Total intravenous anesthesia (TIVA) with propofool and remifentanil during operative endoscopy tracheobronchial laser therapy.

Background: The aim of our study was to assess how total intra-venous anaesthesia (TIVA) achieved by propofol and remifentanil continuous infusion could ensure proper success of the endobronchial laser therapy, in optimal conditions for the endoscopist, determining at the same time an adequate hypnosis and a good analgesia. Methods: We studied 50 patients (28M - 22F), ASA class I-IV, mean age 42 ± 32.5 years , subjected to laser endoscopy to repair tracheal stenosis. TIVA was performed in all patients, and spontaneous breathing was maintained. Results: 10.2% of patients experienced episodes of coughing during induction. The depth of the anaesthesia plan, monitored by BIS, was 55 ± 5. The awakening was fast in all patients, with an Aldrete score of 7.71 ± 1.14 at 1 minute and 9.31 ± 1.12 at 10 minutes. Conclusion: The results of this study allow us to state that the continuous infusion of propofol and remifentanil proved to be the gold standard in patients ASA I-II-III undergoing endobronchial laser therapy. The use of TIVA has also allowed to perform endoscopic intervention on patients who suffered from a significant decrease of both cardiac and respiratory functions.

Fracture and migration in right atrium of a permanent venous central access system in a elderly patient: case report and literature review.

Abstract: Catheter dislocation and fracture with migration of central venous lines have been reported in the International literature. Catheter fracture with consequent migration has been observed in 0.5-3.0% and may either be consequent to catheter removal or it can occur spontane-ously. Our case report concerns the migration of a Hickman catheter connected to a venous port to the right atrium in a 61-year old patient. A literature up-to-date has been performed to assess the risk of port-a-cath positioning. The position of catheter tip is considered critical for the risk of migration, that is greater as higher the tip localization respect to the carina. The aim of our study is to underline the critical role of X-ray to visualize the exact location of the catheter tip, regard-less of the approach used for catheter positioning.

Association between respiratory distress time and invasive mechanical ventilation in COVID-19 patients: A multicentre regional cohort study.

AIM: To determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes. MATERIALS AND METHODS: An observational multicentre cohort study of patients hospitalised in five COVID-19-designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO2/FiO2 ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission. MEASUREMENTS AND MAIN RESULTS: We analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p < 0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48-12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89-39.41], p < 0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles. DISCUSSION: Albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients' need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.

Effect of HBO therapy on adipose-derived stem cells, fibroblasts and co-cultures: In vitro study of oxidative stress, angiogenic potential and production of pro-inflammatory growth factors in co-cultures1.

BACKGROUND: A key moderator of wound healing is oxygen. Wound healing is a dynamic and carefully orchestrated process involving blood cells, cytokines, parenchymal cells (i.e. fibroblasts and mesenchymal stem cells) and extracellular matrix reorganization. Human adipose derived stem cells as well as human fibroblasts produce soluble factors, exhibit diverse effects on inflammation and anti inflammation response and are involved in wound healing processes.Hyperbaric oxygen therapy is an effective adjunct treatment for ischemic disorders such as chronic infection or chronic wounds. In vitro effects of hyperbaric oxygen therapy on human cells were presented in many studies except for those on mono- and co-cultures of human adipose derived stem cells and fibroblasts. OBJECTIVE: The aim of this study was to investigate the effects of hyperbaric oxygen therapy on mono- and co-cultures of human adipose derived stem cells and fibroblasts. METHODS: Mono- and co-cultures from human adipose derived stem cells and fibroblasts were established. These cultures were exposed to hyperbaric oxygen therapy every 24 h for five consecutive days. Measuring experiments were performed on the first, third and fifth day. Therapy effects on the expression of VEGF, IL 6 and reactive oxygen species were investigated. RESULTS: After exposure to hyperbaric oxygen, cell culturess showed a significant increase in the expression of VEGF after 3 and 5 days. All cultures showed significantly reduced formation of reactive oxygen species throughout the experiments. The expression of IL-6 decreased during the experiment in mono-cultures of human adipose derived stem cells and co-cultures. In contrast, mono-cultures of human skin fibroblasts showed an overall significantly increased expression of IL-6. CONCLUSIONS: Hyperbaric oxygen therapy leads to immunmodulatory and proangiogenetic effects in a wound-like enviroment of adipose derived stem cells and fibroblasts.

