Demographic Study of Epileptic Burn Patient in a Tertiary Level Hospital of Bangladesh.

Burns are very common and important injuries associated with epilepsy. Epileptics are afflicted with burns when they come in contact with fire or other burning agents while seizing, due to loss of consciousness. The aim of the study was to identify the causes of burn, pattern and characteristics of burn in patients with epilepsy, duration of hospital stay and pattern of treatment in these patients. This prospective observational study was conducted in the Department of Burn and Plastic Surgery, Mymensingh Medical College Hospital, Bangladesh from January 2022 to December 2023. Epileptics were found in 0.84% (n=19) of the total admission (2274) in Burn unit. Majority of the patients were females (84.2%) and the mean age was (31.42±1.32) years. Maximum patients were housewives (78.9%). Among 19 cases, 11 cases (57.89%) had history of irregularly taking antiepileptic drugs and 8 cases (42.11%) had no history of treatment for epilepsy. Two cases (10.53%) had history of previous burn injury. Flame burn was the major etiology (89.5%). Mean total burn surface area (TBSA) was (6.94±4.12%). Most patients had full thickness burns (63.2%). Regarding distribution of burn, maximum involvement was in upper limb i.e. 68.21% cases. Surgical treatment was needed in the majority of the patients (68.5%). Mean hospital stay of these patients was (5.36±2.26) weeks. Epilepsy patients whose seizures are inadequately controlled are at increased risks of injury, especially burn. For prevention of burn, epilepsy should be treated properly.

Developments in Hand Surgery: Experience from a Tertiary Hospital of Northern Bangladesh.

Hand Surgery is a specialized branch of Plastic and Reconstructive surgery. There are many conditions that require hand surgery, for example, congenital deformity, electric or flame burn, mechanical or road traffic injury, and post burn or post traumatic deformity. A retrospective observational study was conducted in the department of Burn and Plastic surgery, Mymensingh Medical College Hospital, Bangladesh during a 2 years period extending from 9th September 2021 to 8th September 2023. The objective of this study was to see the hand surgery status in a tertiary hospital of Bangladesh during the post Covid pandemic period. During this period 236 hand surgery procedures were performed in 176 patients. The age of the patients ranged from 02 to 78 years (Mean 31.14±1.52). One hundred and four (59.0%) were male and 72(41.0%) were female. Thirty-four (19.32%) patients had co-morbidities e.g., Epilepsy, Diabetes Mellitus, Chronic Kidney Diseases and HBsAg +ve. Causes of surgery included, wound due to electric burn 49(27.84%), flame burn 36(20.45%), post traumatic 24(13.64%), post infective 11(06.25%), tumor excision 02(2.24%), Dupuytren's contracture 03(1.70%), congenital anomalies 06(3.41%), post burn scar contractures 41(23.29%), nerve injury 01(00.57%) and carpal tunnel syndrome 01 (00.57%). Procedures were performed: post burn scar contracture release 41(17.37%), syndactly release 06(2.54%), release of post traumatic contracture 06(2.54%), carpal tunnel release 01(00.42%), release of Dupuytren's contracture 03(01.27%), nerve repair 01(00.42%), debridement, amputation and Fillet flap 29(12.29%), split thickness skin graft 46 (19.49%), V-Y advancement flap 06(2.54%), transposition flap 18(07.63%), cross finger flap 16 (06.78%), reverse cross finger flap 02 (00.85%), first dorsal metacarpal artery (FDMA) flap 05 (02.12%), reverse FDMA flap 01 (00.42%), metacarpal artery perforator flap 08(3.39%), radial artery perforator flap 04(01.69%), posterior interosseous artery flap 05(2.12%), abdominal flap 11(04.46%) and flap division and insetting 27(11.44%). Outcome of surgery was satisfactory in 225(95.34%) and 11(04.46%) cases had complications (p value 0.453), which was not significant. So, it can be concluded that the outcome of various types of hand surgery procedures in tertiary hospital of northern Bangladesh during the post Covid period was satisfactory overall.

