Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Prosthetic carotid bypass grafts for atherosclerotic lesions: a prospective study of 198 consecutive cases.

OBJECTIVES: Carotid endarterectomy (CEA) is the standard treatment for atherosclerotic lesions involving the carotid bifurcation. However, CEA can be challenging under some conditions. The goal of this study was to determine the outcome and durability of prosthetic carotid bypass grafting (PCB) with polytetrafluoroethylene (PTFE) grafts as an alternative to CEA. METHODS: This is a prospective series of 198 consecutive patients with PCB, representing 12.4% of 1595 patients with a carotid reconstruction procedure performed in our department between September 1986 and December 2006. Qualifying event was stroke in 67 patients (34%) and transient ischaemic attack (TIA) in 45 (23%), and 86 patients (43%) were asymptomatic. Primary indications for PCB were extensive atherosclerotic lesions (n=71; 36%), carotid stenosis associated with kinking (n=49; 25%), recurrent stenosis (n=47; 23%), stenosis after radiation therapy (n=18; 9%) and technical failure of CEA (n=13; 7%), with excessive arterial wall thinning and perforation after endarterectomy (n=10) or intimal flap on completion digital angiography (n=3). RESULTS: The combined stroke and death rate at 30 days were 0.5% (one stroke). Median follow-up was 9.5 years (interquartile range (IQR): 6.2-18.3 years). At 10 years, primary patency was 97.9+/-3.4%. Six PCBs (3.0%) became occluded during follow-up; one patient had a restenosis greater than 50% and 18 patients (9.1%) had a restenosis of less than 50%. Five patients had an ipsilateral stroke (one postoperative stroke, one at 103 days with a patent PCB and three related to occlusion of the PCB at 4, 13 and 15 years after the procedure). At 10 years, cumulative stroke-free survival was 98.4+/-3.2%, and cumulative survival was 78.8+/-7.0%. CONCLUSIONS: PCB is a safe surgical alternative and is durable, with a low incidence of graft restenosis, when CEA seems hazardous.

Total laparoscopic aortic repair for occlusive and aneurysmal disease: first 95 cases.

OBJECTIVES: To analyze the outcome of our preliminary experience with total laparoscopic aortic repair in patients with occlusive or aneurysmal disease. MATERIAL AND METHODS: From September 2002 to April 2005, we performed 95 consecutive total laparoscopic aortic repair procedures including 72 for aortic occlusive disease (group A) and 23 for abdominal aortic aneurysm (group B). RESULTS: In group A, mean operating time was 216+/-50 min with a mean clamp time of 57+/-21 min and surgical conversion was required in two cases (2.7%). No postoperative death occurred but there were three postoperative complications necessitating re-intervention (retroperitoneal hematoma, embolic ischemia, and early prosthetic infection). Mean duration of hospitalization was 8 days (range, 5-42 days). All grafts were patent at 2 months. In group B, mean operating time was 251+/-57 min with a mean clamp time of 101+/-15 min and surgical conversion was required in seven cases (30%). There was one postoperative death (4.3%) due to pulmonary embolism and one non-fatal complication (retroperitoneal hematoma). Mean duration of hospitalization was 6.4 days (range, 4-12 days). All grafts were patent at 2 months. CONCLUSION: Total laparoscopic repair is feasible and safe for occlusive and aneurysmal aortic disease. Operators must acquire technical skills using simulators.

Cutaneous infection caused by Aspergillus ustus, an emerging opportunistic fungus in immunosuppressed patients.

We report a case of primary cutaneous infection by the emerging fungus Aspergillus ustus in an immunosuppressed patient after a domestic accident. The patient failed to respond to itraconazole and died before receiving a new treatment with amphotericin B. There have been eight other cases reported since 1973, and only two patients survived the infection. In vitro susceptibility testing of seven antifungal drugs showed that terbinafine and the new azole derivative UR-9825 were the most active against this fungus.

Common genetic variants that relate to disorders of lipid transport in Spanish subjects with premature coronary artery disease.

Fifteen common polymorphic variants at six loci (apolipoproteins AI, B, CIII and E, hepatic lipase and lipoprotein lipase) involved in plasma lipid transport have been studied in 210 northern Spanish men, of whom 98 had proven coronary artery disease. The other 112 men were clinically free from coronary artery disease and acted as controls. The genotypes were investigated for relationships with plasma lipid and lipoprotein levels, as well as for the presence of coronary artery disease. As expected, the mean levels of plasma triacylglycerols (triglycerides) and lipoprotein (a) and the number of smokers were significantly higher in the disease group, and high-density lipoprotein (HDL)-cholesterol was significantly lower. Surprisingly, plasma cholesterol and low-density lipoprotein cholesterol were not different between the two groups. With regard to the common mutations, plasma triacylglycerol levels were related to the HindIII variants of lipoprotein lipase (P<0.05), to the apolipoprotein CIII variant (C3175G in exon 4) and to the apolipoprotein AI XmnI polymorphisms (P<0.05 and P<0.02 respectively). The apolipoprotein E variants were related to plasma cholesterol (P<0.05), HDL-cholesterol (P<0.02), plasma triacylglycerols (P<0.05) and the triacylglycerol/HDL ratio (P<0.01). Only the three-codon insertion/deletion variants of the apolipoprotein B signal peptide region discriminated between the two groups with or without arterial disease (P=0.02). The possible functional effects of these common mutations are discussed.

Lipoprotein(a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction.

Platelet glycoprotein IIb/IIIa may be involved in the pathogenesis of myocardial infarction as the key element in platelet aggregation and as the binding site of lipoprotein(a) to platelets, inhibiting plasminogen binding and activation. Recently, a strong association between the P1A2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis has been reported. although this has not been confirmed. In an associated study, we determined plasma lipoprotein levels, the apo E genotype and the P1A genotype in 250 males under 55 years with myocardial infarction and they were compared with 250 age- and sex-matched controls. Patients showed an over-representation of the epsilon3/4 genotype with respect to the control group. We found that there were no differences in the allelic frequency of P1A2 between case patients and age-matched controls (chi2 = 0.05, P = 0.92) and that subjects bearing the P1A2 allele showed higher plasma lipoprotein(a) concentration than p1A1/P1A1 individuals. Therefore, in this population there is no association between carriage of p1A2 allele and increased risk of myocardial infarction but the carriage of P1A2 is associated with higher plasma Lp(a) concentration.

[Systemic capillary leak syndrome]. / Sindrome de la hiperpermeabilidad capilar generalizada.

The systemic capillary leak syndrome is a rare condition, with a high mortality rate, characterised by recurrent episodes of generalized edema, with hemoconcentration and hypoproteinemia, associated with paraproteinemia. Pathophysiologically, this syndrome is caused by a sudden, reversible increase in capillary permeability, with a rapid shift of plasma from the intravascular to the extravascular compartment with subsequent hypovolemic shock. We report a new patient of this unusual condition, and we review its diagnostic and therapeutic aspects.