Immune checkpoint inhibitors for POLE or POLD1 proofreading-deficient metastatic colorectal cancer.

BACKGROUND: POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity and efficacy of immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking and it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs. PATIENTS AND METHODS: In this global study, we collected 27 patients with mCRC harboring POLE/D1 mutations leading to proofreading deficiency and treated with anti-programmed cell death-ligand 1 alone +/- anti-cytotoxic T-lymphocyte antigen-4 agents. We collected clinicopathological and genomic characteristics, response, and survival outcomes after ICIs of POLE/D1pd mCRC and compared them with a cohort of 610 dMMR/MSI-H mCRC patients treated with ICIs. Further genomic analyses were carried out in an independent cohort of 7241 CRCs to define POLE and POLD1pd molecular profiles and mutational signatures. RESULTS: POLE/D1pd was associated with younger age, male sex, fewer RAS/BRAF driver mutations, and predominance of right-sided colon cancers. Patients with POLE/D1pd mCRC showed a significantly higher overall response rate (ORR) compared to dMMR/MSI-H mCRC (89% versus 54%; P = 0.01). After a median follow-up of 24.9 months (interquartile range: 11.3-43.0 months), patients with POLE/D1pd showed a significantly superior progression-free survival (PFS) compared to dMMR/MSI-H mCRC [hazard ratio (HR) = 0.24, 95% confidence interval (CI) 0.08-0.74, P = 0.01] and superior overall survival (OS) (HR = 0.38, 95% CI 0.12-1.18, P = 0.09). In multivariable analyses including the type of DNA repair defect, POLE/D1pd was associated with significantly improved PFS (HR = 0.17, 95% CI 0.04-0.69, P = 0.013) and OS (HR = 0.24, 95% CI 0.06-0.98, P = 0.047). Molecular profiling showed that POLE/D1pd tumors have higher tumor mutational burden (TMB). Responses were observed in both subtypes and were associated with the intensity of POLE/D1pd signature. CONCLUSIONS: Patients with POLE/D1pd mCRC showed more favorable outcomes compared to dMMR/MSI-H mCRC to treatment with ICIs in terms of tumor response and survival.

Spontaneous cervical extradural hematoma in a cutaneo-meningospinal angiomatosis (Cobb syndrome): case report.

Spontaneous spinal extradural hematoma is a rare clinical entity, commonly associated with coagulopathies, tumours or vascular malformations. They are often a neurosurgical emergency, therefore prompt diagnosis and early treatment are necessary. The Cobb syndrome is a neurocutaneous syndrome in which there are metameric vascular skin nevus and spinal arteriovenous malformation. The authors report the case of a 52-year-old woman with acute cervical myelopathy and a cervical cutaneous hemangioma on clinical examination. It is stressed the importance of clinical suspicion of cutaneo-meningospinal angiomatosis based on a spinal cord syndrome in the presence of a vascular skin nevus of the same metameric level.

Unilateral supraorbital keyhole approach in patients with middle cerebral artery (M1-M2 segment) symmetrical aneurysms.

A left middle cerebral artery aneurysm at the bifurcation (M1-M2 segment) and a right smaller aneurysm, symmetrical to the previous one were diagnosed in a 69-year-old female after angiographic examination for subarachnoid hemorrhage. The preoperative radiological study did not enable us to identify the bleeding aneurysm so a left supraorbital keyhole approach was performed to operate on the bigger aneurysm. In the same surgical session, using the same way of approach, we decided to attack also the right aneurysm which then revealed itself as being responsible for bleeding. The postoperative angiograms confirmed the complete exclusion of both aneurysms and the patient was discharged after good recovery. Although there are remarkable controversies about the surgical strategies for multiple aneurysms, our experience gives us the opportunity to emphasize the supraorbital keyhole approach and to reconsider the "timing" of multiple/bilateral aneurysms.

Neurocysticercosis treated with albendazole long term follow-up of a case.

The authors report a case of neurocysticercosis treated with Albendazole (methyl-5-propyl-thio-2-benzimidazilcarbamate). Computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain presented various small bilateral parenchymal calcifications in the white matter and two inflammatory granulomatous formations localized respectively in the left and right posterior parietal lobe. After the serological diagnosis (Elisa-test) of cysticercosis, the patient was treated with albendazole (Zentel) with oral doses of 15 mg/kg/die for 20 days, and successively with a lower dose for another 40 days. Repeated CT and MRI showed a gradual reduction in the granulomas in comparison with the ones previously found, until the complete disappearance of the neuroradiological evidence of them. No side-effects were recorded during the treatment nor symptoms or neurological consequences in the period up until two years after the initial observation.