Coverage of defects over Posterior aspect of Ankle Joint and Heel with Lateral Calcaneal Artery Flap- Experience in Mymensingh Medical College Hospital.

Lateral calcaneal artery flap is randomly used by many Plastic Surgeons for covering any defect on the posterior aspect of heel. A prospective observational study was conducted in the Department of Burn and Plastic Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2020 to June 2022, to see the outcome of the flap for coverage of defects over the posterior aspect of ankle joint and heel. A total number of 09 patients, selected by purposive sampling, were included in the study. The age of the patients ranged from 06 years to 70 years. The cause of the defects were post traumatic in 07 cases, electric burn in 01 case and pressure sore in 01 case. The defect sizes varied from 3×2 to 6×3cm. and flap size ranged from 4×2.5 to 7×4.5cm. The follow-up period ranged from 3 to 6 months. All the flaps survived completely without any complications; except in two cases. In one case, there was marginal epidermal necrolysis that healed secondarily without the need of any further surgical intervention. In the other case, there was gangrene of about 0.5 cm area at the flap tip, which was debrided and the resulting wound healed secondarily. The average operating time was 63 minutes. The results were satisfactory on the context of adequate coverage, and flap and donor site morbidity. So, the lateral calcaneal artery flap can be a good and safe option for the coverage of posterior ankle and heel defects.

Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML.

Although the landscape for treating acute myeloid leukemia (AML) patients has changed substantially in recent years, the majority of patients will eventually relapse and succumb to their disease. Allogeneic stem cell transplantation provides the best anti-AML treatment strategy, but is only suitable in a minority of patients. In contrast to B-cell neoplasias, chimeric antigen receptor (CAR) T-cell therapy in AML has encountered challenges in target antigen heterogeneity, safety, and T-cell dysfunction. We established a Fab-based adapter CAR (AdCAR) T-cell platform with flexibility of targeting and control of AdCAR T-cell activation. Utilizing AML cell lines and a long-term culture assay for primary AML cells, we were able to demonstrate AML-specific cytotoxicity using anti-CD33, anti-CD123, and anti-CLL1 adapter molecules in vitro and in vivo. Notably, we show for the first time the feasibility of sequential application of adapter molecules of different specificity in primary AML co-cultures. Importantly, using the AML platform, we were able to demonstrate that chronic T-cell stimulation and exhaustion can be counteracted through introduction of treatment-free intervals. As T-cell exhaustion and target antigen heterogeneity are well-known causes of resistance, the AdCAR platform might offer effective strategies to ameliorate these limitations.

A Comparative Study of Collagen Sheet versus 1% Silver Sulfadiazine Dressing in Superficial Partial Thickness Burns.

Burn injury causes a lot of suffering. The goal of burn management is to achieve rapid wound healing, pain relief, rehabilitation with minimum scars and optimal functional ability. Objective of this study was to compare the efficacy of collagen sheets and 1% silver sulfadiazine dressing (SSD) for superficial partial thickness burns. This prospective observational study was conducted among the patients of Department of Plastic surgery, Dhaka Medical College Hospital, and Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, from 1st April 2020 to 31st March 2021. Total 60 patients with superficial partial thickness burns by purposive sampling 30 patients of them were treated with collagen sheet dressing (Group A) and 30 patients with 1.0% silver sulfadiazine dressing (Group B). First case was selected by tossing a coin. Then every alternate patient was provided the same kind of dressing material (either collagen sheet or 1.0% silver sulfadiazine). Data were collected by semi structured data collection sheets. Pearson's chi-square test and student's 't' test were used for data analysis (p value was significant at <0.05). It was observed that a total of 18(60.0%) patients belonged to age <10 years in Group A and 17(56.7%) patients in Group B. The mean age was 14.9±14.2 years in Group A and 11.6±10.2 years in Group B. Good quality of healing was significantly higher in the collagen group compared to the SSD group (<0.05). The mean complete healing time in the collagen group was 10.47±2.21 days and in the 1.0% SSD group were 13.07±2.33 days. The mean healing time was significantly lower in the collagen group compared to the 1.0% SSD group (p<0.001). There was no significant difference in infection rate between the two groups (p>0.05). Considering the overall outcome, Collagen sheet dressing decreases pain, reduces the need for analgesics, aids in early healing as compared to the patients treated with 1% silver sulfadiazine.

