Effect of systemic urokinase infusion after lower limb percutaneous transluminal angioplasty on limb salvage rate in patients with late-stage critical limb ischemia.

OBJECTIVE: To evaluate the effect of systemically administered urokinase (UK) after percutaneous transluminal angioplasty with or without stent (PTA ± stent) on the reduction in the rate and level of amputation in patients with critical limb ischemia (CLI) with tissue loss. METHODS: This was an observational, nonrandomized, retrospective study of 183 Taiwanese patients with Rutherford stage 5 or 6, and Fontaine stage 4 lower extremity CLI. Patients received either PTA ± stent or PTA ± stent + UK infusion (250,000 IU, daily for 5 days). PTA of the iliac, femoral, anterior tibial artery, posterior tibial artery, and peroneal arteries was included. Amputation was classified as minor, with direct wound healing, and minor amputation or surgical debridement of toes and major, with below- (BKA) and above-knee amputation (AKA). RESULTS: In groups of patients with comparable baseline characteristics, 85 and 90 patients received PTA ± stent and PTA ± stent + UK, respectively. There were 24 major limb amputations performed. A significant majority (20/24 (83.3%) were performed in patients who did not receive adjuvant urokinase, compared with 4/24 (16.7%) of patients who did receive urokinase (p = 0.000287). There was a significant increase in the limb salvage rate for infrapopliteal lesions in patients treated with PTA + UK (12/72 with UK; 60/72 without UK; p ≤ .0001). Intracranial hemorrhage (n = 1) and bleeding at the inguinal puncture site (n = 2) were reported in the PTA ± stent + UK group. Eight deaths (one in the PTA ± stent + UK group; seven in the PTA ± stent) occurred during the study. CONCLUSION: Systemic administration of UK with the PTA ± stent procedure may reduce the requirement for major amputation in patients with CLI with tissue loss (Rutherford 5 or 6). The difference is more pronounced in patients undergoing infrapopliteal interventions. However, these findings need to be confirmed in a randomized prospective study.

Long-term outcomes following neoadjuvant chemoradiotherapy in patients with clinical T2N0 esophageal squamous cell carcinoma.

The optimal treatment for patients with local esophageal cancer (cT2N0 disease) has not yet been defined. We sought to determine whether neoadjuvant chemoradiotherapy (CRT) can improve prognosis compared with direct esophagectomy in this patient group. Between 1994 and 2005, patients with cT2N0 esophageal squamous cell carcinoma who underwent either neoadjuvant CRT or surgery as first-line treatment were retrospectively reviewed. We collected information on their demographic characteristics, staging modality, clinical and pathological stages, perioperative course, and survival. The study endpoints included tumor recurrence, disease-specific survival (DSS), and overall survival rate. Of the 71 eligible patients, 14 received an esophagectomy first, whereas the remaining 57 received neoadjuvant CRT first. Despite the high pathological complete response (pCR) rate of 37% after neoadjuvant CRT, routine neoadjuvant CRT did not translate into better survival compared to direct surgery (5-year DSS: 39% vs. 68%, P= 0.17). The dramatic survival difference between pCR and non-pCR patients (5-year DSS: 85% vs. 4%, P < 0.001) accounts for these unsatisfactory results. In our series, the administration of neoadjuvant CRT to patients with clinical stage T2N0 esophageal squamous cell carcinoma did not significantly improve outcomes compared with direct esophagectomy.

Granulation tissue formation following Dumon airway stenting: the influence of stent diameter.

OBJECTIVES: The present study aimed to determine whether stent diameter influences granulation tissue formation following stent placement for major airway stenosis. PATIENTS AND METHODS: Forty-two stent procedures (32 tracheal stents, 3 carinal stents, and 7 bronchial stents) were performed in 40 patients. Seventy-nine stent edge regions (62 tracheal, 17 bronchial stents) were evaluated in this study. RESULTS: Granulation tissue formation was encountered in 11 patients (28.21%). Of the 34 upper ends of evaluated tracheal stents, granulation tissue formation was observed in 6 (17.65%), whereas granulation tissue formation was observed in 2 (7.14%) of the 28 lower ends of tracheal stents evaluated. Of the 17 bronchial stent edge regions, granulation tissue formation occurred in 3 (17.65%) ( P = 0.4352). The rate of granulation tissue formation was higher in those patients with a stent-to-airway diameter ratio of > 90% ( P < 0.0001). Receiver operating characteristic curve analysis further demonstrated that a cut-off stent-to-airway diameter ratio of 90% was effective in predicting granulation tissue formation (AUC: 0.897, Std. error = 0.036, P < 0.0001, 95% CI = 0827-0.968, n = 79). CONCLUSIONS: A stent-to-airway diameter ratio of 90% was found to be the critical cut-off point for predicting granulation tissue formation. Therefore, the optimal stent-to-airway diameter ratio should be ascertained before stent placement.

