Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

Effect of 5% transdermal lidocaine patches on postoperative analgesia in dogs undergoing hemilaminectomy.

OBJECTIVES: To investigate the effect of 5% lidocaine patches on postoperative analgesia in dogs undergoing hemilaminectomy. MATERIALS AND METHODS: Client-owned dogs undergoing hemilaminectomy for a single acute intervertebral thoracolumbar disc extrusion were enrolled in this prospective, randomised, blinded clinical trial. Following methadone administration, anaesthesia was induced with propofol, and maintained with isoflurane in oxygen and fentanyl infusion, in both groups. After skin closure, two 1∙5 cm wide 5% lidocaine patch strips were attached along both sides of the wound in dogs allocated to Group L. In Group C, the two lidocaine patch strips were applied but the transparent isolating liner was not removed. Postoperatively, all dogs received a non-steroidal anti-inflammatory drug, gabapentin and diazepam. Methadone was administered according to the short form of Glasgow Composite Pain Scale with pain assessed every 2 hours for 48 hours by observers unaware of the treatment. RESULTS: Thirty-nine dogs completed the study. Demographic data, end-expiratory fraction of isoflurane, fentanyl consumption, anaesthesia and surgical times were similar between groups. The number of dogs requiring postoperative methadone and the number of doses of methadone administered were not different between groups. No macroscopic skin reaction was noticed once the patches were removed. CLINICAL SIGNIFICANCE: In this setting, 5% lidocaine patches did not provide additional postoperative analgesia in dogs undergoing hemilaminectomy.

Retrospective clinical evaluation of hypobaric spinal anaesthesia in dogs undergoing pelvic limb orthopaedic surgery.

OBJECTIVE: To evaluate intraoperative effects, complications, postoperative rescue analgesia requirement and presence of postoperative unilateral blockade after hypobaric spinal anaesthesia in dogs. METHODS: Retrospective review of case records of dogs that underwent pelvic limb orthopaedic surgery and received hypobaric spinal anaesthesia. Cases that contained complete information on perioperative analgesia, end tidal anaesthetic agent, arterial blood pressure, postoperative urination, motor function and assessment at the sixth week re-examination were selected. RESULTS: Twenty-four of forty-eight records were sufficiently complete to meet the selection criteria. Local anaesthetic dose and volume of the solution administered were 0 · 22 (±0 · 06) mg/kg and 0 · 16 (±0 · 05) mL/kg, respectively. Fentanyl was administered intraoperatively in seven dogs (29%); mean ± sd end-expired isoflurane was 1 · 09 ± 0 · 17%; hypotension was observed in nine dogs (37 · 5%). Unilateral blockade was documented in 18 dogs (75%); 6 dogs (25%) required methadone postoperatively; urinary retention was not observed. One dog developed steroid responsive meningitis arteritis. CLINICAL SIGNIFICANCE: Hypobaric spinal anaesthesia achieved unilateral postoperative pelvic limb motor blockade in dogs, although bilateral block occurred in a proportion of animals; intraoperative hypotension was not infrequent. Fentanyl and postoperative methadone might be required to control nociception and pain, despite technical success in performing spinal anaesthesia.

Retrospective comparison of two peripheral lumbosacral plexus blocks in dogs undergoing pelvic limb orthopaedic surgery.

OBJECTIVES: To compare the lateral pre-iliac approach to the lumbar plexus combined with lumbar paravertebral sciatic nerve block, and the dorsal paravertebral approach to the lumbar plexus combined with sciatic nerve block in dogs. METHODS: Retrospective examination of case records of dogs that received the blocks and underwent pelvic limb orthopaedic surgery between 2010 and 2012. Success rate (intraoperative fentanyl consumption <2·1 µg/kg/hour), type and dose of local anaesthetic used, multiple of minimum alveolar concentration of volatile anaesthetic agent administered, incidence of intraoperative hypotension, postoperative methadone administration, postoperative contralateral limb paralysis and neurological complication at 6 weeks re-examination were analysed. RESULTS: Ninety-six and 95 records were retrieved in which lateral pre-iliac - lumbar paravertebral sciatic nerve and dorsal paravertebral - sciatic nerve were used, respectively. Success rates were 82·3% in lateral pre-iliac - lumbar paravertebral sciatic nerve and 74·7% in dorsal paravertebral - sciatic nerve groups. Bupivacaine, levobupivacaine and ropivacaine were used. Total local anaesthetic doses, intraoperative hypotension and postoperative methadone administered were similar between groups; minimum alveolar concentration multiple was significantly (P<0·001) lower in lateral pre-iliac - lumbar paravertebral sciatic nerve group. No neurological complications were noted. CLINICAL SIGNIFICANCE: Although success rates and perioperative analgesic requirements were not significantly different, the different exposure to anaesthetic agents suggests that the two techniques may not be equivalent.

