Use of perampanel oral suspension for the treatment of refractory and super-refractory status epilepticus.

INTRODUCTION: Status epilepticus (SE) is a medical emergency associated with a significant risk of disability and death. The treatment of SE follows a step-wise approach, with limited data on ideal antiseizure medications (ASMs) for refractory and super refractory SE (RSE/SRSE). Perampanel (PER), an AMPA receptor antagonist, has shown promise in animal models but still has limited data in humans. This study tried to evaluate optimal dosage and safety of PER in RSE and SRSE patients. MATERIALS AND METHODS: We retrospectively analysed 17 adult patients with RSE (1) or SRSE (16) treated with PER. Demographic and clinical data, including EEG patterns, ASMs administered, PER dosages, and PER plasma concentrations, were collected. For patients receiving a 24 mg PER loading dose (full dose group), the following treatment regimen was applied: 24 mg per day for 48 h following by 16 mg per day. The response to PER was assessed based on electroencephalographic (EEG) improvement from high to low epileptiform activity or from low to the absence of epileptiform activities. Safety was evaluated monitoring hepatic and renal function. RESULTS: A response rate of 58.82 % was observed, with significantly higher responses in the full dose group (81.82 %) compared to those receiving PER doses below 24 mg (low dose group) (16.67 %) (p-value = 0.004; OR 0.044, 95 % CI 0.003 to 0.621, p = 0.021). No other clinical factors significantly influenced treatment response. Hepatic enzymes become elevated in most patients (70.59 %) but spontaneously decreased. DISCUSSION: Our findings suggest that a 24 mg PER dose administered for 48 h may be more effective in managing RSE and SRSE compared to doses below 24 mg, potentially due to pharmacokinetic factors. CONCLUSION: More robust data on PER in RSE and SRSE, including standardized dosing procedures and plasma level monitoring are needed. PER's potential benefits should be explored further, particularly in patients with RSE and SRSE.

Lumacaftor/ivacaftor in cystic fibrosis: effects on glucose metabolism and insulin secretion.

PURPOSE: The question whether the new cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs aimed at restoring CFTR protein function might improve glucose metabolism is gaining attention, but data on the effect of lumacaftor/ivacaftor treatment (LUMA/IVA) on glucose tolerance are limited. We evaluated the variation in glucose metabolism and insulin secretion in CF patients homozygous for Phe508del CFTR mutation after one-year treatment with LUMA/IVA in comparison to patients with the same genotype who did not receive such treatment. METHODS: We performed a retrospective case-control study on 13 patients with a confirmed diagnosis of CF, homozygous for the Phe508del CFTR mutation, who received LUMA/IVA for one year (cases) and 13 patients with identical genotype who did not receive this treatment (controls). At the beginning and conclusion of the follow-up, all subjects received a modified 3 h OGTT, sampling at baseline, and at 30 min intervals for plasma glucose, serum insulin, and c-peptide concentrations to evaluate glucose tolerance, and quantify by modeling beta-cell insulin secretion responsiveness to glucose, insulin clearance and insulin sensitivity. RESULTS: LUMA/IVA did not produce differences in glucose tolerance, insulin secretory parameters, clearance and sensitivity with respect to matched controls over one-year follow-up. CONCLUSION: We found no evidence of improvements in glucose tolerance mechanisms in patients with CF after one-year treatment with LUMA/IVA.

Nasal Vestibulitis and Vestibular Furunculosis: a systematic review about two common nasal infections and considerations about correct diagnosis and management.

Background: Nasal vestibulitis (NV) and nasal vestibular furunculosis (NVF) are two infectious processes of the nasal vestibule, sharing common etiology, the same risk of complications, and similar treatment while remaining two different pathological entities. Methods: We performed a comprehensive literature research on NV and NVF in PubMed, Cochrane, and Google Scholar databases, with the aim to review the evidence on these two conditions and discuss the therapeutic approaches. Results: We identified a total of 248 records; according to our inclusion/exclusion criteria, 27 of them, published over a period of 59 years (1962-2021), were included in this review. Conclusion: NV and NVF are reported to be common conditions, with well-known etiological agents and risk factors. The diagnosis is clinical and topical antibiotics are the mainstay of treatment. Complications appear to be infrequent. Further studies are necessary to clarify the pathogenetic mechanisms and the exact prevalence of both conditions.

Evaluation of Discomfort in Nasopharyngeal Swab Specimen Collection for SARS-CoV-2 Diagnosis.

