SARS-CoV-2 infection as cause of in-utero fetal death: regional multicenter cohort study.

OBJECTIVE: Placental infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to placental insufficiency and in-utero fetal death (IUFD). The objective of this study was to confirm and quantify the extent to which fetoplacental infection with SARS-CoV-2 is a cause of fetal death. METHODS: This was a multicenter retrospective cohort study of fetal deaths that underwent postmortem examination between January 2020 and January 2022 in three fetal pathology units in Paris, France. All cases of IUFD and termination of pregnancy (TOP) occurring in 31 maternity hospitals in the Paris region undergo detailed placental pathological examination in these units. Databases were searched for cases of IUFD and TOP. Cases with fetal malformation or cytogenetic abnormality were excluded to avoid bias. We included cases of IUFD with a placental or undetermined cause and cases of TOP in the context of severe intrauterine growth restriction (IUGR). Placentas were sent to a single virology unit for reverse-transcription polymerase chain reaction (RT-PCR) testing by a single laboratory technician blinded to the initial postmortem examination report. Our primary endpoint was the proportion of positive placental SARS-CoV-2 RT-PCR tests in the cohort. RESULTS: Among 147 722 deliveries occurring over 2 years, 788 postmortem examinations for IUFD and TOP for severe IUGR were recorded, of which 462 (58.6%) were included. A total of 13/462 (2.8%) placentas tested positive for SARS-CoV-2 by RT-PCR. Wild-type virus and alpha and delta variants were identified. All positive cases had histological lesions consistent with placental dysfunction. There was a strong correlation between SARS-CoV-2 placentitis and the presence of chronic intervillositis and/or massive fibrin deposits in the placenta. When both lesion types were present, the specificity and negative predictive value for the diagnosis of placental SARS-CoV-2 infection were 0.99 (95% CI, 0.98-1.00) and 0.96 (95% CI, 0.94-0.98), respectively. CONCLUSIONS: At the height of the SARS-CoV-2 pandemic, the cause of more than half of fetal deaths in the Paris area was determined by postmortem analysis to be of placental or undetermined origin. Of these cases, 2.8% were due to placental SARS-CoV-2 infection with a specific pattern of histological involvement. This study highlights the need for SARS-CoV-2 screening in stillbirth assessment. The impact of vaccination coverage remains to be established. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cancer biomarkers in human atherosclerotic lesions: detection of DNA adducts.

Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abdominal aorta specimens taken at surgery from seven patients. DNA adducts were evaluated in three laboratories by means of different molecular dosimetry methods, including: (a) HPLC/fluorescence, which specifically identifies the DNA adducts of the anti-benzo(a)pyrene (BPDE) isomer; (b) two- and three-dimensional synchronous fluorescence spectrophotometries, which detect DNA adducts of BPDE and other reactive metabolites of polycyclic aromatic hydrocarbons; and (c) 32P postlabeling, which reveals the presence of a variety of types of DNA adducts. The HPLC/fluorescence method provided for the first time evidence for the presence of BPDE-DNA specific adducts in three of six specimens tested. Synchronous fluorescence spectrophotometry displayed broad areas of fluorescence in all seven specimens, thereby suggesting the occurrence not only of BDPE-DNA but also of other DNA adducts with similar fluorescence characteristics. All specimens were also positive at 32P postlabeling, which revealed multiple spots detectable following enrichment either with nuclease P1 or butanol, indicative of the presence of different aromatic DNA adducts. Thus, the data obtained by applying typical cancer biomarkers provide further support to the hypothesis that there may be similarities between the carcinogenic and the atherogenic processes, and in particular that genetic alterations caused by DNA-binding agents in the artery wall may be detected in atherosclerotic lesions.

Cancer biomarkers in human atherosclerotic lesions: no evidence of p53 involvement.

