Thoracoscopic biopsy in children with diffuse parenchymal lung disease

Lung biopsy is necessary for establishing the diagnosis in patients with otherwise unclassified diffuse or localized parenchymal lung disease. This study aimed to assess the safety and accuracy of video-assisted thoracoscopic (VATS) lung biopsy in children with diffuse parenchymal lung disease (DPLD). In addition we aimed to evaluate the value of this technique with respect to the spectrum of diseases encountered, correlating histological diagnosis with treatment decisions and subsequent clinical outcome. Data from all patients (n = 21) who underwent surgical lung biopsy for suspected DPLD between March 2001 and August 2006 were collected prospectively. Median age was 3 years, 8 months (range 11 days to 15 years, 2 months). All lung biopsies were performed by VATS under general anesthesia. Median operative time was 45 min (range 25-100 min). Conversion to minithoracotomy due to cardiorespiratory difficulties was necessary in two young infants. There were no further intraoperative complications. In 8/21 children, a chest tube was inserted postoperatively for a median of 2 days (range 1-5 days). In one patient, prolonged air-leakage was managed thoracoscopically on postoperative day 9. There were no other postoperative complications. The specimens were of adequate volume and quality and a histopathological diagnosis was obtained for all patients. There was a broad spectrum of different diagnoses which led to specific therapeutic decisions. Subsequent medical treatment was beneficial in the majority of the patients. In conclusion, VATS is a safe and effective procedure for diagnosis of children with suspected DPLD. Diagnostic accuracy is high, morbidity rates are low, and patients may benefit from avoiding thoracotomy.     

先天性左冠状动脉主干闭锁的Revolution CT诊断

目的探讨Revolution CT对先天性左冠状动脉主干闭锁的诊断价值。方法回顾性分析2012年2月至2019年3月我院收治的6例先天性左冠状动脉主干闭锁患者的资料,男女各3例;年龄10个月至48岁,体重7.7~55 kg。采用GE公司Revolution CT扫描仪进行前瞻单心跳收缩期(45%~50%)扫描成像。5例婴幼儿于基础麻醉及自由呼吸状态下行冠状动脉扫描,1例成人患者在清醒状态及屏气条件下进行检查。所有CT图像均由放射影像科2名具有5年以上心血管影像阅片经验的医师在AW4.6工作站进行阅读和评估。诊断结果与心血管造影结果作对比。结果Revolution CT成像显示所有患者右冠状动脉均开口于主动脉右冠状动脉窦,5例患者诊断为先天性左冠状动脉主干闭锁,1例患儿可疑左冠脉主干开口闭锁或狭窄。所有患者左心房室均有扩大,2例患者二尖瓣下腱索走行区可见钙化。3例患者行手术治疗并证实为左冠脉主干闭锁,其中2例婴幼儿患者左主干开口及近段闭锁,1例成人患者左主干开口闭锁。结论Revolution CT检查可在低辐射剂量条件下显示冠状动脉及心脏的病理解剖学信息,对绝大多数的先天性左冠脉主干闭锁患者可做出明确诊断。     

Recurrent anorectal abscesses

A prospective study of 100 recurrent anorectal abscesses in 97 patients was carried out to elucidate the cause of recurrence. Sixty-four patients had had one, 12 had had two, and the rest had had more than two prior abscesses. In 32 patients, the previous diagnosis was erroneous; the patients had hidradenitis suppurativa which was excised. In 68 patients, the cause of recurrence was insufficient prior treatment. Thirty-one patients (45 per cent) had fistulous abscesses requiring fistulotomy. Twenty-two patients (32 per cent) had large abscesses associated with fistula necessitating unroofing of the abscess along with fistulotomy. In 15 patients (22 per cent), no associated fistula was detected, but they were found to have missed components (i.e., ischiorectal, supralevator, postanal abscesses) and were successfully treated with drainage of the missed abscess component. All recurrent abscesses must be examined carefully under anesthesia to identify associated fistulas or missed components, or to exclude hidradenitis suppurativa. Read at the Meeting of the American Society of Colon and Rectal Surgeons, Colorado Springs, Colorado, June 7 to 11, 1981.     

