Alcohol use disorder in the COVID-19 era: Position paper of the Italian Society on Alcohol (SIA).

Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment.

Alcohol-Related Liver Disease in the Covid-19 Era: Position Paper of the Italian Society on Alcohol (SIA).

BACKGROUND: Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. AIMS: The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. METHODS: A panel of experts of the Italian Society of Alcohology (SIA) met via "conference calls" during the lockdown period to draft the SIA's criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. RESULTS AND CONCLUSIONS: The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.

Diagnosis and treatment of acute alcohol intoxication and alcohol withdrawal syndrome: position paper of the Italian Society on Alcohol.

The chronic use of alcohol can lead to the onset of an alcohol use disorder (AUD). About 50% of subjects with an AUD may develop alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption and, in 3-5% of them, convulsions and delirium tremens (DTs), representing life-threatening complications, may occur. Unfortunately, few physicians are adequately trained in identifying and treating AWS. The Italian Society on Alcohol has, therefore, implemented a task force of specialists to draw up recommendations for the treatment of AWS with the following main results: (1) while mild AWS may not require treatment, moderate and severe AWS need to be pharmacologically treated; (2) out-patient treatment is appropriate in patients with mild or moderate AWS, while patients with severe AWS need to be treated as in-patients; (3) benzodiazepines, BDZs are the "gold standard" for the treatment of AWS and DTs; (4) alpha-2-agonists, beta-blockers, and neuroleptics may be used in association when BDZs do not completely resolve specific persisting symptoms of AWS; (5) in the case of a refractory form of DTs, the use of anaesthetic drugs (propofol and phenobarbital) in an intensive care unit is appropriate; (6) alternatively to BDZs, sodium oxybate, clomethiazole, and tiapride approved in some European Countries for the treatment of AWS may be employed for the treatment of moderate AWS; (7) anti-convulsants are not sufficient to suppress AWS, and they may be used only in association with BDZs for the treatment of refractory forms of convulsions in the course of AWS.

Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate.

BACKGROUND: Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. METHODS: This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. RESULTS: Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%) had plasma lactate ≥2 mmol/L. Fourteen (10.4%) of them had PE-related complications versus 6 of 361 patients with low lactate (negative predictive value 98.3%; p<0.001). Patients with elevated plasma lactate had an increased rate of PE-related complications (adjusted OR 5.3; 95% CI 1.9 to 14.4; p=0.001) compared with those with low lactate. The combination of elevated plasma lactate with markers of right ventricular dysfunction (by echocardiogram) and myocardial injury (by cardiac troponin) was a particularly useful prognostic indicator (positive predictive value 17.9%; 95% CI 6.1% to 36.9%). CONCLUSIONS: Plasma lactate represents a powerful predictor of short-term PE-related complications and may provide guidance for decision-making in PE care.

Imaging after GliaSite brachytherapy: prognostic MRI indicators of disease control and recurrence.

PURPOSE: In this study, we analyzed the magnetic resonance imaging (MRI) changes in patients after GliaSite treatment and characterized the prognostic MRI indicators in these patients. METHODS AND MATERIALS: A total of 25 patients with recurrent glioblastoma multiforme were treated with the GliaSite Radiation Therapy System. Patients at the Johns Hopkins Hospital with recurrent glioblastoma multiforme underwent surgical resection followed by GliaSite balloon implantation. Available MRI scans for 20 patients were obtained throughout the post-GliaSite treatment course. These were reviewed and analyzed for prognostic significance. RESULTS: After GliaSite treatment, all patients developed some degree of T(1)-weighted contrast and T(2)-weighted hyperintensity around the resection cavity. The development of enhancement on T(1)-weighted contrast-enhanced imaging and the size of these lesions, in the absence of increasing T(2)-weighted hyperintensity, before clinical progression was not associated with decreased survival. Patients with T(1)-weighted enhancement >1 cm had a median survival of 13.6 months and those with T(1)-weighted lesions

Coronary flow reserve in hypertensive patients with hypercholesterolemia and without coronary heart disease.