Alcohol addiction: evaluation of alcohol abstinence after a year of psycho-medical-social treatment.

The aim of this study was to evaluate alcohol abstinence in alcoholics and their family relationships after a year of treatment. The 100 alcoholics recruited were divided into two groups: ALC, where treatment consisted of clinical control and meetings of with the family consulting together with their relatives at the Centre for Study and Treatment of Alcoholism and CAT, where treatment consisted of clinical control and weekly attendance together with their relatives at Alcoholics-in-Treatment-Clubs (CAT). The clinical condition of the sample was assessed by laboratory data. The subjects were given an MQ-Quant questionnaire, based on an artificial neural network (ANN) model, which analyses the communicative fatigue of their interactions. The same examination was applied after 1 year excluding patients relapsed and their relatives. Psycho-medical-social treatment by the attendance of alcoholics and their families into a Multifamily Community induces alcohol abstinence of about 79%. This percentage is greater than psycho-medical treatment carried out in the Centre of Alcoholism for ALC group (50%). We observed a significant difference between the communicative fatigue of the ALC group compared to the CAT group.

Lofexidine versus clonidine in rapid opiate detoxification.

The aim of the present study is to evaluate lofexidine and clonidine, in an accelerated opiate detoxification procedure (3 days), without anaesthesia. Forty heroin-dependent individuals were detoxified, evaluating withdrawal symptoms, craving levels, mood changes, urine toxicologic screens, and dropout during therapy with either (1) clonidine, oxazepam, baclofen, and ketoprofene, with naloxone and naltrexone for 3 days (20 subjects) or (2) lofexidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone for 3 days (20 subjects). Both clonidine and lofexidine rapid detoxifications were found effective. The subjects treated with lofexidine showed significantly lower levels of withdrawal symptoms, fewer mood problems, less sedation and hypotension. No significant differences in craving levels, morphine metabolites in urine, or dropout rate were evidenced between the two groups. The early use of naltrexone during detoxification in combination with either alpha-2-agonist facilitated the acceptance for long-term naltrexone treatment. Lofexidine appeared to be more useful than clonidine in a 3-day accelerated opiate detoxification, not only to counteract withdrawal symptoms, but also in the treatment of dysphoria and mood changes. Because lofexidine does not produce hypotension, safe outpatient treatment, without hospital support, could be possible.

Sodium sensitivity of blood pressure in long-term detoxified alcoholics.

To investigate whether sodium sensitivity of blood pressure participates in the relationship of arterial hypertension to chronic alcohol consumption, 30 alcoholics detoxified from 6 to 12 months and 30 teetotaler controls underwent a dietary sodium manipulation study. They received a daily 55 mmol sodium diet for 7 days, followed by a 260 mmol sodium diet for 7 days. Changes in 24-hour urinary sodium excretion between the end of each period were similar in alcoholics and controls (202+/-16 SEM mmol and 227+/-11, respectively). Plasma renin activity in alcoholics was lower than in controls at both low (2.4+/-0.4 ng angiotensin I/mLxh(-1) versus 3. 7+/-0.2, P<0.003) and high sodium intake (0.47+/-0.10 versus 0. 82+/-0.10, P<0.05), with smaller variations in alcoholics (-1.9+/-0. 3 versus -2.9+/-0.2, P<0.009). In alcoholics, alteration in sodium intake was followed by greater changes in both systolic and mean blood pressure (ambulatory blood pressure monitoring), which rose by 10.6+/-2.2 mm Hg and 7.3+/-1.5 versus 4.7+/-1.4 and 3.9+/-1.0 in controls, respectively (P<0.03 for systolic and P<0.05 for mean blood pressure). The ratio of changes in mean blood pressure to those in 24-hour urinary sodium excretion was higher in alcoholics (0.044+/- 0.011 mm Hgxmmol(-1) versus 0.018+/-0.0041, P<0.005). Our data show that in detoxified alcoholics, there is an abnormal response of both blood pressure and plasma renin activity to variations in salt intake similar to that in sodium-sensitive arterial hypertension. The precise relationship between the sodium sensitivity of blood pressure in detoxified alcoholics and the long-term influence of alcohol on blood pressure remains to be elucidated.

Failure of gammahydroxy butyric acid to stimulate growth hormone secretion in cocaine addicts.