Aspects of transition cow metabolomics-Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver, blood, and urine in cows with different liver metabotypes.

Dairy cows in modern production systems are at risk to develop metabolic disorders during the transition period. Reasons for individual differences in susceptibility, as well as the underlying pathomechanisms, are still only partially understood. The development of metaphylactic treatment protocols is needed. In this context, an on-farm prospective 3-fold blinded randomized study involving 80 German Holstein cows was performed throughout 1 yr. The trial involved a thorough recording of the production and clinical traits, clinical chemistry, and liver biopsies and blood and urine sampling at d 14 (mean: 12 d, range: 1-26 d) antepartum (AP), and d 7 (7, 4-13) and 28 (28, 23-34) postpartum (PP) for metabolomics analyses. Two groups received a treatment with butaphosphan and cyanocobalamin (BCC) at either the dosage recommended by the manufacturer or the double dosage (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin (Catosal, Bayer Animal Health), n = 20 in each group, parity: 4.2 ± 2.0 and 3.4 ± 1.3, respectively (mean ± SD)] and one group a placebo treatment (NaCl 0.9%, n = 40, parity: 4.0 ± 1.9). The animals were treated at 6 time points (7, 6, and 5 d AP, and 1, 2, and 3 d PP) via intravenous injection. Mass spectroscopy-based targeted metabolomics analysis of blood plasma and liver samples were performed using the AbsoluteIDQ p180 kit (Biocrates Life Sciences), whereas the urine samples were analyzed by nuclear magnetic resonance spectroscopy. Statistical analysis was performed using multivariate [partial least squares discriminant analysis (PLS-DA)] and univariate methods (linear mixed model). Multivariate data analysis (PLS-DA plots) of the liver metabolome revealed 3 different metabotypes (A = medium, B = minor, C = large alterations in liver metabolome profile between AP and PP status). Metabotype B animals were characterized by higher PP lipomobilization (stronger PP body condition decrease and higher blood bilirubin, fatty acids, gamma-glutamyltransferase, and triglyceride levels) and a higher occurrence of transition cow diseases, compared with the animals in metabotype C. Analysis of the feeding data showed that the period of metabotype B animals (calving in a distinct time frame) was characterized by a decreased grass silage quality. The PP liver metabolome of the metabotype C animals was characterized by higher concentrations of AA, acylcarnitines, lysoPC and sphingomyelins compared with metabotype B. For the metaphylactic treatment with BCC a dose-dependent effect was confirmed, differing between the metabotypes. In all matrices and metabotypes at various time points significant treatment effects were observed, with different profiles in clinical chemistry and as well in metabolomics data. The most clear-cut treatment effect was observed in metabotype B in the liver at 7 d PP, characterized by an increase in several acylcarnitines and phosphatidylcholines, indicating a more efficient influx and oxidation of fatty acids in mitochondria and thereby an increase in energy supply and more efficient triglyceride export in the liver. The results from the liver metabolomics analysis support the application of an indication-based metaphylactic treatment with BCC.

Aspects of transition cow metabolomics-Part II: Histomorphologic changes in the liver parenchyma throughout the transition period, in cows with different liver metabotypes and effects of a metaphylactic butaphosphan and cyanocobalamin treatment.

