Critical illness-associated limb and diaphragmatic weakness.

PURPOSE OF REVIEW: In the current review, we aim to highlight the evolving evidence on the diagnosis, prevention and treatment of critical illness weakness (CIW) and critical illness associated diaphragmatic weakness (CIDW). RECENT FINDINGS: In the ICU, several risk factors can lead to CIW and CIDW. Recent evidence suggests that they have different pathophysiological mechanisms and impact on outcomes, although they share common risk factors and may overlap in several patients. Their diagnosis is challenging, because CIW diagnosis is primarily clinical and, therefore, difficult to obtain in the ICU population, and CIDW diagnosis is complex and not easily performed at the bedside. All of these issues lead to underdiagnosis of CIW and CIDW, which significantly increases the risk of complications and the impact on both short and long term outcomes. Moreover, recent studies have explored promising diagnostic techniques that are may be easily implemented in daily clinical practice. In addition, this review summarizes the latest research aimed at improving how to prevent and treat CIW and CIDW. SUMMARY: This review aims to clarify some uncertain aspects and provide helpful information on developing monitoring techniques and therapeutic interventions for managing CIW and CIDW.

Neurological complications of sepsis.

PURPOSE OF REVIEW: Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of hospital and ICU admission. The central and peripheral nervous system may be the first organ system to show signs of dysfunction, leading to clinical manifestations such as sepsis-associated encephalopathy (SAE) with delirium or coma and ICU-acquired weakness (ICUAW). In the current review, we want to highlight developing insights into the epidemiology, diagnosis, prognosis, and treatment of patients with SAE and ICUAW. RECENT FINDINGS: The diagnosis of neurological complications of sepsis remains clinical, although the use of electroencephalography and electromyography can support the diagnosis, especially in noncollaborative patients, and can help in defining disease severity. Moreover, recent studies suggest new insights into the long-term effects associated with SAE and ICUAW, highlighting the need for effective prevention and treatment. SUMMARY: In this manuscript, we provide an overview of recent insights and developments in the prevention, diagnosis, and treatment of patients with SAE and ICUAW.

LZER0: A Cost-Effective Multi-Purpose GNSS Platform.

Recent advances in Global Navigation Satellite System (GNSS) technology have made low-cost sensors available to the mass market, opening up new opportunities for real-time ground deformation and structure monitoring. In this paper, we present a new product developed in this framework by the National Institute of Oceanography and Applied Geophysics-OGS in collaboration with a private company (SoluTOP SAS): a cost-effective, multi-purpose GNSS platform called LZER0, suitable not only for surveying measurements, but also for monitoring tasks. The LZER0 platform is a complete system that includes the GNSS equipment (M8T single-frequency model produced by u-blox) and the web portal where the results are displayed. The GNSS data are processed using the RTKLIB software package, and the processed results are made available to the end user. The relative positioning mode was adopted both with real-time and post-processing RTKLIB engines. We present three applications of LZER0-cadastral, monitoring, and automotive-which demonstrate that it is a flexible, multi-purpose platform that is easy to use in terms of both hardware and software, and can be easily deployed to perform various tasks in the research, educational, or professional sectors.

Surfactant therapy for COVID-19 related ARDS: a retrospective case-control pilot study.

BACKGROUND: COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. METHODS: We performed retrospective analyses of data from patients receiving off-label use of exogenous natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. RESULTS: Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. CONCLUSIONS: Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration did not cause acute decompensation, may reduce mortality and mechanical ventilation duration in COVID-19 ARDS patients. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous sub-bronchial lavage with surfactant as treatment for patients with COVID-19 ARDS.

Monitoring Patient Respiratory Effort During Mechanical Ventilation: Lung and Diaphragm-Protective Ventilation.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Determination of Imminent Brain Death Using the Full Outline of Unresponsiveness Score and the Glasgow Coma Scale: A Prospective, Multicenter, Pilot Feasibility Study.

