Adjuvant chemotherapy in average-risk adult medulloblastoma patients improves survival: a long term study.

BACKGROUND: Medulloblastoma is extremely rare in adults. The role of chemotherapy for average-risk adult patients remains controversial. Surgery and radiotherapy provide a significant disease control and a good prognosis, but about 25% of average-risk patients have a relapse and die because of disease progression. No data in average-risk adult patients are available to compareradiotherapy alone and radiotherapyfollowed byadjuvant chemotherapy. METHODS: We analyzed 48 average-risk patients according to Chang classification diagnosed from 1988 to 2016. RESULTS: Median age was 29 years (range 16-61). Based on histological subtypes, 15 patients (31.3%) had classic, 15 patients (31.3%) had desmoplastic, 5 patients (10.4%) had extensive nodularity and 2 patients (4.2%) had large cells/anaplastic medulloblastoma. Twenty-four patients (50%) received adjuvant radiotherapy alone and 24 (50%) received radiotherapy and chemotherapy. After a median follow-up of 12.5 years, we found that chemotherapyincreases progression-free survival (PFS-15 82.3 ± 8.0% in patients treated with radiotherapy and chemotherapyvs. 38.5% ± 13.0% in patients treated with radiotherapy alone p = 0.05) and overall survival (OS-15 89.3% ± 7.2% vs. 52.0% ± 13.1%, p = 0.02). Among patients receiving chemotherapy, the reported grade ≥ 3 adverse events were: 9 cases of neutropenia (6 cases of G3 neutropenia [25%] and 3 cases of G4 neutropenia [13%]), 1 case of G3 thrombocytopenia (4%) and 2 cases of G3 nausea (8%). CONCLUSIONS: Our study with a long follow up period suggests that adding adjuvant chemotherapy to radiotherapy might improve PFS and OS in average-risk adult medulloblastoma patients.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Predictive genetic tests in neurodegenerative disorders: a methodological approach integrating psychological counseling for at-risk individuals and referring clinicians.

The identification of the molecular basis of numerous hereditary neurological disorders allowed the feasibility of predictive genetic tests for at-risk family members. In agreement with international guidelines, we tested a protocol for a predictive test to optimize cooperation among specialists, well-being of participants, and organization of clinical activities. The psychiatrist/psychologist did not meet the at-risk subjects, but cooperated with the team, integrating psychological support for participants and clinicians. We enrolled 60 subjects at risk for Huntington disease, and 32 at risk for spinocerebellar ataxias. Seventy-two subjects (78%) continued the visit program; 55 (60%) received the genetic result, and 38 subjects (41%) completed the program. Participation and outcome were similar in both groups. Mean psychological scores were all below significant levels; however, the need for psychological support was recognized for 5 mutation carriers and a non-carrier. Our data provide a methodological example of a simple and safe procedure for a predictive test, and indicate that the clinical conference represents a good setting to handle psychosocial impact associated with disclosure of genetic results in hereditary late-onset disorders.

Data on the stability of darunavir/cobicistat suspension after tablet manipulation.

The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. In the absence of authorised pharmacological treatments, many antiretrovirals, including darunavir/cobicistat fixed combination, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Unfortunately, for most of them, the drug products available on the market are not designed to be administered by a nasogastric tube to inpatients of intensive care units. Therefore, their manipulation, even if it can strongly affect the product quality, is necessary for the preparation of suspension to meet patients' need. In this situation, it is urgent to provide data and guidance to support hospital pharmacists and clinicians in their activity. The data in this article indicate that darunavir/cobicistat suspensions compounded by pharmacists using as active ingredient a commercially available tablet can be stable at least for one week.

Data on compounding lopinavir and ritonavir suspension for non-cooperative COVID-19 patients.

The COVID-19 outbreak is now one of the most critical crises to manage for most of national healthcare systems in the world. The situation is complicated by the absence of vaccines and authorized pharmacological treatments, except for remdesivir. In this context, many medicaments, including different Ebola and HIV antivirals, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Authorized medicaments manipulation is sometimes necessary because they are not always formulated to be administered to non-cooperative patients or they are in shortage. It is this the case of the fixed combination of lopinavir/ritonavir, which was extensively used in the first phase of the outbreak inducing a shortage of the oral solution available in the EU market. This work provides data on size distribution, osmolarity other than drug chemical stability of a lopinavir/ritonavir extemporaneous preparation made by using the solid dosage form (i.e., tablet) available on the market as drug source. The reported data indicate that such preparation is suitable to be delivered through a nasogastric tube, and enough stable for two weeks from the preparation at room temperature.

Behavioral and neurochemical effects of dopaminergic drugs in models of brain injury.

