Active Therapeutic Intervention Research Articles

Indocyanine green near-infrared fluorescence bowel perfusion assessment to prevent anastomotic leakage in minimally invasive colorectal surgery (AVOID): a multicentre, randomised, controlled, phase 3 trial

Anastomotic leakage is a severe postoperative complication in colorectal surgery and compromised bowel perfusion is considered a major contributing factor. Conventional methods to assess bowel perfusion have a low predictive value for anastomotic leakage. We therefore aimed to evaluate the efficacy of real-time assessment with near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in the prevention of anastomotic leakage. This multicentre, randomised, controlled, phase 3 trial was done in eight hospitals in the Netherlands. We included adults (aged >18 years) who were scheduled for laparoscopic or robotic colorectal surgery (with planned primary anastomosis) for benign and malignant diseases. Preoperatively, patients were randomly assigned (1:1) to fluorescence-guided bowel anastomosis (FGBA) or conventional bowel anastomosis (CBA) by variable block randomisation (block sizes 4, 6, and 8) and stratified by site. The operating surgeon and investigators analysing the data were not masked to group assignment. Patients were unmasked after the surgical procedure or after study end. In the FGBA group, surgeons marked anastomosis levels per conventional perfusion assessment and then administered 5 mg of ICG by 2 mL intravenous bolus. They assessed bowel perfusion using NIR fluorescence imaging and adjusted (or kept) transection lines accordingly. Only conventional methods for bowel perfusion assessment were used in the CBA group. The primary outcome was the difference in the rate of clinically relevant anastomotic leakage (ie, requiring active therapeutic intervention but manageable without reoperation [grade B] or requiring reoperation [grade C], per the International Study Group of Rectal Cancer) between the FGBA group and the CBA group within 90 days post-surgery. The primary outcome and safety were assessed in the intention-to-treat population. This study was registered with ToetsingOnline.nl (NL7502) and ClinicalTrials.gov (NCT04712032) and is complete. Between July 2, 2020, and Feb 21, 2023, 982 patients were enrolled, of whom 490 were assigned to FGBA and 492 were assigned to CBA. After excluding 51 patients, the intention-to-treat population comprised 931 (463 assigned FGBA and 468 assigned CBA). Patients had a median age of 68·0 years (IQR 59·0-75·0) and 485 (52%) were male and 446 (48%) were female. Ethnicity data were not available. The overall 90-day rate of clinically relevant anastomotic leakage was not significantly different between the FGBA group (32 [7%] of 463 patients) and the CBA group (42 [9%] of 468 patients; relative risk 0·77 [95% CI 0·50-1·20]; p=0·24). No adverse events related to ICG use were observed. 313 serious adverse events in 229 (25%) patients were at 90-day follow-up (159 serious adverse events in 113 [24%] patients in the FGBA group and 154 serious adverse events in 116 [25%] patients in the CBA group). 18 (2%) people died by 90 days (ten in the FGBA group and eight in the CBA group). ICG NIR fluorescence imaging did not reduce 90-day anastomotic leakage rates in this trial across all types of colorectal surgeries. Further research should be done in subgroups, such as rectosigmoid resections, for which evidence suggests ICG NIR might be beneficial. Olympus Medical, Diagnostic Green, and Intuitive Foundation.

Effects of Progressive Physiotherapy Along with or Without Active Bed Rest at Hospital for the Management of Chronic Low Back Pain (LBP) Patients in Bangladesh

