Isolated basilar artery dissection following blunt trauma challenging the Glasgow coma score: A case report.

Blunt cerebrovascular injury is a very rare complication of blunt trauma and a diagnostic challenge. A 14 year old male fell 10 m sustaining multi system trauma. The atypical Glasgow Coma Score was six with a fully preserved eye component. Initial whole-body CT scanning demonstrated multiple injuries but no obvious brain injury. Trauma management involved non-operative resuscitation and was successful, however profound coma occurred and brain stem reflexes disappeared on day two. Repeat brain CT scan demonstrated multiple cerebral and cerebellar ischemic lesions and no opacification of the vertebral or basilar arteries. Secondary analysis of the first CT scan demonstrated a small focal basilar artery dissection not initially reported. Our case report highlights an unusual cause of coma after traumatic brain injury where the clinical scenario mimics locked in syndrome. In such circumstances cerebrovascular injury, and in particular traumatic basilar artery dissection, must be actively excluded.

Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases.

Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

Non-invasive evaluation of portal hypertension using shear-wave elastography: analysis of two algorithms combining liver and spleen stiffness in 191 patients with cirrhosis.

BACKGROUND: Two algorithms based on sequential measurements of liver and spleen stiffness using two-dimensional shearwave elastography (2D-SWE) have been recently proposed to estimate clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] ≥10 mm Hg) in patients with cirrhosis, with excellent diagnostic accuracy. AIM: To validate externally these algorithms in a large cohort of patients with cirrhosis. METHODS: One hundred and ninety-one patients with stable cirrhosis (Child-Pugh class A 39%, B 29% and C 31%) who underwent liver and spleen stiffness measurements using 2D-SWE at the time of HVPG measurement were included. Diagnostic accuracy of the 2 algorithms was assessed by calculating sensitivity, specificity, positive and negative predictive values. RESULTS: The first algorithm, using liver stiffness <16.0 kilopascals (kPa) and then spleen stiffness <26.6 kPa, was used to rule-out HVPG ≥10 mm Hg. In our population, its sensitivity and negative predictive value were 95% and 63% respectively. The second algorithm, using liver stiffness >38.0 kPa, or liver stiffness ≤38.0 kPa but spleen stiffness >27.9 kPa, was used to rule-in HVPG ≥10 mm Hg. In our population, its specificity and positive predictive value were 52% and 83% respectively. Restricting the analyses to the 74 patients without any history of decompensation of cirrhosis or to the 65 patients with highly reliable liver stiffness measurement did not improve the results. CONCLUSION: In our population, diagnostic accuracies of non-invasive algorithms based on sequential measurements of liver and spleen stiffness using 2D-SWE were acceptable, but not good enough to replace HVPG measurement or to base clinical decisions.

High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment.

PURPOSE: The role played by radiation therapy after pleurectomy/decortication or surgical biopsy in malignant pleural mesothelioma is uncertain. We treated patients with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy in an attempt to keep lung toxicity to a minimum. The present study reports the feasibility and toxicity of this approach. MATERIAL AND METHODS: Between 2008 and 2012, 36 patients with malignant pleural mesothelioma underwent accelerated hypofractionated radiotherapy to the hemithorax after pleurectomy/decortication (19 patients) or biopsy (17 patients). The prescription dose was 25Gy in five fractions over 5 consecutive days. RESULTS: We observed three patients with G3 pneumonitis, five cases of grade 2 dyspnea and six cases of grade 2 cough. The median follow-up was 37 months (range: 3-54 months). The median overall survival for patients who underwent pleurectomy/decortication followed by radiotherapy was 21.6 months [95% confidence interval (95% CI): 15.5-24.1] compared to 19.4 months for patients not submitted to surgery. CONCLUSION: Treatment of intact lung with pleural intensity-modulated arc irradiation in malignant pleural mesothelioma patients with malignant pleural mesothelioma proved safe and feasible, with an acceptable rate of pneumonitis. Survival rates were encouraging for both biopsy-only and pleurectomy/decortication groups. We are currently conducting a phase II dose escalation trial in a similar patient setting to prospectively evaluate the impact of radiotherapy on toxicity, disease-free survival and overall survival.

Common and uncommon pitfalls in pancreatic imaging: it is not always cancer.

Despite advances in multimodality imaging of pancreas, there is still overlap between imaging findings of several pancreatic/peripancreatic disease processes. Pancreatic and peripancreatic non-neoplastic entities may mimic primary pancreatic neoplasms on ultrasound, CT, and MRI. On the other hand, primary pancreatic cancer may be overlooked on imaging because of technical and inherent factors. The purpose of this pictorial review is to describe and illustrate pancreatic imaging pitfalls and highlight the basic radiological features for proper differential diagnosis.