Evaluation of a novel index by tissue Doppler imaging in patients with advanced heart failure: relation to functional class and prognosis.

BACKGROUND: Despite the ability of tissue Doppler imaging (TDI) to detect left ventricular (LV) systolic and diastolic myocardial functions in patients with heart failure, the added value of TDI to clinical variables and conventional echocardiography in predicting the symptoms and outcome of advanced heart failure has not been clearly defined. METHODS AND RESULTS: Two hundred and thirty adult patients diagnosed with congestive heart failure were assigned to study groups based on the New York Heart Association functional classes. Pulsed-wave TDI (PWTDI), including average of peak systolic (Sm), early (Em) and late diastolic (Am) velocities from six mitral annular sites was evaluated. PWTDI was also calculated to create a combined index (EAS index) of diastolic and systolic performances. All patients were followed up for cardiac-related death and hospitalisation as a result of heart failure. Patients with functional class III-IV had a significantly higher EAS index (0.21 ± 0.19 vs. 0.13 ± 0.08, p < 0.05) than those with class I-II and the control (0.10 ± 0.04, p < 0.05). Except for Sm and Em, all conventional echocardiographic Doppler parameters and TDI variables significantly correlated with functional class. Moreover, according to multiple stepwise analysis, EAS index and percentage of chronic renal insufficiency (CRF) were the only two independent predictors of functional class (EAS index, p = 0.006; CRF, p = 0.019). During follow-up (median, 30 months), 93 participants had cardiac events. EAS index, LV mass index and CRF were significant predictors of cardiac mortality and hospitalisation [EAS index, hazard ratio (HR) 4.962, p = 0.006; LV mass index, HR 1.007, p = 0.003; CRF, HR 1.616, p = 0.040]. CONCLUSIONS: The EAS index, which reflects systolic and diastolic performances, is a highly effective means of differentiating between patients with functional class I-II and those with III-IV. The index also correlates with cardiac mortality and hospitalisation for worsening heart failure, thus providing additional value to conventional echocardiographic measures.

Spaced learning versus massed learning in resuscitation - A systematic review.

AIM: Skill decay is a recognised problem in resuscitation training. Spaced learning has been proposed as an intervention to optimise resuscitation skill performance compared to traditional massed learning. A systematic review was performed to answer 'In learners taking resuscitation courses, does spaced learning compared to massed learning improve educational outcomes and clinical outcomes?' METHODS: This systematic review followed the PRISMA guidelines. We searched bibliographic databases (Embase, MEDLINE and the Cochrane Library (CENTRAL)) from inception to 2 December 2019. Randomised controlled trials and non-randomised studies were eligible for inclusion. Two reviewers independently scrutinized studies for relevance, extracted data and assessed quality of studies. Risk of bias of studies and quality of evidence were assessed using RoB, ROBINS-I tool and GRADEpro respectively. Educational outcomes studied were skill retention and performance 1 year after completion of training; skill performance between completion of training and 1 year; and knowledge at course conclusion. Clinical outcomes were skill performance at actual resuscitation, patient survival to discharge with favourable neurological outcome. This systematic review was registered in PROSPERO (CRD42019150358). RESULTS: From 2,042 references, we included data from 17 studies (13 randomised studies, 4 cohort studies) in courses with manikins and simulation in the narrative synthesis. Eight studies reported results from basic life support training (with or without automatic external defibrillator); three studies reported from paediatric life support training; five were in neonatal resuscitation and one study reported results from a bespoke emergency medicine course which included resuscitation teaching. Fifteen out of seventeen studies reported improved performance with the use of spaced learning. The overall certainty of evidence was rated as very low for all outcomes primarily due to a very serious risk of bias. Heterogeneity across studies precluded any meta-analyses. There was a lack of data on the effectiveness of spaced learning on skill acquisition compared to maintaining skill performance and/or preventing skill decay. There was also insufficient data to examine the effectiveness of spaced learning on laypeople compared to healthcare providers. CONCLUSIONS: Despite the very low certainty of evidence this systematic review suggests that spaced learning can improve skill performance at 1 year post course conclusion and skill performance between course conclusion and 1 year. There is a lack of data from this educational intervention on skill performance in clinical resuscitation and patient survival at discharge with favourable neurological outcomes.

Hypokalemic thyrotoxic periodic paralysis: clinical characteristics and predictors of recurrent paralytic attacks.