Multimodal surveillance of healthcare associated infections in an intensive care unit of a large teaching hospital

BACKGROUND: Healthcare-associated infections (HAIs), or nosocomial infections, represent a significant burden in terms of mortality, morbidity, length of stay and costs for patients hospitalized in intensive care units (ICUs). Surveillance systems are recommended by national and international institutions to gather data on HAIs in order to develop and evaluate interventions that reduce the risk of HAIs. STUDY DESIGN: Here we describe the methodology and the results of the surveillance system implemented in the ICU of the Policlinico Umberto I, a large teaching hospital in Rome, from April 2016 to October 2018. METHODS: The multimodal infection surveillance system integrates four different approaches: i) active surveillance of inpatients; ii) environmental microbiological surveillance; iii) surveillance of isolated microorganisms; and iv) behavioral surveillance of healthcare personnel. Data were collected on catheter-related bloodstream infections, ventilation-associated pneumonia, catheter-associated urinary tract infections and primary bloodstream infections that developed in patients after 48 h in the ICU. For environmental surveillance 14 points were selected for sampling (i.e. bed edges, medication carts, PC keyboards, sink faucets). The system of active surveillance of HAIs also included surveillance of microorganisms, consisting of the molecular genotyping of bacterial isolates by pulsed-field gel electrophoresis (PFGE). From 1 November 2016, monitoring of compliance with guidelines for hand hygiene (HH) and proper glove or gown use by healthcare personnel was included in the surveillance system. After the first six months (baseline phase), a multimodal intervention to improve adherence to guidelines by healthcare personnel was conducted with the ICU staff. RESULTS: Overall, 773 patients were included in the active surveillance. The overall incidence rate of device-related HAIs was 14.1 (95% CI: 12.2-16.3) per 1000 patient-days. The monthly device-related HAI incident rate showed a decreasing trend over time, with peaks of incidence becoming progressively lower. The most common bacterial isolates were Klebsiella pneumoniae (20.7%), Acinetobacter baumannii (17.2%), Pseudomonas aeruginosa (13.4%) and Staphylococcus aureus (5.4%). Acinetobacter baumannii and Klebsiella pneumoniae showed the highest proportion of isolates with a multidrug-resistant profile. A total of 819 environmental samples were collected, from which 305 bacterial isolates were retrieved. The most frequent bacterial isolates were Acinetobacter baumannii (27.2%), Staphylococcus aureus (12.1%), Enterococcus faecalis (11.1%), Klebsiella pneumoniae (5.2%) and Pseudomonas aeruginosa (4.7%). All Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae environmental isolates were at least multidrug-resistant. Genotyping showed a limited number of major PFGE patterns for both clinical and environmental isolates of Klebsiella pneumoniae and Acinetobacter baumannii. Behavioral compliance rates significantly improved from baseline to post-intervention phase. CONCLUSIONS: By integrating information gathered from active surveillance, environmental microbiological surveillance, surveillance of bacterial isolates and behavioral surveillance of healthcare personnel, the multimodal infection surveillance system returned a precise and detailed view of the infectious risk and microbial ecology of the ICU.

Takotsubo Syndrome: Clinical Features, Pathogenesis, Treatment, and Relationship with Cerebrovascular Diseases.

