Direct observation of reversible bond homolysis by 2D EXSY NMR

Bond homolysis is one of the most fundamental bond cleavage mechanisms. Thus, understanding of bond homolysis influences the development of a wide range of chemistry. Photolytic bond homolysis and its reverse process have been observed directly using time-resolved spectroscopy. However, direct observation of reversible bond homolysis remains elusive. Here, we report the direct observation of reversible Co–Co bond homolysis using two-dimensional nuclear magnetic resonance exchange spectroscopy (2D EXSY NMR). The characterization of species involved in this homolysis is firmly supported by diffusion ordered NMR spectroscopy (DOSY NMR). The unambiguous characterization of the Co–Co bond homolysis process enabled us to study ligand steric and electronic factors that influence the strength of the Co–Co bond. Understanding of these factors will contribute to rational design of multimetallic complexes with desired physical properties or catalytic activity

Acute adrenal crisis after orthopedic surgery for pathologic fracture

BACKGROUND: Adrenal crisis after surgical procedure is a rare but potentially catastrophic life-threatening event. Its manifestations, such as hypotension, tachycardia, hypoxia, and fever mimic the other more common postoperative complications. Clinical outcome is dependent upon early recognition of the condition and proper management with exogenous steroid administration. CASE PRESENTATION: We report a 75-year-old man who presented with shock immediately after surgery for a femoral fracture from lung cancer metastasis. Anemia and severe hyponatremia were detected. Despite adequate fluid resuscitation, nonspecific symptoms including hypotension, tachycardia, hypoxia, fever and confusion occurred. Emergent CT revealed enlarged bilateral adrenal glands. Under the diagnosis of adrenal crisis due to metastatic infiltration of adrenal glands, the patient was treated with appropriate steroid replacement resulting in rapid improvement and recovery. CONCLUSION: We describe a case of adrenal crisis caused by the lack of adrenal reserve based on metastatic involvement and surgical stress, the first published case of adrenal crisis after surgery for a pathologic fracture from lung cancer metastasis. Surgeons treating pathologic fractures should be aware of this complication and familiar with its appropriate therapy because of increasing opportunity to care patients with metastatic bone tumors due to recent advances in cancer treatment

Exposure to PM2.5 and Lung Function Growth in Pre- and Early-Adolescent Schoolchildren: A Longitudinal Study Involving Repeated Lung Function Measurements in Japan.

Rationale: Epidemiological evidence indicates that ambient exposure to particulate matter ⩽2.5 μm in aerodynamic diameter (PM2.5) has adverse effects on lung function growth in children, but it is not actually clear whether exposure to low-level PM2.5 results in long-term decrements in lung function growth in pre- to early-adolescent schoolchildren. Objectives: To examine long-term effects of PM2.5 within the 4-year average concentration range of 10-19 μg/m3 on lung function growth with repeated measurements of lung function tests. Methods: Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8-12 years from 16 school communities in 10 cities around Japan, covering a broad area of the country to represent concentration ranges of PM2.5, was done with a multilevel linear regression model. Forced expiratory volume in 1 second, forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC were used as lung function indicators to examine the effects of 10-μg/m3 increases in the PM2.5 concentration on relative growth per each 10-cm increase in height. Results: The overall annual mean PM2.5 level was 13.5 μg/m3 (range, 10.4-19.0 μg/m3). We found no association between any of the lung function growth indicators and increases in PM2.5 levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O3 or NO2 did not change the null results. Conclusions: This nationwide longitudinal study suggests that concurrent, long-term exposure to PM2.5 at concentrations ranging from 10.4 to 19.0 μg/m3 has little effect on lung function growth in preadolescent boys or pre- to early-adolescent girls

Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy

The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBAS, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBAS variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.A1a371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg5SHis, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.A1a371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufml in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.A1a371Thr variant in trans with a loss-of-function allele in UBAS underlies a severe infantile-onset encephalopathy.Peer reviewe

A Prospective Multicenter Observational Study of Venous Thromboembolism after Gastric Cancer Surgery (SHISA-1601).

