Septic Pulmonary Embolism Induced by Dental Infection

Dental infection can be an important source for septic pulmonary embolism (SPE), but only a few cases of SPE accompanying dental infection have been reported. The aim of this study was to characterize the clinical features of SPE induced by dental infection. Patients who fulfilled the diagnostic criteria described in the text were recruited in a retrospective fashion. All 9 patients were men, with a median age of 59 years (range:47 to 74 years). Eight patients had chest pain (88.9%), 5 had a preceding toothache (55.6%) and 3 had preceding gingival swelling (33.3%). Blood cultures obtained from 7 patients were negative. Periodontitis was found in all of the cases, periapical periodontitis in 5 cases, and gingival abscess in 3 cases. The median duration of hospitalization was 15 days, and symptoms were mild in some cases. In addition to antimicrobial therapy, tooth extraction was performed in 3 cases, tooth scaling in 6. SPE induced by dental infection has prominent clinical characteristics such as male preponderance, chest pain, preceding toothache, and mild clinical course

トクシマケン ニオケル キュウセイ シンキンコウソクショウ ニ タイスル チリョウ ノ ゲンジョウ : タシセツ ゴウドウ ケンキュウ ケッカ

Although considerable information is available regarding the prognosis after acute myocardial infarction (AMI) in urban populations, little is known about the local subjects in Japan. The purpose of this study was to assess short-term mortality and reperfusion therapy after AMI in Japan. From October 1999 to October 2000, 256 patients with AMI from 16 hospitals in Tokushima Prefecture were studied. Mean age of AMI in Tokushima was elder than another country (men : 65.0 yrs, women : 71.6 yrs). Although, patients of in-hospital death were twenty-three (9.0%). Two patients were cardiopulmonary arrest on arrival. Reperfusion therapy performed for 82.8% of all patients. Only one patient treated by CABG (coronary artery bypass grafting). Hospital admission within 6 hours of symptom onset was 61.6% of all patients. These data suggest that short-term mortality was reasonable by adequate reperfusion therapy. Earlier reperfusion therapy will improve clinical outcome in Tokushima

Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial

Background The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC. Methods Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest. Results Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred. Conclusions Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events

Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status

Most clinical trials of non-small-cell lung cancer (NSCLC) exclude patients with poor ECOG performance status (PS). Thus, the efficacy of immune checkpoint inhibitors (ICIs) in patients with poor PS remains unclear. Herein, we used data from a retrospective cohort to assess the potential clinical benefits of ICIs in NSCLC patients with poor PS. Data from NSCLC patients who received ICI monotherapy at 9 institutions between December 2015 and May 2018 were retrospectively analyzed. After excluding 4 patients who lacked PS data, a total of 527 ICI-treated patients, including 79 patients with PS 2 or higher, were used for our analyses. The progression-free survival (PFS) and overall survival (OS) of patients with PS 2 or higher were significantly shorter compared with those of PS 0-1 patients (median PFS, 4.1 vs 2.0 months;P < .001 and median OS, 17.4 vs 4.0 months;P < .001). Among NSCLC patients with programmed cell death protein-ligand 1 (PD-L1) expression of 50% or higher who were treated with pembrolizumab as first-line therapy, the median PFS times of patients with PS 2 and 0-1 were 7.3 and 8.1 months, respectively. There was no significant difference in PFS between patients with PS 2 and 0-1 (P = .321). Although poor PS was significantly associated with worse outcomes in NSCLC patients treated with ICIs, pembrolizumab as a first-line treatment in NSCLC patients expressing high levels of PD-L1 could provide a clinical benefit, even in patients with PS 2

