Phase II Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Over 75 Years Old with Alternating Bortezomib/dexamethasone and Lenalidomide/dexamethasone: the MARBLE Trial

Elderly multiple myeloma (MM) patients, who are generally ineligible for transplantation, have high risks of death and treatment discontinuation, and require a regimen incorporating novel agents that balance safety, tolerability, and efficacy. We evaluated alternating bortezomib-dexamethasone and lenalidomide-dexamethasone treatments administered over a 63-day cycle in transplant-ineligible elderly patients with newly diagnosed MM. Subcutaneous bortezomib 1.3 mg/m2 was administered weekly on Days 1, 8, 15, and 22; oral lenalidomide 15 mg daily on Days 36-56; and oral dexamethasone 20 mg on Days 1, 8, 15, 22, 36, 43, 50, and 57 for 6 cycles. The primary endpoint was the overall response rate

Clinical outcomes of left atrial circumferential ablation and box ablation for paroxysmal atrial fibrillation

Left atrial circumferential ablation （LACa） and box ablation （BOXa） are two common treatments for paroxysmal atrial fibrillation （PAF）. However, only a few studies have compared these two approaches. This study aimed to compare the clinical outcomes of these two therapeutic modalities. Patients with PAF who underwent catheter ablation were randomly assigned to either the LACa or BOXa groups and were followed up for 6 months. The primary outcomes were the rate of atrial fibrillation （AF） recurrence after 6 months and changes in the left atrial ejection fraction （LAEF） measured via magnetic resonance imaging from baseline to follow-up. The secondary outcomes included the frequency of supraventricular premature beats （SPBs） and short supraventricular runs （SVRs） on a 24-h electrocardiogram at follow-up. A total of 40 patients were randomly assigned to the LACa （n＝21） or BOXa group （n＝19）. No significant between-group differences were observed in the patient characteristics and LAEF at baseline or the rate of AF recurrence at 6 months （LACa, 4.8％ ［1/21］ vs. BOXa, 5.3％ ［1/19］; P＝0.94） as well as changes in the LAEF at 3 and 6 months. However, the frequency of SPB and SVR at 6 months was significantly lower in the LACa group than in the BOXa group （0.2 ［−0.2, 0.50］/24h vs. 0.8 ［0.5, 1.2］/24h, P＝0.01; 2.2 ［−4.2, 8.7］/24h vs. 11.9 ［4.8, 18.9］/24h, P＝0.04, respectively）. Although the rates of AF recurrence and changes in the LAEF were comparable between the LACa and BOXa groups, the higher incidence of SPBs and SVRs at 6 months in the BOXa group suggests that BOXa provided no advantage in the treatment of PAF patients

High-dose Dexamethasone Therapy as the Initial Treatment for Idiopathic Thrombocytopenic Purpura: Protocol for a Multicenter, Open-label, Single Arm Trial

Standard therapy for idiopathic thrombocytopenic purpura (ITP) has not been established. We are conducting a multicenter, prospective trial to determine the efficacy and safety of short-term, high-dose dexamethasone therapy in ITP patients aged 18-80 years with platelet counts of <20, 000 /μL, or with <50, 000/ μL and bleeding symptoms. The primary endpoints of this trial are the proportion of responses (complete plus partial response) on day 180 (day 46+180) after the completion of the 46-day high-dose dexamethasone therapy. The results of this investigation of the effectiveness and safety of this regimen will be essential for the establishment of standard therapy for ITP

Inward or Outward Costophrenic Angles: A Simple Sign on Chest X-ray for the Screening of Metabolic Syndrome

Prevention of cardiovascular diseases is a top-priority issue in Japan. To this end, we have developed a new screening method for metabolic syndrome (MetS) using chest X-ray. We recruited 200 patients who visited our outpatient cardiology clinic from March 2014 to August 2014. Patients with severe lung disease, acute coronary syndrome, and end-stage renal failure were excluded. We collected data on each patient\u27s medical history, laboratory results, waist circumference (WC), body weight, and height. Additionally, we measured two parameters from the chest X-ray: (A) width at the level of right dome of diaphragm and (B) width between the costophrenic (CP) angles. We classified the CP angles as either inward (A≥B) or outward (A<B). Increased WC was defined as ≥85cm in males and ≥90cm in females. Patients with outward CP angles had a significantly larger WC compared to those with inward CP angles (92.3±8.9 vs. 80.5±7.8cm, P<0.001). In particular, the percentage of male patients with increased WC (≥ 85cm) was significantly higher in patients with outward CP angles than in those with inward CP angles (89.2% vs. 41.3%, P<0.001). Body weight and BMI were both significantly higher in patients with outward CP angles than in those with inward CP angles in both gender groups. When laboratory data and risk factors were compared, patients with outward CP angles and those with positive WC criteria consistently tended toward high morbidity from hypertension, dyslipidemia, and diabetes. The inward/outward CP identified candidates for MetS, especially in the male subjects. Chest X-ray could become a useful screening tool for the detection of increased WC and coronary risk factors

