Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.     

Dual antibiotic loaded bone cement in patients at high infection risks in arthroplasty: Rationale of use for prophylaxis and scientific evidence

In view of the demographic changes and projected increase of arthroplasty procedures worldwide, the number of prosthetic joint infection cases will naturally grow. Therefore, in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance. In the absence of a "miracle weapon" priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks, the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen. Instead of a "one size fits all" philosophy, it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors. A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre. The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.     

Nocardia ignorata, a new agent of human nocardiosis isolated from respiratory specimens in Europe and soil samples from Kuwait

Nocardia ignorata is a recently described species identified on the basis of a single isolate of unknown origin. Here we describe the epidemiological, phenotypic, and phylogenetic characteristics of this new species, based on five new clinical and soil isolates.     

Expression of cripto-1 in human colorectal adenomas and carcinomas is related to the degree of dysplasia

The expression and localization of cripto-1 (CR-1) and epidermal growth factor receptor (EGFR) were assessed by immunocytochemistry in 41 human colorectal carcinomas, 57 adenomas, 9 hyperplastic polyps and in 98 noninvolved colonic mucosa samples that were adjacent to adenoma and/or carcinoma. Thirty-two (78.0%) and 19 (46%) carcinomas showed staining for CR-1 and EGFR, respectively, whereas 24 (42.0%) and 25 (43.8%) of the adenoma samples were reactive with the anti-CR-1 and anti-EGER antibodies, respectively. Two (22.2%) and 1 (11.1%) of the hyperplastic polyps demonstrated moderate levels of staining with anti-CR-1 and anti-EGFR antibodies. In contrast, none of the normal, noninvolved colonic mucosa samples reacted with the CR-1 antibody, whereas only 1 (1.0%) reacted with the EGFR antibody. Between EGFR and CR-1 expression, there was no significant association within either adenomas or carcinomas. A significant difference in the incidence for CR-1 expression was observed between adenomas and carcinomas (p<0.001). Within adenomas, the frequency of CR-1 was related to the histological degree of atypia. Immunostaining for p53 was also observed in 10 (24%) of the carcinomas, in 10 (17%) of the adenomas and in none of the hyperplastic polyps nor colonic mucosa samples. No statistically significant difference for p53 staining was observed between the adenomas and carcinomas. However, adenomas with moderate atypia exhibited relatively strong positive staining for p53 (p<0.05) compared to either adenomas with mild or severe atypia. A slight trend (p<0.05) for coexpression of p53 and CR-1 was detected in adenomas but not in carcinomas. These data demonstrate that CR-1 is a tumor marker for colon carcinomas and additionally that the expression of CR-1 may be an important factor in the early stages of colon cancer development during the adenomacarcinoma transition.     

Tumor necrosis factor-{alpha} up-regulates Bcl-2 expression and decreases calcium-dependent apoptosis in human B cell lines

Group I and Epstein–Barr virus-negative Burkitt's lymphomacell lines and the B104 lymphoma cell line which expresses aphenotype of immature B cells undergo apoptosis after cross-linkingof their surface Ig receptors or after exposure to a calciumionophore. We show here that tumor necrosis factor (TNF)- protectsthese B cell lines against Ca²⁺-dependent apoptosis. Protectionwas associated with up-regulatlon of bcl-2 mRNA and proteinexpression. The increase of Bcl-2 expression induced by TNF-was inhibited by chelerythrine, a specific inhibitor of proteinkinase C (PKC), suggesting that Bcl-2 expression was dependenton PKC activation. Furthermore, we show that phorbol estersand cyclosporin A (CsA), which prevent Ca²⁺-dependent apoptosis,up-regulated Bcl-2 expression. The effect of CsA on Bcl-2 expressionis controlled by calcineurin since we have shown that FK506but not rapamycin had the same effect on Bcl-2 expression, whereasokadaic acid, an inhibitor of phosphatases 1, 2A and 2C, wasineffective. These data provide direct evidence that TNF- preventsCa²⁺-dependent apoptosis by a Bcl-2-dependent mechanism mediatedby PKC.     

Association of Epidermal Growth Factor-related Peptides and Type I Receptor Tyrosine Kinase Receptors with Prognosis of Human Colorectal Carcinomas

The frequency of expression and localization of cripto-1 (CR-1),amphiregulin (AR), transforming growth factor alpha (TGF), epidermalgrowth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistryin 45 carcinomas and adjacent non-involved normal colon mucosa.Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%)of the 45 carcinomas showed positive staining for CR-1, AR,TGF, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%),15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involvednormal mucosa specimens were reactive. Among 13 carcinomas withlymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8(61.5%) and 7 (53.8%) exhibited positive staining for CR-1,AR, TGF-, EGFR and erbB-2, respectively. There was a statisticallysignificant association between the frequency of either TGF(P<0.05) or erbB-2 (P<0.05) expression and lymph nodemetastasis. In addition, a signficantly higher frequency ofpositive staining for TGF was observedin Dukes' grade C carcinomas(P<0.05). Finally, significant trends for coexpression ofEGFR and either TGF (P<0.01) or AR (P<0.05) were detectedin carcinomas. These data suggest that AR and TGF may play animportant role in the development of colorectal carcinomas throughan autocrine mechanism involving EGFR, and demonstrate thatTGF and erbB-2 may be more reliable indicators of metastasisor prognosis than CR-1, AR or EGFR in human colon cancers.     

Penetrating trauma to the tricuspid valve and ventricular septum: delayed repair

Penetrating cardiac trauma can result in a wide range of injuries to intracardiac structures. Missile injury, in particular, can cause damage in more than one cardiac chamber that may be difficult to identify at initial emergent operation. We report a case of late repair of traumatic ventricular septal defect and tricuspid valve perforation from gunshot wound. This case illustrates the importance of thorough examination of intracardiac anatomy during emergent and delayed repair for penetrating cardiac trauma.