BACKGROUND: The rapid spread of COVID-19 worldwide has impo-sed the need to identify a test that quickly recognizes affected subjects, both symptomatic and asymptomatic. The most reliable option has been proven to be the RT-PCR, which allows to detect virus RNA on a specimen from a high viral load site, such as nasopharynx. Nasopha-ryngeal sample collection is possible by means of a nasopharyngeal swab (NPS) and is a practical and relatively non-invasive technique, but rather bothersome for the recipient. AIM: The aim of the present study is to evaluate the discomfort evoked during NPS. MATERIALS AND METHODS: We surveyed 429 patients receiving NPS before hospitalization or other procedures non related to COVID-19. For each one we noted the discomfort level felt during the swab using a 11-point numeric rating scale (NRS) for pain and the total time needed for the procedure to be taken. Sex, age, smoking status and positive history of previous swab have been taken into account. RESULTS: We found that, among the variables, sex had a statistically significant impact on the perceived discomfort of nasal swab, with females experiencing slightly more discomfort. CONCLUSIONS: NPS is largely a none-to-minimum discomfort in-ducing procedure. The differences in perceived discomfort could be explained based on anatomical features, and should remark the need for a tailored and anatomy-oriented approach in each patient.

Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement.

BACKGROUND: Gut-liver axis (GLA) dysfunction appears to play a role in obesity and obesity-related hepatic complications. OBJECTIVES: This study sought to concurrently explore several GLA components in a paediatric obese population with/without liver disease. METHODS: Thirty-two children (mean age 11.2 years) were enrolled: nine controls with normal weight and 23 patients with obesity (OB+). Of the 23 patients OB(+), 12 had not steatosis (ST-), and 11 had steatosis (ST+) (associated [n = 8] or not [n = 3] with hypertransaminasaemia [ALT +/-]). Subjects were characterized by using auxologic, ultrasonographic and laboratory parameters. A glucose hydrogen breath test was performed to test for small intestinal bacterial overgrowth, a urinary lactulose/mannitol ratio (LMR) was obtained to assess intestinal permeability, and tests for transaminases, blood endogenous ethanol, endotoxin and faecal calprotectin were also conducted. RESULTS: Eleven out of 23 patients OB(+) (p < 0.05) exhibited pathological (>90th percentile of the control group values) LMR, with values paralleling the grade of liver involvement (normal weight < OB[+] < OB[+]ST[+]ALT[-] < OB[+)]ST[+]ALT[+] [p < 0.05]). LMR significantly correlated with ethanolaemia (r = 0.38, p = 0.05) and endotoxaemia (r = 0.48, p = 0.015) concentrations. Increased permeability was a risk factor for the development of steatosis (p < 0.002). SIBO was present only in patients with obesity. Faecal calprotectin concentrations were within normal limits in all subjects. CONCLUSIONS: Increased permeability, endogenous ethanol and systemic endotoxin concentrations reflect some GLA dysfunction in obesity and its hepatic complications. Pending further results to establish their potential causative roles, the modulation of the GLA appears to represent a possible target for the prevention and treatment of these conditions.

Estimating the Impact of Workplace Bullying: Humanistic and Economic Burden among Workers with Chronic Medical Conditions.

BACKGROUND: Although the prevalence of work-limiting diseases is increasing, the interplay between occupational exposures and chronic medical conditions remains largely uncharacterized. Research has shown the detrimental effects of workplace bullying but very little is known about the humanistic and productivity cost in victims with chronic illnesses. We sought to assess work productivity losses and health disutility associated with bullying among subjects with chronic medical conditions. METHODS: Participants (N = 1717) with chronic diseases answered a self-administered survey including sociodemographic and clinical data, workplace bullying experience, the SF-12 questionnaire, and the Work Productivity Activity Impairment questionnaire. RESULTS: The prevalence of significant impairment was higher among victims of workplace bullying as compared to nonvictims (SF-12 PCS: 55.5% versus 67.9%, p < 0.01; SF-12 MCS: 59.4% versus 74.3%, p < 0.01). The adjusted marginal overall productivity cost of workplace bullying ranged from 13.9% to 17.4%, corresponding to Italian Purchase Power Parity (PPP) 2010 US$ 4182-5236 yearly. Association estimates were independent and not moderated by concurrent medical conditions. CONCLUSIONS: Our findings demonstrate that the burden on workers' quality of life and productivity associated with workplace bullying is substantial. This study provides key data to inform policy-making and prioritize occupational health interventions.

Influence of age, gender, height and education on vibration sense. A study by tuning fork in 192 normal subjects.