PURPOSE OF REVIEW: This review paper aims to provide a complete and updated overview on the clinical and pathophysiological aspects of Takotsubo syndrome (TTS), including prognosis, therapy, and the association with cerebrovascular conditions. RECENT FINDINGS: TTS is an increasingly recognized non-ischemic cardiomyopathy characterized by sudden, temporary weakening of the myocardium, of which the pathogenesis is unknown. Although pathogenesis of TTS remains unclear, a complex interaction between catecholamine-mediated stimulation, myocardial stunning, and subsequent stress-related myocardial dysfunction seems to be the main pathophysiological mechanism. Stroke is linked to TTS by a dual relationship since it may induce TTS by catecholamine release even if TTS itself also may be complicated by left ventricular thrombi leading to stroke. Given its possible complications, including the association with neurological diseases, both cardiologist and neurologists should be aware about TTS in order to diagnose it promptly and to initiate appropriate therapeutic measures.

Arsenic in the health of ecosystems: spatial distribution in water, sediment and aquatic biota of Pampean streams.

A survey of arsenic and phosphorus in Pampean streams of Buenos Aires province was performed. Nitrates and ammonia were also determined. Stream water was sampled as well as stream sediment and filamentous algae. Results show that 32 streams exceeded the arsenic recommended guidelines for human consumption of 10 µg L-1 and six exceeded recommended values for aquatic organisms' protection of 50 µg L-1. The average concentration found was 36.54 µg L-1 and areas with more concentration of As are located in the southern region of the province, in streams that are tributaries of the Atlantic Ocean. Other regions with high As concentration are the Matanza River tributaries and the Arrecifes River tributaries. No differences of As concentration was found between stream sediments. Also, no seasonal pattern of As concentration was observed in one stream sampled during a year, but a positive correlation between As and the conductivity (p = 0.0002) and pH (p = 0.01) of the streams was found. Also, As bioaccumulation was detected for all the algae sampled, but no correlation between As accumulated and As in the stream water was found. Ammonia levels exceeded recommended guidelines for human consumption in the Argentinean law in 30 streams. The characterization performed in this study provides relevant information on the distribution of arsenic and its origin and mobility.

Vascular malformations of upper and lower extremity - from radiological interventional therapy to surgical soft tissue reconstruction - an interdisciplinary treatment.

This article presents our experience in managing peripheral vascular malformations of upper and lower extremities over a 4-year period in a series of 46 patients of the Department of Plastic Surgery treated in the Interdisciplinary Center of Vascular Anomalies (ICVA) at the University of Regensburg. The patients presented vascular malformations of upper and lower extremity and were selected from our prospective vascular anomalies file archive from 2012 to 2016. During this period in the ICVA at University of Regensburg were performed more than 1400 radiological interventional treatments in patients with vascular malformations.The purpose of this retrospective study was to review combined embolotherapy, sclerotherapy (embolo/sclerotherapy), and surgical procedures (surgical excision and soft tissue reconstruction) to manage vascular malformations. Treatments were principally induced to reduce pain, daily physical limitations, social discomfort and recover tegument continuity after ulceration.The 46 patients were first examined with noninvasive radiological procedures. After diagnosis was posed, embolo/sclerotherapy, surgical procedures and clinically as well as radiological follow-ups were coordinated and established by the multidisciplinary team. All vascular malformations were categorized according to the classification approved at the April 2014 General Assembly of International Society for the Study of Vascular Anomalies (ISSVA) in Melbourne, Australia. Arteriovenous malformations (AVMs) were further classified following the Cho-Do and Schobinger classification.Embolo/sclerotherapy shows to be the most appropriate procedure in vascular malformations treatment. Nevertheless was found that in case of complications or lack of improvement as well as to improve functional or aesthetical results, a following partial or complete surgical excision and immediate soft tissue reconstruction seems to be the gold-standard treatment. In addition, the precise clinical and radiological diagnosis as well as an intensive postoperative patient care have a significant positive influence on the clinical outcome and patient satisfaction while decreasing morbidity and recurrence during early and late follow-up.Vascular malformations require a multidisciplinary approach and individual treatment after complex excision and indispensable reconstruction.

Transepidermal oxygen flux during arterial occlusion using ratiometric luminescence imaging.