The aims of this study were to evaluate histopathologic changes during the transition period, describe the histopathological features of the metabotypes identified in Part I (Schären et al., 2021b), and investigate effects of a metaphylactic treatment with butaphosphan and cyanocobalamin (BCC) on the liver parenchyma. Eighty German Holstein cows (mean 305-d production: 10,957 kg, range: 6,480-15,193 kg; mean lactation number: 3.9, range: 2-9) from a commercial dairy farm in Saxony, Germany, were enrolled in a randomized, prospective, triple-blinded study. Two groups received a treatment with BCC (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin, Catosal, Bayer Animal Health, n = 20 each) and one group a placebo treatment (NaCl 0.9%, n = 40). Liver biopsy specimens were collected 14 d antepartum (AP) and 7, 28, and 42 d postpartum (PP), routinely processed for histologic examination, and stained with hematoxylin and eosin, Sudan III, periodic acid-Schiff, and picrosirius red stains. The sections were assessed for fat and glycogen content and degenerative, inflammatory, fibrotic, and proliferative changes. The statistical analysis included the effects of the sampling day, the lactation number, the treatment, and the metabotype (A = medium, B = minor, C = large alterations in the liver metabolome profile between AP and PP status). There was mild to moderate fat infiltration in the liver of 37% of cows in the last 2 wk AP, and moderate to severe fat infiltration in 66% of cows in the first days PP. The degree of fat infiltration increased from 2 wk AP until the end of the first week PP, and then decreased until the end of the study period, at which time about 25% of cows had moderate to severe fatty infiltration. Lipidosis was positively correlated with the severity of liver cell degeneration, and negatively correlated with the degree of glycogen deposits. Complete glycogen depletion of hepatocytes was not observed in cows, even in the presence of severe hepatic lipidosis. Moderate to severe lymphocytic hepatitis was seen in 39% of cows throughout the study period, and cows with lactation numbers 5 or greater had perisinusoidal fibrosis more often than younger cows. Severe fibrosis and cirrhosis of the liver did not occur. Metabotype B animals exhibited a higher chance of fatty infiltration, lower glycogen storage, and perisinusoidal fibrosis and for this metabotype positive correlations were calculated between increased fat deposition in the liver and marked glycogen depletion, and increased degenerative, inflammatory, fibrotic, and proliferative changes of hepatic tissue. For the treatment with BCC, no significant effect was observed. In summary, during the transition period, the liver of dairy cows is characterized by fat accumulation and glycogen depletion and histologic signs of hepatitis and hepatocyte degeneration. These histomorphologic changes were accentuated in animals exhibiting little alterations in their liver metabolome profile across the transition period (metabotype B) and support the assumption of a decreased grass silage quality as a causative factor.

[Evaluation of treatment adaptation for low response to ASA in vascular surgery]. / Evaluation einer Therapieanpassung bei ASS-Low-Response in der Gefäßchirurgie.

BACKGROUND: A decreased antiplatelet prophylaxis (low response, LR/high on-treatment platelet reactivity, HPR) with acetylsalicylic acid (ASA) is associated with an increased risk of thromboembolic events. The prevalence of a LR is frequent with about 20% and a therapeutic regimen is not yet established. The aim of this prospective study was to evaluate the effectiveness of a therapeutic regimen for treatment adaptation when LR/HPR is detected in vascular surgery patients. METHODS: Overall, 36 patients under long-term antiplatelet treatment with 100 mg/day ASA and a detected ASA low response (ALR) were included in the study. In this patient group a modification of the prophylactic medication was carried out according to the established treatment plan and a control aggregometry was performed. The therapeutic regimen followed the test and treat principle. To evaluate the effect of ASA impedance, aggregometry with multiple electrodes was used (multiplate). RESULTS: All 36 patients were successfully transferred to response status with the treatment scheme. In 32 (88.89%) patients an increased dose of 300 mg/day ASA was carried out and in 2 (5.56%) patients the medication was changed from ASA to clopidogrel. A further 2 (5.56%) patients were switched to oral anticoagulation with phenprocoumon, due to other indications. Bleeding complications or other side effects did not occur. CONCLUSION: The chosen treatment regime for a low response proved to be effective and safe in vascular surgery patients. A guideline-compliant increase of the ASA dose from 100 mg to 300 mg/day predominantly led to an effective inhibition of platelet aggregation in the aggregometry.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Crane Principle in Plastic Surgery- Experience in Mymensingh Medical College Hospital.

