Unless clear criteria for overt hydrocephalus are present, it is recommended to perform craniofacial surgery as a first step in the management of patients with SC in order to preserve the expansive effect of CSF for cranial vault expansion. In our experience, the use of externally programmable valves allows for the treatment of hydrocephalus while maintaining the expansive effect of CSF for the remodeling of the cranial vault. Prospective evaluations are needed to determine causality.

GRB 090423 at a redshift of z approximately 8.1.

Gamma-ray bursts (GRBs) are produced by rare types of massive stellar explosion. Their rapidly fading afterglows are often bright enough at optical wavelengths that they are detectable at cosmological distances. Hitherto, the highest known redshift for a GRB was z = 6.7 (ref. 1), for GRB 080913, and for a galaxy was z = 6.96 (ref. 2). Here we report observations of GRB 090423 and the near-infrared spectroscopic measurement of its redshift, z = 8.1(-0.3)(+0.1). This burst happened when the Universe was only about 4 per cent of its current age. Its properties are similar to those of GRBs observed at low/intermediate redshifts, suggesting that the mechanisms and progenitors that gave rise to this burst about 600,000,000 years after the Big Bang are not markedly different from those producing GRBs about 10,000,000,000 years later.

Necessity of therapy for post-thyroidectomy hypocalcaemia: a multi-centre experience.

PURPOSE: Hypoparathyroidism is one of the most common and most feared complications of total thyroidectomy (TT). The aim of this study is to detect possible markers that may facilitate early tracing of hypocalcaemia-prone patients in order to reduce clinical cost by optimizing patient discharge and to avoid unnecessary treatment. METHODS: Over an 18-month period, 995 patients, 23 % male and 77 % female, aged 52.9 ± 13.4 years, underwent TT in ten Lombardy hospitals. The following parameters were analyzed: calcaemia before and 12-24 and 48 h after surgery, pre- and post-operative parathyroid hormone (PTH) at 24 h and pre-operative 25OH vitamin D. RESULTS: Mortality was nil and morbidity was 22.4 %. Mean 24-h calcaemia and PTH were 2.17 ± 0.15 mmol/l and 31.81 ± 20.35 pg/ml, respectively; mean 24-h PTH decay was 36.7 ± 34.12 %. Four hundred seventy-three (47.5 %) patients were hypocalcaemic at discharge; 142 of whom had transient hypoparathyroidism that became permanent in 27. Patients developing hypocalcaemia had significantly higher values of PTH and calcium decay. At multiple logistic regression, only 24-h calcium decay, PTH drop and the presence of symptoms and parathyroid auto-grafting were significantly related to hypoparathyroidism. The association of these factors had a 99.2 % negative predictive value (NPV) for the development of hypoparathyroidism. A 70 % PTH drop had a 93.75 NPV for transient hypoparathyroidism. A 12 % calcaemia decay had a 95.7 NPV for hypoparathyroidism. CONCLUSIONS: Hypocalcaemic asymptomatic patients with less than 70 % PTH and 12 % calcaemia decay may be safely discharged without treatment. Symptomatic patients and those with parathyroid grafting should receive calcium and vitamin D.

An enigmatic long-lasting gamma-ray burst not accompanied by a bright supernova.

Gamma-ray bursts (GRBs) are short, intense flashes of soft gamma-rays coming from the distant Universe. Long-duration GRBs (those lasting more than approximately 2 s) are believed to originate from the deaths of massive stars, mainly on the basis of a handful of solid associations between GRBs and supernovae. GRB 060614, one of the closest GRBs discovered, consisted of a 5-s hard spike followed by softer, brighter emission that lasted for approximately 100 s (refs 8, 9). Here we report deep optical observations of GRB 060614 showing no emerging supernova with absolute visual magnitude brighter than M(V) = -13.7. Any supernova associated with GRB 060614 was therefore at least 100 times fainter, at optical wavelengths, than the other supernovae associated with GRBs. This demonstrates that some long-lasting GRBs can either be associated with a very faint supernova or produced by different phenomena.

Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study.