BACKGROUND: A physiological oxygen transport through a circulatory and microcirculatory system is essential for execution of cellular functions. Several pathological conditions e.g. infections, ischemia, cancer, diabetes, hypertension or chronic wounds show a change of oxygen distribution and oxygen tension in cellular microenvironment. Additionally complex operative procedures in order to reconstruct tissue defects require a reliable monitoring of microcirculation. OBJECTIVE: Target of this study was to evaluate skin oxygenation during an ischemia-reperfusion experiment using transepidermal oxygen flux imaging. METHODS: Twelve patients at the Department of Plastic and Reconstructive surgery of the University hospital of Regensburg underwent to elective hand operations. During the operation a tourniquet is standardly set on the upper arm to create ischemia in order to facilitate the operative procedure. Measurements were performed at the different time intervals: in rest, under ischemia and after reperfusion. RESULTS: The transepidermal oxygen flux increased during the ischemic condition compared to normal condition and decreased to a lower value during reperfusion (rest: 0.043±0.007, ischemia: 0.063±0.014, reperfusion: 0.030±0.028). CONCULSION: Transepidermal oxygen flux imaging by ratiometric luminescence imaging seems to be a reliable tool to assess skin oxygenation. However dynamic changes seem to be more informative than absolute thresholds. Further investigations are necessary to prove these promising results.

Observational multicentric study on chronic sciatic pain: clinical data from 44 Italian centers.

OBJECTIVE: To provide information on the clinical presentation of sciatic neuropathy and its management in a real-world setting, and to analyze the effects of a multimodal approach based on the association of physical and pharmacological therapy. PATIENTS AND METHODS: A multicentric observational prospective study was conducted in 44 Italian tertiary centers specialized in Physical Medicine and Rehabilitation, Orthopedics, Neurology, Neurosurgery, and Rheumatology. To develop a shared management of LPB with sciatica, a dedicated clinical record was proposed to collect data about diagnosis, treatment, and outcomes. Pain, disability, and quality of life were recorded trough validated questionnaires at baseline and after a two-month follow-up. RESULTS: 394 patients (age, mean ± SD 55.7 ± 14.1 years, 57.1% females) with chronic LBP and sciatica were enrolled in the study. The characteristics of the selected group showed a certain variability in the clinical presentation. At baseline, patients received several different therapeutic options among physical, pharmacological and neurotrophic treatments. A subgroup of 312 patients was treated with a combination of neurotrophic agents containing alpha-lipoic acid (ALA). After a two-month follow-up, a general improvement in both perceived pain and functional disabilities was observed. A significant improvement (p < 0.001) in the Pain Numeric Rating Scale (NRS), Roland e Morris Disability Questionnaire (RMDQ) and Brief Pain Inventory (BPI) Italian short version was observed. CONCLUSIONS: Sciatic neuropathy is a multifaceted condition managed by means of a wide spectrum of therapeutic options. The results of this study suggest that a multimodal approach based on the association of ALA with physical and pharmacological therapies can be beneficial in the treatment of LBP with sciatica.

p14ARF interacts with the focal adhesion kinase and protects cells from anoikis.

The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase. In line with its recruitment to focal adhesions, we observe that hampering ARF function in cancer cells leads to gross defects in cytoskeleton organization resulting in apoptosis through a mechanism dependent on the Death-Associated Protein Kinase. Our data uncover a novel function for p14ARF in protecting cells from anoikis that may reflect its role in anchorage independence, a hallmark of malignant tumor cells.

Transepidermal oxygen flux measurement - First clinical application for postoperative wound monitoring.