Background: Low Back Pain (LBP) is a significant health condition globally suffered by the middle and older aged population due to its impact on work disability, absenteeism and costs. Physiotherapy with active rest and therapeutic intervention, including mobilization, manipulation, exercise therapy and electrotherapy, is the choice of treatment as conservative management, whereas surgery is required in case of advanced neurological involvement. Specific level-induced spinal mobilization has a greater impact on correcting the faulty biomechanics of the spinal column if considered active rest at an early stage, whereas generalized spinal physiotherapy without rest is also effective for managing mechanical spinal pain. Objective: To determine the effects of physiotherapy with or without active rest for chronic low back pain. Method: Experimental research design with simple random sampling was used in this study to find out the effects of Progressive Physiotherapy along with or without active rest at the hospital for the management of patients with chronic Low Back Pain (LBP) in Bangladesh of 20-55 years of aged peoples with pre and posttest basis. Results: The study showed that physiotherapy with or without active rest effectively reduces pain and back disability for low back pain patients, whereas physiotherapy with active rest is more effective than physiotherapy without active rest for back pain patients. Comparison of within-group and between-group results showed that the P<0.05. The comorbidities were about 40% diabetic, 33% spinal deformity and 6.67% spinal and other surgical conditions which influence LBP. The experimental group reduced 64% pain and the control group reduced 24% pain. Conclusion and Recommendations: Physiotherapy with active rest is more effective than physiotherapy without active rest for LBP patients, whereas both treatment groups are significantly effective individually. RCT study can proceed for further evaluation.

The Sustainable Personalised Interventions for Cognition, Care, and Engagement (SPICE) Program: A twelve week reablement intervention for people with dementia and carers

AbstractBackgroundThere is a need for integrated and effective reablement programs to promote the quality of life of people with dementia and their carers.MethodThe Sustainable Personalised Interventions for Cognition, Care, and Engagement (SPICE) Program is currently being evaluated in Canberra, Australia. SPICE is a multicomponent active therapeutic intervention delivered by allied health professionals over twelve weeks. The five components are: 1) cognitive stimulation therapy (CST); 2) carer education, support and capacity building; 3) physical activity; 4) Care of People with dementia in their Environments (COPE) program; and 5) dietary assessment and advice. Six people with dementia and their six carers participate in a small group twice per week for the CST, carer, and physical activity components, while COPE and dietary assessment and advice are completed as a dyad. Pre‐ and post‐intervention outcome measures on quality of life, neuropsychiatric symptoms, cognitive function, and physical function are being collected, in addition to a program evaluation interview. After four groups have completed the protocol, the SPICE waiting‐list pilot trial will finish data collection in early 2024. Here we report on the first group to complete the program.ResultAttendance to the in‐person components of the program were 94% for people with dementia and 92% for carers. All participants completed the COPE program, and compliance with the dietary appointments was 94%. Quantitative outcome measures suggest benefits, but inferences cannot be drawn due to small sample size. Both people with dementia and carers reported high program satisfaction and perceived benefits, supporting the feasibility of the intervention. The program was rewarding for all participants, and carers felt the strategies and lessons learned had immediate benefits. The social aspects, inclusiveness, and group cohesiveness were key drivers of their satisfaction with the program.ConclusionThe results from the first group to complete the SPICE program shows that an intensive, multicomponent active therapeutic program is feasible and considered valuable for people with dementia and their carers. Findings from the pilot trial are required to confirm the results from the first group to potentially support a randomised controlled trial.

Differential diagnosis of thrombocytosis (lecture for practitioners)

Thrombocytosis (an increase in the level of platelets in the peripheral blood above 450×109/l) has different causes and mechanisms of formation: it can be familial, primary (clonal), secondary (reactive). The ability to interpret peripheral blood parameters, knowledge of the main differential diagnostic criteria for diseases accompanied by thrombocytosis, allow the doctor to conduct the necessary examination to determine the cause of an increase in the platelet count in the blood. Clarification of the nature of thrombocytosis is very important, since clonal thrombocytosis is more often accompanied by the development of thrombotic complications and requires more active therapeutic intervention, specific therapy. Timely diagnosis helps to prevent the development of thrombosis, improves the prognosis, quality of life and survival of patients.