We measured perception time of the vibratory stimulus from a 128 cps tuning fork in 96 male and 96 female normal subjects equally subdivided into 8 age decades. The following sites were examined: clavicula, olecranon, styloid apophysis of ulna and radius, anterosuperior spina of ilium, rotula (patella), internal and external malleolus. Reproducibility between different examiners and between tests by the same examiner on different days was good. There was a marked regional variation with longer perception times at the distal regions of upper limbs. A non linear age-related decrease in vibration sense was found in all regions. Males had longer perception times at clavicula, females at distal limbs; the latter finding might be explained by shorter stature in females. Perception times at distal limbs were longer in subjects with higher education levels. The study provides normative data for vibration sense in different regions and defines the effects on it of age, gender, height and education.

Octreotide treatment in secretory and cyrptosporidial diarrhea in patients with acquired immunodeficiency syndrome (AIDS): clinical evaluation.

Our objective was to evaluate the efficacy of octreotide in the treatment of AIDS patients with persistent diarrhea refractory to conventional therapy. We have treated 11 patients with AIDS related diarrhea (M/F-5/2, mean age 28 +/- 3 yr). The stool volume was in all pts > or = 21/24h. In 4 pts the diarrhea was secondary to cryptosporidium infection (Group A); in 7 pts the reason for the diarrhea could not be identified (Group B). Octreotide was administered in subcutaneous escalation doses, from 50 micrograms q8h to a maximum dose of 500 micrograms q8h. The minimal dose controlling symptoms was maintained for 21 days. In all patients stool volume and frequency decreased significantly. Group A pts were "partial responders" (stool 50% of initial daily volume); group B patients were "complete responders" (stools < 250-300 ml/day). Drug suspension resulted in a prompt return of diarrhea, especially in group A and in these patients, the cryptosporidium was continuously eliminated in the stool. With octreotide therapy there was a reduction in stool volume and frequency; whether this treatment is effective as long-term therapy for this AIDS manifestation is unknown.

Clinical trial with 5-fluorouracil and leucovorin.

Many clinical trials with 5-fluorouracil and leucovorin have been reported. This combination therapy seems to play an important role in untreated advanced colorectal cancer. In other neoplasms (gastric, head and neck, breast cancer) further studies are required.

Elderly patients with migraine: an open-label study on prophylaxis therapy with levetiracetam.

In the last years, the hypothesis that cortical hyperexcitability may play a role in the physiopathology of migraine led to the therapeutic use of some antiepileptic drugs. To evaluate the efficacy of levetiracetam as prophylactic treatment for migraine without aura in elderly patients. We performed a small open-label trial treating 13 elderly patients(8F 5M) mean age 64.7 years (SD 3.4), range 60-72 years affected by migraine without aura (ICDH '04 criteria). The mean age of disease was 21.3 years (SD13.4) range 2-45 years. At baseline: the frequency of attacks was 12.2/month (SD 5.9), range 6-25; the mean number of drugs for acute attacks was 12.6 (SD 6.5) tablets/month. All patients took concomitant medication for other chronic diseases. After recruitment Levetiracetam 500 mg/die was administered for 1 week and 1000 mg/die for six months. The basal frequency of attack was 12,2 (SD 5.9) and 8,3 (SD 4.9), 4,1 (SD2.6), 1,3 (SD1.4) after 1, 3 and 6 months respectively [P=0.079; P<0.0001; P<0.0001].The basal value of intaking drugs for acute attacks was 12,6 (SD 6.5) and 6,7 (SD 4.3), 2,8 (SD 2.2), 1,4 (SD1.7) after 1, 3 and six months respectively [P=0.012; P<0.0001; P<0.0001](T-test analysis). Levetiracetam was well tolerated (7 patients complained somnolence, lack of concentration and gastralgia but none patient withdrew the study). In our study levetiracetam showed a good efficacy in frequency and intensity reduction of headache attack and showed a very good tolerability despite all elderly patients took drugs for concomitant diseases.

Migraine and coronary artery disease: an open study on the genetic polymorphism of the 5, 10 methylenetetrahydrofolate (MTHFR) and angiotensin I-converting enzyme (ACE) genes.

