GMP-manufactured CRISPR/Cas9 technology as an advantageous tool to support cancer immunotherapy.

BACKGROUND: CRISPR/Cas9 system to treat human-related diseases has achieved significant results and, even if its potential application in cancer research is improving, the application of this approach in clinical practice is still a nascent technology. MAIN BODY: CRISPR/Cas9 technology is not yet used as a single therapy to treat tumors but it can be combined with traditional treatment strategies to provide personalized gene therapy for patients. The combination with chemotherapy, radiation and immunotherapy has been proven to be a powerful means of screening, identifying, validating and correcting tumor targets. Recently, CRISPR/Cas9 technology and CAR T-cell therapies have been integrated to open novel opportunities for the production of more efficient CAR T-cells for all patients. GMP-compatible equipment and reagents are already available for several clinical-grade systems at present, creating the basis and framework for the accelerated development of novel treatment methods. CONCLUSION: Here we will provide a comprehensive collection of the actual GMP-grade CRISPR/Cas9-mediated approaches used to support cancer therapy highlighting how this technology is opening new opportunities for treating tumors.

Hinged external fixation for complex fracture-dislocation of the elbow in elderly people.

The authors report their experience of treating complex elbow fracture-dislocations in elderly people, using a minimally-invasive approach with a new articulated external fixator that is associated with minimal internal fixation. The clinical results for 19 patients are presented according to outcome factors, such as range of motion, pain and function, rate and type of complications, and reoperation rate. The results indicate that this treatment strategy should be considered as a good alternative to other treatment options reported in the literature, including conservative treatment, ORIF with angular stable plates and total elbow arthroplasty.

[Splenic artero-venous fistula and portal hypertension. A case report with review of the literature]. / Ipertensione portale secondaria a fistola artero-venosa splenica. Descrizione di un caso clinico e revisione della letteratura.

Splenic artero-venous fistula (SAVF) is a rare but potentially curable cause of pre-hepatic portal hypertension. About 100 cases have been reported in the world medical literature. The Authors report a case of 46-year-old man with a splenic artery aneurysm and a large SAVF treated by surgical resection of splenic vessels and splenectomy. The literature about SAVF is reviewed to recognize etiology, anatomical location, main symptoms at presentation, diagnostic findings and management of this rare syndrome.

6-Phosphogluconate dehydrogenase deficiency in an Italian family.

A rare case of hereditary erythrocyte enzymopathy, namely 6-phosphogluconate dehydrogenase (6PGD) deficiency, was found in an Italian family. The activity of the enzyme was reduced to 35% in the propositus and her mother, but was normal in the other three members of the family. The 6PGD deficiency was associated with a variable reticulocyte count and recurrent increased unconjugated bilirubinemia without anemia in the propositus, while no clinical or hematological symptoms were evident in her mother. Increased levels of erythrocyte pyruvate kinase (PK) activity and reduced glutathione (GSH) were observed, indicating a slight decrease in mean red blood cell (RBC) age and an activation of reducing systems. The episodic hemolytic events with jaundice observed in the propositus may be the result of a defective RBC ability to counteract conditions of marked oxidative stress. In this report the importance of 6PGD estimation for a proper analysis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is also highlighted. In fact in the present study, the presence of 6PGD deficiency could be mistaken for a partial G6PD deficiency if the assay of G6PD activity was performed without correcting for 6PGD activity.

[Glucose-6-phosphate dehydrogenase deficiency and hereditary hemolytic anemia]. / Deficit di glucosio-6-fosfato deidrogenasi ed anemia emolitica ereditaria.

G6PD deficiency is the most common enzymopathy in the world. The highest frequency values are found in tropical Africa, in the Middle East, in some areas of the Mediterranean, in tropical and sub-tropical Asia and in Oceania. This genetic defect shows sex linked inheritance and a marked heterogeneity. At least 400 abnormal variants with different biochemical characteristics and about 100 diverse mutations have been identified. In most cases the phenotypic expression is a marked decrease in erythrocyte G6PD activity. The most common clinical consequences are neonatal jaundice and sporadic haemolytic crises caused by a number of drugs, by infections or by ingestion of fava beans. A few cases of chronic non-spherocytic haemolytic anaemia associated with rare molecular variants have been reported. Early diagnosis, education and epidemiologic surveillance have been proved to be cornerstones in the prevention of the haemolytic disease. Therefore they should be taken into account in the national health programmes, especially in the countries with high prevalence rates.