BACKGROUND: Coronary flow reserve (CFR) may be reduced both in arterial hypertension and in hypercholesterolemia. The aim of the study was to assess an association between CFR and levels of plasma total cholesterol (TC) in untreated arterial hypertension. METHODS: We studied 54 consecutive, untreated hypertensive outpatients free of coronary heart disease. Twenty of them had normal TC and 34 high TC (>/=200 mg/dL). Standard echocardiograms and transthoracic Doppler interrogation of the distal left anterior descending artery were obtained. Coronary diastolic peak velocities were measured both at rest and after low-dose dipyridamole. The CFR was calculated as dipyridamole/resting velocities ratio. RESULTS: The two groups had similar age, body mass index, heart rate, and diastolic blood pressure (BP). Patients with high TC had higher systolic BP (P < .05), triglycerides (P < .02), LDL-cholesterol, and TC/HDL-cholesterol ratio (both P < .0001) than controls. Left ventricular (LV) mass index, relative wall thickness, and fractional shortening did not differ between the two groups. Coronary diastolic peak velocities were similar at rest but lower after dipyridamole in patients with high TC (P < .02). As a consequence, CFR was reduced (P < .002). In multiple linear regression analyses, adjusting for age, heart rate, systolic BP, smoking, and relative wall thickness, TC (beta = -0.338) or high LDL-cholesterol (beta = -0.301) (both P < .001) were predictors of lower CFR independently of the concomitant effect of potential confounders. CONCLUSIONS: In hypertensive patients free of coronary artery disease, the degree of impairment in coronary vasodilator capacity is independently associated with plasma cholesterol and LDL-cholesterol.

Early detection of biventricular involvement in myotonic dystrophy by tissue Doppler.

BACKGROUND: Myotonic dystrophy is associated with arrhythmias and risk of sudden death but also with symptoms of heart failure. Our study aimed to identify early biventricular dysfunction in asymptomatic patients with myotonic dystrophy by tissue Doppler. METHODS: Thirty-six patients with myotonic dystrophy (M/F=20/16, mean age=36.4 years), asymptomatic for heart failure, and 36 age- and sex-matched healthy controls underwent Doppler echocardiography and pulsed tissue Doppler of lateral mitral annulus and of tricuspid annulus. RESULTS: The two groups had similar body mass index, blood pressure, heart rate, cardiac mass and endocardial shortening. Standard Doppler showed significantly lower transmitral early (E) diastolic peak velocity, longer transmitral deceleration and isovolumic relaxation times and higher tricuspid inflow atrial peak velocity in myotonic dystrophy than in controls. Tissue Doppler of mitral annulus showed lower myocardial systolic velocity (p<0.02), lower early diastolic velocity (E(m)) (p<0.05) and atrial velocity (A(m)) (p<0.005), but no difference of E(m)/A(m) ratio. At tricuspid annulus, E(m) and E(m)/A(m) ratio were lower (p<0.02 and p<0.005, respectively). The ratio between tricuspid inflow E velocity and E(m), index of the degree of right ventricular filling pressure, was higher (p<0.001) than in controls. Tissue Doppler derived left ventricular and right ventricular measurements were all associated with the disease condition, independent of age and heart rate. CONCLUSIONS: Tissue Doppler identifies subclinical biventricular involvement in myotonic dystrophy. Early left ventricular myocardial systolic and diastolic changes are evident. Right ventricular dysfunction, involving myocardial relaxation and right ventricular filling pressure, might be the arrhythmogenic substratum of these patients.

The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas.