Safety and accuracy of transbronchial lung cryobiopsy in diagnosing desquamative interstitial pneumonia

IntroductionTransbronchial lung cryobiopsy (TBLC) is a new technique to obtain specimens for diagnosis of interstitial lung disease (ILD) in recent years. The objective of this study is to evaluate the safety and the diagnostic accuracy of TBLC in patients of desquamative interstitial pneumonia (DIP).MethodsIn this study twelve patients confirmed with DIP were selected from January 2019 to December 2020 at the department of pulmonary and critical care medicine in China‐Japan Friendship Hospital. All cases underwent TBLC in a hybrid cone beam CT (CBCT) operation room with a single general anesthesia. The definitive diagnosis was made by a multidisciplinary team that involved clinicians, radiologists and pathologists. This study analyzed the biopsy sample surface areas, main complications and the consistency between TBLC pathology and multidisciplinary discussion (MDD) diagnosis for DIP.ResultsAn average of 3.1 ± 1.1 specimens were obtained per patient. The mean surface area of the specimen was 23.7 ± 6.1 mm². None of the cases had pneumothorax or massive hemorrhage. Ten cases (83.3%) had no or mild bleeding and two cases (16.7%) had moderate bleeding. All cases had the typical pathologic characteristics of DIP, which was highly consistent with the diagnosis of MDD.ConclusionTBLC can obtain sufficient samples for the pathological diagnosis of DIP, which has high security and accuracy in experienced specialist centers.     

Diverticulitis of the right colon

The authors' experience with right-sided diverticulitis is reviewed. The symptoms among 18 patients were continuous right lower quadrant abdominal pain and periumbilical pain radiating to the right lower quadrant. Only three patients had nausea and vomiting. Twelve patients (67 per cent) had an abnormally high white blood cell count; three had granulocytosis. Barium enema examination was not a helpful diagnostic aid; and in only two patients was the preoperative diagnosis correct. The operative procedures undertaken were right colectomy with ileotransverse colostomy (15 patients), partial right colectomy with ileoascending colostomy (two patients), and diverticulectomy and appendectomy (one patient). There were no deaths; the average hospital stay was 14.2 days (range 5 to 30 days). The authors conclude that there is no characteristic clinical pattern pointing to this diagnosis; diagnostic maneuvers are usually unrewarding; right hemicolectomy is a safe and expeditious procedure; and open cecotomy is not favored, as recommended in the medical literature, to establish the diagnosis. Read at the meeting of the American Society of Colon and Rectal Surgeons, Colorado Springs, Colorado, June 7 to 11, 1981.     

新生儿心脏手术132例麻醉处理

目的 探讨新生儿心脏手术的麻醉处理。方法 行心脏手术患儿132例，年龄9h～31d，体重1.12～4.15kg，经气管插管行静脉复合全身麻醉。结果 主动脉阻断时间84～200min，体外循环时间135～600min，术中死亡8例，其余124例心脏自动复搏;术后渗血16例;肺部感染8例;无麻醉并发症。结论 平稳的复合麻醉，术中早期纠正凝血功能，早期使用血管活性药物，加强肺保护，有利于新生儿心脏手术的成功。     

Complications and outcome of percutaneous endoscopic gastrostomy in different patient groups

A retrospective study of percutaneous endoscopic gastrostomy (PEG) was performed to evaluate the complications of PEG and determine the role of prophylactic antibiotics in preventing early wound infection and to evaluate the outcome of patients in different groups (neurological disease, head injury, AIDS). Percutaneous endoscopic gastrostomy was performed on 50 patients between March 1991 and November 1993 and the survey was completed in July 1994. The average time to PEG placement post-cerebrovascular accident or head injury was 5 weeks. No deaths were attributable to the procedure. Four of 50 (8%) patients died in the first 30 days (early mortality). Wound infection (early eight, late five) was the most common complication: two of 13 patients receiving prophylactic antibiotics and six of 37 not receiving antibiotics had early wound infection. At completion of follow-up 19 of 26 patients with neurological disease had died (median survival = 370 days), three resumed oral feeding and four continued PEG feeding. All head injury patients (n= 6) were alive and had resumed oral feeding; five returned home. All AIDS patients (n= 7) died within 12 months (median survival = 138 days), although improved nutritional state was found after gastrostomy feeding. In conclusion, PEG placement is a useful procedure to assist feeding in multiple patient groups. Wound infection is a common but not life threatening complication. The need for prophylactic antibiotics to prevent early wound infection has not been proven. The 5 week delay in PEG insertion may contribute to lower early mortality. The 100% survival rate in head injury patients may reflect their young age and absence of underlying medical illness. In AIDS patients, improved nutritional state is not known to translate into better quality of life or prolonged survival.     