PURPOSE: To evaluate the accuracy of the imminent brain death (IBD) diagnosis in predicting brain death (BD) by daily assessment of the Full Outline of Unresponsiveness (FOUR) score and the Glasgow Coma Scale (GCS) with the assessment of brain stem reflexes. MATERIALS AND METHODS: Prospective multicenter pilot study carried out in 5 adult Italian intensive care units (ICUs). Imminent brain death was established when the FOUR score was 0 (IBD-FOUR) or the GCS score was 3 and at least 3 among pupillary light, corneal, pharyngeal, carinal, oculovestibular, and trigeminal reflexes were absent (IBD-GCS). RESULTS: A total of 219 neurologic evaluations were performed in 40 patients with deep coma at ICU admission (median GCS 3). Twenty-six had a diagnosis of IBD-FOUR, 27 of IBD-GCS, 14 were declared BD, and 9 were organ donors. The mean interval between IBD diagnosis and BD was 1.7 days (standard deviation [SD] 2.0 days) using IBD-FOUR and 2.0 days (SD 1.96 days) using IBD-GCS. Both FOUR and GCS had 100% sensitivity and low specificity (FOUR: 53.8%; GCS: 50.0%) in predicting BD. CONCLUSIONS: Daily IBD evaluation in the ICU is feasible using FOUR and GCS with the assessment of brain stem reflexes. Both scales had 100% sensitivity in predicting IBD, but FOUR may be preferable since it incorporates the pupillary, corneal, and cough reflexes and spontaneous breathing that are easily assessed in the ICU.

A novel non-invasive method to detect excessively high respiratory effort and dynamic transpulmonary driving pressure during mechanical ventilation.

BACKGROUND: Excessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (ΔPocc) could be used as a highly feasible non-invasive technique to screen for these conditions. METHODS: Respiratory muscle pressure (Pmus), dynamic transpulmonary driving pressure (ΔPL,dyn, the difference between peak and end-expiratory transpulmonary pressure), and ΔPocc were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔPL,dyn and Pmus from ΔPocc was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China). RESULTS: Fifty-two daily recordings were collected in 16 patients. In this sample, Pmus and ΔPL were frequently excessively high: Pmus exceeded 10 cm H2O on 84% of study days and ΔPL,dyn exceeded 15 cm H2O on 53% of study days. ΔPocc measurements accurately detected Pmus > 10 cm H2O (AUROC 0.92, 95% CI 0.83-0.97) and ΔPL,dyn > 15 cm H2O (AUROC 0.93, 95% CI 0.86-0.99). In the external validation cohort (n = 12), estimating Pmus and ΔPL,dyn from ΔPocc measurements detected excessively high Pmus and ΔPL,dyn with similar accuracy (AUROC ≥ 0.94). CONCLUSIONS: Measuring ΔPocc enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients.

Management of intrathecal baclofen therapy for severe acquired brain injury: consensus and recommendations for good clinical practice.

Although widespread in the treatment of generalised spasticity due to severe acquired brain injury, clinical use of intrathecal baclofen administered through an implanted catheter is not yet supported by full scientific evidence. The aim of the study is to provide recommendations for good clinical practice regarding intrathecal baclofen therapy. We used a modified RAND Delphi method to develop consensus-based medical guidelines, involving clinicians who use intrathecal baclofen therapy throughout Italy. The clinicians were asked 38 questions grouped in six areas (patient selection, contraindications for implant, tests prior to implant, method of implant and management of therapy, efficacy evaluation and goal setting, and management of complications). To establish consensus, 75% agreement was required in answers to every question. Consensus was reached on the second round of the Delphi process on 27/38 questions (71%), specifically those regarding identification of objectives, efficacy evaluation, and method of implant and management of therapy, whereas management of complications and contraindications for implant remained critical areas. Despite the limits of our method, a set of recommendations was drawn up for clinical practice in this sector. The study also revealed residual critical areas and indicated future lines of research necessary to reach evidence-based consensus.

Post-stroke spasticity: follow-up and functional implications of chronic long-term treatment with botulinum toxin.