21セイキ ノ カンドウミャク インターベンション

Coronary intervention has come to achieve good results with the use of new devices, such as Rotablator (ROTA), new directional coronary atherectomy (DCA), and a special guide wire, even for lesions in which good results were not obtained with plain old balloon angioplasty. In the present study, we evaluated the initial results in patients who underwent ROTA procedures, coronary intervention for chronic total occlusion (CTO), and new DCA procedures in our hospital between January and December 2001. (1) There were 99 patients who underwent ROTA, with an average age of 68±12 years, a lesion length of 15.9±9.9 mm, a reference vessel diameter of 2.7±0.6 mm, and a success rate of 98%. Among these 99 patients, there were 82 patients (83%) with B2 or C type lesion, which is difficult to treat. (2) There were 61 patients with CTO who underwent coronary intervention, with an average age of 63±9 years, an occlusion length of 22.8±13.3 mm, a reference vessel diameter of 2.6±0.7 mm, and a success rate of 82%. (3) There were 5 patients who underwent DCA for ostial lesion of left anterior desending artery and the target lesion was successfully dilated in all these patients. These results indicated that new devices for coronary intervention have made it possible to treat a wider range of lesions, but restenosis still remains to be solved. In Europe and the U.S.A., restenosis is reported to have been drastically reduced by drug eluting stents, which are expected to be introduced in Japan in the future

ジンソクナ バイスタンダー シンパイ ソセイホウ ニヨリ トツゼンシ オ マヌガレ シャカイ フッキ デキタ コウコウセイ ノ 2 ショウレイ

Bystander CPR means that people who find cardiopulmonary arrest perform cardiopulmonary resuscitation on the spot. Quick CPR contributes to increase in the rate of returning to the society as well as one-month survival rate and neurological prognosis. We report our experience with two high school students who underwent quick Bystander CPR, avoided sudden death, and returned to the society. ［Case 1］ Eighteen-year-old man : He collapsed suddenly in his home. Bystander CPR was performed by his family until emergency crews arrived there. Automated external defibrillator （AED） worked twice and his heartbeat started again. In electrocardiogram, coved type ST elevation in lead V1 was observed, and he was diagnosed as Brugada syndrome. We implanted an implantable cardioverter-defibrillator. Since his condition was stable, he was discharged on the 19th day. ［Case 2］ Seventeen-year-old woman : She collapsed suddenly walking with her family. Her father confirmed that she had no response, and started Bystander CPR. Her father got AED quickly and AED worked once, and she started to breathe again. She was admitted to our hospital for a work-up. Torsades de pointes （TdP） was observed in monitor electrocardiogram, and her QTc time was 513 msec in 12‐lead electrocardiogram. She was diagnosed as congenital long QT syndrome because genetic test showed that she had LQT2. Her QTc time was improved （approximately 350 msec） by medication, and she was discharged on the 25th day. Utstein-style statistics in Japan shows that the rate of returning to the society can be doubled by performing Bystander CPR on patients with cardiopulmonary arrest. However, performing rate of Bystander CPR is less than 50％ in Japan. In order to increase survival rate of patients with cardiopulmonary arrest for the future, it is important to inform people about CPR and to promote CPR, and in fact, we have been promoting CPR

BCL6 inhibition ameliorates resistance to ruxolitinib in <i>CRLF2</i>-rearranged acute lymphoblastic leukemia

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is an intractable disease and most cases harbor genetic alterations that activate JAK or ABL signaling. The commonest subtype of Ph-like ALL exhibits a CRLF2 gene rearrangement that brings about JAK1/2-STAT5 pathway activation. However, JAK1/2 inhibition alone is insufficient as a treatment, so combinatorial therapies targeting multiple signals are needed. To better understand the mechanisms underlying the insufficient efficacy of JAK inhibition, we explored gene expression changes upon treatment with a JAK1/2 inhibitor (ruxolitinib) and found that elevated BCL6 expression was one such mechanism. Upregulated BCL6 suppressed the expression of TP53 along with its downstream cell cycle inhibitor p21 (CDKN2A) and pro-apoptotic molecules, such as FAS, TNFRSF10B, BID, BAX, BAK, PUMA, and NOXA, conferring cells some degree of resistance to therapy. BCL6 inhibition (with FX1) alone was able to upregulate TP53 and restore the TP53 expression that ruxolitinib had diminished. In addition, ruxolitinib and FX1 concertedly downregulated MYC. As a result, FX1 treatment alone had growth-inhibitory and apoptosis- sensitizing effects, but the combination of ruxolitinib and FX1 more potently inhibited leukemia cell growth, enhanced apoptosis sensitivity, and prolonged the survival of xenografted mice. These findings provide one mechanism for the insufficiency of JAK inhibition for the treatment of CRLF2-rearranged ALL and indicate BCL6 inhibition as a potentially helpful adjunctive therapy combined with JAK inhibition