Thoracic surgical operations performed under local anesthesia and sedation for diagnosis and treatment

Generally, the operative procedures for the diagnosis or treatment of mediastinal, intrathoracic and/or chest wall lesions requiring rib resection are performed under general anesthesia. Although evidence suggests that thoracoscopy can be performed under local anesthesia, no report has indicated that some major thoracic procedures can be accomplished without general anesthesia. In our study, we advocate that certain surgical procedures could be performed under local anesthesia with a performance similar to that of general anesthesia. Thirty patients underwent thoracic procedures with local anesthesia and sedation for diagnosis and treatment. Seventeen of the patients were men, and the mean age of the patients was 49.6 years (range 16 to 71 years). There were 13 diagnostic procedures, and 17 procedures were for treatment purposes. The operative procedures performed using only local anesthesia were mini-thoracotomy (n = 9), mediastinotomy (n = 4), revision of a full-thickness posterolateral thoracic incision (n = 7), resection of the chondroma (n = 4), Eloesser flap (n = 1), metastasectomy of the chest wall (n = 3), empyectomy (n = 1), and video-assisted thoracoscopy (n = 2). Severity of pain was evaluated by VAS. There were no oral or intravenous analgesic requirements in the early postoperative period. No complications attributable to the procedure were observed. Thoracic surgical procedures for diagnosis and treatment performed under local anesthesia are simple, effective, economical and comfortable for the patient.     

The risk of advanced heart block in surgical patients with right bundle branch block and left axis deviation

The risk of advanced atrioventricular block during anesthesia was studied prosepctively in 44 patients with right bundle branch block and left axis deviation who underwent a total of 52 operations over a 14 month period. All patients had continuous electrocardiographic monitoring throughout anesthesia induction, operation, and surgical recovery. Of the 52 operative procedures, 24 were done under general anesthesia, 11 under spinal, and 17 under local. The preoperative cardiac rhythms were atrial fibrillation in two patients, atrial tachycardia with block in one patient, atrial flutter in one patient, and sinus rhythm in the remaining patients. Temporary pacemakers were inserted preoperatively in six patients, usually because of PR interval prolongation on the preoperative electrocardiogram. There was only one episode of transient complete heart block in 51 of the 52 operative procedures. In two of the six patients with temporary pacemakers, significant pacer-related ventricular irritability occurred. This study indicates that temporary pacemaker insertion is rarely required in patients with chronic right bundle branch block and left axis deviation who require noncardiac surgery.     

Increased excretion of four acetyl-CoA precursors during clinical episode of propionic acidaemia

Propionic acidaemia (McKusick 23200) is caused by reduced activity of propionyl-CoA carboxylase (EC 6.4.1.3). A number of metabolites characteristic of this disease are excreted in patients' urine. We have developed a method of chemical diagnosis using gas chromatography-mass spectrometry (GC-MS). Since our first chemical diagnosis (Matsumotoet al., 1978), we have diagnosed seven patients. Profiles of urinary acids, however, varied from patient to patient. Factors affecting these profiles may be genetic make-up, age, or the patient's clinical and nutritional conditions. We have compared two metabolic profiles of a girl under different clinical conditions and found increased excretion of acetyl-CoA precursors during clinical episodes.     

Surgical procedures are well tolerated by patients with asymptomatic chronic hepatitis

In a retrospective study I assessed operative mortality in patients with biopsy-proven chronic hepatitis. Most patients had no symptoms from their liver disease. All patients were considered to have a viral cause of their chronic hepatitis--five were hepatitis-B surface antigen positive. Seven patients had chronic persistent hepatitis, and 13 had chronic active hepatitis (including four with cirrhosis). Twenty patients underwent 34 operative procedures, including 28 general endotracheal anesthesia and six spinal anesthesia. Although two patients who had preoperative bilirubin levels of 2.5 mg/dl or greater sustained further increases in serum bilirubin postoperatively, the serum liver chemistries of the entire group did not significantly worsen postoperatively. There was no anesthesia-related liver failure or operative mortality. Patients with asymptomatic chronic hepatitis tolerate surgical procedures well.     