BACKGROUND: Myocardial ischemic damage is reduced by volatile anaesthetics in patients undergoing low-risk coronary artery bypass graft surgery; few and discordant results exist in other settings. We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery. METHODS: Patients with coronary artery disease undergoing mitral surgery were randomly allocated to receive either sevoflurane (50 patients) or propofol (50 patients) as main hypnotic. The primary endpoint of the study was peak post-operative cardiac troponin release defined as the maximum value among the post-operative values measured at intensive care unit arrival, 4 h later, on the first and second post-operative day. RESULTS: There was no significant difference in post-operative peak troponin release, the median (25th-75th percentiles) values being 14.9 (10.1-22.1) ng/ml and 14.5 (8.8-17.6) ng/ml in the sevoflurane and propofol groups, respectively (P = 0.4). Fentanyl administration was different between the two groups: 1347 ± 447 µg in patients receiving sevoflurane and 1670 ± 469 µg in those receiving propofol, P = 0.002. The 1-year follow-up identified two patients who died in the propofol group (one myocardial infarction and one low cardiac output syndrome) and one in the sevoflurane group (myocardial infarction). CONCLUSION: In this study, patients with coronary artery disease undergoing mitral surgery did not benefit from the cardioprotective properties of halogenated anaesthetics. Sevoflurane anaesthesia was not associated to lower cardiac troponin release when compared with propofol anaesthesia.

Aflibercept, ranibizumab and bevacizumab upcoming biosimilars: a general overview.

Anti-vascular endothelial growth factors currently are the first-line treatment option for neovascular age-related macular degeneration (nAMD) and other retinal vascular disorders, and their clinical use is associated with high financial burden. Biosimilars are a type of biological product highly similar to referral biologic drugs; they are increasing competition among biologics and have the potential to reduce the overall expenditures on biologics. In this comprehensive literature review, the current investigational biosimilars acting on retinal diseases are discussed. The authors review the results of clinical studies and highlight ongoing trials. Several biosimilar candidates are under evaluation and the pipeline will rapidly change in the future, as soon as each patent expires. Clinicians have to know these new therapeutic agents, which might come in the mainstream clinical practice as a more cost-efficient option.

An update on ripasudil for the treatment of glaucoma and ocular hypertension.

Ripasudil (K-115) is a novel Rho-associated protein kinase (ROCK) inhibitor. The Rho-ROCK pathway regulates key downstream effectors involved in many cellular functions, in particular in the actin cytoskeleton activity. The clinical effects of ripasudil expected on the eye include an intraocular pressure-lowering effect and a wound-healing activity on corneal endothelial cells, but many other functions are currently under investigation. To date, ripasudil has been approved in Japan (2014) for the treatment of glaucoma and ocular hypertension, and several clinical trials are currently investigating its role in the treatment of Fuchs' corneal dystrophy. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile.

Nonsteroidal antiinflammatory drugs for cancer pain: comparison between misoprostol and ranitidine in prevention of upper gastrointestinal damage.

PURPOSE: The prophylactic strategy of nonsteroidal antiinflammatory drug (NSAID)-induced upper gastrointestinal (UGI) damage has largely been studied in arthritic patients, but not in cancer patients. The efficacy of misoprostol and ranitidine in the prevention of gastroduodenal damage in patients taking diclofenac for their cancer pain has been compared in this study. PATIENTS AND METHODS: Patients who needed high-dose (200 to 300 mg/d) diclofenac for cancer pain and without mucosal lesions at baseline gastroduodenal endoscopy were randomized to receive misoprostol (200 micrograms twice daily; M group) or ranitidine (150 mg twice daily; R group). UGI endoscopy was repeated after 4 weeks. RESULTS: Twenty-three patients treated with misoprostol and 26 treated with ranitidine concluded the study. The M group showed a significantly (P < .02) lower incidence of gastroduodenal lesions (two patients; 8.7%) than the R group (10 patients; 38.5%). Gastric ulcers occurred in one (4%) misoprostol-treated patient and in six (23%) ranitidine-treated patients. Six of seven patients with ulcers were asymptomatic. Seventy-one percent and 86% of ulcers occurred in patients older than 60 years and in those who received greater than 3.1 mg/kg of diclofenac, respectively. CONCLUSION: Misoprostol was significantly more effective than ranitidine in the prevention of gastroduodenal lesions in cancer patients receiving diclofenac.

Central venous thrombosis: an early and frequent complication in cancer patients bearing long-term silastic catheter. A prospective study.