Temozolomide (TMZ) administered daily with radiation therapy (RT) for six weeks, followed by adjuvant TMZ for six months, has become standard therapy for patients with glioblastoma multiforme (GBM). After several newly diagnosed patients at our institution developed severe (grade 3-4), prolonged thrombocytopenia, we conducted a retrospective review to define the incidence, depth, and duration of thrombocytopenia associated with this therapy. We reviewed the medical records and laboratory data of all adult patients with newly diagnosed high-grade gliomas who started treatment with this regimen between June 2004, when the regimen was first used at our institution, and August 2005. Of the 52 patients who met the criteria for this review, grade 3-4 thrombocytopenia occurred in 10 (19%; 95% CI, 10%-33%). In eight patients, the thrombocytopenia was attributable to concurrent daily TMZ and RT. The median duration of grade 3-4 thrombocytopenia was 32 days (range, 1-389 days). Five patients (10%) required platelet transfusions, two (4%) have required continued biweekly platelet transfusions for over six months, and nine (17%) discontinued therapy because of thrombocytopenia. Grade 3-4 thrombocytopenia occurred in 25% of women and 14% of men. Grade 3-4 neutropenia and anemia were noted in 10% and 8% of patients, respectively, and were not clinically significant. Between 15% and 20% of our newly diagnosed patients receiving TMZ and RT developed severe (grade 3-4) and potentially irreversible thrombocytopenia. The factors that predispose patients to this toxicity have yet to be determined. This toxicity should be considered when (1) prescribing this regimen to patient populations where a clinical benefit has yet to be shown, (2) contemplating empirical escalations of the dose or duration of TMZ, or (3) combining it with other potentially myelosuppressive therapies.

Primary brain tumors treated with steroids and radiotherapy: low CD4 counts and risk of infection.

PURPOSE: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. METHODS AND MATERIALS: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. RESULTS: CD4 counts decreased to <200/mm3 in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm3 before RT, but 6 (24%) of 25 fell to <200/mm3 during RT. Patients with counts <200/mm3 were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of steroids, mean minimal white blood cell count, and number of patients treated with Gliadel wafers were not significantly different between the groups. CONCLUSION: The results of this study have confirmed the clinical impression that the use of high-dose corticosteroids and RT in patients with primary brain cancer is sufficient to result in severe immunosuppression and place these patients at risk of life-threatening opportunistic infections. A protocol of prophylactic antibiotics for those at risk may help prevent a potentially fatal side effect of treatment. A prospective study is underway to determine the frequency, depth, and prognostic implications of this finding.

Treatment of recurrent glioblastoma multiforme with GliaSite brachytherapy.

PURPOSE: In this study, we assess the efficacy of GliaSite brachytherapy in the treatment of patients with recurrent glioblastoma multiforme (GBM). METHODS AND MATERIALS: Between 1999 and 2004, 24 patients with recurrent glioblastoma multiforme were treated with the GliaSite Radiation Therapy System (RTS). The GliaSite is an inflatable balloon catheter that is placed in the resection cavity at the time of surgical resection. Low-dose-rate radiation is then delivered locally by temporarily inflating the balloon with an aqueous solution of organically bound (125)I (Iotrex [sodium 3-((125)I)-iodo-4-hydroxybenzenesulfonate]). Patients at the Johns Hopkins Hospital with recurrent GBM, who were previously treated with surgery and external beam radiotherapy, underwent surgical resection followed by GliaSite balloon implantation. Subsequently, the patients received radiation therapy using the GliaSite to a mean dose of 53.1 Gy. Ten patients were male, and 14 patients were female. The mean age was 48.1 years. All patients had pathologically confirmed recurrent GBM. The median Karnofsky performance status (KPS) was 80. Median follow-up time was 21.8 months. RESULTS: At the time of analysis, 18 patients (75%) had died; 6 patients (25%) were alive. Median survival from diagnosis for all patients was 23.3 months. Median survival after GliaSite brachytherapy was 9.1 months. Patients with a KPS > or =70 had a median survival of 9.3 months, whereas patients with a KPS <70 had a median survival of 3.1 months (p < 0.003). Survival was not significantly different between patients receiving 45 Gy and patients receiving a dose greater than 45 Gy. Acute side effects were minor, consisting of mild nausea and/or headache. One patient developed a wound infection. No incidents of meningitis were observed. Late sequelae were rare, but 2 incidents of symptomatic radiation necrosis were observed. One patient developed transient expressive aphasia. CONCLUSIONS: GliaSite radiotherapy confers a prolongation of survival in patients with recurrent glioblastoma multiforme compared to historical controls with recurrent GBM. GliaSite therapy leads to a favorable survival outcome of 9.3 months in patients with KPS > or =70, but only 3.1 months in patients with KPS <70. Favorable survival is observed for patients within each recursive partitioning analysis class. Treatment with GliaSite is safe and generally well tolerated. Additional data are needed to fully assess the therapeutic benefit of GliaSite brachytherapy for recurrent GBM.