This study discusses the effect of gammahydroxy butyric acid (GHB) on growth hormone (GH) secretion changes in cocaine addicts. Ten male cocaine users and 10 normal controls were tested with a single oral administration of GHB at a dose of 25 mg/kg body weight. Cocaine addicts were tested before and after 30 days of abstinence. All subjects underwent a control with a placebo. Basal GH levels were similar in normal controls and cocaine users and remained unmodified during the control test. In the normal control subjects, plasma GH levels rose significantly after the administration of GHB; in contrast, plasma GH concentrations failed to increase after GHB treatment in cocaine addicts. These data show that a chronic abuse of cocaine induces alterations of the GABAergic system which were unmasked by the absent GH response to GHB.

Interleukin-6 receptor antagonists inhibit interleukin-11 biological activity.

The IL-6 receptor system comprises two functionally different chains: a binding chain (IL-6R) and a signal-transducing chain (gp130). The IL-6/IL-6R complexes associate with gp130, induce its dimerization and signal transduction. When IL-6 is complexed to IL-6R, two distinct sites of IL-6 are able to bind gp130. Other cytokines-oncostatin M (OM), leukemia inhibitory factor (LIF) or ciliary neurotrophic factor (CNTF) also use the gp130 transducer and induce its heterodimerization with LIF receptor (LIFR). A series of IL-6 mutants have been generated which function as IL-6 receptor antagonists (IL-6RA). These IL-6RA carried substitutions that increased their affinity with IL-6R and abolished 1 or the 2 sites of interaction with gp130. All the IL-6RA inhibited wild-type IL-6. The IL-6RA with one mutated binding site to gp130 inhibited IL-11 activity. They did not affect those of CNTF, LIF and OM, even when used at a very high concentration at which virtually all membrane IL-6R were bound to IL-6RA. IL-6RA with two mutated gp130 binding sites did not affect IL-11, CNTF, LIF or OM activities. The results indicate that the interaction of one gp130 chain with IL-6R/IL-6R complexes inhibited further the dimerization of gp130 induced by IL-11/IL-11R but not its heterodimerization with LIFR. Thus these IL-6RA can also function as IL-11 antagonists.

Circadian variations in plasma ACTH, cortisol and beta-endorphin levels in normal-weight bulimic women.

In order to establish possible alterations in the secretory patterns of adrenocorticotropic hormone (ACTH), cortisol and/or beta-endorphin in bulimia nervosa, the circadian fluctuations of these hormones were evaluated in blood samples taken at 1-hour intervals over 24 h. Eleven bulimic women with normal body weight and 8 weight- and age-matched normal controls were tested during the follicular phase (days 6-8) of normal menstrual cycles. All women were hospitalized for bulimia or for checkup examinations and were tested 3 days after hospital admission. Both normal and bulimic women showed maximal ACTH, cortisol and beta-endorphin levels at 08.00 h, with minimal ACTH and beta-endorphin levels at midnight and cortisol levels at 02.00 h. The general temporal structure of all hormonal secretions coincided in the two groups. However, whereas all measured ACTH/cortisol levels were quantitatively similar in the two groups, plasma beta-endorphin concentrations were significantly higher in bulimic than in control subjects at all examined time points. The enhancement in the overall 24-hour beta-endorphin secretion suggests the presence of an increased opioid tonus in bulimic women, which might play a role in the pathophysiology of the eating disorder.

Analysis of CA/GT microsatellite polymorphism in IVS8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a study of Italian CF families.

Forty-six CF Italian patients and their parents were screened for a highly polymorphic microsatellite consisting of a variable number of CA/GT repeats in intron 8 of the CFTR gene. A strong degree of association was found between alleles 2 and 6 and the CF mutation delta F508. Moreover, considering the haplotypes at the closely linked locus D7S23 and the microsatellite's alleles, a strong linkage disequilibrium was again found for delta F508 and also for non-delta F508 CF chromosomes and the eight commonest haplotypes (B2, B6, C7, A6, A7, B7, D2 and D7). These data, compared with those described in the Spanish population, further support the common origin of the delta F508 mutation in Southern European populations.

Carrier detection for prenatal diagnosis of hemophilia A in Italian families.

BACKGROUND: The results obtained from a comparative analysis between phenotypic bioassays as the ratio of factor VIII: C clotting activity to factor VIII: C-related antigen, and DNA haplotypes from RFLP's TaqI/St14 and BclI/F8A in 12 hemophilia A (HeA) families are described. METHODS: DNA from HeA patients and related at-risk women has been analyzed by Southern blotting with two probes: the intragenic F8A and the extragenic St14. Factor VIII: C coagulant activity was measured by a one-stage method, and the Factor VIII-related antigen (FVIII: RAg) was assayed with bidimensional electrophoresis. Linkage analysis was performed with the LINKAGE computer programs; in particular, the risks of carrying HeA were calculated using the MLINK program. RESULTS: The observed heterozygosity for the flanking marker DXS 52 (TaqI/St14 RFLP) in combination with intragenic BclI/F8A polymorphism was 0.94. A statistically significant difference in frequency was detected at the DXS 52 locus (allele 4) in comparison with other Caucasian populations. Linkage analysis made it possible to combine the plasma bioassay values with the DNA marker haplotypes to determine the probability of carriership; 22 females at risk were investigated: 4 of them were identified as carriers and 18 were excluded. The risk of carrying hemophilia A for some women at risk in six families is reported. CONCLUSIONS: This study compares a classic method and DNA analysis in genetic counselling for hemophilia A. In some cases the two methods may give different results when identifying carriers in at-risk families. From these data it is possible to conclude that DNA analysis combined with the phenotypic bioassays for carrier detection gives more information that the two analyses taken separately.