BACKGROUND: Around 40% of stroke survivor develop spasticity. Plantar flexors (PF) muscles are often affected, with severe functional impairment. The treatment of choice is botulinum toxin type A (BoNT-A) combined with adjuvant treatments. The temporary pharmacological effect implies periodic reassessment and reinjection. These long-term chronic programs require monitoring the functional impact of each cycle and the clinical evolution in relation to aging and repeated interventions. AIM: Evaluating changes of functional level in patients with post-stroke spasticity treated with BoNT-A by assessing the long-term maintenance of the therapeutic efficacy. DESIGN: Retrospective longitudinal observational study. SETTING: Outpatients. POPULATION: Chronic stroke survivors undergoing BoNT-A treatment and subsequent intensive rehabilitation (10 sessions in a day-hospital regime). METHODS: Medical records of the enrolled patients were consulted. The primary endpoint was the change in PF spasticity by at least 1 point on the Modified Ashworth Scale (MAS) at each cycle. Secondary endpoints were the assessment of possible trends in gait parameters (Six Minute Walking Test [6MWT]; Timed Up and Go [TUG], and 10 Meters Walking Test [10mWT]) pre- and post-injection and at each cycle. RESULTS: Thirty-six patients were enrolled. A reduction of at least one MAS point for PF was recorded after each cycle in all subjects. A time-dependent reduction in the proportion of patients reporting an improvement higher than the minimal clinically important difference (MCID) in 6MWT and 10mWT was observed. In the case of TUG, this data kept stable at all cycles. A one-point increase in the basal functional ambulation classification (FAC) score resulted in a reduction in the probability of having a TUG improvement greater than the MCID. The opposite correlation was found for 6MWT and 10mWT. CONCLUSIONS: With the proposed treatment, the clinical significance TUG improvement remains constant throughout repeated cycles and the proportion of patients with improvement in 6MWT and 10mWT tends to decline over time. The predictive value of basal FAC on the functional variables expected improvement may provide a potential treatment targeting tool. CLINICAL REHABILITATION IMPACT: These results may deliver prognostic indication allowing an optimized integration of different post-BoNT-A rehabilitation approaches, agreeing with current evidence. Adequate monitoring and treatment protocols are crucial for the stability of functional level and may prevent excessive fluctuations.

Long-term physical impairments in survivors of COVID-19-associated ARDS compared with classic ARDS: A two-center study.

PURPOSE: This work aimed to compare physical impairment in survivors of classic ARDS compared with COVID-19-associated ARDS (CARDS) survivors. MATERIAL AND METHODS: This is a prospective observational cohort study on 248 patients with CARDS and compared them with a historical cohort of 48 patients with classic ARDS. Physical performance was evaluated at 6 and 12 months after ICU discharge, using the Medical Research Council Scale (MRCss), 6-min walk test (6MWT), handgrip dynamometry (HGD), and fatigue severity score (FSS). We also assessed activities of daily living (ADLs) using the Barthel index. RESULTS: At 6 months, patients with classic ARDS had lower HGD (estimated difference [ED]: 11.71 kg, p < 0.001; ED 31.9% of predicted value, p < 0.001), 6MWT distance (ED: 89.11 m, p < 0.001; ED 12.96% of predicted value, p = 0.032), and more frequent significant fatigue (OR 0.35, p = 0.046). At 12 months, patients with classic ARDS had lower HGD (ED: 9.08 kg, p = 0.0014; ED 25.9% of predicted value, p < 0.001) and no difference in terms of 6MWT and fatigue. At 12 months, patients with classic ARDS improved their MRCss (ED 2.50, p = 0.006) and HGD (ED: 4.13 kg, p = 0.002; ED 9.45% of predicted value, p = 0.005), while those with CARDS did not. Most patients in both groups regained independence in ADLs at 6 months. COVID-19 diagnosis was a significant independent predictor of better HGD (p < 0.0001) and 6MWT performance (p = 0.001), and lower prevalence of fatigue (p = 0.018). CONCLUSIONS: Both classic ARDS and CARDS survivors experienced long-term impairments in physical functioning, confirming that post-intensive care syndrome remains a major legacy of critical illness. Surprisingly, however, persisting disability was more common in survivors of classic ARDS than in CARDS survivors. In fact, muscle strength measured with HGD was reduced in survivors of classic ARDS compared to CARDS patients at both 6 and 12 months. The 6MWT was reduced and fatigue was more common in classic ARDS compared to CARDS at 6 months but differences were no longer significant at 12 months. Most patients in both groups regained independent function in ADLs at 6 months.

Electrophysiological neuromuscular alterations and severe fatigue predict long-term muscle weakness in survivors of COVID-19 acute respiratory distress syndrome.