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves

Molecular Detection of Multiple Emerging Pathogens in Sputa from Cystic Fibrosis Patients

Background: There is strong evidence that culture-based methods detect only a small proportion of bacteria present in the respiratory tracts of cystic fibrosis (CF) patients. Methodology/Principal Findings: Standard microbiological culture and phenotypic identification of bacteria in sputa from CF patients have been compared to molecular methods by the use of 16S rDNA amplification, cloning and sequencing. Twenty-five sputa from CF patients were cultured that yield 33 isolates (13 species) known to be pathogens during CF. For molecular cloning, 760 clones were sequenced (7.263.9 species/sputum), and 53 different bacterial species were identified including 16 species of anaerobes (30%). Discrepancies between culture and molecular data were numerous and demonstrate that accurate identification remains challenging. New or emerging bacteria not or rarely reported in CF patients were detected including Dolosigranulum pigrum, Dialister pneumosintes, and Inquilinus limosus. Conclusions/Significance: Our results demonstrate the complex microbial community in sputa from CF patients, especially anaerobic bacteria that are probably an underestimated cause of CF lung pathology. Metagenomic analysis is urgentl

Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study

Study Design:Retrospective study of registry data.Objectives:Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions.Methods:A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury.Results:Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss ≥500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time ≥180 min (HR = 2.78, P = .007) was significantly associated with major complications.Conclusions:Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients

Risk Factors for Delirium After Spine Surgery in Extremely Elderly Patients Aged 80 Years or Older and Review of the Literature: Japan Association of Spine Surgeons with Ambition Multicenter Study

Study Design:Retrospective database analysis.Objective:Spine surgeries in elderly patients have increased in recent years due to aging of society and recent advances in surgical techniques, and postoperative complications have become more of a concern. Postoperative delirium is a common complication in elderly patients that impairs recovery and increases morbidity and mortality. The objective of the study was to analyze postoperative delirium associated with spine surgery in patients aged 80 years or older with cervical, thoracic, and lumbar lesions.Methods:A retrospective multicenter study was performed in 262 patients 80 years of age or older who underwent spine surgeries at 35 facilities. Postoperative complications, incidence of postoperative delirium, and hazard ratios of patient-specific and surgical risk factors were examined.Results:Postoperative complications occurred in 59 of the 262 spine surgeries (23%). Postoperative delirium was the most frequent complication, occurring in 15 of 262 patients (5.7%), and was significantly associated with hypertension, cerebrovascular disease, cervical lesion surgery, and greater estimated blood loss (P < .05). In multivariate logistic regression using perioperative factors, cervical lesion surgery (odds ratio = 4.27, P < .05) and estimated blood loss ≥300 mL (odds ratio = 4.52, P < .05) were significantly associated with postoperative delirium.Conclusions:Cervical lesion surgery and greater blood loss were perioperative risk factors for delirium in extremely elderly patients after spine surgery. Hypertension and cerebrovascular disease were significant risk factors for postoperative delirium, and careful management is required for patients with such risk factors

Mikulicz ビョウ ノ チリョウ チュウ ニ カン ショウガイ デ ハッショウ シタ ジコ メンエキセイ スイエン ノ 1レイ

69 歳,女性.2004 年に他院耳鼻科にてシェーグレン症候群と診断され治療中であった.2010 年5月に肝機能障害を指摘されたために当科を受診した.初診時に両側上眼瞼の腫脹と両側耳下腺の腫大(約1 cm)を認めた.血液生化学検査では胆道系酵素の上昇を認め,またIgG は2308 mg/dl,IgG4 は498 mg/dl と高値を呈した.造影CT では膵はびまん性に腫大していた.内視鏡的逆行性膵胆管造影で膵管に特徴的な狭細像を認めたため自己免疫性膵炎と診断した.本症例の眼瞼腫脹と顎下腺腫脹は現在の診断基準ではMikulicz 病と診断が可能である.Mikulicz 病と自己免疫性膵炎の合併は少なくないものの,本邦における文献報告例は本例で11 例目である.A 69-year-old woman presented with a chief complaintof liver dysfunction in May 2010. Both palpebrae superiorand the parotid gland had been swollen for six years. Bloodtests showed increased levels of biliary system enzymesand serum IgG and IgG4. Enhanced computed tomographyrevealed a diffusely enlarged pancreas. A narrowed pancreaticduct revealed by endoscopic retrograde cholangio-pancreatographywas diagnosed as autoimmune pancreatitis.The swollen eyelid and enlarged submandibular gland indicateda diagnosis of Mikulicz\u27s disease. Case reports of Mikulicz\u27sdisease complicated with autoimmune pancreatitisare very rare