Introduction:This study aimed to clarify the frequency and risk factors of intercurrent venous thromboembolism (VTE) in patients undergoing major curative gastric cancer surgery.Methods:This prospective, multicenter, observational study included patients with gastric cancer who underwent radical gastrectomy at 5 hospitals between June 2016 and May 2018. Patients who were preoperatively administered anticoagulants were excluded.Results:A total of 126 patients were eligible to participate. VTE occurred within 9 days postoperatively in 5 cases (4.0%; 2 symptomatic and 3 asymptomatic). Postoperative day (POD) 1 plasma D-dimer and soluble fibrin (SF) levels were significantly higher in the VTE group than in the non-VTE group. Receiver-operating characteristic curve (ROC) analysis indicated a statistically significant ability of POD 1 D-dimer and SF levels to predict postoperative VTE development after gastrectomy; this finding was reflected by an area under the curve (AUC) of 0.97 (95% CI 0.92-1.0) and 0.87 (95% CI 0.74-1.0), respectively. Cutoff values of D-dimer (24.6 µg/mL) and SF (64.1 µg/mL) were determined. Intraoperative blood transfusion (odds ratio [OR] 7.86), POD 1 D-dimer ≥24.6 µg/mL (OR 17.35), and POD 1 SF ≥64.1 µg/mL (OR 19.5) were independent predictive factors for postoperative VTE (p < 0.05).Conclusion:VTE occurred in 4.0% patients (1.6% symptomatic and 2.4% asymptomatic) after gastric cancer surgery; however, with an early diagnosis and anticoagulant therapy, no patients experienced progression. Careful observation of patients with a high risk for VTE, including intraoperative blood transfusion and high POD 1 D-dimer or SF levels, would contribute to the early detection of VTE

ショクドウ ソウカン ニヨル フンゴウブ カンゼン リカイ オ カイケッチョウ サイケン デ シュウフクシタ ショクドウ セツジョ ノ 1レイ

症例は60 歳代, 男性. 身長162.6 cm, 体重40.0 kg, Body Mass Index（BMI）15.1 kg / m2であり, 既往歴に慢性閉塞性肺疾患（COPD）を認めた. 胸部上部食道癌 T1b N0 M0 Stage Iに対して食道亜全摘, 3領域リンパ節郭清, 胸骨後胃管再建を施行した.術当日に抜管したが, 術後肺炎に伴う呼吸不全のため, 術後6日目に気管内挿管を試みたが、食道挿管となった．再挿管, 人工呼吸管理の後に軽快し術後13日目に抜管となったが, 術後透視で吻合部周囲に造影剤漏出を認めた. 2ヶ月間の保存的加療で造影剤漏出は消失したが吻合部に長径4 cmの高度狭窄を認めた．内視鏡的拡張術での改善は困難であり, 術後243日目に消化管再建術を施行した. 手術所見として, 第2肋間より頭側の胸骨を切除したところ, 胃管の口側断端は第2肋間の高さの胸骨後面に位置していた.食道断端までは肉芽で置換されていた.胸骨前経路回結腸再建を施行し, 再建術後 8日目に食事を開始し, 合併症なく再建術後30日目に退院となった. 回結腸再建後2年経過後も食道癌の再発は認めず, 通過障害なく経口摂取のみでの生活が可能となっている．A 60s-year-old man underwent endoscopic screening during which a tumor was detected in the upper thoracic esophagus, which was diagnosed as T1bN0M0 Stage I esophageal squamous cell carcinoma. He had a history of chronic obstructive pulmonary disease. He underwent subtotal esophagectomy with 3 field lymph node dissection. Reconstruction was performed by gastric tube through the posterior sternal route. Extubation was performed on the day of surgery. Respiratory failure by postoperative pneumonia occurred, and ventilatory management was performed on the sixth postoperative day. However, the intubation was put into the esophagus. He became well and extubation was performed on the 13th postoperative day. Postoperative fluoroscopy showed contrast leakage around the anastomotic site. After 2 months of conservative treatment, the contrast leak disappeared, but there was a severe stenosis of 4 cm in length at the anastomosis. Endoscopic dilatation was not sufficient to improve the stenosis. Gastrointestinal reconstruction was performed on the 243rd postoperative day. The cephalic sternum was resected, and the gastrointestinal canal opening margin was located on the posterior surface of the sternum, at the level of the second intercostal space. The segment was replaced by a granulation. The patient underwent anterior sternal ileocolic reconstruction. Oral intake started on the 8th day after the reconstruction, and hospital discharge was on the 30 th day after the reconstruction without any complications. Two years after ileocolic reconstruction, there has been no cancer recurrence, and he lives well on oral intake only