Studies on catheter-related central venous thrombosis (CRCVT) have been focused mainly on clinically evident CRCVT due to occlusive thrombi, underestimating therefore the actual thrombosis prevalence. This prospective study was aimed at evaluating prevalence, timing and evolution of thrombosis, and identifying involved veins and risk factors in cancer patients (pts) undergoing percutaneous subclavian central venous catheterization (CVC) for chemotherapy, parenteral nutrition or both. We enrolled 127 consecutive pts requiring partially or totally implanted central venous silastic catheters. The study protocol included peripheral phlebography (P) at day 8, 30 and every two months following CVC and/or when clinically indicated, along with peripheral and pullout P on catheter withdrawal. A quantitative scale was developed to evaluate thrombus grading in subclavian, innominate and cava veins. Age, sex, coagulation profile tumor histotype, metastases, therapy, catheter type, and catheter insertion side were also investigated. Only pts who underwent at least two P were evaluated, and chi 2 test was adopted for statistical analysis. Altogether, 95 pts were evaluable. CRCVT was observed in 63/95 (66%) pts. At day 8, 30 and 105 (representing the median days in which first, second and last P were performed) CRCVT was evidenced in 64%, 65% and 66% of the pts, respectively. Thrombus grading did not differ among first, second and last P. CRCVT was symptomatic in 4/63 (6%) pts. Thrombosis prevalence was higher in subclavian (97%) with respect to innominate (60%) or cava (13%) veins (p < 0.001). Thrombosis was higher in left subclavian catheters (14/16; 87.5%) than in right ones (49/79; 62%), p < 0.01. No associations were established between CRCVT and other investigated parameters. Our data show a very high actual frequency of CRCVT in cancer pts, and emphasize that first days following CVC are at the highest risk for CRCVT development. Based on our results, a study on short-term antithrombotic prophylaxis in cancer pts requiring CVC is warranted. Finally, our data indicate that left subclavian vein catheterization represents a risk factor for CRCVT.

Antithrombin III deficiency as a risk factor for catheter-related central vein thrombosis in cancer patients.

The fibrin sleeve of venous catheters (VC) and parietal thrombi represent frequent and dangerous side-effects of central venous catheterization (CVC), due to the risk of embolism. Reduced levels of coagulation clotting factors inhibitors (such as Antithrombin III) are known to be associated with increased thrombogenic risk. The aim of this study was to evaluate the role of Antithrombin III (AT III) deficiency as a risk factor for thrombosis in cancer patients undergoing CVC. The study groups included patients with a reduced AT III activity (< 70%, 20 consecutive patients) and with normal AT III values (> 70%, 20 randomly selected patients), requiring a VC for chemotherapy and/or total parenteral nutrition. The study protocol included evaluation of Hb, PLTs, PT (INR), aPTT, Fibrinogen and AT III at days 0, 1, 3 and 8 after CVC and upon VC removal. Peripheral and pullout phlebographies were performed in all patients on catheter withdrawal. A quantitative scale was developed to evaluate both VC and parietal thrombus degree in each catheter-containing venous segment (subclavian, innominate, superior vena cava); the sum of the mean values was defined as overall thrombus. The average VC dwelling time was similar in both groups. There were no significant differences in Hb, PLTs, PT (INR), aPTT, Fibrinogen and in the remaining parameters of the study between the two groups. The group with AT III deficiency presented a higher degree of both parietal (p < 0.05) and overall thrombus (p < 0.02). Data showed a higher severity of CVC-related thrombosis in patients with AT III deficiency than in the control group. Further studies are needed to evaluate whether the therapeutically-induced normalization of AT III levels can reduce the thrombosis degree.

Mediopatellar synovial plica of the knee in athletes: results of arthroscopic treatment.

The long-term results (9-87 months) of the arthroscopic treatment of unilateral mediopatellar synovial plica of the knee in 102 athletes are reported. In all patients a large and/or fibrotic inflamed mediopatellar plica impinging on the femoral condyle on knee flexion was identified and trimmed. Chondromalacia patellae was detected in 38 patients. The impingement lesion was seen in 13 knees. In one patient, a minor tear of the lateral meniscus was trimmed, and one patient was found to suffer from a clinically asymptomatic partial tear of the anterior cruciate ligament. Isometric strength testing of the quadriceps revealed marked decrease at the second postoperative week, with subsequent gradual recovery. The results obtained justify arthroscopic treatment in a young, extremely active population.

Ultrasound-guided percutaneous longitudinal tenotomy for the management of patellar tendinopathy.