[Ambulatory monitoring of left ventricular function in patients with ischemic heart disease: effects of coronary revascularization]. / Monitoraggio ambulatoriale della funzione ventricolare sinistra (VEST) in pazienti con cardiopatia ischemica: effetti della rivascolarizzazione coronarica.

The aim of this study was to assess the efficacy of coronary artery bypass using an ambulatory radionuclide monitoring system of left ventricular function (VEST) during daily activities in patients with previous myocardial infarction and coronary artery disease. Ten patients with previous myocardial infarction, clinical evidence of residual angina and angiocardiographically proven coronary artery disease of at least two epicardial vessels were studied by VEST 8 +/- 2 days before and 15 +/- 3 days after surgical myocardial revascularization. VEST allows to monitor both left ventricular function and 2 ECG leads. During the radionuclide monitoring (at least 60 min) all patients underwent handgrip test (compression of a dynamometer for 2 min at the 75% of maximal capacity), a mental stress (arithmetic operation consisting in subtracting 17 from 17,000 for 4 min), walking (140 yards) and climbing stairs (8 flights). No significant changes in left ventricular function during mental stress and handgrip both before and after the surgical procedure were observed. In the preoperative evaluation, walking induced a significantly increase in heart rate from rest to peak exercise (73 +/- 13 versus 79 +/- 11 b/min, respectively; p < 0.01). After coronary artery bypass, heart rate (rest: 92 +/- 18 b/min, effort: 98 +/- 19 b/min; p < 0.01), ejection fraction (rest: 47 +/- 8%, effort: 53 +/- 10%; p < 0.01), cardiac output (rest: 43 +/- 8 edv/min, effort: 51 +/- 11 edv/min, p < 0.01), and stroke volume (rest: 47 +/- 9%, effort: 53 +/- 9%; p < 0.01) increased at maximal effort compared to the control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[The usefulness of bioimpedance in patient monitoring in an intensive-therapy heart-surgery unit: a comparison with thermodilution]. / Utilità della bioimpedenza nel monitoraggio del paziente in unità di terapia intensiva di cardiochirurgia: comparazione con la termodiluizione.

Haemodynamic monitoring of intensive care unit (ICU) patients can be carried out by thermodilution system. This method is invasive, does not give a continuous monitoring and complications can occur. Thoracic electrical bioimpedance (TB), a non invasive, fast, easily repeatable method, is able to measure some important haemodynamic parameters: end diastolic volume (EDV), stroke volume, cardiac output (CO), ejection fraction (EF), some contractility indexes, systemic vascular resistances (SVR) and cardiac work. The aim of the present study is to compare CO and SVR obtained by thermodilution with the same indexes obtained by TB. Therefore, 20 ICU patients (12 males and 8 females, mean age 54 +/- 11 years) were studied. Out of them, 16 had been submitted to cardiac surgery in the previous 7 days and 4 were waiting for cardiac surgery. The patients were divided in 2 groups: Group A (N 4) included patients with valvular malfunction and/or cardiac arrhythmias and Group B (N 16) included patients with normal valvular function and sinus rhythm. CO obtained by TB was well related with the one obtained by invasive (INV; r = 0.878; p < 0.001). The mean value of difference of the 2 methods was 12.29 +/- 11.83 for the whole group of 20 patients but it was 26.07 +/- 14.16 in the Group A and 8.84 +/- 8.09 in the Group B confirming the less reliability of the method in patients with abnormal valvular function or in the presence of cardiac arrhythmias. As a consequence, SVR obtained by TB and INV resulted well related (r = 0.752; p < 0.001). The mean value of differences was 11.14 +/- 9.01 in the group of 20 patients and particularly 19.55 +/- 10.87 in the Group A and 9.04 +/- 7.07 in the Group B. In a subgroup of 9 patients, CO was measured at successive times (0, 30, 60, 90 min) by both TB and INV; when comparing the 2 CO values a significant correlation was observed. In conclusion, TB represents a valid method in haemodynamic monitoring of the ICU patients.