トウイン ニオケル キョウクウ キョウカ ショクドウ セツジョ ノ ドウニュウ ト タンキ チリョウ セイセキ ノ ケントウ

【背景】食道癌に対する胸腔鏡手術は本邦で広く行われており、施設ごとに手術手技の定型化がなされている.胸腔鏡下手術の利点として拡大視効果や緻密な手術操作が可能となることが挙げられるが、当院でも2016年より腹臥位胸腔鏡下食道手術を導入し、出血の少ない安全かつ確実な郭清を目指し、定型化に向けてその手技を刷新している.【対象と方法】】2016年4月から2019年4月までに当院で施行した胸腔鏡下食道切除38例につき、その短期成績を検討した.【結果】男:女＝32:6、年齢中央値 66歳(41-76)、cStage I / II / III / IVa: 17 / 6 / 13 / 2であった.胸腔内出血量中央値は10ml(0-53)、胸部操作時間中央値は192分(97-478)、胸腔内郭清リンパ節個数中央値は17個(1-42)であった.術後合併症は、縫合不全3例(7.9％)、反回神経麻痺7例(18.4％)、肺炎12例(31.6％)であった.術後在院日数中央値は19日(11-38)であった.導入期からの前半19例では反回神経麻痺を6例(31.6％)に認めたが、後半19例では１例(5.2％)であった(p=0.036).【結語】当院における胸腔鏡下食道切除術は安全に導入、施行可能であった.手術手技が定型化されることで反回神経麻痺を少なくする郭清が可能になると考えられた.Background: Thoracoscopic esophagectomy (TE) is increasingly being used worldwide in patients with esophageal cancer. In this study, we investigated the clinical short-term outcomes of TE performed in patients placed in the prone position. Method: We investigated the surgical and clinical outcomes in 38 patients with esophageal cancer who underwent TE at our hospital between April 2016 and April 2019. Results: Of the 39 patients investigated, 32 were men. Median patient age was 66 (range 41–76) years, the median intraoperative blood loss was 10 (0–53) mL, and the median operation time for thoracoscopy was 192 (97–478) min. The mean operation time for thoracoscopy in the latter group was significantly shorter than that in the former group (188 min vs. 232 min, p=0.013). The following postoperative complications were observed: 7 (18.4%) cases of recurrent nerve palsy, 3 (7.9%) cases of anastomotic leakage, 12 (31.6%) cases of pneumonia, and 0 (0%) cases of chylothorax. The incidence of recurrent nerve palsy was lower in the latter group than in the former group (5.2% vs. 31.6%, p=0.036). Conclusions: TE in the prone position is safe and feasible. As experience performing the procedure increases, the performance of the procedure stabilizes

ドウニュウ カガク リョウホウ ニテ コンチ セツジョ ガ カノウ トナッタ ケイブ ショクドウガン ノ 1レイ

　症例は50歳代，男性．咽頭痛，嚥下障害を主訴に近医受診し，上部消化管内視鏡検査にて頸部食道に1/4周性のtype3病変(squamous cell carcinoma)と食道胃接合部に0-IIa+IIc病変(adenocarcinoma)を指摘され，当院当科紹介となった．造影CT検査にて左頸部に原発巣と一塊となった腫瘤を認め，左総頸動脈及び気管への浸潤を認めた．精査の結果，頸部食道癌cT4bN2M0 cStageIVa，バレット食道腺癌cT1bN0M0 cStageIと診断し，切除不能局所進行食道癌であり導入化学療法の方針とした．DCF(Docetaxel/Cisplatin/5-Fluorouracil) 療法3コースで病変の縮小が得られ，頸部腫瘍は長径37mmから17mmとなり，総頸動脈の浸潤が解除されたため，根治術を行う方針とした．手術は咽頭喉頭食道全摘，頸部縦隔腹部リンパ節郭清，後縦隔経路遊離空腸付加胃管再建，腸瘻造設術を施行した．術中偶発症なく，手術時間846分，出血量670mLであった．病理組織学的検査では，頸部食道癌ypT4aN2M0 ypStegeIII，治療効果Grade 1b，バレット食道癌ypT1b-SM2N0M0 ypStageI，治療効果Grade 1aであった．術後経過は概ね良好で術後9日目より経口摂取を開始し，術後18日目に退院となった．　切除不能局所進行食道癌に対する標準治療は化学放射線療法であるが，近年，DCF療法による導入化学療法後の外科的切除の有用性が報告されている．今回，導入化学療法により根治切除可能であった頸部食道癌，食道腺癌の重複例を経験したため報告する．　A 58-year-old man with sore throat and dysphagia revealed type 3 lesion in cervical esophagus and 0-IIa+IIc lesion in esophagogastric junction on upper gastrointestinal endoscopy. Histopathologic examination of biopsy specimens showed squamous cell carcinoma at cervical esophagus and adenocarcinoma at esophagogastric junction. Computed tomography suggested that the large tumor in left neck infiltrated into the common carotid artery and trachea. According to these findings, we diagnosed locally advanced unresectable cervical esophageal cancer (cT4bN2M0, cStageIVa) and Barret’s esophageal adenocarcinoma (cT1bN0M0, cStageI), and decided to perform induction chemotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil (DCF). After 3 courses of that, the primary tumor decreased from 37 mm to 17 mm as major axis and released infiltration into the common carotid artery. Therefore, we performed conversion surgery, pharyngolaryngectomy and total esophagectomy. Histopathological findings showed cervical esophageal cancer (ycT4aN2M0, ycStageIVa) and Barret’s esophageal adenocarcinoma (ycT1b-SM2N0M0, ycStageI). The postoperative course was uneventful, he resumed eating 9 days after surgery and was discharged 18 days after surgery.　Conversion surgery after induction chemotherapy for locally advanced unresectable esophageal cancer may contribute to radical resection and better clinical outcome