The dopaminergic drugs, ropinirole and dihydroergocryptine (DHECP) were injected subcutaneously (s.c.) at doses of 0.5 and 1 mg/kg/day for 7 days into male rats of the Sprague-Dawley strain. The drug pretreatment reverted amnesia induced in rats by hypobaric hypopxia and tested in active and passive avoidance tasks. Furthermore, a partial restoration of memory retention was found in animals with a 2-month brain occlusive ischemia induced by manipulation of the four major arteries of the brain. No major changes were found in spontaneous motor activity, but drug treatment increased ambulation of animals subjected to acute or chronic experimental manipulation. In a model of kainate-induced epilepsy, ropinirole or DHECP did not affect seizure parameters, but reduced mortality rate. At the end of behavioral procedures, in all animals subjected to hypobaric hypoxia or to brain occlusive ischemia glutathione redox index (glutathione reduced/glutathione oxidized ratio) was measured in the frontal cortex, striatum and hippocampus. It was found that experimental models of brain injury were followed by a decrease of reduced glutathione content in all brain areas. The glutathione redox index was augmented by ropinirole or DHECP treatment in all brain areas. These behavioral and neurochemical findings suggest that ropinirole and DHECP may exert either protective activity (as found in animals pretreated with these drugs and exposed to hypobaric hypoxia) or reversal of brain injury (as found in animals treated after two-month occlusive brain ischemia). Thus, both drugs may be studied as therapeutic agents in brain injuries of various origin.

In vitro short-term chemosensitivity test in head and neck tumors.

A new method to test the sensitivity of human tumor cells has been developed. A suspension of mechanically dissociated tumor cells is kept in continuous incubation for 24h, in cultures with antineoplastic agents. Drug induced cell cycle perturbations are monitored by flow cytometric computer analysis and DNA distributions of the cells stained with propidium iodide are expressed in percentage. The test is used in 15 head and neck human solid tumors. The drugs tested were: VCR, EpiDx, CDDP, MTX, 5-FU, CPM, BLM. The results obtained reveal that tumor sensitivity varies independently from the stage and malignity grading. Therapeutic combinations are assigned by selecting the drugs on the basis of the individual in vitro response.

[Laparoscopic cholecystectomy: evaluation of intraoperative complications with respect to 2 different kinds of anesthesia]. / Colecistectomia laparoscopica: stima di alcune complicanze perioperatorie in rapporto a due differenti metodiche di anestesia.

Two anaesthetic managements for elective laparoscopic cholecystectomy were compared in 64 patients in order to investigate some perioperative complications: 1) bowel distension during surgery. 2) recovery from anaesthesia. 3) post-surgery incidence of emesis and pain. In addition, the quality of postoperative peristalsis as well as the time of dimissal were recorded. Group I (n = 30) was treated with NLA in N2O-O2 and Group II (n = 34) received propofol plus fentanyl in air-O2. Bowel distension, evaluated by surgeon at 15 min intervals throughout the operation was similar in both the groups as well as postoperative peristalsis recuperation. During the first 12 hours after laparoscopy no differences were found at any times of observation in the incidence or severity of emesis and pain between the two different anaesthesia patients. In subjects which were given propofol the psychomotor recovery was more rapid than after NLA, particularly during the first 6 hours after surgery. The patients were discharged between 36-48 hours following the operation independently from anaesthetic management. It is concluded that both the anaesthetic techniques provide similar intra/postoperative conditions, except the early recovery that is more rapid for the propofol patients. The overall frequency of emesis and pain was rather high in both the groups, suggesting a routine medication with analgesics and antiemetics.

[The use of Mersilene mesh in the treatment of giant laparoceles]. / L'impiego della rete di Mersilene nel trattamento dei grandi laparoceli.

The paper reports on experience with the use of Mersilene mesh in 6 patients with giant laparoceles. Besides being physiologically compatible, Mersilene mesh is recommended when traditional techniques fail. The Rives technique was used, placing the prostheses between the posterior sheath and the rectus muscle; in one case it was inserted under the peritoneum. A good local and general preparation for the operation is recommended. Even though the introduction of prosthetic materials into the body is not always non-injurious, the use of Mersilene mesh is advised because of its easy positioning and the low incidence of complications.

[Fistula following emergency total colectomy: an efficient method of treatment]. / Fistola dopo colectomia totale in urgenza: un metodo efficace di trattamento.

A personal case of enterocutaneous fistula secondary to total emergency colectomy is reported with particular emphasis on an effective form of radiological management, based on the percutaneous sclerosing of the fistulous tract using absolute ethanol and a hyperosmotic contrast medium (Angioconray 80%). By this approach a rapid closure of the fistulous tract was obtained. Moreover the procedure was easy to perform, well tolerated by the patient and devoid of untoward side effects.

The treatment of cranio-facial pain by electroacupuncture and laser irradiation.

Craniofacial neuralgias represent an interesting medical challenge, especially regarding the complex therapeutical aspects. Our study was performed treating more than 700 patients, applying steel inox needles variable in diameters and length for about 20 minutes, with a total application number ranging between 10 and 20. Results have been defined referring to a 4-grades response scale: excellent, good, fairly good and insufficient. It is important to emphasise that the best results have been achieved with patients who chose the acupuncture as the first therapeutic approach, while patients who underwent other previous medical and/or surgical treatment have had a worse response. The authors assert that acupuncture and infrared laser reflex therapy represent a harmless and effective treatment of such a diffuse and invalidating disease.