Delay in diagnosis and treatment of gastric cancer: from the beginning of symptoms to surgery - an Iranian study.

Background/aims: In developed countries, diagnosis of gastric cancer is performed in early stages through screening, and the five-year survival rate has risen to 86%. Although patients in developing countries have digestive symptoms for some time, they do not undergo early endoscopy. The patients refer to physicians in developed stages. This research was conducted to determine the median time of delay from the beginning of symptoms to surgery. Methods: In this research, 63 patients suffering from gastric cancer were investigated during 2004-2005. A research questionnaire was completed from patient's admission to endoscopy until surgery through patient interview. Mann-Whitney statistical test and SPSS software were used for data analysis. Results: Out of 63 patients, 48 (76.2%) were male and 43 (68.3%) were rural residents. The most common cancer area was cardia (31 patients) and the most common symptom was abdominal pain (28 patients). The results showed that the median total delay from the beginning of symptoms until surgery was 96 days. Median patient delay [from first symptom to presentation to general practitioner] was determined as 8 days, general practitioner delay (from the first referral to endoscopy) as 57 days, pathologist delay (from endoscopy to pathology confirmation) as 12 days, and surgeon delay (from pathology confirmation to surgery) as 7 days. Factors such as place of residence, education, income and gender had no significant effect on time of delay. Conclusions: Delays from referral to endoscopy performance and from performance of endoscopy to pathologic confirmation were higher than expected. A screening plan for timely referral of patients and performance of endoscopy seems essential. To reduce the time of delay, efforts such as physician education, cooperation between hospital units and pathologists and provision of necessary hospital equipment are highly recommended.     

Stapled Hemorrhoidectomy With Local Anesthesia can be Performed Safely and Cost-Efficiently

PURPOSE: This prospective study was designed to assess the feasibility of performing the procedure for prolapsing hemorrhoids, or stapled hemorrhoidectomy, under local anesthesia supplemented with conscious sedation.METHODS: Seventy consecutive patients (mean age, 56 years; 37 males) with Grade 3 or 4 hemorrhoids underwent the procedure for prolapsing hemorrhoids after perianal infiltration of 0.5 percent lidocaine with 1:200,000 epinephrine and supplemental conscious sedation. The procedure was performed in an outpatient setting, with the patient being discharged within two hours of checking into the ambulatory facility. All patients were assessed the following day by telephone, and then in the office at three weeks and two months for degree of postoperative pain, bleeding, continence, and time back to work or social activities. Additionally, all excised mucosal anastomotic rings were analyzed for presence or absence of muscle.RESULTS: Each patient rated the pain as minimal or none. Five patients complained of mild, transient perineal pressure, and three complained of fecal urgency and seepage before their first office visit; one complained of external skin tags at the second office visit. All subjects were back to work or social activities within three to four days—most within 48 hours. Complications included urinary retention in five patients, two of whom had a concomitant urinary tract infection, and one had urosepsis requiring hospitalization. One patient required immediate reoperation for bleeding from the staple line. Another patient was admitted for postoperative bleeding and packed with a hemostatic agent the evening of surgery. Muscularis propria fibers were identified in 68 of 70 pathologic specimens.CONCLUSIONS: Administration of general, spinal, or epidural anesthesia for the procedure for prolapsing hemorrhoids is well described. This study suggests that the use of local anesthesia supplemented with conscious sedation for the procedure for prolapsing hemorrhoids yields results equivalent to those achieved with general or regional anesthesia without the attendant risks and additional costs. This study also suggests that the presence of muscle fibers in the pathologic specimen does not seem to lead to increased pain or impaired continence, although it was not specifically designed to address this issue.Reprints are not available.     

Mycobacterium tuberculosis infection in allogeneic bone marrow transplantation patients.

