A case of Sjögren's syndrome in which diffuse cystic lung lesions led to an accurate diagnosis.

Key Clinical Message: Even in the absence of other symptoms or other pulmonary manifestations suggesting Sjögren's syndrome (SS), it is necessary to include SS in the differential diagnosis of diffuse cystic lung disease (CLD). Abstract: A case of SS that presented initially with diffuse CLD is reported. This case is considered rare because diffuse pulmonary cysts were observed in the early stage with few symptoms, only cysts were observed without other lung lesions on imaging, cyst formation was histologically considered to be alveolar loss, and airway lesions not observed on imaging were suspected based on lung function testing. The details of this case provide extremely important information to consider for the diagnosis and management of CLD and SS.

Development of novel waxy bone haemostatic agents composed of biodegradable polymers with osteogenic-enhancing peptides in rabbit models.

OBJECTIVES: The use of bone wax (BW) is controversial for sternal haemostasis because it increases the risk of wound infection and inhibits bone healing. We developed new waxy bone haemostatic agents made from biodegradable polymers containing peptides and evaluated them using rabbit models. METHODS: We designed 2 types of waxy bone haemostatic agents: peptide wax (PW) and non-peptide wax (NPW), which used poly(ε-caprolactone)-based biodegradable polymers with or without an osteogenesis-enhancing peptide, respectively. Rabbits were randomly divided into 4 groups based on treatment with BW, NPW, PW or no treatment. In a tibial defect model, the bleeding amount was measured and bone healing was evaluated by micro-computed tomography over 16 weeks. Bone healing in a median sternotomy model was assessed for 2 weeks using X-ray, micro-computed tomography, histological examination and flexural strength testing. RESULTS: The textures of PW and NPW (n = 12 each) were similar to that of BW and achieved a comparable degree of haemostasis. The crevice area of the sternal fracture line in the BW group was significantly larger than that in other groups (n = 10 each). The PW group demonstrated the strongest sternal flexural strength (n = 10), with complete tibial healing at 16 weeks. No groups exhibited wound infection, including osteomyelitis. CONCLUSIONS: Waxy biodegradable haemostatic agents showed satisfactory results in haemostasis and bone healing in rabbit models and may be an effective alternative to BW.

Impact of Early Ambulation on the Prognosis of Coronary Artery Bypass Grafting Patients.

BACKGROUND: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation. CONCLUSIONS: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.

Challenges in left sleeve pneumonectomy in the left lateral decubitus position.

We report the case of a 20-year-old woman with carinal adenoid cystic carcinoma who underwent left sleeve pneumonectomy in the left lateral decubitus position, during which severe desaturation was encountered. After transecting the left main bronchus, the left lung was selectively intubated and ventilated. However, oxygenation was inadequate. Hence, venoarterial extracorporeal membrane oxygenation (ECMO) was introduced. Initially, Barclay's procedure was planned to preserve the left lung, but this plan was altered due to the extent of the tumor and unstable ventilation. After the lesion was removed, the trachea and right main bronchus were anastomosed end-to-end. During left pneumonectomy, the right lung was selectively ventilated, but oxygen saturation (SpO2) dropped to <70% despite ECMO. SpO2 improved on additionally ventilating the left lung using another breathing circuit. Temporary right chest closure was performed with ventilation of the left lung across the thoracotomy wound. The patient was turned to the semi-supine position, and tolerated selective right lung ventilation with ECMO. Subsequently, left thoracotomy and pneumonectomy were successfully performed. Careful management is required for desaturation in left sleeve pneumonectomy in the left lateral decubitus position.

Multiple giant coronary artery aneurysms with extended coronary ectasia emerging 12 years after previous coronary artery bypass grafting.

A 73-year-old man presented with multiple giant coronary artery aneurysms. Twelve years prior to the presentation, he had undergone coronary artery bypass grafting. At that time, he exhibited small aneurysms (16 mm diameter) in the right coronary artery and a single aneurysm (10 mm diameter) in the left circumflex artery. During follow-up, the aneurysms gradually increased in size (to 45 and 30 mm, respectively, at 12 years after surgery). We resected all of the aneurysms and performed coronary artery bypass grafting of the left circumflex artery through re-sternotomy.

Rhabdomyolysis with Multiple Electrolyte Imbalances under Proton Pump Inhibitor Treatment after Total Thyroidectomy.

