Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance ('clinical super response'): Week 28 results from the ongoing phase IIIb randomized, double-blind, parallel-group, GUIDE study.

BACKGROUND: Guselkumab is an interleukin (IL)-23 inhibitor with demonstrated efficacy in patients with psoriasis. OBJECTIVES: Evaluate the impact of early disease intervention on clinical responses following 28 weeks of guselkumab treatment in patients with moderate-to-severe plaque psoriasis. Correlate clinical response and disease duration data with serum biomarker data. METHODS: GUIDE is a phase IIIb randomized, double-blind, parallel-group, multicentre study of adults with moderate-to-severe plaque psoriasis. In study part 1, patients with a short disease duration (SDD [≤2 years]) or a long disease duration (LDD [>2 years]) received guselkumab 100 mg at Week (W) 0, 4, 12, and 20. Those achieving complete skin clearance at W20 and W28 were defined as a super responder (SRe). A multivariable logistic regression analysed the association between baseline factors and the likelihood of becoming an SRe. The relationship between clinical response, disease duration and serum biomarker data was assessed at W0 and 4. RESULTS: In total, 880 patients were enrolled (SDD/LDD = 40.6%/59.4% of patients). More SDD than LDD patients achieved absolute Psoriasis Area and Severity Index (PASI) = 0 at W28 (51.8% vs. 39.4%) and were SRes (43.7% vs. 28.1% [overall 34.4%]). SDD patients also achieved PASI = 0 quicker than LDD patients (median 141 vs. 200 days). Disease duration and prior biologic use had the greatest impact on becoming an SRe, with no strong association among these independent variables. At baseline, there were no significant differences in the serum biomarker levels of IL-17A, IL-17F, IL-22 and ß-defensin 2 between SDD and LDD patients, or between SRe and non-SRe patients. Guselkumab rapidly decreased these markers of systemic inflammation across all patient groups analysed at W4. Guselkumab was well tolerated. CONCLUSIONS: Guselkumab efficacy was consistent across subpopulations, on the skin and systemically. The proportion of SRes was higher in SDD than LDD patients, indicating early treatment intervention may improve clinical outcomes.

'Organic Anxiety' in a Middle-aged Man Presenting with Dyspnoea: a Case Report.

We report a case of pulmonary embolism in a patient who presented with repeated anxiety attacks and psychotic symptoms and was misdiagnosed as having withdrawal seizure or anxiety disorder not otherwise specified. This case highlighted the nonspecific clinical features of pulmonary embolism and the principles in making psychiatric diagnosis. Careful history taking, thorough physical examination, appropriate investigation, and a high index of suspicion led to the correct diagnosis. The principle of hierarchy of psychiatric diagnosis (ie, organic over non-organic) and the possibility of comorbidities should always apply.

Abnormal voiding parameters in children with severe idiopathic constipation.

OBJECTIVE: It is suggested that idiopathic constipation may associate with abnormal voiding parameters. In this study, we investigate the voiding parameters in children with constipation. METHODS: Since 2010, seventeen consecutive children (12 boys, 5 girls) aged 5-17 (median = 14) with significant constipation according to Rome III criteria and who were not responding to conventional treatment (diet, laxatives & bowel training) for over 6 months were recruited. The rectal diameter (RD) was measured by transpubic ultrasonography (USG), RD >3.5 cm was considered as dilated. Each patient had uroflow measurement and bladder USG done to measure the maximal flow rate (Vmax), voided volume (VV), and post-void residual urine (PVR). Abnormal voiding parameters were defined as Vmax <12 ml/sec, VV <65 or >150% of age-adjusted expected bladder capacity (EBC) and/or PVR >20 ml. RESULTS: Rectal diameter ranged from 1.7 to 8.2 cm (median = 3 cm) and was abnormally dilated in eight children. Vmax was normal in all children (median = 23.7 ml/sec). Voided volume ranged from 30 to 289% of EBC and was abnormal in six children (35.5%). Post-void residual urine varied from 0 to 85 ml and was abnormal in six (35.5 %) children. Three children (17.6 %) had both abnormal VV and PVR. On the whole, the prevalence of abnormal voiding parameters in constipated children was 52.9 %. Mean RD in normal and abnormal parameters groups was 2.8 and 4.7 cm, respectively. Rectal dilation was associated with abnormal voiding parameters (p = 0.015). CONCLUSION: Abnormal voiding parameters including voided volume and post-void residual urine are prevalent in constipated children. Dilated rectum is associated with abnormal voiding parameters.

Voiding urosonography with second-generation ultrasound contrast versus micturating cystourethrography in the diagnosis of vesicoureteric reflux.