[Vascular damage in arterial hypertension: its noninvasive assessment]. / Il danno vascolare nell'ipertensione arteriosa: valutazione non invasiva.

Arterial hypertension is a definite risk factor for the atherosclerotic disease and thus has a primary role in the genesis of cardiovascular diseases, but it acts also though a direct structural damage of great and small arteries and arterioles. Up to date, clinical research and technological advancements have made possible the development of instruments and methods for the evaluation of the vascular damage. Ultrasonographic methods are now the better non invasive tools for the study of arterial diseases, allowing a definition power comparable to angiography, and giving useful data on characters and composition of plaques, also minimal, at the level of the arterial district of lower limbs, epiaortic, renal, and abdominal vessels. These methods allow the study of the vascular lesion under the hemodynamic (CW or pulsed Doppler with spectral signal analysis) and the morphological profile (high resolution echotomography) or both echo-Doppler duplex scanning or color flow imaging). Arterial compliance of great vessels can be studied through the Doppler evaluation of pulsed wave velocity along the arterial tree. Other useful parameters are the aortic distensibility (ratio between % change in arterial volume and blood pressure), the elastic module, the index of arterial rigidity and the aortic index (ratio between pulse pressure and stroke volume). By using this latter parameter we demonstrated a significant decrease of arterial compliance that is proportional to the severity of blood pressure values. Small vessels may be studied through strain-gauge plethysmography, that allows to obtain the regional blood flows at the hand and forearm (skin circulation) and the calf (muscular circulation) both in basal conditions and after ischaemic stimulus. From the ratio between mean arterial pressure and post-ischemic blood flow it is possible to obtain minimal vascular resistances, expression of the maximal vasodilatation capacity in the arteriolar bed. With this method we showed that minimal vascular resistances increase proportionally with the increase of blood pressure in borderline hypertensives, in mild, moderate and severe stable arterial hypertension and in hypertension of the aged. The cutaneous microcirculation may be studied also by laser Doppler and capillaroscopy, that show a reduced capillary perfusion in hypertension. Clinically, these diagnostic tools are also extremely useful for studying the effects of antihypertensive treatment on structure and function of arterial vessels, as it seems that some drugs are able to counteract the structural alterations related to hypertension.

delta F508 deletion in cystic fibrosis in Italian families.

In 20 Italian families with cystic fibrosis (CF), restriction fragment length polymorphisms were detected by five linked markers; a strong linkage disequilibrium is observed between the haplotype B (alleles 2/1 with respect to KM19/XV2c) and CF. The frequency of the delta F508 deletion in CF chromosomes of this sample is 50%. A significant correlation is found between the absence of the delta F508 mutation and pancreatic sufficiency.

[Cardiac arrhythmia in relation to the leaflet morphology in subjects with mitral valve prolapse]. / Disturbi del ritmo cardiaco in rapporto alla morfologia dei lembi in soggetti con prolasso valvolare mitralico.

Aim of this study was to verify the prevalence of cardiac arrhythmias in subjects with mitral valve prolapse (MVP) and redundant leaflets in comparison with subjects with MVP without leaflets redundance. So, 60 subjects (aged 13 to 39 years), were subdivided in 3 groups on the basis of mitral leaflets shape at 2D-echocardiography; a continuous ECG monitoring (24 hours) was also performed. Arrhythmias were more frequent and more severe in the Group III (subjects with MVP and redundant leaflets), in comparison with both Group II (subjects with MVP without leaflets redundance) and Group I (control subjects). In particular, analysing the mean values of the single arrhythmias in the 24 hours, ventricular ectopic beats (VEB), were more frequent in Group II (p less than 0.01) and Group III (p less than 0.05) in comparison with Group I; the couplets and the runs of ventricular tachycardia were more frequent in Group III than in the other groups (p less than 0.001). The number of the subjects with a Lown class greater than 3 was higher in Group III than in the other groups (p less than 0.01). In conclusion, this study confirms that MVP is a disease presenting a large variability arrhythmic risk, that seems to be real only for a subgroup of these subjects.