A 90-year-old man presented with muscle weakness, difficulty concentrating, and dysphagia. About eighteen months prior to presentation, lansoprazole had been initiated to prevent stress ulcers; he also had a history of total thyroidectomy due to papillary thyroid cancer ten years prior. Laboratory findings were as follows: K 2.4 mEq/L, Ca 3.7 mg/dL, Mg 1.3 mg/dL, CK 5386 U/L, and intact PTH (iPTH) 14 pg/mL. Rhabdomyolysis with multiple electrolyte imbalances under proton pump inhibitor (PPI) treatment was diagnosed. We initiated intravenous hydration and electrolyte supplementation with discontinuation of PPI. After discontinuing PPI, the patient's serum magnesium, potassium, and calcium levels normalised with oral vitamin D and calcium supplementation. PPIs can cause hypocalcaemia and hypokalaemia via hypomagnesemia; hypocalcaemia is also a common postoperative complication of thyroidectomy. Careful monitoring of electrolyte levels is required in patients with long-term PPI treatment, especially in post-thyroidectomy cases.

Higher F-wave frequency associates with poor procedural success rate after Maze procedure.

OBJECTIVES: Persistent atrial fibrillation (AF) causes atrial remodeling, which causes myocardial fibrosis and micro-reentry. Fibrosis may reduce wave voltage and micro-reentry may enhance the dominant frequency (DF) of the F-wave. We investigated whether the DF predicts procedural success by the Maze procedure. METHODS: In 138 consecutive patients who underwent mitral valve surgery and a modified Cox-Maze III procedure for persistent AF in Nagoya University in 2002-2018, 96 (70%) were successfully cardioverted (group S); 42 had persistent or relapsed AF after surgery (group F). Patient data were compared between the groups. Cut-off values were determined by an ROC analysis and predictors of procedural success were evaluated. The DF was obtained from the F-wave of V1 by a high-speed Fourier analysis using the CEPAS software program. RESULTS: Group F showed a significantly larger LA diameter, better LVEF, lower F-wave voltage, higher DF, and longer duration of AF. The cut-off values were as follows: LA diameter, 56 mm; EF, 64.5%; F-wave voltage, 0.13 mV; DF, 7.3 Hz; and duration of AF, 44 months. Each factor showed statistical significance in a univariate analysis; DF lost significance in the multivariate analysis. The higher (DF ≥ 7.3 Hz) and lower voltage group (≤ 0.13 mV) showed the worst procedural success rate (36%), while the lower DF (< 7.3 Hz) and higher voltage group (> 0.13 mV) showed a good rate (86%). CONCLUSIONS: The DF of the F-wave is a useful predictor of procedural success after the Maze procedure in addition to the voltage of F-wave.

Comprehensive metabolic study of IOX4 in equine urine and plasma using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometer for the purpose of doping control.

IOX4 is a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, which was developed for the treatment of anemia by exerting hematopoietic effects. The administration of HIF-PHD inhibitors such as IOX4 to horses is strictly prohibited by the International Federation of Horseracing Authorities and the Fédération Équestre Internationale. To the best of our knowledge, this is the first comprehensive metabolic study of IOX4 in horse plasma and urine after a nasoesophageal administration of IOX4 (500 mg/day, 3 days). A total of four metabolites (three mono-hydroxylated IOX4 and one IOX4 glucuronide) were detected from the in vitro study using homogenized horse liver. As for the in vivo study, post-administration plasma and urine samples were comprehensively analyzed with liquid chromatography/electrospray ionization high-resolution mass spectrometry to identify potential metabolites and determine their corresponding detection times. A total of 10 metabolites (including IOX4 glucuronide, IOX4 glucoside, O-desbutyl IOX4, O-desbutyl IOX4 glucuronide, four mono-hydroxylated IOX4, N-oxidized IOX4, and N-oxidized IOX4 glucoside) were found in urine and three metabolites (glucuronide, glucoside, and O-desbutyl) in plasma. Thus, the respective quantification methods for the detection of free and conjugated IOX4 metabolites in urine and plasma with a biphase enzymatic hydrolysis were developed and applied to post-administration samples for the establishment of elimination profiles of IOX4. The detection times of total IOX4 in urine and plasma could be successfully prolonged to at least 312 h.

Predictors of Failure of Mitral Valve Repair Using Artificial Chordae.