Preliminary Findings of an Active Multicomponent Lifestyle Intervention for People with Dementia and Their Carers: Mixed Methods Study

There is a need for integrated and effective postdiagnostic rehabilitation programs for community-dwelling people with dementia and their carers to promote their quality of life and management of dementia. Here, we report on preliminary findings of the Sustainable Personalised Interventions for Cognition, Care, and Engagement (SPICE) Program conducted in Canberra, Australia. Over twelve weeks, six people with dementia and their carers completed five hours of weekly small group activities and separate individual appointments. SPICE is an active therapeutic intervention with five components delivered by allied health professionals: (1) cognitive stimulation therapy; (2) carer education, support, and capacity building; (3) physical activity; (4) Care Of People with dementia in their Environments (COPE) program; and (5) dietary assessment and advice. Participants completed questionnaires pre- and post-intervention and a program evaluation interview which was analysed by qualitative thematic analysis. The program demonstrated high program satisfaction ratings and program adherence (94% people with dementia and 92% carers) which supports intervention feasibility. The results of quantitative outcome measures suggest positive effects, but inferences cannot be drawn due to small sample size. Qualitative themes from participant experiences highlighted the following: (1) social connection, engagement, and interaction were key drivers of the success of the program; (2) clinicians fostered a positive and respectful culture; (3) carers were supported with strategies and skills to reframe dementia; and (4) reablement can be fun. The new combination of evidence-based interventions was feasible and considered valuable. Further results are required to confirm these findings and support a longer-term trial.

TMT-Based Quantitative Proteomic and Physiological Analyses on Serums of Chinese Patients with Active Vitiligo.

Vitiligo is an acquired depigmented skin disorder. Though genetic background, autoimmune dysregulation, and oxidative stress were reported involved in the development of vitiligo, the exact pathogenesis remains largely unknown. This study aimed to investigate potential functional proteins, pathways, and serum biomarkers involved in active vitiligo. Tandem Mass Tags (TMT) method was used to determine differentially expressed proteins (DEPs) in serum samples between 11 active vitiligo patients and 7 healthy controls of Chinese Han population. A total of 31 DEPs were identified (P < 0.05, fold change >1.2), with 21 proteins upregulated and 10 proteins downregulated in the vitiligo group. DEPs were enriched in GO terms such as "extracellular exosome" and "immunoglobulin receptor binding", as well as KEGG pathways including "cysteine and methionine metabolism" and other immune-related pathways. Furthermore, ALDH1A1 and EEF1G achieved areas under receiver-operating characteristic (ROC) curve of 0.9221 and 0.8571, respectively. The expression levels of these 2 proteins were validated in another active vitiligo patient group. Our research provided novel insight into serum proteomic profile for vitiligo patients, detecting ALDH1A1 and EEF1G as potential biomarkers for active vitiligo and therapeutic intervention. Our work also detected several DEPs and associated pathways in the serum of active vitiligo patients, reinforcing the roles of retinoic acid and exosome processes in vitiligo pathogenesis.

Clinical symptoms of patients with Kawasaki disease include smoldering fever.

Persistent low-grade fever has been observed in some patients during intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD); however, smoldering fever (SF) has not previously been reported in patients with KD. This study aimed to clarify the clinical characteristics of SF in patients with KD. A single-center retrospective cohort study, which included a total of 621 patients who received IVIG therapy, was conducted. Patients with a fever of 37.5-38°C lasting ≥3 days after 2 days of the initial-IVIG were defined as the SF group. Patients were divided into four groups according to the fever course: SF (n = 14), biphasic fever (BF, n = 78), non-fever after initial-IVIG (NF, n = 384), and persistent fever (PF, n = 145). The clinical features of SF were described and compared between the groups. The median duration of fever in the SF group was 16 days, which was longer than that in any other group. The neutrophil fraction after IVIG therapy in the SF group was higher than that in the BF and NF groups but similar to that in the PF group. Repeated IVIG administration in the SF group resulted in increased IgG levels but decreased serum albumin levels. In the SF group, 29% of the patients had coronary artery lesions at 4 weeks. The frequency of SF in KD was 2.3%. Patients with SF continued to have moderate inflammatory responses. Repeated administration of IVIG doses was not effective in treating SF, and acute coronary artery lesions were occasionally observed. Active therapeutic intervention was needed.

71P Aromatase inhibitors and fracture prevention: Is our current approach correct?