Vesicoureteric reflux has been associated with paediatric urinary tract infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold standard of diagnostic test for decades; however, it has been criticized owing to its lower detection rate and radiation dose to children. Therefore, new radiation-free reflux imaging modalities have been developed, in which ultrasound-based contrast-enhanced voiding urosonography (ceVUS) is a good example. However, ultrasonography has been considered as an operator-dependent examination. Therefore, our study aimed to examine the inter-observer agreement of this sonographic technique, which has not been evaluated before. Moreover, the second-generation ultrasound contrast SonoVue has been recently marketed, and the data on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also aimed to investigate the diagnostic performance and safety profile of SonoVue-enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective comparative study compared the diagnostic performance of ceVUS with MCU in young children presenting with first episode of urinary tract infection. We performed sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units). Perfect inter-observer agreement (Cohen's kappa statistics = 1.0, p < 0.001) was achieved in ceVUS, suggesting its good reliability in reflux detection and grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity and carried higher reflux detection rate than MCU (p < 0.001). There was no complication encountered. Conclusion: Voiding urosonography is a reliable, sensitive, safe and radiation-free modality in the investigation of vesicoureteric reflux in children. It should be incorporated in the diagnostic algorithm in paediatric urinary tract infection.

Scrotal antegradesclerotherapy demonstrates anatomical variations on venous drainage in paediatric, adolescent and young adult varicoceles.

AIM OF THE STUDY: Anatomical variations on venous drainage in varicoceles are under-reported. We report our experience in scrotal antegrade sclerotherapy (SAS) for adolescent varicoceles. METHODS: Since 2011, 15 consecutive boys with left varicoceles were recruited. Under general anaesthesia, a 5-mm transverse incision was made at scrotal neck, testicular vein was cannulated at pampiniform plexus with venogram performed. Foam sclerosant by mixing sodium tetradecyl sulphate (STS), Lipiodol(®) and air was slowly injected under fluoroscopy. Postoperatively the patients were followed-up for varicocele grading, testicular size, and complications. MAIN RESULTS: Median age at operation was 14 (10-19) years. 80 % had grade three varicoceles, 33.3 % had smaller left testis before operation. Intra-operative venogram showed three different anatomical variations. Group I: eleven patients (73.3 %) had single distinct internal spermatic vein; Group II: two patients demonstrated duplication of internal spermatic vein draining into left renal vein; Group III: two patients had pampiniform plexus draining to iliac and/or paraspinal veins. SAS was performed in Group I and II patients. Sclerosant volume injected ranged from 1.5 to 4.5 ml. In Group III patients, surgical ligation of testicular veins was performed rather than SAS to avoid uncontrolled systemic sclerosant spillage. Mean length of stay was 1.13 day. One patient with scrotal haematoma and one other with minor wound dehiscence were managed conservatively. Mean follow-up period was 10.9 (1-22) months. Thirteen patients (86.7 %) achieved varicocele grading ≤ 1. There was no postoperative testicular atrophy, hydrocele and epididymo-orchitis. CONCLUSION: Scrotal antegrade sclerotherapy using STS foam is a safe and effective treatment for adolescent varicoceles. Anatomical variations on venous drainage in varicoceles are common.

The clip and drop back technique in the management of multifocal necrotizing enterocolitis: a single centre experience.

AIM: The surgical management of multifocal necrotizing enterocolitis (NEC) remains a major challenge. The "clip-and-drop" strategy with a second-look laparotomy permits re-assessment of bowel viability after optimization, thus offering the potential of both improving survival and conserving bowel length. This study reviews the outcome of this strategy in a single regional center. METHODS: Since 2000, NEC patients undergoing emergency laparotomy selectively underwent a "clip-and-drop" operation if there was peri-operative instability and/or multifocal disease with uncertain bowel viability. Bowel with full thickness gangrene was resected and bowel-ends were temporarily tied-off; a second-look definitive procedure was performed when the patient had stabilized. For this review, in-hospital and follow-up records were studied retrospectively for demographics, 30-day mortality and long-term outcome. MAIN RESULTS: Between 2000 and 2010, 16 patients underwent a "clip-and-drop" operation. The mean post-conception age was 32.8 weeks (27.7-41.7 weeks) with a median body weight of 1.4 kg (0.76-4.4 kg) at first operation. Preoperative radiograph showed free gas in 43.8% and portal venous gas in 37.5% of patients. 2 patients did not survive to the second laparotomy. 14 patients received a second laparotomy, after a mean of 51 h (35-74 h). 2 patients were found to suffer from NEC totalis on the second laparotomy and died without further procedures. All other patients (n = 12) had stoma formation. 1 patient died 4 days after stoma formation. The 30-day mortality for NEC with the "clip-and-drop" strategy was 31.6% (5/16). Among the 11 survivors, 1 died from liver failure complicated by short bowel syndrome at 5 months post operation, 2 others died from respiratory complications of prematurity despite adequate gastrointestinal function. The median follow-up time for the 8 long-term survivors was 45 months (7-129 months). Their median time to achieving full feeds was 41 days (range 21-105 days) after the second operation. CONCLUSION: The "clip-and-drop" strategy, when used in selected patients with multifocal NEC, may help bowel conservation in survivors.