Four years experience of primary intra-arterial chemotherapy (PIAC) for locally advanced and recurrent breast cancer.

AIMS: To find a means of achieving operability very quickly without the additional discomfort of prolonging systemic chemotherapy. To improve the patient's quality of life by obtaining quick tumor reduction and decreasing systemic toxicity. MATERIALS AND METHODS: From January 1991 to January 1995, 13 patients with locally advanced breast cancer (LABC) and 8 patients with recurrent breast cancer (RBC), were treated by transfemoral Seldinger technique, with the catheter tip placed into the subclavian artery at the basis of the internal mammary artery. The patients received 5-fluorouracil (5FU) 1000 mg, epirubicin (EPI) 30 mg/m2, mitomycin (MMC) 7 mg/m2 over an infusion for 30 minutes. The cycle was repeated every two weeks for three times. RESULTS: The overall response rate was 62%. Stage IIIb and RBC patients had a response rate of 100% and 25% respectively. In respondent patients a measurable response was seen after the first cycle. Ten patients were radically operated. After a media follow-up of 21 months, the overall survival is 52% at 48 months (68% at 48 months and 65% at 34 months for stage IIIb and RBC patients respectively). CONCLUSIONS: PIAC is feasible and effective. In LABC patients it reaches 100% of response rate. Systemic toxicity was absent and the local one was mild. The interval between the starting of PIAC and operation is short. There was an optimal compliance of the patients.

[Perioperative complications in traditional surgery of the rectum]. / Le complicanze perioperatorie nella chirurgia tradizionale del retto.

The authors report their experience of 136 operations for rectal neoplasms, on all of 652 colo-rectal neoplasms, treated from January 1987 to May 1994. In detail the perianastomotic complications have been tested after "traditional" rectal operations: Anterior Resection (RA), Abdomino-perineal amputation (AAP) and Hartmann's procedure. A series of 24 AAP (18%), 81 RA (60%) and 7 Hartmann's procedure have been considered; conversely 18 final and palliative colostomies (13%) and 7 trans-anal operations haven't been taken in to account. Perioperative mortality was comparatively reasonable: 2.7%. No patient died after AAP. The most common complication proved to be anastomotic leak (17.3%), after RA; otherwise the rate of further complications was very moderate. It is feasible to avoid anastomotic leaks, by carrying out a temporary colostomy.

[Doppler ultrasound assessment of lower limbs arterial occlusive disease (author's transl)]. / L'indagine Doppler nella diagnosi e nella terapia chirurgica delle arteriopatie periferiche.

The Authors evaluate the Doppler ultrasonic detection in the assessment of lower limbs arterial occlusive disease, particularly concerning the haemodynamic pattern of those patients undergoing a surgical treatment. The research is accomplished on a group consisting in hundred not selected patients, all subjected to aortography. A comparative study was undertaken between angiographic findings and ankle sistolic pressure measurement together with flow velocity profile. Reduction of ankle sistolic pressure and appearance of flow velocity profile changes, resulted highly correlated with clinical stage and angiographic alterations. The Authors consider therefore the Doppler ultrasound assessment as being able to give, together with the always necessary angiographic study, more accurate informations either on the run-off and the haemodynamic consequences of a stenosis, or on the overall evaluation of multisegmental lesions.

[Doppler observations in migraine patients (author's transl)]. / Osservazioni sonografiche Doppler in pazienti emicranici.

The Authors have subjected 14 migraine patients to Doppler ultrasonic technique. Examinations have been performed on both common carotid arteries, either in headache phase or in pain-free periods. Results in each case suggest variable hemodynamic patterns during migraine attacks. Possible pathogenic mechanisms are discussed.