Thirty-eight athletes with unilateral patellar tendinopathy (17 with a tendinopathy of the main body of the tendon, and 21 with an insertional tendinopathy) underwent ultrasound-guided multiple percutaneous longitudinal tenotomy under local anaesthetic infiltration after failure of conservative management. Thirty-four patients were reviewed at least 24 months after the operation. Sixteen patients were rated excellent, nine good, eight fair, and five poor. Nine of the 13 patients with a fair or poor result had an insertional tendinopathy, and eight of them underwent a formal exploration of the patellar tendon. Before the operation, there were some areas of altered echogenicity at and around the site of involvement. These were still visible 6 wk after surgery in 70% of the patients. At the latest follow-up, in the patients with an excellent or good result, the tendon was generally isoechogenic but slightly thicker (P = 0.06) than the normal contralateral. In the patients with a fair or poor result, the tendon was significantly thicker than the contralateral (P = 0.03), and showed some areas of mixed echogenicity. In the patients in whom the procedure was successful, the thicker operated tendon did not interfere with physical training. Bilateral isokinetic peak torque (Nm), average work (Joules), and average power (Watts) were tested at 90 degrees x s(-1). Immediately before the operation, there was no significant difference in peak torque, but total work and average power were significantly lower in the limb to be operated (0.01 < P < 0.05). By the end of the study, although peak torque was, on average, within 7% of the unoperated limb, total work and average power were still significantly lower than in the unoperated limb (0.01 < P < 0.04). Percutaneous longitudinal internal tenotomy is simple, can be performed on an outpatient basis, requires minimal follow-up care, does not hinder further surgery should it be unsuccessful, and, in our experience, has produced no significant complications. In our hands, it has become the first line operative intervention in the treatment of chronic patellar tendinopathy after failure of conservative management. However, patients should be advised that, if they suffer from an tendinopathy at the attachment of the patellar tendon at the lower pole of the patella, a formal surgical exploration with stripping of the paratenon is preferable.

Indices of sustained aerobic power in young middle distance runners.

Sixteen young endurance athletes underwent physiological testing to determine their maximal oxygen uptake (VO2max), lactate threshold (lacAT), ventilatory threshold, and the slope variation point (SVP) of the linear relationship between running speed (RS) and heart rate (HR) both on the treadmill and during a field test, and the onset of blood lactate accumulation point. The RS, HR, VO2, and blood lactate concentration at which the different thresholds occurred were highly correlated, with r ranging from 0.82 to 0.90. The highest correlation was shown by RS at lacAT and RS at SVP during the field test. Various indices of sustained aerobic power in athletic children examined were shown to occur at a percentage of their VO2max similar to adult endurance runners. The tests developed for older athletes can be used in this age group as well.

Use of a tourniquet in the internal fixation of fractures of the distal part of the fibula. A prospective, randomized trial.

A prospective, randomized trial was undertaken to determine the rate of complications after the use of a tourniquet during open reduction and internal fixation of simple, closed fractures of the distal part of the fibula. Forty patients were operated on with use of a tourniquet (Group 1) and forty patients, without use of a tourniquet (Group 2). The average duration of the operation was significantly different between the two groups (41 +/- 9 minutes for Group 1 compared with 53 +/- 12 minutes for Group 2 [p = 0.026]). There were more complications in the patients in Group 1, two of whom had an isolated deep-vein thrombosis of the calf. The wound was possibly infected in eleven patients (seven in Group 1 and four in Group 2 [p < 0.05]) and frankly infected in three patients, all in Group 1 (p < 0.05). The plaster-of-Paris cast needed to be changed in three patients from Group 1. The patients in Group 1 returned to work an average of one week later than those in Group 2. The mean duration of follow-up was eighteen months (range, nine to thirty-two months). Given the lower prevalence of postoperative complications and the shorter time to recovery for the patients in Group 2, we believe that it is justified not to use a tourniquet in the operative treatment of simple, isolated fibular fractures.

Parenteral nutrition in cancer patients receiving chemotherapy: effects on toxicity and nutritional status.

The role of total parenteral nutrition (TPN) in reducing toxicity related to cancer chemotherapy (CT) is presently a controversial issue. To evaluate the effectiveness of TPN in reducing CT-associated toxicity and correcting and preventing CT-related impairments of nutritional status, a prospective crossover controlled study was performed in 43 cancer patients (19 normally nourished and 24 malnourished) randomly divided into two groups (A and B). Group A patients received TPN concomitantly with the first course of chemotherapy, and the second course was administered 21 to 28 days later without TPN support; group B patients were treated in the opposite sequence. The rates of myelotoxicities and gastrointestinal toxicities after CT courses with or without TPN were essentially similar in normally nourished and malnourished patients. No changes in nutritional indexes were detected in normally nourished subjects after each course. Conversely, in undernourished subjects, prealbumin, retinol-binding protein, and nitrogen balance increased in CT+TPN courses (p < .02). In CT-only courses, undernourished subjects showed a decrease in prealbumin and nitrogen balance. Significant changes of nitrogen balance in CT vs CT+TPN courses were detected in malnourished subjects. TPN appears to be unable to reduce CT-associated toxicity. CT administration does not result in any impairment of the nutritional status in normally nourished cancer patients. From our study, it appears that TPN should be limited to severely malnourished neoplastic patients undergoing CT, because of its ability to prevent further impairment of nutritional status and to improve the nitrogen balance and the levels of fast-turnover visceral proteins.