The crane principle is a Plastic surgical technique whereby, a pedicled flap can be used as an engineering crane to lift and transport subcutaneous tissue from one area and deposit it in another. The flap can be returned later to its original bed. It takes only one week for the conveyance. Here we present a case of 25 year old female patient with degloving injury of scalp with exposed skull bone was initially managed with transposition flap for coverage of the scalp defect in Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh on 07 December 2017. After 8 months the scalp flap was returned to its original site following the crane principle and the new wound was covered by split-thickness skin graft. The flap survived completely and patient was satisfied.

[Statistical analysis of correlated measurement data in ophthalmology : Tutorial for the application of the linear mixed model in SPSS and R using corneal biomechanical parameters]. / Statistische Auswertung korrelierter Messdaten in der Augenheilkunde : Tutorial zur Verwendung des linear gemischten Modells in SPSS und R anhand biomechanischer Parameter der Hornhaut.

BACKGROUND: In ophthalmology data from both eyes of a person are frequently included in statistical analyses. As correlated data are used this procedure contradicts the independency principle for classical statistical tests, such as Student's t­test and analysis of variance (ANOVA). In this tutorial a new possibility is presented in which data from both eyes can be used for statistical analysis. OBJECTIVE: The statistical approach of linear mixed models (LMM) was used to take correlated data of both eyes of patients into account. METHODS: The LMM is available in several statistical software packages, e.g. SPSS and R, and allows the inclusion of measurement data from both eyes of a person in the statistical analysis. The application was tested on data from a biomechanical characterization of the cornea from healthy participants assessed with the dynamic Scheimpflug analyzer (Corvis ST; Oculus, Wetzlar, Germany). RESULTS: A total of 158 eyes from 79 healthy participants were included. A strong correlation between the right and left eyes of the participants could be observed with respect to the analyzed parameters. Comparison of the biomechanical parameters between the different age groups showed that P-values were increased when using the LMM compared to the ANOVA. Older participants (56-79 years) showed a significantly shorter time to the second applanation (P = 0.002), a significantly increased eyeball movement during the deformation (P = 0.001) and a significantly higher stiffness at the first applanation (P = 0.006) compared to younger participants (18-35 years). CONCLUSION: The analysis of measurement data from both eyes using classical statistical tests, without the consideration of the correlation, leads to an overestimation of the statistical power. This can be avoided by implementation of the LMM.

Posterior Tibial Artery Perforator Based Propeller Flap for Lower Leg and Ankle Defect Coverage: A Prospective Observational Study.

Reconstruction of lower leg and ankle defect with exposed bone or tendon is a challenging task for a Plastic Surgeon. There are various options, among them perforator based propeller flap is a very good option though this is a microsurgical procedure but no need of microvascular anastomosis. This study was designed to see the clinical results of Posterior tibial artery perforator based propeller flap for lower leg and ankle defect coverage. The study was a prospective observational study. It was conducted in the Department of Burn and Plastic Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2017 to June 2018. Sample size was 9. Sampling was carried out purposively. Postoperative follow up period was up to 6 weeks. Among the 9 cases, 8 flaps completely survived, 1 case developed marginal necrosis which was secondarily healed. There were total 2 complications among 9 cases i.e. transient venous congestion and superficial epidermonecrolysis which were resolved spontaneously. Regarding the cause of the defect, maximum cases were post traumatic wound (66.7%), others were post infective, post malignancy excision and post electric burn wound. Defect size was 2cm×2cm to 7cm×5cm. Maximum dimension of the flap was 19cm×6cm and minimum size was 7cm×3cm. Posterior tibial artery perforator location was 4cm to 9cm from lowest level of medial malleolous (mean 6.2±1.6cm). Rotation of the flap was 145°-180° (mean 163°±1.39°). In all cases donor site was covered with split thickness skin graft. Operation time was 120 minutes to 180 minutes; mean operative time was 143.3±2.38 minutes. After operation hospital stay was 10 days to 21 days, mean 11.44±3.64 days. So, posterior tibial artery perforator based propeller flap for lower leg and ankle defect coverage is a very good option.