BACKGROUND: Measurement of skin oxygen is of great interest in diverse fields of medicine. Different pathologies, e.g. infection, ischemia cancer or chronic wounds show a characteristic oxygen distribution and skin oxygen tension. Additionally diverse operative procedures require a reliable postoperative monitoring in order to ensure success of the therapy. OBJECTIVE: Aim of this study was to assess transepidermal oxygen flux for postoperative wound monitoring after operative treatment of fractures close to the hip. METHODS: 22 patients underwent transepidermal oxygen flux measurement at the first postoperative day. Transepidermal oxygen flux measurement was performed using ratiometric luminescence imaging. Examination was conducted in close proximity to the operation wound. The corresponding area at the contralateral side served as reference. RESULTS: Oxygen flux in the operation area was higher (0.084±0.021) than the contralateral side (0.071±0.029). CONCLUSIONS: Transepidermal oxygen flux imaging by ratiometric luminescence imaging seems to be a reliable tool to assess postoperative wound healing. However further investigations in greater populations and under pathologic conditions have to be performed to prove these first results.

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation.

OBJECTIVE: The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. APPROACH: Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. MAIN RESULTS: PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. SIGNIFICANCE: Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

Results of a national multicentric study on compliance to treatment with various disphosphonate formulations in patients with postmenopausal osteoporosis.

AIM: Compliance to pharmacological treatment for osteoporosis is crucial if the risk of fracture is to be reduced. Case series show that treatment with traditional bisphosphonates in the form of tablets has a compliance of between approximately 30% and 70%. The aims of this paper were to assess compliance to treatment with various formulations of bisphonates and to identify those at highest risk of discontinuation. METHODS: In this multicentre retrospective observational study, a population of 387 women diagnosed with postmenopausal osteoporosis under treatment with bisphosphonates (risedronate, ibandronate, alendronate in tablet form, alendronate in a fluid solution per os) was observed for at least a year. Demographic data and information pertaining to the type of drug taken, compliance to treatment, side effects, reasons for discontinuation, the basal examination and follow-up at 18 months and later were recorded. RESULTS AND CONCLUSION: Analysis of patient compliance to a prescribed treatment plan showed a significantly higher persistence (P<0.001) in the group taking alendronate in soluble solution form (83.3%) compared to the group taking any bisphosphonate in tablet form (66.7%). At the same time, patientspresenting comorbidity, receiving more than one therapy, not taking vitamin D, and in surgical menopause, risked discontinuation.

Vestibular implants: Hope for improving the quality of life of patients with bilateral vestibular loss.

The vestibular system plays an essential role in crucial tasks such as postural control, gaze stabilization, and spatial orientation. Currently, there is no effective treatment for a bilateral loss of the vestibular function (BVL). The quality of life of affected patients is significantly impaired. During the last decade, our group has explored the potential of using electrical stimulation to artificially restore the vestibular function. Our vestibular implant prototype consists of a custom modified cochlear implant featuring one to three vestibular electrodes implanted in the proximity of the ampullary branches of the vestibular nerve; in addition to the main cochlear array. Special surgical techniques for safe implantation of these devices have been developed. In addition, we have developed stimulation strategies to generate bidirectional eye movements as well as the necessary interfaces to capture the signal from a motion sensor (e.g., gyroscope) and use it to modulate the stimulation signals delivered to the vestibular nerves. To date, 24 vestibular electrodes have been implanted in 11 BVL patients. Using a virtual motion profile to modulate the "baseline" electrical stimulation, vestibular responses could be evoked with 21 electrodes. Eye movements with mean peak eye velocities of 32°/s and predominantly in the plane of the stimulated canal were successfully generated. These are within the range of normal compensatory eye movements during walking and were large enough to have a significant effect on the patients' visual acuity. These results indicate that electrical stimulation of the vestibular nerve has a significant functional impact; eye movements generated this way could be sufficient to restore gaze stabilization during essential everyday tasks such as walking. The innovative concept of the vestibular implant has the potential to restore the vestibular function and have a central role in improving the quality of life of BVL patients in the near future.

Extracorporeal membrane oxygenation rescue therapy in a case of portopulmonary hypertension during liver transplantation: a case report.