Results of percutaneous longitudinal tenotomy for Achilles tendinopathy in middle- and long-distance runners.

From August 1989 to January 1995 we performed multiple percutaneous longitudinal tenotomies under local anesthetic on 52 middle- and long-distance runners with unilateral Achilles tendinitis or peritendinitis that had failed conservative treatment. Forty-eight patients were reviewed at an average of 22.1 months (SD, 6.5) after surgery. Results were rated as excellent in 25 patients, good in 12, fair in 7, and poor in 4. Four patients developed subcutaneous hematomas. One patient developed a superficial infection at one of the incision sites, which was managed by oral antibiotics with full recovery. Three patients complained of over-sensitivity to the incisions; this was resolved by rubbing hand cream over the incisions several times a day. One patient developed hypertrophic painful scars on three of the five incisions, but corticosteroid injections yielded good functional and cosmetic results. Isometric strength and endurance of the gastrocsoleus complex was measured just before the procedure, and at 6 weeks and 6 months later. Both were within 10% of the normal contralateral limb by the 6th postoperative month. Percutaneous longitudinal tenotomy is simple, can be performed on an outpatient basis, requires minimal follow-up care, and, in our experience, has produced no significant complications. We use this procedure as the operative treatment of choice for cases of chronic tendinitis that have failed conservative treatment.

Giant spinal cord ependymoma in a child. Case report.

Ependymomas of the spinal cord extending to more than ten vertebral segments are rare. A case of a 14-month-old child is described and the other 13 reported cases are reviewed. The finding of a very extensive tumor (from T5 to L5) after only 14 months of life suggests that in our case the tumor was present since birth. Magnetic resonance well shows the real extent of the tumor in height and its different components. Complete removal is often possible even in very extensive ependymomas and results in clinical improvement. Postoperative radiotherapy is necessary only for incompletely removed or malignant ependymomas.

Anaerobic threshold determination in master endurance runners.

Twenty middle aged endurance runners underwent physiological testing to determine their maximal oxygen uptake (VO2max), lactate threshold, ventilatory threshold, the slope variation point (SVP) of the linear relationship between running speed (RS) and heart rate (HR) both on the treadmill and during a field test, and the onset of blood lactate accumulation point. The RS, HR, VO2 and blood lactate concentration at which the different thresholds occurred were highly correlated (0.70 < r < 0.95; p < 0.01). The various indices of aerobic-anaerobic transition in the master athletes examined were shown to occur at a comparable percentage of their VO2max as compared to their younger counterparts. The tests developed for, and commonly used in adult athletes, are equally valid in this age group.

Post-viral fatigue syndrome. A longitudinal assessment in varsity athletes.

Maximal oxygen uptake, anaerobic threshold (AT), isometric strength of the elbow flexor and knee extensor muscles, isometric strength endurance exhaustion time (prolonged contraction at 66% of maximal isometric strength), uphill sprinting exhaustion time were longitudinally studied in eight varsity endurance runners with post-viral fatigue syndrome (PVFS). Prolonged impairment of exercise performance is evident during the course of PVFS. Although maximal oxygen uptake (VO2max) had returned to pre-infection values 13 months after the viral illness (4.160 vs 4.0 L.min-1), AT was still significantly reduced [52 ml.kg-1.min-1, 18.6 km.hr-1, 176 bpm, and 82% of VO2max vs. 49.1 ml.kg-1.min-1 (p < 0.05), 175 bpm (NS), 17.2 km.hr-1 (p < 0.01) and 79% of VO2max (NS)]. Maximal isometric contraction strength of the upper limb remained constant (282 N vs. 274 N), while knee extensor muscles strength decreased significantly (730 N vs. 701 N, p < 0.05). Strength endurance was still significantly reduced by the end of the study (arm average pre-infection: 46.2 sec; end of study: 29.3 sec, p < 0.001; leg average pre-infection: 66.4 sec; end of study: 49.1 sec, p < 0.01). Up hill sprinting time was similarly reduced by the end of the study period (29.3 sec vs. 16.2 sec, p < 0.01). Both aerobic and anaerobic exercise variables are seriously affected by post-viral fatigue syndrome, and one year may not be sufficient to fully recover.

The validity and reliability of measurements in spinal deformities: a critical appraisal.

Quantitative measurement of spinal deformity is the preliminary step in order to plan a therapeutic regimen. The most commonly used methods and, for this matter, practically any measurement methods, may have several sources of errors, namely: a. errors in taking a radiograph; b. errors intrinsic to the measurement method; c. errors due to anatomical deformity of the vertebrae; d. observer errors in measurement technique. These are discussed, and suggestions are given to minimize them.