In order to assess similarities between the atherogenic and the carcinogenic processes, we investigated whether the p53 tumor suppressor gene, the most commonly altered gene in human cancer, may be also involved in human atherosclerotic lesions. The medium layers of abdominal aorta fragments taken at surgery from 32 patients were subjected to immunohistochemical analysis, using either monoclonal (Pab 1801) or polyclonal (CM-1) antibodies, and to molecular analysis by the PCR-based denaturing gradient gel electrophoresis approach. The results obtained indicated that p53 mutations are not involved in the pathogenesis of atherosclerotic lesions, and that no accumulation of the wild-type protein occurs in smooth muscle cells of these lesions. A polymorphism characterized by an AT to GC transition at codon 213 (CGA --> CGG) causing no aminoacid substitution (Arg --> Arg) was detected in the 10.5% of the examined patients. Our negative findings do not support the hypothesis that the atherosclerotic plaques may be pathogenetically akin to benign tumors yet they are not in contrast with this theory, since in most cases p53 is involved in advanced stages of the carcinogenesis process.

Lack of mutations in K-ras codons 12 and 13 in human atherosclerotic lesions.

In the framework of a project investigating the possible involvement of cancer biomarkers in human atherogenesis, we evaluated the occurrence of K-ras mutations in the DNA extracted from smooth muscle cells of abdominal aorta atherosclerotic lesions. The molecular analysis of the DNA from 32 surgical specimens, using PCR-based denaturing gradient gel electrophoresis (DGGE), did not reveal any variant in K-ras codons 12 and 13, which are the most frequently involved codons among the ras genes mutated in various types of human tumors. Analysis of the DNA extracted from four cell lines carrying known K-ras mutational alleles showed typically positive DGGE patterns. Thus, on the whole, the conclusions of this study and of previous studies using the same biological material are consistent with the occurrence of DNA adducts in human atherosclerotic lesions but in the absence of p53 involvement or of K-ras mutations in codons 12 and 13. The search for candidate genes which may possibly be involved in the atherogenetic process warrants further studies.

Factors affecting insufficiency in activity daily living in the elderly.

BACKGROUND: In a "case-control" study we investigated the correlations among twenty-four clinical signs of "functional impairment" and probability of "activity daily living insufficiency". METHODS: The study involved 788 randomised inpatients, aged 65 years and over, of nineteen long-stay hospitals of an Italian region (Lazio, Rome). We measured self care autonomy, mobility and continence, on a modified Barthel's scale; the score on Barthel's scale, Barthel Index (BI), was correlated to twenty-four signs of "functional impairment" (explicative variables). Of these variables entered in stepwise regression only "cognitive impairment" (coef. B-22), "paralysis" (coef. B-21), "body weight reduction over 10 kg vs ideal weight" (coef. B-12), "joint deformation" (coef. B-7) and "visual impairment" (coef. B-5). Insufficiency in daily living is defined by BI < 100. The presence of these five clinical signs leads to the likelihood of "activity daily living insufficiency" to 0.996. The trend of cognitive impairment to rise with age could be responsible for the inverse regression between age and BI. RESULTS: There was no significant correlation between BI and sex. Hearing impairment, serum creatinine level > or = 4 mg/dl, bronchospasm, obstructive and restrictive ventilation disorders, precordial pain on stress or spontaneous and dyspnea are not significantly correlated to the Barthel Index Score and to the likelihood of insufficiency in daily living activity.

Current techniques to reduce blood loss after the Ross procedure.