Introduction: Long-term weakness is common in survivors of COVID-19-associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits. Methods: Muscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), a 6-min walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength and Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for their essential role in ankle control. Results: MVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT. Discussion: Electrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.

Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. METHODS: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. RESULTS: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of -0.62 (95%CI - 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (ß = -1.019, 95% CI - 1.827; -0.210, p-value = 0.0135). CONCLUSIONS: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy.

Sclerosing Mesenteritis as an Uncommon Site of Involvement of IgG4-Related Disease: A Case Report With an Updated Review of the Literature.

Immunoglobulin G4-related disease (IgG4-RD) is an uncommon immune-mediated disorder most commonly involving the pancreas, lacrimal, and salivary glands. Immunoglobulin G4-related sclerosing mesenteritis (IgG4-RSM) is a rare site of involvement that usually mimics the imaging characteristics of mesenteric malignancies. Herein, we report a case of IgG4-RSM followed by an updated and comprehensive review of the literature. A 73-year-old woman presented with colicky abdominal pain in the right hypochondrium. The findings on contrast medium computed tomography (CMCT) showed a swelling of the mesenteric root with vascular structures surrounded by slightly contrast-impregnated tissue and irregular margins. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET) showed an area of inhomogeneous and intense hypermetabolism of the mesenteric root. Hence, laparoscopic resection of the mesenteric root was performed to distinguish such masses from malignant tumors, obtaining specimens for histopathologic examination. The latter exhibited tissue infiltration with lymphocytes, IgG4-positive plasma cells, and fibrosis, indicating a diagnosis of IgG4-RSM in the presence of both elevated serum IgG4 levels and the aforementioned imaging findings. With steroid therapy, no clinical signs of re-exacerbation within a one-year follow-up were observed and serum IgG4 levels returned to normality. Aiming to evaluate the real frequency of IgG4-RSM in view of the 2017 Comprehensive Diagnostic Criteria (CDC) of IgG4-RD, we undertook a complete MEDLINE, EMBASE, Web of Science, and Scopus database search of all case reports of IgG4-RSM published so far. Such criteria were met in only six cases with a definite diagnosis. This case highlights the mesentery as a rare site of involvement of IgG-RD and allows us to advance knowledge of IgG4-RSM.

A Case Report of New-Onset Diabetes Mellitus as an Early Warning Sign of Pancreatic Ductal Adenocarcinoma in an Elderly Patient: The Earlier the Diagnosis and Surgery, the Better the Prognosis.

Studies have been recently conducted to find pancreatic ductal adenocarcinoma (PDAC) in high-risk groups by identifying individuals with pancreatic cystic lesions and elderly people (> 50 years) with new-onset diabetes mellitus (NODM). We report the case of a 91-year-old woman in good health with pancreatic cysts, who firstly displayed a NODM and, one month later, a PDAC. A dehydration syndrome with polydipsia and asthenia led to her hospitalization. High levels of blood glucose and glycated hemoglobin were found. An abdomen US showed a minute pancreas with some cysts. Rehydration and insulin therapy led to a good glycemic compensation. One month after discharge, she displayed weight loss, diarrhea, and jaundice. On the second admission, high levels of total and direct bilirubin, indices of hepatic cholestasis, and Ca 19.9 were found. An abdomen contrast medium CT evidenced a nodule at the pancreatic head, suggesting a malignant lesion, and dilatation of both the Wirsung duct and the whole biliary tract. Despite the lack of a histological diagnosis, the absence of signs of local invasion, metastasis, and co-morbidities as well as the rapid clinical deterioration led us to propose surgical treatment. A few days later, a pancreatoduodenectomy was performed. The histologic examination showed a moderately differentiated (G2) PDAC. The TNM staging was IIA (pT3, N0, M0) (R0). Three weeks after, she was discharged with normal liver function tests, Ca 19.9 levels, and a good glycemic compensation with insulin therapy. Five years after surgical treatment, she is still doing well displaying a normal abdomen CT follow-up, normal blood tests, including Ca 19.9, and a good glycemic compensation. Our case report denotes an exceptional duration of survival of PDAC and highlights the importance to seek its presence in every case of NODM in patients > 50 years, especially if they carry pancreatic cysts.