Management of the second phase of labour: perineum protection techniques.

The obstetric experience alongside scientific evidences in literature indicate several management techniques during the expulsive period of labour to minimize obstetric complications. Among the various methods that can be used for the protection of the perineum during the expulsive phase, some are performed prepartum (perineum massage), while most are used during childbirth. Among the second group, progressively increasing importance is assumed by the manual techniques to protect the perineum (using the "hands-on" and "hands-off") and by episiotomy. These techniques, when used in accordance to the guidelines, may favour the reduction of adverse outcomes for both the mother and the newborn, both immediately after birth and after a longer time. The midwife should be aware of the evidences in literature so that a critical analysis of the available techniques can be made and put in action during the expulsive phase in order to protect the mother and the foetus from any unfavourable outcomes. Currently, clinical evidence in literature is directing obstetric and medical staff towards a careful analysis of the maternal-foetal parameters, in order to achieve a precise assessment of the risks factors of intrapartum and postpartum outcomes. Increasingly, there is the need for close collaboration between the midwife and medical staff to ensure proper personalized assistance based on the peculiar characteristics of the woman and the fetus.

Evaluation of recovery and quality of sexual activity in women during postpartum in relation to the different mode of delivery: a retrospective analysis.

AIM: Aim of the study was to assess the recovery and quality of sexual activity of women during postpartum, in relation to delivery. METHODS: We recruited 200 women at 8 weeks after delivery. For each patient we recorded mode of delivery, age, body mass index (BMI), parity and test Female Sexual Function Index (FSFI) score. RESULTS: Sixty-four women (32%) had spontaneous deliveries without episiotomy, 48 (24%) had it with episiotomy, 88 (44%) had caesarean sections. The analysis of variance (ANOVA) test showed no significant differences among the 3 groups for age, BMI, parity. The test FSFI evidenced 68 cases (34%) of Regular Female Sexual Function (RFSF) and 132 (66%) of Female Sexual Dysfunction (FSD). The ANOVA test showed significant differences among the 3 groups in RFSF (F [2, 14]=8.075, P=0.005), but not in FSD (F [2, 30]=2.646, P=0.087). In RFSF, FSFI score was higher in women who had vaginal delivery with episiotomy compared with the other two groups. Conversely, in FSD (both with or without resumed sexual activity at 8 weeks postpartum) we evidenced that patients who had vaginal delivery with episiotomy showed lower FSFI score than the other two groups, with a decrease in lubrication, orgasm and satisfaction scores. Furthermore, we observed that most of the RFSF patients had a job and breastfed. CONCLUSION: Our results did not evidence a direct and significant correlation between mode of delivery and onset of female postpartum sexual dysfunction, even if FSD patients who underwent episiotomy during delivery markedly showed low FSFI scores.

Analysis of the Influence of Lunar Cycle on the Frequency of Spontaneous Deliveries: A Single-centre Retrospective Study.

BACKGROUND: Man, since ancient times, has been convinced of, and has researched scientific evidence that the barometric and gravitational forces play an important role in structural and biological variation of the planets, influencing the various forms of life. In particular, the synergistic relationships between variations in atmospheric pressure and gravitational forces on human gestation period have been the subject of rigorous observations and statistical calculations, which have not led to a universal conclusion in literature. OBJECTIVES: The aim of our work was to check whether there is a higher incidence of spontaneous deliveries, during the periods of full Moon than during the other phases of the Moon. METHODS: We performed a retrospective analysis of 327 non-induced vaginal deliveries in a year, divided by month. We subsequently analyzed the incidence of these deliveries during periods of full Moon Vs other lunar phases. RESULTS: We evidenced a statistically significant difference between the annual total spontaneous deliveries happened in full Moon periods Vs all other Moon phases (T= 2,3948; p=0,0256). However, we reported a discordant trend of deliveries in full Moon period, depending on each considered month. CONCLUSION: Since these differences were found both in increase and decrease, it is unacceptable the assumption of a linear correlation between periods of full Moon and increased frequency of spontaneous deliveries. For this reason, our data allow us to conclude that there is no need to increase the number of doctors and midwives in obstetric units during these periods.

Structural changes in alpha-crystallin and whole eye lens during heating, observed by low-angle X-ray diffraction.