Bone marrow transplant (BMT) recipients are prone to bacterial, viral and fungal infections. Mycobacterium tuberculosis infection can occur in these patients, but the incidence is lower than that of other infections. This report describes four patients with Mycobacterium tuberculosis infection identified from 641 adult patients who received a BMT over a 12-year period (prevalence 0.6%). The pre-transplant diagnosis was AML in two patients and CML in the other two. Pre-transplant conditioning consisted of BU/CY in three patients and CY/TBI in one. Graft-versus-host disease (GVHD) prophylaxis was MTX/CsA in three patients and T cell depletion of the graft in one patient. Sites of infection were lung (two), spine (one) and central nervous system (one). Onset of infection ranged from 120 days to 20 months post BMT. Two patients had co-existing CMV infection. One patient had graft failure. The two patients who received anti-tuberculous (TB) therapy recovered from the infection. Although the incidence of tuberculosis in BMT patients is not as high as in patients with solid organ transplants, late diagnosis due to the slow growth of the bacterium can lead to delay in instituting anti-TB therapy. A high index of suspicion should be maintained, particularly in endemic areas.     

山东省4地市城区登记肺结核患者诊断状况的调查分析

目的 了解山东省城区登记的结核病人就诊情况和确诊情况，为提高城区的结核病服务质量提出建议。方法 对山东省泰山区等4个地级市的城区结防机构登记的246例肺结核病人进行问卷调查。 结果 病人自发病至初次就诊平均间隔12 d，病人延误的主要原因是对病情不在乎；67.5%的病人存在确诊延误，不同婚姻状况和选择不同首诊机构的患者，确诊延误的差异具有统计学意义。 结论 需要开展群众性健康教育，提高结核病知晓率，使病人出现结核病疑似症状后及时就诊；应鼓励结核可疑者在发病后首选结防机构、区级以上综合医疗机构或专科医院就诊。     

Management of Patients with Colorectal Cancer and Concomitant Abdominal Aortic Aneurysm

PURPOSE: The aim of this study was to determine the optimal management of patients with colorectal cancer and abdominal aortic aneurysm in the elective situation. METHODS: All patients with a history of colorectal cancer and abdominal aortic aneurysm between 1986 and July 2000 were identified, and charts of those with concomitant disease were reviewed. RESULTS: A total of 435 patients with available charts were reviewed. Eighty-three patients with concomitant abdominal aortic aneurysm and colorectal cancer were identified. In 64 patients the colorectal cancer was treated first, and 44 of these patients had an abdominal aortic aneurysm less than 5 cm in diameter (average = 3.8 cm). No abdominal aortic aneurysm ruptured in the postoperative period. Median delay to colorectal cancer surgery from diagnosis was four days. Twenty patients with abdominal aortic aneurysm of 5 cm or greater (average = 5.4 cm) were treated for colorectal cancer first. In two of these patients (with abdominal aortic aneurysms sized 5 and 6.4 cm), the abdominal aortic aneurysm ruptured in the early postoperative period. Median delay to colorectal cancer resection was eight days. Twelve patients had both abdominal aortic aneurysm and colorectal cancer treated at the same time. The average size of the abdominal aortic aneurysm was 6.4 cm. Median delay from colorectal cancer diagnosis to resection was 15 days. No documented cases of graft infection occurred in this group; median follow-up was 3.2 years. Seven patients underwent abdominal aortic aneurysm repair before resection of colorectal cancer; in two patients, colorectal cancer was found at the time of resection. The average size of abdominal aortic aneurysm was 6 cm and median delay to treatment of colorectal cancer was 122 days, a statistically significant longer delay than in the other two groups (P < 0.0001). CONCLUSION: In patients with colorectal cancer and abdominal aortic aneurysm of 5 cm or more, treatment of colorectal cancer first may result in life-threatening rupture, whereas treatment of abdominal aortic aneurysm first may significantly delay treatment of colorectal cancer. Concomitant treatment seems to be a safe alternative. If anatomically suitable, the abdominal aortic aneurysm may be considered for endovascular repair followed by a staged colon resection. The presence of an abdominal aortic aneurysm less than 5 cm does not affect colorectal cancer treatment.     

Technique of laparoscopic cholecystectomy combined with percutaneous papillary balloon dilatation under general anesthesia for cholecystocholedocholithiasis

Since the introduction of laparoscopic cholecystectomy (LC), the treatment of cholecystocholedocholithiasis has become a controversial issue among surgeons and endoscopists all over the world. We evaluated the effectiveness of LC combined with percutaneous papillary balloon dilatation (PPBD) under general anesthesia in the treatment of cholecystocholedocholithiasis in 22 patients. All stones in the bile duct were successfully evacuated into the duodenum in all patients. The PPBD was feasible in all patients under general anesthesia. The mean postoperative stay was 9 days. The overall length hospital stay and the duration of PTBD were 19 ± 7 days and 16 ± 8 days, respectively. There were no deaths nor major complications, although a transient hyperamylasemia was found in 10 patients (45%). Cholecystocholedocholithiasis was able to be treated by means of LC combined with PPBD under general anesthesia without laparotomy, sphincterotomy or choledochotomy. This technique can be a choice for the treatment that enables a patient to avoid any discomfort arisen as a result of papillary dilatation.     