Robotic-assisted laparoscopic repair of rectovesical fistula after Hartmann's reversal procedure.

The case is of a 59-year-old male with history of severe ischemic colitis following emergent intervention for a ruptured infrarenal aortic aneurysm who subsequently underwent left hemicolectomy, partial proctectomy, and Hartmann colostomy. The patient later underwent reversal of the Hartmann colostomy with diverting ileostomy. The surgery was complicated by a right ureteral and posterior bladder injury that resulted in a large rectovesical fistula involving the right hemitrigone and right ureteral orifice. An attempt to repair the rectovesical fistula at an outside facility was unsuccessful. Then, he underwent a robotic-assisted laparoscopic repair of rectovesical fistula, including simple prostatectomy, excision of rectovesical fistulous tract, rectal closure, peritoneal and omental flap interposition, bladder neck reconstruction, vesicourethral anastomosis and right ureteral reimplantation. There were no intraoperative or postoperative complications, and the patient was discharged at postoperative day 4; cystoscopy at 6-week follow-up demonstrated a successful closure of the fistula, at which time the ureteral stents were removed.

[Osteoid osteoma in the scaphoid bone as cause of radiocarpal pain in a 15-year-old patient]. / Osteoidosteom im Os scaphoideum als Ursache für radiokarpale Handgelenksbeschwerden bei einem 15-jährigen Patienten.

Osteoid osteomas are benign bone tumors which rarely occur in the hand and impose severe diagnostic problems. The course of the disease is often protracted before the patient receives an adequate surgical treatment. The case of an osteoid osteoma in the scaphoid bone of a 15-year-old patient is presented, who was completely symptom free after a true diagnostic odyssey by resection of the nidus and reconstruction by crest bone graft and spongiosaplasty.

[Otorhinolaryngology in the field of demography, growing outpatient care and regionalization]. / Die HNO-Heilkunde im Spannungsfeld von Ambulantisierung und Regionalisierung.

BACKGROUND: Otorhinolaryngology (ENT) departments are strongly affected by current changes in the reimbursement schemes for inpatients. The study was designed to investigate these effects on the ENT Department in Rostock and selected comparison clinics, as well as to outline solutions. METHODS: We analyzed diagnosis-related group (DRG) reports of the ENT Clinic at Rostock University Medical Center from 2013 to 2015, according to the size of the outpatient potential. Comparisons were made with other surgical departments such as maxillofacial surgery and ophthalmology in terms of average length of stay and the resulting deductibles. We also compared billing as day surgery and complete outpatient surgery for the main small surgical procedures such as tonsillectomy and septum surgery. Finally, we compared the discounts with 22 ENT departments in other maximum care hospitals. RESULTS: The average case mix index of an ENT department in Germany is 0.75, case load average of 2,500 patients and common length of stay 4.1 days. In a typical academic ENT department as in Rostock, health plans usually discount around 500 T€ (thousand euro), which is considerably higher than comparable departments, e.g., oral and maxillofacial surgery or ophthalmology departments. However, discounts on a DRG for inpatient surgery is still approximately 1,000 € more revenue than surgery in an outpatient setting. The benchmark analysis shows that health plans in rural areas are more likely to accept inpatient surgery with discounts for small procedures than strict billing according to outpatient reimbursement schemes. CONCLUSION: These effects can result in an insufficient cost effectiveness of ENT departments in Germany. As a consequence, substantial restructuring of the in- and outpatient treatment seems necessary, also for academic ENT departments, e.g., in the form of day surgery or ambulatory surgical centers, outpatient clinics with special contracts and specialized inpatient surgery. However, this results in greater demands on the training of young physicians and management of patient flows within the department.

Definitive seton management for transsphincteric fistula-in-ano: harm or charm?