[Effects on ventilation secondary to laparoscopic and laparotomic cholecystectomy]. / Effetti sulla ventilazione secondari a colecistectomia laparoscopica e laparotomica.

OBJECTIVE: Evaluation of respiratory function after 24 hours from intervention related to two different surgical techniques of cholecistectomy. PATIENTS AND METHODS: Thirty patients submitted to cholecystectomy, nine by laparotomy and twenty-one by video-laparoscopy. The ventilatory parameters considered are as follows: CV, FCV, VEF1, FEF25-75%; and moreover also some variables of acid-base balance: pH, paCO2 e paO. RESULTS: In all cases was evidenced a decrease of respiratory activity. This phenomenon was more evident in the laparotomy group (CV = 37, 35, FCV = 41, 47, VEF1 = 40, FEF25-75% = 36.62% related to preoperative values versus 71.20, 80.88, 79.29, 77.91% in the videolaparoscopic group. No significative differences were registered between the two groups as to postoperative paO2, which was moderately lower in all patients, while no variation was observed for pH and paCO2. CONCLUSIONS: Data collected confirm that after laparoscopic cholecystectomy the ventilatory respiratory capacity is better conserved, that clinically means lower incidence of postoperatory pulmonary complications.

[Treatment of trigeminal neuralgia with electroacupuncture. Experience with 104 cases]. / Il trattamento della nevralgia trigeminale con elettroagopuntura. Esperienza su 104 casi.

The essential or secondary trigeminal neuralgia is a very frequent and invalidant disease. In this forms, the medical or surgical conventional therapies are often inadequate. In this study we evaluated the effects of the acupunctural therapy on 104 patients (mean age 52.3 +/- 13 years) with idiopathic or secondary trigeminal neuralgia. Utilizing cycles of twelve sessions, the acupunctural treatment was performed with an electrostimulator on local points and a distance or on aching points, in the secondary forms. The results was evaluated on the basis of three parameters (reappearance of the symptomatology, absence of pain in months and preceding treatments) and was defined using this scale: very well, well, fair and null. In conclusion we can say that acupuncture is an elective treatment in all kinds of secondary tregeminal neuralgia, while, in the idiopathic form, its validity is conditioned by preceding medical treatments and by beginning of the disease.

[Meigs' syndrome. A case report]. / Sindrome di Meigs. Descrizione di un caso.

The authors report on a case of Meigs' syndrome in a patient admitted with vomiting, abdominal pain, peritoneal and right pleural effusion, increased serum levels of CA 125. Surgical excision was successful.

Novel and recurrent spastin mutations in a large series of SPG4 Italian families.

BACKGROUND: Hereditary spastic paraplegias (HSP) are heterogeneous neurodegenerative disorders, genetically classified according to the identified disease gene or locus. Clinically, HSP are distinguished in pure and complicated forms. Mutations in the spastin gene (SPAST) are responsible for SPG4 and account approximately for 50% of the dominantly inherited paraplegias with a pure HSP phenotype. METHODS: Molecular screening of the SPAST gene allowed the identification of 31 Italian mutation carriers, from 19 unrelated families. Genetic testing was performed by direct sequencing and multiplex ligation-dependent probe amplification. Subjects carrying SPAST mutations were retrospectively evaluated for clinical phenotype and disability score assessment. RESULTS: We found 12 recurrent mutations, and 7 novel SPAST mutations. Twenty-eight patients exhibited a pure spastic paraplegia phenotype, while 3 subjects were asymptomatic mutation carriers. Four patients were sporadic cases. Age at onset ranged from 10 to 61 years. Disability score increased with age at examination and disease duration. Patients with onset >38 years presented a faster disease progression, and a higher disability functional index, than the patients with earlier onset (p<0.04). CONCLUSIONS: Our study enlarges the number of pathogenic SPAST mutations, and confirms the association with a pure spastic paraplegia phenotype. Age at onset was highly variable and correlates with the rate of disease progression. Future longitudinal clinical studies are needed to confirm these observations.

The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study.

OBJECTIVE: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1- and 2-year follow-up visits. METHODS: As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. RESULTS: The annual increase of the SARA score was greatest in SCA1 (2.18 ± 0.17, mean ± SE) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 ± 0.34, second year: 1.44 ± 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females. CONCLUSIONS: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression.

Echocardiographic evaluation and clinical management of ductal shunting in hemodynamically unstable preterm neonates without congenital heart disease in the pediatric intensive care unit.

Although significant steps have been taken to monitor complex hemodynamics in neonatal and pediatric intensive care units, cardiovascular function in neonates is still evaluated by measuring blood pressure, heart rate, diuresis, central venous pressure (if a central venous catheter was placed), capillary refill time and oxygen saturation measurement in the upper and lower extremities. The use of other non-invasive or invasive technologies (for example, continuous impedance cardiography, transesophageal Doppler and continuous pulse contour methods) is, in fact, quite problematic in neonates in whom relevant hemodynamic changes are common during the transition to postnatal life. For these reasons, use of transthoracic echocardiography, performed by skilled pediatric intensivists, is increasing in several dedicated centers to guide treatment choices in hemodynamically unstable neonates.