Seeking the Light in Intensive Care Unit Sedation: The Optimal Sedation Strategy for Critically Ill Patients.

The clinical approach to sedation in critically ill patients has changed dramatically over the last two decades, moving to a regimen of light or non-sedation associated with adequate analgesia to guarantee the patient's comfort, active interaction with the environment and family, and early mobilization and assessment of delirium. Although deep sedation (DS) may still be necessary for certain clinical scenarios, it should be limited to strict indications, such as mechanically ventilated patients with Acute Respiratory Distress Syndrome (ARDS), status epilepticus, intracranial hypertension, or those requiring target temperature management. DS, if not indicated, is associated with prolonged duration of mechanical ventilation and ICU stay, and increased mortality. Therefore, continuous monitoring of the level of sedation, especially when associated with the raw EEG data, is important to avoid unnecessary oversedation and to convert a DS strategy to light sedation as soon as possible. The approach to the management of critically ill patients is multidimensional, so targeted sedation should be considered in the context of the ABCDEF bundle, a holistic patient approach. Sedation may interfere with early mobilization and family engagement and may have an impact on delirium assessment and risk. If adequately applied, the ABCDEF bundle allows for a patient-centered, multidimensional, and multi-professional ICU care model to be achieved, with a positive impact on appropriate sedation and patient comfort, along with other important determinants of long-term patient outcomes.

Occurrence and Effects on Weaning From Mechanical Ventilation of Intensive Care Unit Acquired and Diaphragm Weakness: A Pilot Study.

Purpose: Limb intensive care unit (ICU)-acquired weakness (ICUAW) and ICU acquired diaphragm weakness (DW) occur frequently in mechanically ventilated (MV) patients; their coexistence in cooperative and uncooperative patients is unknown. This study was designed to (1) describe the co-occurrence of the two conditions (2) evaluate the impact of ICUAW and DW on the ventilator-free days (VFDs) at 28 days and weaning success, and (3) assess the correlation between maximal inspiratory pressure (MIP) and thickening fraction (TFdi) in patients with DW. Methods: This prospective pilot study was conducted in a single-center on 73 critically ill MV patients. Muscle weakness was defined as a Medical Research Council score < 48 in cooperative patients or a bilateral mean simplified peroneal nerve test < 5.26 mV in uncooperative patients. Diaphragm dysfunction was defined as MIP < 30 cm H2O or as a TFdi < 29%. Weaning success was defined according to weaning according to a new definition (WIND). Results: Fifty-seven patients (78%) had ICUAW and 59 (81%) had DW. The coexistence of the two conditions occurred in 48 patients (65%), without association (χ2 = 1.06, p = 0.304). In the adjusted analysis, ICUAW was independently related to VFDs at 28-days (estimate difference 6 days, p = 0.016), and WIND (OR of 3.62 for having WIND different than short weaning), whereas DW was not. The linear mixed model showed a significant but weak correlation between MIP and TFdi (p < 0.001). Conclusion: This pilot study is the first to explore the coexistence of ICUAW and DW in both cooperative and uncooperative patients; a lack of association was found between DW and ICUAW when considering both cooperative and uncooperative patients. We found a strong correlation between ICUAW but not DW with the VFDs at 28 days and weaning success. A future larger study is warranted in order to confirm our results, and should also investigate the use of transdiaphragmatic twitch pressure measurement during bilateral anterior magnetic phrenic nerve stimulation for the diagnosis of DW.

The Lack of Systemic and Subclinical Side Effects of Botulinum Neurotoxin Type-A in Patients Affected by Post-Stroke Spasticity: A Longitudinal Cohort Study.

Botulinum Neurotoxin type-A (BoNT-A) is the treatment of choice for focal post-stroke spasticity (PSS). Due to its mechanism of action and the administration method, some authors raised concern about its possible systemic diffusion leading to contralateral muscle weakness and autonomic nervous system (ANS) alterations. Stroke itself is a cause of motor disability and ANS impairment; therefore, it is mandatory to prevent any source of additional loss of strength and adjunctive ANS disturbance. We enrolled 15 hemiparetic stroke survivors affected by PSS already addressed to BoNT-A treatment. Contralateral handgrip strength and ANS parameters, such as heart rate variability, impedance cardiography values, and respiratory sinus arrythmia, were measured 24 h before (T0) and 10 days after (T1) the ultrasound (US)-guided BoNT-A injection. At T1, neither strength loss nor modification of the basal ANS patterns were found. These findings support recent literature about the safety profile of BoNT-A, endorsing the importance of the US guide for a precise targeting and the sparing of "critical" structures as vessels and nerves.

Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with unresectable HCC unsuitable for ablative therapies were randomly assigned to undergo conventional or DEB chemoembolization. The primary endpoints of the study were safety, toxicity, and tumor response at 1 month. Secondary endpoints were number of repeated chemoembolization cycles, time to recurrence and local recurrence, time to radiologic progression, and survival. RESULTS: In total, 67 patients (mean age, 70 y ± 7.7) were evaluated. Mean follow-up was 816 days ± 361. Two periprocedural major complications occurred (2.9%) that were treated by medical therapy without the need for other interventions. A significant increase in alanine aminotransferase levels 24 hours after treatment was reported, which was significantly greater after conventional chemoembolization (n = 34) than after DEB chemoembolization (n = 33; preprocedure, 60 IU ± 44 vs 74 IU ± 62, respectively; at 24 h, 216 IU ± 201 vs 101 IU ± 89, respectively; P = 0.007). No other differences were observed in liver toxicity between groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No differences were observed between groups in time to recurrence and local recurrence, radiologic progression, and survival. CONCLUSIONS: Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes.

Complete response for advanced liver cancer during sorafenib therapy: case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common neoplasia in the world. In the past, treatment of advanced HCC with conventional antineoplastic drugs did not result in satisfactory outcomes: recently, in this patient population the oral multikinase inhibitor sorafenib has been able to induce a statistically significant improvement of overall survival. Similarly to other anti-angiogenic drugs employed in other tumour types, also sorafenib seldom induces the dimensional tumour shrinking usually observed with conventional cytotoxic drugs: data gathered from studies carried out with sorafenib and other competitors under development do not report any complete response in HCV-induced HCC. CASE PRESENTATION: An 84-year old man with a long-lasting history of chronic HCV hepatitis was referred to our Institution for an ultrasonography investigation of a focal hepatic lesion. To better characterize the liver disease and clearly define the diagnosis of the focal hepatic lesion, the patient was hospitalized in our department. Laboratory and instrumental investigations confirmed the clinical picture of HCV-related liver cirrhosis and identified a hepatic lesion of about 6 cm featuring infiltrating HCC with thrombosis of the portal trunk. Due to the advanced stage of the disease, therapy with sorafenib 400 mg bid was started. Right from one month after the treatment was started, a reduction of alpha-fetoprotein level was observed which, by the third month, turned down within the normal limits. In addition the CT scan showed 50% reduction of the neoplastic lesion along with canalization of the portal trunk. At the sixth month the normalization of the alpha-fetoprotein level at the lower limit of normality was confirmed and the MRI showed complete disappearance of the neoplasia. In addition a reduction of a metallo-proteinase serum level was observed. At the twelfth month a further MRI confirmed complete response had been maintained. At present the patient is in a follow-up program to evaluate the duration of the complete response. CONCLUSIONS: This case is worth mentioning since, to the best of our knowledge, it represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related HCC.

BoNT-A for Post-Stroke Spasticity: Guidance on Unmet Clinical Needs from a Delphi Panel Approach.

There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based survey Delphi process to provide guidance that can support clinicians in the decision-making process. There was a broad consensus among physicians that BoNT-A intervention should be administered as soon as the spasticity interferes with the patients' clinical condition. Patients monitoring is needed over time, a follow-up of 4-6 weeks is considered necessary. Furthermore, physicians agreed that treatment should be offered irrespective of the duration of the spasticity. The Delphi consensus also stressed the importance of patient-centered goals in order to satisfy the clinical needs of the patient regardless of time of onset or duration of spasticity. The findings arising from this Delphi process provide insights into the unmet needs in managing post-stroke spasticity from the clinician's perspective and provides guidance for physicians for the utilization of BoNT-A for the treatment of post-stroke spasticity in daily practice.