BACKGROUND AND PURPOSE: To study the clinical characteristics of hypokalemic thyrotoxic periodic paralysis (hoTPP) and identify the predictors of recurrent paralytic attacks before achieving the euthyroid status. METHODS: We retrospectively analyzed 45 hoTPP patients who were admitted during the 7-year study period. RESULTS: A tendency towards male predominance was observed among the 45 patients (91.1%, 41/45). The mean onset age was 32.9 +/- 10.0 years (range: 16-54 years). No significant differences were observed in the onset age between male and female patients. Precipitating factors included rest/sleep at night, hot weather, upper respiratory tract infections (URIs), and excessive physical activities. Atypical weakness was observed in nine (20%, 9/45) patients. One patient initially diagnosed with sporadic periodic paralysis eventually developed hoTPP. DISCUSSION: In provocative tests, hypokalemia was not a consistent finding during paralytic attacks. Before achieving the euthyroid status, the rate of recurrent attacks was as high as 62.2%, and peaked in the first 3 months after hoTPP was diagnosed. Patients with URIs exhibited a higher incidence of recurrent paralytic attacks than those without (odds ratio = 13.00; 95% confidence interval = 1.08-156.08; P = 0.04).

Acute cholinergic syndrome following ingestion of contaminated herbal extract.

Herbal preparations are becoming more and more popular and increasingly used in the USA. Herbs are from natural plants and therefore often considered to be harmless compared with western medicines. Nevertheless, as the use of herbal remedies has risen, so has the incidence of acute and chronic herbal intoxication. The case history is presented of a 68-year-old man who presented with an acute cholinergic syndrome soon after ingesting a herbal preparation containing Flemingia macrophylla and ginseng. His red blood cell acetylcholinesterase activity dropped to 50% of the normal reference range. He was treated successfully with atropine and supportive care. It was thought that contamination with pesticides, such as organophosphate residue, was the probable cause. This case highlights the need to be more aware of the possibility of acute pesticide intoxication in herbal users, even when only small amounts are consumed.

Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer.

Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene- rs920778, rs1899663, rs4759314, and rs12427129-were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non-betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non-betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.

Detection of indoxyl sulfate levels in dogs and cats suffering from naturally occurring kidney diseases.

Indoxyl sulfate (IS), a protein-bound uraemic toxin, has been found to accumulate in the serum of people with renal diseases and is associated with free radical induction, nephrotoxicity cardiovascular toxicity, and osteoblast cytotoxicity. Although IS has been studied in humans and in experimental models, the role of IS in dogs and cats with kidney disease has not been investigated. A high performance liquid chromatography system was applied to detect plasma IS concentrations in non-azotaemic animals (63 dogs, 16 cats) and in animals with renal azotaemia (66 dogs, 69 cats). The IS levels of azotaemic animals were significantly higher (P <0.01) than those of non-azotaemic animals (median [IQR] 20.4 (9.5) mg/L vs. 7.2 (8.8) mg/L for dogs; median [IQR] 21 (18.9) mg/L vs. 14.8 (12.3) mg/L for cats). The IS level was significantly correlated with blood urea nitrogen, serum creatinine and phosphate concentrations. Dogs with acute kidney injury had significantly higher IS levels (P <0.01) than those with chronic kidney diseases (CKD) (median [IQR] 57.7 (40.8) mg/L vs. 17.7 (25.1) mg/L). When CKD was graded using the International Renal Interest Society (IRIS) staging system, IS levels were correlated with CKD severity in both dogs and cats. The IS concentration is directly related to loss of renal function. Further studies are necessary to determine whether measurement of IS provides any additional diagnostic or prognostic information in dogs and cats with kidney disease.

Enhancement of endothelium-dependent contraction of the canine coronary artery by UW solution.

University of Wisconsin (UW) solution has been used almost routinely in the preservation of the hepatic, pancreatic, renal, and cardiac allografts. However, its effect on vascular endothelium is unknown. Experiments were designed to evaluate its effect on canine coronary endothelium. Canine coronary arteries (n = 8 in each group) were preserved in cold (4 degrees C) UW solution (group 1) and physiological solution (group 2) for 6 hr immediately after harvesting. Segments of preserved and control (group 3) coronary arteries with or without endothelium were then suspended in organ chambers to measure isometric force. Perfusate hypoxia (pO2 30 +/- 5 mmHg) caused endothelium-dependent contraction in the arteries of all 3 groups. However, vascular segments with endothelium of group 1 exhibited hypoxic contractions (107 +/- 26% of the initial tension contracted by prostaglandin F2 alpha 2 x 10(-6) mol/L, P < 0.05) that were significantly greater than those of the group 2 and group 3 segments with endothelium (25 +/- 5% and 20 +/- 4%). The hypoxic contraction in arteries of group 1 could be attenuated by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell synthesis of the nitric oxide from L-arginine. The action of L-NMMA could be reversed by L-arginine but not D-arginine. Endothelium-dependent relaxation of coronary endothelium to acetylcholine and adenosine diphosphate and endothelium-independent relaxation and contraction of coronary smooth muscle were not altered by the UW solution. After preservation with the UW solution, endothelium-dependent contraction of the canine coronary arteries, occurs by L-arginine-dependent pathway, is enhanced. This augmentation by the UW solution would favor vasospasm after transplantation.