BACKGROUND: We investigated predictors of failure of mitral valve repair (MVr) using expanded polytetrafluoroethylene (ePTFE) and its durability in the long term in a single institution. METHODS: Four hundred twenty-one consecutive patients with primary mitral valve disease underwent MVr using artificial chordae (group A, n = 304) and suture repair (group S, n = 117) at our institution from January 2002 to April 2020. A comparison study was performed to examine the long-term outcomes, reoperation rate, and risk factors for reoperation. RESULTS: One hospital death and 5 late deaths occurred in group S, and 20 late deaths occurred in group A. The reoperation rates were similar: group A, n = 8 (2.6%); and group S, n = 6 (5%). The major cause of reoperation was ruptured ePTFE (CV-4, n = 1; CV-5, n = 6) in group A, and suture rupture in group S. Reoperation was performed after a median of 88 months for ruptured ePTFE, and 26 months for group S. The rate of ePTFE rupture was 1.8% with CV-5 and 0.2% with CV-4. Risk factors for reoperation included postoperative arrhythmia, urgent operation, no annular ring, ruptured ePTFE, and suture rupture. The rates of freedom from reoperation and actuarial mitral valve survival rates at 5, 10, and 15 years were 99%, 95%, and 93% and 96%, 91%, and 89%, respectively, in group A; and 96%, 91%, and 91% and 95%, 94%, and 94%, respectively, in group S. CONCLUSIONS: The long-term surgical outcomes of MVr using both techniques were feasible. Over the long term, the ePTFE rupture rate of CV-5 was higher than that of CV-4.

Sudden circulatory collapse caused by mechanical obstruction of the left main coronary trunk with infective endocarditis vegetation: a case report.

BACKGROUND: Acute coronary syndrome (ACS) caused by mechanical obstruction of the coronary artery with a vegetation is extremely rare but associated with high mortality. The optimal management strategy of this condition remains controversial because of its scarcity. We experienced a case of sudden circulatory collapse due to mechanical occlusion of the left main coronary trunk with a vegetation. CASE PRESENTATION: A 68-year-old woman with aortic and mitral valve infective endocarditis suffered sudden dyspnea followed by heart arrest while awaiting surgery. Despite treatment with adequate antibiotic therapy, she had had multiple embolic infarctions and ruptured infectious cerebral aneurysms. We conducted transcatheter arterial embolization of the aneurysm and postponed the cardiac surgery due to residual aneurysmal blood flow. She suffered sudden cardiac arrest, and extracorporeal membrane oxygenation was applied after cardiopulmonary resuscitation. An echocardiogram revealed diffuse severe hypokinesis, and emergency coronary angiography was performed under suspicion of ACS. It revealed obstruction of the left main coronary trunk by a vegetation. Emergent cardiac surgery was performed. A vegetation had occluded the left coronary orifice. Aortic and mitral valve replacement with coronary artery bypass to the left antero-descending branch was performed. Regarding her cardiac function, she still required extracorporeal membrane oxygenation after surgery. She passed away 19 days after surgery due to multiple organ failure. CONCLUSIONS: ACS caused by mechanical obstruction of the coronary artery with a vegetation is rare but associated with high mortality. When circulatory collapse acutely occurs in patients with aortic valve infective endocarditis, we should suspect acute coronary artery obstruction. Urgent coronary angiography is mandatory to rescue the patient while preparing for emergency surgery.

Prediction of disease flare by biomarkers after discontinuing biologics in patients with rheumatoid arthritis achieving stringent remission.

To elucidate the disease-flare process in rheumatoid arthritis (RA) after discontinuing biological disease-modifying antirheumatic drugs (bDMARDs), we first focused on RA-flare prediction after achieving stringent remission criteria. Patients with RA who maintained a simplified disease activity index ≤ 3.3 for ≥ 3 months during November 2014-January 2018 in our medical centre in Tokyo, Japan, were eligible. The primary endpoint was flare (disease activity score 28-erythrocyte sedimentation rate ≥ 3.2 with increase from baseline > 0.6) within 2 years after bDMARD discontinuation. Comprehensive clinical assessments, ultrasonographic evaluation of 40 joints, and blood sampling for 12 biomarkers were performed every 2-3 months for 2 years unless patients experienced flare. Flare-positive and flare-negative patients were compared using univariate and Kaplan-Meier analyses. Thirty-six patients (80.6% female, median disease duration, 5.2 years; median treatment period with discontinued bDMARD, 2 years; median remission duration, 18 months) were enrolled. Twenty patients (55.6%) experienced RA flare 43-651 (median, 115) days after the first skipped date of bDMARDs. Two patients who withdrew without disease flare were excluded from the comparison. Clinical and ultrasonographic evaluations did not show significant between-group differences; Kaplan-Meier analysis showed that higher baseline soluble tumour necrosis factor receptor 1 (sTNFR1) concentration impacted subsequent disease flare (p = 0.0041); higher baseline interleukin (IL)-2 concentration was exclusively beneficial to patients with lower sTNFR1 (p = 0.0058), resulting in remission maintenance in 83.3% of patients with lower sTNFR1 and higher IL-2. We demonstrated the usefulness of combined biomarker evaluation for predicting sustained remission after bDMARD discontinuation in RA.