Management of primary spontaneous pneumothorax in Chinese children.

OBJECTIVES: To (1) determine the demographics of Chinese children admitted with primary spontaneous pneumothorax, (2) suggest how they may be quantified radiologically, (3) compare the difference in outcomes after their primary management by thoracentesis and chest tube insertion, and (4) review the local experience with surgical intervention for such children. DESIGN: Retrospective, descriptive study. SETTING: Acute tertiary public hospital, Hong Kong. PATIENTS: Consecutive patients younger than 18 years and admitted with primary spontaneous pneumothorax between 1 January 1999 and 30 September 2007. MAIN OUTCOME MEASURES: Hospital stay and risk of recurrence after thoracentesis versus chest tube insertion. RESULTS. Seventy-seven patients with 114 episodes of primary spontaneous pneumothorax were reviewed. They were significantly taller (P<0.001) and thinner (P<0.001) than the population mean percentile. Both the Light index and Collins formula were accurate in quantifying pneumothorax volume, but as the former was simpler and more user-friendly, this was more applicable in children. Thoracentesis resulted in shorter hospital stays (mean, 4.6; standard deviation, 1.9 days) than chest tube insertion (6.9; 3.0 days), but there was no significant difference in the recurrence rates within 6 months (P=1.0), 1 year (P=0.9), and 2 years (P=0.1). Insignificant pneumothorax was treated with observation alone in 16% of the patients. For patients with a clinically significant pneumothorax, thoracentesis and chest tube insertion were successful in 78% and 67%, respectively (P=0.34). The success rate of video-assisted thoracoscopic surgery was 89%, and postoperative recurrence occurred more commonly in patients without a lung bleb. CONCLUSION: Chinese children with primary spontaneous pneumothorax exhibited similar demographic characteristics to Caucasian children. Light index is simple and accurate for quantifying pneumothorax volume in children. Conservative treatment including observation, thoracentesis, and chest tube insertion should suffice for most patients with first episode of primary spontaneous pneumothorax. Early surgery is warranted for any patient who fails conservative treatment, for which video-assisted thoracoscopic surgery is safe and effective.

Thoracic actinomycosis in an adolescent mimicking chest wall tumor or pulmonary tuberculosis.

Actinomycosis is a rare disease in children and young adolescents and its thoracic manifestations accounted for a minority of all cases. We report a case of a 12-year-old boy who presented with a right anterior chest wall mass for one week together with weight loss and low grade fever for one month. His symptoms and signs as well as the results of the radiological investigations (i.e. chest X-ray and computed tomography (CT) of thorax with contrast) mimicked pulmonary tuberculosis or chest wall tumor. The definite diagnosis of actinomycosis relies on the Gram stain microscopy and culture of the chest wall lesion aspirates. An early and accurate diagnosis can prevent the patient from unnecessary invasive procedures such as open lung biopsy or thoracotomy. The mainstay of the treatment of actinomycosis remains to be a combination of abscess drainage as well as prolonged antibiotics such as penicillin. Follow-up CT scan of thorax with contrast is useful in monitoring the progress of disease recovery.

Identifying prognostic factors for survival in advanced cancer patients: a prospective study.