Application of thoracoscopy for lung metastases.

Lung nodules in patients with a history of malignancy usually require tissue diagnosis that will provide prognostic information and dictate further therapy. Patients with a favorable tumor histologic condition and limited tumor burden were often considered for resection. This is usually accomplished by wedge resection through open thoracotomy when the lesions were peripheral. However, complications related to open thoracotomy often exclude poor-risk patients, especially those with impaired pulmonary function. Currently, technique of thoracoscopic resection is opening up new vistas and unimagined options for the thoracic surgeon in the management of pulmonary diseases. With the application of thoracoscopy and small incisions, it is now possible for the thoracic cavity and its contained organs to be thoroughly explored. Our recent experience with the thoracoscopic resection as a primary treatment for lung metastases is the focus of this report. Forty-seven patients with a history of malignancy and new lung metastases underwent this type of resection. Postoperatively, there is less pain, quick functional recovery, and excellent cosmetic healing. It is a safe and promising approach.

Thoracoscopic-assisted lobectomy. Preliminary experience and results.

A preliminary report is made on the use of videothoracoscopy to achieve pulmonary lobectomy in 16 patients, including 12 with centrally located pulmonary metastases and 4 with benign lesions (3 bronchiectases and 1 endobronchial hamartoma). Videothoracoscopy was performed on eight right-lower lobes, one middle lobe, two right-upper lobes, four left-lower lobes, and one left-upper lobe with a thoracoscope and conventional thoracic instruments. All patients received standard pulmonary lobe resection with lymph node clearance similar to that achieved with open thoracotomy. The mean operative time was 3 h (range, 2.5 to 4 h). Average blood loss was 100 mL and mean length of hospital stay was 6 days (range, 4 to 8 days). A combination of videothoracoscopy with use of conventional instruments resulted in similar performance but less chest wall interruption than in conventional pulmonary lobectomy. Videothoracoscopy showed safer and faster lung resection, which subsequently minimized the perioperative morbidity. Pain intensity was lessened, functional recovery was quicker, and hospital stays were shorter in the patients we reviewed.

Thoracoscopic surgery as a routine procedure for spontaneous pneumothorax. Results from 82 patients.

A total of 82 consecutive patients with recurrent or persistent spontaneous pneumothorax were considered for thoracoscopic blebectomy or bullectomy and pleurodesis. The median age was 47 years, and 70% were men. All the patients were successfully treated using a video-assisted thoracoscopic technique. There were no deaths attributable to the procedure. Complications occurred in 6 patients (7.3%). Three patients (4%) with diffuse bullous lung disease had prolonged intubation (9, 11, and 12 days, respectively). Persistent air leaks lasting from 10 to 14 days occurred in 2 patients (3%). One patient had an endoloop slip from the lung parenchyma after a forceful sneeze 2 days after the operation. Air leak subsided after the second operation using a conventional suturing technique. Blebs or bullae were present in 69 patients (83%). These were ablated by endoscopic stapling (37 patients) and through thoracoscopic ligation using an endoloop technique (32 patients). In this group of patients, the median postoperative hospital stay was 5 days. Thirteen patients with air leaks and diffuse bullous lung disease received only talc insufflation thoracoscopically. All of them showed good lung expansion after the operation. There are no recurrences, with a mean follow-up of 22 months. These results suggest that thoracoscopic ablation of blebs or bullae and pleurodesis may be applicable to patients with spontaneous pneumothorax who require surgical intervention.

University of Wisconsin solution extends lung preservation after prostaglandin E1 infusion.