Is Hybrid Repair for an Entire Shaggy Aorta Feasible?

OBJECTIVE: This paper reviewed clinical experiences to evaluate the feasibility of a surgical strategy for an entire shaggy aorta. METHODS: Fifty-two (52) surgeries (47 men, average age 72±7 years) were performed for an entire shaggy aorta at the current institution from 2002-2017. Open surgery was performed in 30 cases, including total arch replacement in 12, extended aortic arch replacement via L-shaped thoracotomy in 10 and median sternotomy combined with left thoracotomy in two, and thoracoabdominal aortic replacement in six. Hybrid procedures were performed in 22 cases: type I hybrid arch repair in six, type II hybrid arch repair in seven and type III hybrid arch repair in nine. RESULTS: Hospital mortality was significantly higher with a hybrid repair: surgical, one case (3%); hybrid, six cases (27%), (p=0.0125). Stroke occurred at relatively high rates in both groups: surgical, seven cases (23%); hybrid, six cases (27%) (p=0.75). Spinal cord injury was significantly higher in hybrid repair: surgical, one case (3%); hybrid, seven cases (32%), (p=0.004). Open surgery revealed a better long-term survival rate than the hybrid procedure at 5 and 10 years: surgical, 82%, 65.7%; hybrid, 53%, 35.1%, respectively (p=0.0452). The rate of freedom from aortic events was significantly better with open surgery than a hybrid procedure at 5 and 10 years: surgical, 96%, 85%; hybrid, 83%, 41.3%, respectively (p=0.0082). CONCLUSIONS: Surgery for an entire shaggy aorta was frequently associated with embolic complications such as stroke, paraplegia, renal failure, and bowel necrosis. However, open surgical repair may produce better early and late outcomes and freedom from aortic events compared with hybrid repair.

Surgery for Anomalous Papillary Muscle Directly Into the Anterior Mitral Leaflet.

BACKGROUND: The anomalous insertion of papillary muscle directly into the anterior mitral leaflet is a rare congenital anomaly concomitant with hypertrophic cardiomyopathy. We herein report our surgical technique, which is designed to relieve left ventricular obstruction and preserve the mitral valve and subvalvular apparatus. METHODS: Among 38 patients who underwent septal myectomy from 2007 to 2020, 4 had an anomalous mitral subvalvular apparatus with papillary muscle with direct insertion into the anterior mitral leaflets. In all cases, mitral valve repair was accomplished with excision and reconstruction of all anomalous papillary muscles, concomitant with septal myectomy. In another 34 patients, 20 cases needed mitral valve repair with regard to systolic anterior motion by hypertrophic cardiomyopathy. The comparison study was conducted between the anomalous papillary muscle group (group A) and the others (group B). RESULTS: There was no early or late death in group A, and there were 3 early deaths and 2 late deaths in group B. The mean peak gradient in the left ventricle was significantly decreased in both groups. Mitral valve regurgitation grade was also significantly decreased from 3 to 0.5 without valve replacement in group A, and from 2 to 0.6 in group B. Six patients needed mitral valve replacement because of the thickness of anterior mitral leaflet in group B. CONCLUSIONS: Hypertrophic obstructive cardiomyopathy associated with the anomalous insertion of papillary muscle can be successfully treated without mitral valve replacement. Excision and reconstruction with the anomalous papillary muscle seems to be a feasible operation to reduce mitral regurgitation and relieve outflow tract obstruction.

Upper thoracoabdominal aortic repair through partial posterior incision of the diaphragm via left thoracotomy.

During surgical repair of a thoracoabdominal aortic aneurysm, division of the diaphragm should be minimized to avoid pulmonary complications. We herein describe a modified exposure technique that avoids ordinary circumferential division of the diaphragm. The diaphragm was detached from the aneurysm at the level of the aortic hiatus via a modified anterior lateral thoracotomy incision through the pleural space. The diaphragmatic incision around the aneurysm was extended posteriorly. This partial division of the diaphragm provided sufficient exposure of the distal anastomosis site for thoracoabdominal aneurysms that do not extend below the upper part of the abdomen.

