Negative‐pressure closure was superior to tie‐over technique for stabilization of split‐thickness skin graft in large or muscle‐exposing defects: A retrospective study

Skin grafts are frequently used for the reconstruction of skin defects, and optimal stabilization of the graft is essential for successful reconstruction. Although the tie‐over technique has been widely used as a standard method in Japan, we sometimes encounter cases with significant graft loss due to suboptimal stabilization of the graft. Reported risk factors for increased graft loss include the following: defects of a large size, with muscle exposure, and located in the trunk and extremities. Recent studies have demonstrated the usefulness of negative‐pressure closure (NPC) for the stabilization of skin grafts due to the uniform pressure it provides across the graft. Therefore, since March 2017, we have used NPC for skin graft stabilization in patients with defects in the trunk and extremities of more than 10 cm in size or with muscle exposure. We carried out a retrospective comparative study of the outcome of the conventional tie‐over technique versus NPC. Mann–Whitney U‐test revealed that NPC showed significantly higher graft survival rate than tie‐over method (P = 0.0012). In addition, NPC showed a tendency toward shorter operative times (from skin graft harvest to the completion of the graft stabilization) than the tie‐over method (P = 0.0931). These results suggest that NPC may be superior to the tie‐over method for stabilization of skin grafts especially in large or muscle‐exposing defects in the trunk or extremities.     

M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP

Wee1, the Cdc2 inhibitory kinase, needs to be down-regulated at the onset of mitosis to ensure rapid activation of Cdc2. Previously, we have shown that human somatic Wee1 (Wee1A) is down-regulated both by protein phosphorylation and degradation, but the underlying mechanisms had not been elucidated. In the present study, we have identified the beta-transducin repeat-containing protein 1/2 (beta-TrCP1/2) F-box protein-containing SKP1/Cul1/F-box protein (SCF) complex (SCF(beta-TrCP1/2)) as an E3 ubiquitin ligase for Wee1A ubiquitination. Although Wee1A lacks a consensus DS(p)GXXS(p) phospho-dependent binding motif for beta-TrCP, recognition of Wee1A by beta-TrCP depended on phosphorylation, and two serine residues in Wee1A, S53 and S123, were found to be the most important phosphorylation sites for beta-TrCP recognition. We have found also that the major M-phase kinases polo-like kinase 1 (Plk1) and Cdc2 are responsible for the phosphorylation of S53 and S123, respectively, and that in each case phosphorylation generates an unconventional phospho-degron (signal for degradation) that can be recognized by beta-TrCP. Phosphorylation of Wee1A by these kinases cooperatively stimulated the recognition and ubiquitination of Wee1A by SCF(beta-TrCP1/2) in vitro. Mutation of these residues or depletion of beta-TrCP by small-interfering RNA treatment increased the stability of Wee1A in HeLa cells. Moreover, our analysis indicates that beta-TrCP-dependent degradation of Wee1A is important for the normal onset of M-phase in vivo. These results also establish the existence of a feedback loop between Cdc2 and Wee1A in somatic cells that depends on ubiquitination and protein degradation and ensures the rapid activation of Cdc2 when cells are ready to divide.     

Studies on percutaneous transvenous mitral commissurotomy using a modified transseptal approach

Summary A modified version of Brockenbrough's trans-septal catheterization technique was carried out in 11 patients indicated for percutaneous transvenous mitral commissurotomy (PTMC). In 8/11 (72.7%), a coiled guide-wire was successfully inserted through theforamen ovale without atrial septal puncture. The Brockenbrough needle was used merely to maintain stiffness and the orientation of the dilator. PTMC was performed with an Inoue single balloon without incident.Patent foramen ovale was found by transesophageal echocardiography prior to the operation in only 1/11 patients (9.0%); nonetheless, it proved not to be a critical factor for the success of the procedure. This procedure seems to have much potential to enable the treatment of mitral stenosis with a lowered risk to the patient, as long as it is performed with precision and caution.     

Clinical significance of changes in Torque teno virus DNA titer after chemotherapy in patients with primary lung cancer

Background

Several studies have reported that viral infections are related to lung cancer. We previously reported the involvement of Torque teno virus (TTV) in patients with lung cancer and idiopathic pulmonary fibrosis. However, the role of TTV in lung cancer growth, and its influence on changes in TTV DNA titers due to idiopathic pulmonary fibrosis (IPF) in lung cancer patients are poorly understood.

Chemotherapy for patients with advanced lung cancer receiving long-term oxygen therapy

Background

Long-term oxygen therapy (LTOT) is sometimes prescribed for patients with advanced lung cancer who are potential candidates for chemotherapy. The aim of this study was to assess the usefulness of chemotherapy for patients with this disease who require LTOT.

Methods

The medical records of 40 patients with advanced lung cancer who received LTOT while undergoing systemic chemotherapy at our institution between January 2009 and December 2014 were retrospectively reviewed. Chemotherapy consisted of cytotoxic or molecular-targeted agents.

Results

Twenty-four patients had adenocarcinoma, 6 had squamous cell carcinoma, and 10 had small cell lung cancer (SCLC). The median survival time from the date of the first chemotherapy cycle performed in conjunction with LTOT was 194 days. In a multivariate analysis, the only factor significantly associated with better prognosis was the line (first or second) of the first chemotherapy with LTOT (hazard ratio =0.42; 95% confidence interval, 0.18 to 0.94). Among the 40 patients, 10 (25%) received chemotherapy during the last 30 days of their lives, 2 of whom died of chemotherapy-related adverse events.

Conclusions

Chemotherapy for patients with advanced lung cancer who receive LTOT may be acceptable if it is the first- or second-line treatment. However, we should be mindful of the potential overuse of chemotherapy and its negative impact on quality of life.