Portopulmonary hypertension has been reported in 2% to 9% of candidates for liver transplantation (OLT). If it is moderate to severe, it represents a contraindication to the procedure until pulmonary vasodilatative therapy has been optimized. We report the case of a 43-year-old man, scheduled for OLT due to alcoholic cirrhosis with hemosiderosis. His Model for End-Stage Liver Disease was 25 at that time. The preoperative evaluation showed a severe alteration of diffusion (pO2 68 mm Hg), without hepatopulmonary syndrome or portopulmonary hypertension (PPH) upon basal and dobutamine stress echocardiography. At the beginning of the OLT the hemodynamic profile showed mean pulmonary artery pressure (mPAP) 38 mm Hg, wedge pressure (WP) 19 mm Hg, cardiac output (CO) 9.1 L/min, pulmonary vascular resistance (PVR) 166 dyne s/cm(5), transpulmonary gradient (TPG) 19 mm Hg, which lead us to promptly initiate inhaled nitric oxide (iNO) and intravenous epoprostenol 2 to 5 ng/kg/min. Upon graft reperfusion the hemodynamic profile was: mPAP 47 mm Hg, WP 23 mm Hg, CO 14.2 L/min, PVR 135 dyne s/cm(5), TPG 24 mm Hg, and at the end of surgery, mPAP 39 mm Hg, WP 20 mm Hg, CO 10.6 L/min, PVR 123 dyne s/cm(5), TPG 19 mm Hg. On postoperative day (POD) 3, we observed severe worsening of PPH: mPAP 60 mm Hg, WP 10 mm Hg, CO 9.8 L/min, PVR 395 dyne s/cm(5), TPG 50 mm Hg even with maximal pulmonary vasodilatatory therapy (ambrisentan 5 mg, intravenous sildenafil 20 mg × 3 and epoprostenol 22 ng/kg/min, iNO). Severe acute respiratory distress syndrome (ARDS) was presents. Therefore we decided to begin veno-venous extracorporeal membrane oxygenation (v-v ECMO) to correct the hypoxic vasoconstriction. Subsequent weaning from inotropic support with iNO and epoprostenol was possible on POD 7 due to mPAP 42 mm Hg, WP 15 mm Hg, CO 7.9 L/min, PVR 273 dyne s/cm(5), and TPG 27 mm Hg. On POD 11 he was weaned from ECMO due to: mPAP 40 mm Hg, WP 16 mm Hg, CO 6.5 L/min, PVR 295 dyne s/cm(5) and TPG 24 mm Hg. The patient was extubated on POD 17. The cardiac catheterization 1 month after OLT showed: mPAP 28 mm Hg, WP 13 mm Hg, CO 5.4 L/min, PVR 220 dyne s/cm(5) and TPG 15 mm Hg. ECMO rescue therapy in this "extreme" case allowed us to correct hypoxemia responsible for worsening of pulmonary hypertension allowing time to reach the goal of vasodilatatory therapy.

Molecular and clinical analysis of a neonatal severe hyperparathyroidism case caused by a stop mutation in the calcium-sensing receptor extracellular domain representing in effect a human 'knockout'.

OBJECTIVE: Loss-of-function calcium-sensing receptor (CAR) mutations cause elevated parathyroid hormone (PTH) secretion and hypercalcaemia. Although full Car deletion is possible in mice, most human CAR mutations result from a single amino acid substitution that maintains partial function. However, here, we report a case of neonatal severe hyperparathyroidism (NSHPT) in which the truncated CaR lacks any transmembrane domain (CaR(R392X)), in effect a full CAR 'knockout'. CASE REPORT: The infant (daughter of distant cousins) presented with hypercalcaemia (5.5-6  mmol/l corrected calcium (2.15-2.65)) and elevated PTH concentrations (650-950  pmol/l (12-81)) together with skeletal demineralisation. NSHPT was confirmed by CAR gene sequencing (homozygous c.1174C-to-T mutation) requiring total parathyroidectomy during which only two glands were located and removed, resulting in normalisation of her serum PTH/calcium levels. DESIGN AND METHODS: The R392X stop codon was inserted into human CAR and the resulting mutant (CaR(R392X)) expressed transiently in HEK-293 cells. RESULTS: CaR(R392X) expressed as a 54  kDa dimeric glycoprotein that was undetectable in conditioned medium or in the patient's urine. The membrane localisation observed for wild-type CaR in parathyroid gland and transfected HEK-293 cells was absent from the proband's parathyroid gland and from CaR(R392X)-transfected cells. Expression of the mutant was localised to endoplasmic reticulum consistent with its lack of functional activity. CONCLUSIONS: Intriguingly, the patient remained normocalcaemic throughout childhood (2.5 mM corrected calcium, 11 pg/ml PTH (10-71), age 8 years) but exhibited mild asymptomatic hypocalcaemia at age 10 years, now treated with 1-hydroxycholecalciferol and Ca2+ supplementation. Despite representing a virtual CAR knockout, the patient displays no obvious pathologies beyond her calcium homeostatic dysfunction.