OBJECTIVE: To identify potential prognostic factors affecting the survival in patients with advanced cancer in a local palliative care unit. DESIGN: Prospective cohort study. SETTING: Palliative Care Unit of a regional hospital in Hong Kong. PATIENTS: All advanced cancer in-patients and out-patients who were enrolled into the palliative care service of the United Christian Hospital between January and December 2002 were recruited. MAIN OUTCOME MEASURES: Potential prognostic factors including demographic data, tumour characteristics, blood parameters, functional status, co-morbidities, total symptom score, and psychosocial parameters were recorded upon enrollment. RESULTS: A total of 170 patients were eligible for analysis; their mean age was 69 (standard deviation, 12) years, of which 106 (62%) were male. Overall median survival was 77 (interquartile range, 31-160) days. The most frequent primary malignancy was lung (n=58, 34%), followed by liver (n= 24, 14%) and lower gastro-intestinal tract (n=24, 14%). By univariate analysis, 11 factors affected survival, including: age (P=0.040), number of metastatic sites involved (P=0.001), peritoneal metastases (P=0.009), skin metastases (P=0.011), tachycardia (P=0.009), serum albumin concentration (P<0.001), white cell count (P=0.002), Karnofsky Performance Status score (P<0.001), Hamilton Depression Scale score (P=0.004), Edmonton Symptom Assessment System score (P=0.003), and McGill Quality of Life (Hong Kong)-single item score (P=0.002). Multivariable Cox regression analysis revealed that only age (hazard ratio=0.84; 95% confidence interval, 0.73-0.96), number of metastatic sites involved (1.33; 1.13-1.56), serum albumin concentration (0.95; 0.92-0.98), Karnofsky Performance Status score (0.86; 0.78-0.96), and Edmonton Symptom Assessment System score (1.22; 1.05-1.41) were independent prognosticators. CONCLUSION: Age, number of involved metastatic sites, serum albumin, Karnofsky Performance Scale score, and Edmonton Symptom Assessment System score were independent prognosticators. Further studies are needed to provide a prognostic instrument applicable in local clinical settings.

Minimal access surgery for sigmoid volvulus in children.

A 12-year-old boy presented with large-bowel obstruction due to sigmoid volvulus. Temporary relief was achieved with rectal tube decompression. Elective laparoscopic-assisted sigmoid colectomy was performed. Post-operative recovery was uneventful. The patient remained well with no recurrence after 4 years of follow-up. Laparoscopic-assisted sigmoid colectomy may be the procedure of choice for selected children with sigmoid volvulus.

Electrical stimulation and biofeedback exercise of pelvic floor muscle for children with faecal incontinence after surgery for anorectal malformation.

We report our experience of electrical stimulation and biofeedback exercise of pelvic floor muscle for children with faecal incontinence after surgery for anorectal malformation (ARM). Electrical stimulation and biofeedback exercise of pelvic floor muscle were performed on children with post-operative faecal soiling following repair of intermediate or high type ARM. Children under the age of 5 years or with learning difficulties were excluded. They had 6 months supervised programme in the Department of Physiotherapy followed by 6 months home based programme. Bowel management including toilet training, dietary advice, medications and enemas were started before the pelvic floor muscle exercise and continued throughout the programme. Soiling frequency rank, Rintala continence score, sphincter muscle electromyography (EMG) and anorectal manometry were assessed before and after the programme. Wilcoxon signed rank test was performed for statistical analysis. From March 2001 to May 2006, 17 children were referred to the programme. Twelve patients (M:F = 10:2; age = 5-17 years) completed the programme. There was a trend of improvement in Rintala score at sixth month (p = 0.206) and at the end of programme (p = 0.061). Faecal soiling was significantly improved at sixth month (p = 0.01) and at the end of the programme (p = 0.004). Mean sphincter muscle EMG before treatment was 1.699 microV. Mean EMG at sixth month and after the programme was 3.308 microV (p = 0.034) and 3.309 microV (p = 0.002) respectively. After the programme, there was a mean increase in anal sphincter squeeze pressure of 29.9 mmHg (p = 0.007). Electrical stimulation and biofeedback exercise of pelvic floor muscle is an effective adjunct for the treatment of faecal incontinence in children following surgery for anorectal malformation.

Laparoscopic mobilization of testicular vessels: an adjunctive step in orchidopexy for impalpable and redo undescended testis in children.

The testicular position after conventional inguinal orchidopexy for canalicular, "peeping" and redo undescended testes may not be satisfactory despite retroperitoneal dissection. Laparoscopy allows extensive mobilization of testicular vessels to gain additional length. We review our experience of using laparoscopic mobilization of testicular vessels (LMTV) in orchidopexy for these difficult undescended testes. From January 2003 to May 2004, LMTV was performed in 18 boys. The testicular vessels were mobilized from just proximal to the internal inguinal ring to the level of caecum and sigmoid colon respectively. Fifteen patients had clinically impalpable testes. Diagnostic laparoscopy revealed 13 "peeping" and 2 canalicular testes. LMTV was performed together with inguinal orchidopexy. There were three cases of redo orchidopexies because of unfavourable testicular position after previous surgery. LMTV was performed following inguinal dissection. The median follow-up period is 11.7 months. Sixteen testes are located at the base of scrotum, and two at mid-scrotum. The size is normal in 17 testes, whereas 1 testis is smaller than the contralateral one. LMTV is a safe and efficient adjunctive step in orchidopexy for impalpable and redo undescended testes.