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.

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.

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.