上消化道异物内镜急诊处理162例

目的:探讨上消化道异物内镜下急诊诊断及取出的处理方式.方法:2002-07/2011-07龙岗区第二人民医院胃镜室共完成内镜下急诊异物取出上消化道异物患者162例,男89例,女73例,年龄0.8-82岁,异物吞入后就诊时间为3min-9d,分析患者临床资料.结果:采用局麻或全麻下急诊用内镜直视下明确诊断,按照异物的位置、形态、大小、选择合适的器械,取出异物或设法让异物通过肠道排出体外.162例患者中155例通过上述方法治疗后取得满意疗效,7例患者治疗失败后改为手术处理,内镜下急诊取出治疗上消化道异物成功率为95.7%,部分并发咽喉黏膜损伤.结论:经内镜局麻或全麻下急诊取出上消化道异物是一种安全、有效的方法;手法得当,用内镜上消化道异物急诊取出应为首选方法,有器质性病变的患者取出异物后应尽早病因治疗.     

Omental transposition: the final solution for major sternal wound infection

Sternal osteomyelitis after median sternotomy for cardiac surgery is associated with considerable morbidity and mortality. The ideal reconstruction after sternal debridement is still debated. From 2000 to 2004, we treated 15 patients for sternal osteomyelitis (type IIIB, IVA, IVB) after median sternotomy for cardiac surgery. Total or partial resection of the sternum and extensive debridement were performed in all cases. The defect was covered by omental transposition. In 11 cases, a single-stage operation took place, and a two-stage procedure was employed in 4. All patients had antibiotics postoperatively. There were 3 (20%) deaths due to cardiac failure. Hospital stay ranged from 21 to 45 days. Transient paradoxical movement of the anterior chest wall disappeared within one month. No recurrence was observed during 6 to 24 months of follow-up. Radical debridement along with omental flap transposition provides definitive control of the infection in cases of failure of other semi-conservative or surgical interventions. Prognosis depends on the general condition of the patient.     

Delays in the diagnosis and treatment of lung cancer

STUDY OBJECTIVES: This study was undertaken to measure delays of diagnosis and to assess the causes for those delays in patients with lung cancer. In addition, the relation of delay times and survival was analyzed. DESIGN: A retrospective study based on patient records. Dates for symptoms, visits to doctors, investigations, treatment, and death were recorded. SETTING: Patients who were found to have lung cancer at Turku University Hospital, Finland, during 2001. PATIENTS: Records of 132 patients were reexamined. RESULTS: The median delay in patient presentation from first symptoms to first appointment with a general practitioner (GP) was 14 days. The median delay by the GP before writing a referral was 16 days, the median referral delay was 8 days, the median delay from the first visit to a specialist until the diagnosis was 15 days, and the median treatment delay was also 15 days. Thirty percent of patients received treatment within 1 month from the first hospital visit, and 61% received treatment within 2 months. The median symptom-to-treatment delay was almost 4 months. The delay in seeing a specialist was shorter in patients with advanced cancer and small cell lung cancer. About half of our patients fulfilled the criteria of the British Thoracic Society recommendations. A longer specialist treatment delay seemed to correlate with better survival in advanced disease, but it was not an independent significant factor for survival. CONCLUSIONS: Several reasons for long delays were found, but on many occasions patients underwent numerous consecutive procedures before a diagnosis of cancer was confirmed. Shortening the diagnostic and treatment delay times might be possible with little extra cost by a multidisciplinary team approach and by rapid access to carefully planned investigations, but decreasing the patient delay might be more difficult. This study shows that long specialist treatment delays are not correlated with worse prognosis in patients with advanced disease. In patients with more limited disease, the delay time may be more critical, and if curative treatment is the goal, the diagnostic process should proceed without needless delay to avoid a situation in which curable disease becomes incurable.