AIM: The treatment of transsphincteric anal fistula requires a balance between eradication of the disease and preservation of faecal control. A cutting seton is an old tool that is now out of vogue for many surgeons. We hypothesized that the concept remains reliable and safe with results that exceed those reported for many of the more recently described methods. METHOD: A retrospective review was conducted of real-time electronic health records (single institution, single surgeon) of patients presenting during the 14 years between 2001 and 2014 with a transsphincteric anal fistula who were treated with a cutting seton. Excluded were patients with Crohn's disease, fistulae related to malignancy or a previous anastomosis and patients whose fistula was treated by another method including a loose draining seton. Data collection included demographics, duration of the disease, duration of the treatment, outcome and continence. RESULTS: In all, 121 patients (80 men) of mean age 40.2 ± 12.2 years (range 18-76) with a mean follow-up of 5.1 ± 3.3 (1-24) months were included in the analysis. The median duration of symptoms was 6 (1-84) months; 36% had failed other fistula surgery, 12% had a complex fistula with more than one track and 35% had some form of comorbidity. The median time to healing was 3 (1-18) months; 7.4% required further surgery, but eventually 98% had complete fistula healing. The incontinence rate decreased postoperatively to 11.6% from 19% before treatment with 17/121 with pre-existing incontinence resolved and 8/107 new cases developing. CONCLUSION: Despite its retrospective non-comparative design, the study has demonstrated that a cutting seton is a safe, well tolerated and highly successful treatment for transsphincteric anal fistula and is followed overall by improved continence. The results compare very favourably with other techniques.

Towards a commercial process for the manufacture of genetically modified T cells for therapy.

The recent successes of adoptive T-cell immunotherapy for the treatment of hematologic malignancies have highlighted the need for manufacturing processes that are robust and scalable for product commercialization. Here we review some of the more outstanding issues surrounding commercial scale manufacturing of personalized-adoptive T-cell medicinal products. These include closed system operations, improving process robustness and simplifying work flows, reducing labor intensity by implementing process automation, scalability and cost, as well as appropriate testing and tracking of products, all while maintaining strict adherence to Current Good Manufacturing Practices and regulatory guidelines. A decentralized manufacturing model is proposed, where in the future patients' cells could be processed at the point-of-care in the hospital.

Gemcitabine plus sorafenib versus gemcitabine alone in advanced biliary tract cancer: a double-blind placebo-controlled multicentre phase II AIO study with biomarker and serum programme.

BACKGROUND: Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer (BTC) patients, we evaluated first-line gemcitabine plus sorafenib in a double-blind phase II study. PATIENTS AND METHODS: 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts, Eastern Cooperative Oncology Group (ECOG) 0-2 were randomised to gemcitabine (1000 mg/m2 once weekly, first 7-weeks+1-week rest followed by once 3-weeks+1-week rest) plus sorafenib (400 mg twice daily) or placebo. Treatment continued until progression or unacceptable toxicity. Tumour samples were prospectively stained for sorafenib targets and potential biomarkers. Serum samples (first two cycles) were measured for vascular endothelial growth factors (VEGFs), vascular endothelial growth factor receptor 2 (VEGFR-2) and stromal cell-derived factor 1 (SDF1)α by enzyme-linked immunosorbent assay (ELISA). RESULTS: Gemcitabine plus sorafenib was generally well tolerated. Four and three patients achieved partial responses in the sorafenib and placebo groups, respectively. There was no difference in the primary end-point, median progression-free survival (PFS) for gemcitabine plus sorafenib versus gemcitabine plus placebo (3.0 versus 4.9 months, P=0.859), and no difference for median overall survival (OS) (8.4 versus 11.2 months, P=0.775). Patients with liver metastasis after resection of primary BTC survived longer with sorafenib (P=0.019) compared to placebo. Patients who developed hand-foot syndrome (HFS) showed longer PFS and OS than patients without HFS. Two sorafenib targets, VEGFR-2 and c-kit, were not expressed in BTC samples. VEGFR-3 and Hif1α were associated with lymph node metastases and T stage. Absence of PDGFRß expression correlated with longer PFS. CONCLUSION: The addition of sorafenib to gemcitabine did not demonstrate improved efficacy in advanced BTC patients. Biomarker subgroup analysis suggested that some patients might benefit from combined treatment.