Whole eye lens and alpha-crystallin gels and solutions were investigated using X-ray scattering techniques at temperatures ranging from 20 degrees C to 70 degrees C. In whole lens isolated in phosphate-buffered saline, the spacing of the dominant X-ray reflection seen with low-angle scattering was constant from 20 degrees C to 45 degrees C but increased at 50 degrees C from 15.2 nm to 16.5 nm. At room temperature, the small-angle X-ray diffraction pattern of the intact lens was very similar to the pattern of alpha-crystallin gels at near-physiological concentration (approximately 300 mg/ml), so it is reasonable to assume that the alpha-crystallin pattern dominates the pattern of the intact lens. Our results therefore indicate that in whole lens alpha-crystallin is capable of maintaining its structural properties over a wide range of temperature. This property would be useful in providing protection for other lens proteins super-aggregating. In the alpha-crystallin gels, a moderate increase in both the spacing and intensity of the reflection was observed from 20 degrees C to 45 degrees C, followed by an accelerated increase from 45 degrees C to 70 degrees C. Upon cooling, this effect was found to be irreversible over 11 hours. Qualitatively similar results were observed for alpha-crystallin solutions at a variety of lower concentrations.

Heat-induced quaternary transitions in hetero- and homo-polymers of alpha-crystallin.

PURPOSE: To compare the effects of heat incubation on the structure and function of native alpha-crystallin, urea denatured/renatured alpha-crystallin, and alphaA and alphaB-crystallin homo-polymers purified from bovine lenses. METHODS: Each of the alpha-crystallin samples were incubated for 1 h at temperatures ranging from 35 degrees C to 70 degrees C. After heat incubation structural perturbations in each of the samples were studied using non-denaturing gel electrophoresis, transmission electron microscopy (TEM) and far-UV circular dichroism. The chaperone-like activity of each of the heat-treated samples was measured using the DTT induced insulin aggregation assay. RESULTS: The native alpha-crystallin samples showed secondary structure perturbations, an increase in aggregate size and asymmetry, and an increase in chaperone-like activity after heat incubation above 50 degrees C. The other three sample types showed secondary structure perturbations beginning at lower incubation temperatures, and a progressive decrease in chaperone-like activity with exposure to increasing temperatures. TEM showed all samples formed large asymmetric high molecular weight aggregates after incubation at 65 degrees C. CONCLUSIONS: The urea denaturation/renaturation of alpha-crystallin has been shown to result in the loss of a small amount of alpha-helix, but to have no effect on chaperone-like activity under standard test conditions. The present results indicate this lost alpha-helix may be responsible for the differential effects of heat incubation on the different forms of alpha-crystallin.

Correlation between the chaperone-like activity and aggregate size of alpha-crystallin with increasing temperature.

alpha-Crystallin, the major protein of the mammalian eye lens, is also found in the major tissues of the body, where one or the other of its two isoforms is characteristically expressed. Both isoform sequences are highly related to others of the small heat shock protein superfamily, leading to speculation about their functions in vivo outside of the lens. Tests of chaperone-like activity at 37 and 66 degrees C indicate that the protein can act to prevent the superaggregation of partially denatured proteins, but both alpha-crystallin aggregate size and shape are significantly altered with increasing temperature. Characterization of these changes indicates that secondary, tertiary, and quaternary structure are modified, with the latter effect especially striking above 50 degrees C. Furthermore, these changes appear to be irreversible when the temperature is returned to 25 or 37 degrees C. Functionally, the protein is effective in chaperone-like activity at all temperatures, but exhibits a somewhat increased capability after a cycle of heating and cooling. The results presented here indicate the heat-induced formation of high-molecular-weight aggregates of alpha-crystallin is a slow progressive process. The increased activity of these aggregates suggests that chaperone-like activity depends in part on the packing parameters of the aggregate and on conformation of the subunit within that aggregate.

Allosteric modulation by single enantiomers of a C3-chiral 1,4-benzodiazepine of the gamma aminobutyric acid type A receptor channel expressed in Xenopus oocytes.

Xenopus laevis oocytes injected with Poly(A)(+)-RNA isolated from neuronal tissue express membrane proteins peculiar to the origin of mRNA. The translation of gamma aminobutyric acid type A (GABAA) receptors has been shown by dose/ response behavior of GABA and the reversible blockade of the GABA-induced current by picrotoxin. This current was analyzed quantitatively under two electrode voltage-clamp conditions. This methodology has been applied for the first time to study the functional properties of the receptor as a function of the stereochemistry of the ligands. The (+)-S and (-)-R enantiomers of a water-soluble benzodiazepine derivative, 7-chloro-1,3-dihydro-3-hemisuccinyloxy-5-phenyl-1,4-benzodiazep in-2-one (OXHEM), obtained by preparative high performance liquid chromatographic (HPLC) resolution on chiral stationary phase, act as agonists in the in vitro modulation of the chloride channel. The (+)-S-OXHEM enantiomer was the more active.