Modified sutureless repair using left atrial appendage flap for acquired left-sided pulmonary vein stenosis.

Pulmonary vein stenosis is a well-known complication after radiofrequency catheter ablation of atrial fibrillation. Although surgical repair is indicated for younger patients and patients with multiple stenoses, the appropriate procedure for acquired pulmonary vein stenosis has not been established. In this study, we report the successful outcome of our modified sutureless technique using a left atrial appendage flap for left-sided pulmonary vein stenosis after radiofrequency catheter ablation.

Drug prescription patterns and factors associated with polypharmacy in >1 million older adults in Tokyo.

AIM: To determine the patterns of concomitant drug use for chronic diseases and examine the risk factors of polypharmacy in older outpatients. METHODS: Data were extracted from an anonymized health insurance claims database of a public insurance program for older adults in Tokyo, Japan. We analyzed individuals aged ≥75 years who had visited an outpatient clinic, and were regularly prescribed orally administered drugs for chronic diseases for ≥14 days between May and August 2014. The prescription patterns for 16 main drug types were studied using exploratory factor analysis, and the risk factors of polypharmacy, defined as the concomitant prescription of five or more drugs, were identified using multivariate logistic regression models. RESULTS: A total of 1 094 199 outpatients were analyzed (mean age 81.8 years, 38.4% men). We identified five prescription patterns that explained almost 40% of all observed variance: edema/heart failure/atrial fibrillation-related drugs, insomnia/anxiety-related drugs, pain-related drugs, lifestyle disease-related drugs and dementia-related drugs. The significant risk factors of polypharmacy included men, octogenarians and nonagenarians, higher number of medical institutions visited, use of physician home visits, and hospitalization during the study period. The main drug types most strongly associated with polypharmacy were analgesics, diuretics and antidiabetics. CONCLUSIONS: Polypharmacy was found to be prevalent in older outpatients aged ≥75 years in Tokyo. These findings might provide useful evidence that can contribute to the development of practical countermeasures against adverse events associated with polypharmacy in clinical practice. Geriatr Gerontol Int 2020; 20: 304-311.

The incidence and risk factors of hypofibrinogenemia in cardiovascular surgery.

OBJECTIVE: Cardiovascular surgery often causes massive bleeding due to coagulopathy, with hypofibrinogenemia being a major causative factor. We assessed the intraoperative incidence of hypofibrinogenemia and explored predictors of hypofibrinogenemia. METHODS: The intraoperative serum fibrinogen level (SFL) was routinely measured in 872 consecutive patients [mean age: 66.9 ± 13.3 years; 598 men (68.6%)] undergoing cardiovascular surgery from July 2013 to November 2016 at Nagoya University Hospital. There were 275 aortic surgeries, 200 cases of coronary artery bypass grafting (CABG), 334 valvular surgeries and 63 other surgeries. We estimated hypofibrinogenemia incidence (intraoperative lowest SFL ≤ 150 mg/dL) and identified its predictors by a logistic regression analysis. RESULTS: The average intraoperative lowest SFL of all cases, aortic surgery, CABG and valvular surgery was 185 ± 71, 156 ± 65, 198 ± 69 and 198 ± 68 mg/dL, respectively. Aortic surgery had a significantly lower intraoperative lowest SFL than CABG (p < 0.001) and valvular surgery (p < 0.001). The incidence of hypofibrinogenemia was 32.8%, 50.2%, 26.5% and 22.8% in all cases, aortic surgery, CABG and valvular surgery, respectively. The predictors of hypofibrinogenemia were the preoperative SFL, re-do surgery and perfusion time. A receiver operating characteristics curve analysis showed that the best preoperative SFL cutoff value for predicting hypofibrinogenemia was 308.5 mg/dL. Assuming preoperative SFL 300 mg/dL as the cutoff, the odds ratio for hypofibrinogenemia was 7.22 (95% confidence interval 5.26-9.92, p < 0.001). CONCLUSIONS: The incidence of hypofibrinogenemia in aortic surgery was high. The preoperative SFL, re-do surgery and perfusion time were identified as predictors for hypofibrinogenemia. Intraoperative measurement of SFL is important for detecting hypofibrinogenemia and applying appropriate and prompt transfusion treatment.