Genetic factors that increase susceptibility to oxidative stress, endothelial disfunction and, possibly, stroke include angiotensin-converting enzyme gene deletion polymorphism (ACE-DD) and the methylentetrahydropholate reductase (MTHFR) C677-TT polymorphism. The relationship of ACE-DD genotype to ischemic stroke and cardiovascular disease is controversial, but it has been independently linked to lacunar infarction, in the absence of carotid atheroma. Lea et al. (2005) reported that the ACE DD genotype acts in combination with the MTHFR T/T genotype to increase migraine susceptibility, with the greatest effect in those with aura. The "TT" polymorphism is also associated with an increased risk of migraine with aura, independent of other cardiovascular risk factors. The aim of our study was to evaluate the incidence of ACE and MTHFR genes polymorphisms in a consecutive series of migrainous patients and of patients affected by myocardial infarction. We studied a series of 103 migrainous patients (1), whose age was between 13 and 75 years (81 suffering from migraine without aura, MwA, 9 from migraine with aura, MWA, 13 from mixed forms MwA-MWA, according to ICHD-II 2004 criteria) and of 336 patients (2) suffering from ischaemic cardiopathy (myocardial infarction, MI). The analysis, based on Polymerase Chain Reaction (PCR) and on reverse-hybridization, showed as follows: MTHFR (C677T): 60 patients (58%) (1) and 186 (56%) (2) were heterozygous; 9 patients (9%) (1) and 54 (16%) (2) were mutated. The result of 1 patient (2) was unknown. MTHFR (A1298C): 54 patients (52%) (1) and 146 (44%) (2) were heterozygous, 7 patients (7%) (1) and 33 (10%) (2) were mutated. The result of 1 patient (2) was unknown. ACE (evaluated on 101 patients (1) and 245 (2)): 45 patients (43%) (1) and 133 (54%) (2) had an ID genotype; 42 (41%) (1) and 87 (36%) (2) had a DD genotype. The results of our study confirm the high incidence in the genetic polymorphisms ACE and MTHFR in migraineuse. These data are confirmed in the sample of patients affected by myocardial infarction. This gives evidence of a strong relationship between migraine and major vascular diseases and let us hypothesize an important role of ACE and MTHFR system in the pathogenetic model of migraine for its capability to interfere with the endothelial regulation tone. Once an effective role in the genesis of migraine and in the increased risk of migrainous patients to evolve into an ischemic pathology has been obviously assigned to this genetic mutation, future researches must aim through wider and more controlled casistics also to clarify the role that drugs acting on these systems may have on the resolution of these diseases.

[Clinical description of three cases of cerebral cryptococcosis in patients with AIDS treated with fluconazole]. / Descrizione clinica di tre casi di criptococcosi cerebrale in pazienti con AIDS trattati con Fluconazolo.

The authors have evaluated the efficacy of Fluconazole (400 mg/iv/die for three days and after 200 mg/iv/die for 18 days) in three AIDS and SNC Cryptococcal infection patients. Two patients have shown healing of meningeal syndrome and negative isolation after 21 days of therapy; one patient, however, died because of Cytomegalovirus pneumonia. It is of note that early spinal puncture in AIDS patients with neurological symptoms enables an early diagnosis and immediate therapy. Fluconazole treatment has been well tolerated and immediately effective to resolve two of the cases observed; the oral prophylaxis with 100 mg/die of Fluconazole after 6 months has been effective to prevent the relapses of the disease.

[Serologic evaluation of circulating immune complexes in patients with HIV infections]. / Valutazione sierologica degli immunocomplessi circolanti (CIC) in pazienti con infezione da HIV.

In AIDS, immunitary system dysfunctions are manifold and regard both T and B-lymphocytes. The increased levels of circulating immune complexes (CIC) in HIV-Ab positive patients, immune complexes abnormalities, should be considered as an epiphenomenon of humoral immunity altered function; therefore, they are devoid of any diagnostic value.

[Clinical-echocardiography of 210 HIV-Ab positive patients: retrospective study]. / Indagine clinica-ecocardiografica su 210 pazienti HIV Ab positivi: studio retrospettivo.

Through the retrospective study of 210 HIV Ab+ patients in different disease's stages, recovered in the "D. Cotugno-Naples" hospital during the period February 1989-February 1991, the authors have valued the prevalence of cardiological alterations underlined by ecocardiograph. Pericardial pouring has been observed in four patients out of thirty, belonged to stages II, III and ARC. Ventricles' movement alterations have been observed in twenty patients out of thirty (66%), belonged prevalently to the fourth group. Kaposi's sarcoma has been observed in two patients out of thirty (6.6%), belonged to the fourth group. In the patients showing alterations, the authors have also noticed a correlation among the observed cardiological alterations and the immunital outline and the frequent homosexuality's presence. The follow up between the alterations' observation and the possible patient's death is on an average 4.3 months (range 1-12). They suggest that a wider and more precocious ecocardiographical research of HIV Ab+ patients is the only way, at the moment, to underline and follow the cardiac alterations' evolution, also in relation to a precocious antiretroviral therapy.

[Seroepidemiologic and behavioral characteristics of a group of HIV-Ab positive homosexuals]. / Indagine sieroepidemiologica e del comportamento di un gruppo di omosessuali HIV ab positivi.

The present study was designed to demonstrate the role of homosexuality in transmission of HIV infection. The results, in cases showed by authors, suggest that the homosexuality is not significative for transmission in HIV infection. Whereas it is significative (56.52%) in transmission of syphilis. The study has demonstrated that homosexuals are not disposed very much to the use of sexual prevention.