University of Wisconsin (UW) solution has been demonstrated to enhance and extend the preservation of the hepatic, pancreatic, renal, and cardiac allografts. Prostaglandin E1 (PGE1), which has been used to produce pulmonary vasodilatation, has improved preservation in lung transplantation. Experiments were designed to evaluate their potential role in 24-h preservation of the allografts in lung transplantation. Thirty-six dogs underwent left lung transplantation. The donor lungs (n = 6 in each group) were flushed with UW solution (group 1 and 2) or modified Euro-Collins (EC) solution (group 3) after PGE1 infusion (500 micrograms). In group 1, donor lungs were transplanted immediately. Lung allografts of group 2 and 3 were cold stored (4 degrees C) in the same preservation solution for 24 h in the inflated state and then transplanted. The right pulmonary artery and right main bronchus were ligated 1 h after completion of the transplantation, forcing the recipient dogs to survive with the transplanted left lung. The recipients were ventilated with an inspired oxygen fraction of 0.4 and end-expiratory pressure 10 cm H2O. Two dogs died prematurely in group 3, whereas all dogs in group 1 and 2 survived the experimental period. The arterial oxygen tension and saturation and dynamic lung compliance were significantly higher in dogs of group 1 and 2. Transplanted lungs of group 1 and 2 had significantly lower pulmonary vascular resistance, alveolar-arterial oxygen difference, and wet/dry lung weight ratio. Histologically, pulmonary edema, congestion, sloughing of bronchial mucosa, and peribronchial and peripulmonary arterial hemorrhage were shown in lungs of group 3, but not in those of group 1 and 2. Airway mucosa and pulmonary vascular structure were well preserved in lungs of group 1 and 2. There was no significant difference between group 1 and 2 in lung functions, hemodynamics, or morphologic features. We concluded that PGE1 and UW solution could effectively extend lung preservation up to 24 h in this in vivo canine lung allotransplantation model.

Thoracic actinomycosis.

Actinomycotic infection is uncommon and primary actinomycosis of the lung and chest wall has been less frequently reported. This disease may present as chronic debilitating illness with radiographic manifestation simulating lung tumor, pulmonary infiltrating lesion, or chronic suppuration. From 1984 to 1990, we experienced 17 cases of thoracic actinomycosis. There were nine patients who presented with a clinical picture of a suppurative lesions and the remaining eight were suspected of having primary lung tumor initially. In no case was an accurate diagnosis made at the time of hospital admission. Final diagnosis was based on aspiration (n = 3), anaerobic sputum culture (n = 1), bronchoscopic biopsy specimens (n = 4), and histologic examination of the resected tissue in the remaining 9 patients who received surgical excision. Among the 17 patients, 8 were treated medically and the other 9 received surgical intervention followed by antibiotic treatment. Regarding the surgically treated patients, suspected malignancy is the most common indication for operation (seven of nine). However, both medically and surgically treated patients achieved good clinical results, and the postoperative courses were uneventful. We would like to remind physicians of this unusual entity and review our own experience with particular emphasis on the clinical diagnosis and management of this unique disease.

An alternative technique in the management of bullous emphysema. Thoracoscopic endoloop ligation of bullae.

STUDY OBJECTIVES: With the improvements in video-assisted thoracoscopic surgery, more older patients and patients with respiratory impairments are undergoing bulla ablation using new and costly technology. We evaluated the cost-effective technique of thoracoscopic endoloop ligation of bullae in patients with bullous emphysema. PATIENTS: From March 1992 through January 1996, 79 advanced age (mean age, 64 years) and oxygen dependency patients underwent thoracoscopic procedure using endoloop ligation for treatment of bullous emphysema. Clinical data were collected from chart review. Only patients with radiographically confirmed diagnosis of bullous emphysema were included in this evaluation. Thoracoscopic endoloop ligation of bulla was carried out under general anesthesia with double-lumen endotracheal tube and single-lung ventilation. RESULTS: Sixty-five patients (82%) exhibited subjective improvement in their symptom status at 3-month follow-up (from grade 2 or 3 to grade 1 or 2) according to the Modified Medical Research Council dyspnea scale. The mean duration of chest drainage was 6 days (range, 4 to 16 days). Average hospital stay was 9.5 days (range, 5 to 26 days). There was no postoperative death. A comparison of preoperative and postoperative functional evaluation was available in only 16 patients who showed an increase in FEV1 (from 0.85 to 1.02 L) and a decline in residual volume after operation. Complications include persistent airleak over 10 days in seven patients (8.9%), wound infection in three patients, and localized empyema in two patients. There was no recurrence after a mean follow-up of 21 months. CONCLUSION: These encouraging results have shown that thoracoscopic endoloop ligation of bulla has proved to be a safe, reliable, and cost-effective technique for bullous emphysema. With careful preoperative evaluation and meticulous postoperative care, many patients could be rehabilitated by endoloop litigation of the bullae.