BACKGROUND AND AIMS OF THE STUDY: Although pulmonary autograft (PA) offers many theoretical advantages, the operation is more complex and the need for extensive reconstruction carries an increased risk for postoperative bleeding. The study aim was to evaluate the impact of different pharmacological and surgical strategies on total blood loss and blood product requirements after PA use. METHODS: Between July 1994 and March 1997, 26 patients (22 males) with a mean age of 26 +/- 8 years (range: 11 to 36 years) underwent aortic valve replacement with PA (22 root; four subcoronary implant). A relatively high incidence of re-exploration for bleeding (n = 3) and significant total blood loss during our early experience (Group I, n = 8), prompted the subsequent introduction of different strategies (Group II, n = 18). These included perioperative use of aprotinin, reinforcement of suture lines of the neo-aortic root with autologous pericardium and accurate hemostasis of the raw surface on the back of the right ventricular outflow tract (RVOT) during a brief period of circulatory arrest, also with application of fibrin glue, RESULTS: There were no hospital deaths. No patients in group II required re-exploration or transfusion, and mean total postoperative blood loss was reduced (group I, 720 +/- 465 ml/m2 body surface area (BSA), versus group II, 323 +/- 84 ml/m2 BSA). By-pass and aortic cross-clamp times were not significantly longer in group II patients. At a mean follow up of 15 months, all 25 survivors are asymptomatic, in NYHA functional class I, and with normal social interactions. CONCLUSIONS: Early survival after aortic valve replacement with the PA appears comparable with the use of more conventional valve substitutes. Blood loss containment by routine application of medical and surgical strategies appears feasible. In view of the common concern about blood transfusion, particularly in young patients, these findings may help to widen the range of indications for the Ross procedure.

Lung resections concomitant to coronary artery bypass grafting.

From 1980 through 1993 ten patients underwent concomitant coronary artery bypass grafting and lung resection via median sternotomy. In eight patients a lung malignancy was resected, of which one was a small cell lung cancer. The lung resection was carried out before cardiopulmonary bypass in eight patients and during cardiopulmonary bypass in two. Coronary artery bypass grafting was performed using saphenous vein in eight patients; internal mammary artery was used as arterial conduit in two patients. There was one postoperative death while postoperative complications during hospital stay occurred in two patients. Pulmonary bleeding did not occur in any patient in whom lung resection was performed either before or during cardiopulmonary bypass. Both the patients who had internal mammary artery grafting experienced complications related to an associated lobectomy. A staged procedure is advisable if internal mammary artery has to be used and a lobectomy is required. The long-term survival in the patients with lung cancer was less than expected but the number of patients is too small to draw definite conclusions.

A nonsurgical technique for removal of a Swan-Ganz catheter entrapped in the right atrium.

Although rare in occurrence, entrapment of Swan-Ganz catheter during open heart surgery can be a serious complication. Several methods have been used to free such catheters with nonsurgical techniques. A case of entrapment in the right atrium is presented and a method for nonsurgical removal is described.

[A new surgical instrument for the removal of varicose branches of the saphenous vein]. / Un nuovo strumento chirurgico per l'asportazione delle collaterali varicose della safena.

A new instrument, specially devised and constructed for varicose saphenous vein branches excision through small skin incisions non requiring suture, is described. The instrument's utilization in the surgical treatment of varices of the lower limbs is explained. The significant shortening of the whole surgical procedure and the optimal cosmetic appearance of the operated limbs, are the most outstanding advantages of the presented technique compared with the commonly employed ones.

[Scintigraphy with 99mTc-HMPAO-marked leukocytes and abdominal tumors: clinical interpretation of scintigraphy results]. / La scintigrafia con leucociti marcati con 99mTc-HMPAO e i tumori addominali: interpretazione clinica dei risultati scintigrafici.

The 99mTc-HMAPAO-labelled leucocyte scan is a widely employed diagnostic tool in the assessment of inflammatory and infective diseases. Nevertheless, leucocytes accumulation in neoplastic lesions has been reported. In the present study, aimed at the exploration of the abdomen and performed on 62 patients, positive scintigraphic findings were obtained in 66.6% (4/6) of the neoplasms and in 6.45% (4/62) of the studied cases. These scintigraphic results, even if they have to be considered as false positive cases, effectively reflect histopathologic changes present in the neoplastic tissue. On the basis of the obtained results, leucocytes accumulation in abdominal malignancies is probably due to the presence of necrosis and ulceration and to the resulting infection of the tumour.