Safety and efficacy of incobotulinum toxin type A (NT 201-Xeomin) for the treatment of post-stroke lower limb spasticity: a prospective open-label study.

BACKGROUND: In recent years, NT 201, a new botulinum toxin type A (BTX-A) free of complexing proteins, has been used for treating several movement disorders, showing safety and efficacy in upper limb spasticity. AIM: To assess the safety and evaluate the effects of BTX-A NT 201 free from complexing proteins for the treatment of post-stroke lower limb spasticity evaluating spasticity grade, passive ankle dorsi-flexion motion, and muscle's spasms, as well as its efficacy and rate of satisfaction for patients and for the physicians. DESIGN: Prospective open-label study. POPULATION: Patients (71) with post-stroke lower limb spasticity at least 5 months by the event. METHODS: Intramuscular injections of BTX-A NT 201 in soleus, medial, and lateral gastrocnemius with a maximum total dose of 180 U. Each patients was assessed at baseline, 30, and 90 days after treatment using Modified Ashworth Scale, Spasm Frequency Scale, evaluating passive ankle dorsi-flexion motion, and the rate of satisfaction for patients and investigators. RESULTS: Patients treated with BTX-A NT 201 reported a statistically significant reduction in muscle tone and spasms daily increasing passive ankle dorsi-flexion at 30 days, persisting also at 90 days of follow-up. CONCLUSION: BTX-A NT 201 for the treatment of post-stroke lower limb spasticity was safe and efficacious reducing muscle tone and spasms, and improving passive ankle dorsi-flexion movement. CLINICAL REHABILITATION IMPACT: These results confirmed the safety and effectiveness of a new type of BTX-A, with low immunogenity, useful to improve rehabilitative treatment of post-stroke lower limb spasticity.

Botulinum toxin type A in cervical dystonia.

Cervical dystonia is a syndrome characterized by anomalous postures and unintentional repetitive movements of the head and the neck. Aim of this study is to show the effectiveness of the combined treatment botulinum toxin-FKT through the use of a recent methodic of investigation, myoton, and of the classical clinical evaluations, such as Tsui and VAS scales. 15 patients (9 females, 6 males) have been selected. During the initial visit and in the following controls, performed every month, patients have been submitted to physiatric examination, clinical evaluation of the dystonia through the Tsui scale, clinical evaluation of the pain through the VAS scale, myometric evaluation. We obtained a statistical reduction of muscular tone values in passive elongation (t0=16,34±1,23) until 4 month (t4 =16,11±1,23), when we performed a second infiltration. After 4 months from the second infiltration (t8=15,99±1,11) value did not present more some statistical correlation and was necessary to perform a new infiltration. Values of elasticity, stiffness, Tsui and VAS scale followed the same course of the tone. Our study demonstrates that combined treatment botulinum toxin-FKT is effective. It emerges that if to the treatment with botulinum toxin follows a suitable FKT treatment, the effect of the drug lasts 4 months and not 3 months as described by the literature. Our study has underlined that using myometric measurement we can consider least changes in muscular tone, elasticity and stiffness; we have a broader view of the spastic muscle, and we can better plan appropriate rehabilitative care for each patient.