Breast cancer remains a common diagnosis. Aromatase inhibitors (AI) are recommended for their mortality benefit in postmenopausal women with hormone sensitive disease. AI bone loss is a recognised adverse event with resultant increase in fracture risk. In 2017, a consensus statement of international bone and cancer societies published an algorithm based on risk factors and bone mineral densities (BMD) threshold for bone active therapeutic intervention.

IDF21-0234 The Virtual COVID In-patient (VCIP) Care and Post Covid Symptoms: a Comparison with Conventional Care

Background: VCIP is a home based interventional economic model wherein a consenting patient will remain in their home and consult the VCIP team via audio-video consultations to treat COVID-19 in a manner similar to inpatient care. While the widely prevalent home-based care that is currently available is often limited to monitoring of vital signs, the VCIP program described here involves active therapeutic intervention. Aim: We assessed the impact of VCIP in the management of COVID and post COVID symptoms. Method: Since September 2020, our center has been practicing VCIP for our patients with diabetes, already enrolled in our hospital, to treat COVID and Post COVID symptoms. This is a retrospective analysis of the data of 243 COVID-19 positive patients who enrolled in VCIP. A 24/7 dedicated WhatsApp group of patients, their relatives, doctors, nurses, dietitian and a psychologist was created for remote monitoring of temperature, blood pressure, blood glucose, respiratory and pulse rate along with the symptoms and then to follow up them for 4-6 months post-COVID. The vital parameters and general wellbeing of patients are monitored once every 4 hrs. Contrary to conventional domiciliary care, in VCIP, lab investigations, corticosteroids and other interventions were carried out as and when necessary, at home for the successful management of COVID-19. For patients with diabetes on insulin, the dosages were titrated based on SMBG values or real time CGM. We also assessed the post-COVID symptoms in these patients. Results: Out of 243 patients who availed of the VCIP facility, all 243 of them recovered. However, 2 hospitalizations were there, one, due to the impending fear of death and the other one, due to intolerance to oral corticosteroids, yielding a 99.5% success rate in preventing hospitalization. There was a wide range of post-COVID-19 symptoms and illnesses experienced by <10% of the patients, which was very low compared to patients in conventional care, including headache(5%), generalized itching(7%), fatigue(20%), vertigo(<1%), urticaria(<1%), exacerbation of sinusitis(<1%), insomnia(15%), and bacterial infection(30%). The patients recovered from these symptoms within 2-3 months. Some patients who experienced more severe complications such as atrial fibrillation and ventricular ectopics (<1%) picked up in Apple watch ECG was referred to a cardiologist for evaluation. The arrhythmias disappeared spontaneously with clinical improvement in the majority of the patients. Discussion: VCIP when compared to hospitalizations have proven to be cost effective, with significantly better immediate outcomes. With regular and structured teleconsultations and lab assessments, patients likely to deteriorate are identified quite early and treatment initiated without wasting any time. The comorbidities were also aggressively managed. The significantly less occurrence of post Covid symptoms in the VCIP group compared to hospitalized patients could have resulted from these early interventions.

AVOID; a phase III, randomised controlled trial using indocyanine green for the prevention of anastomotic leakage in colorectal surgery

IntroductionAnastomotic leakage (AL) is one of the major complications after colorectal surgery. Compromised tissue perfusion at the anastomosis site increases the risk of AL. Several cohort studies have shown that...

Diagnostic accuracy of apoptosis markers in non-alcoholic fatty liver disease in children

Introduction. Non-alcoholic fatty liver disease (NAFLD) is recognized as one of the most common chronic liver diseases in children and adults worldwide. Early diagnosis of rapidly progressive forms of NAFLD – non-alcoholic steatohepatitis (NASH) – is crucial, because therapeutic intervention in the early disease stages creates unique opportunities for the reversal of pathological changes and restoration of liver structure and function. Despite the variety of currently available diagnostic scales and indices, laboratory diagnosis of NAFLD in children requires new non-invasive tests and their validation.Aim: To investigate the differences of cytokeratin-18 (CK18) and the combined marker MACK-3 levels in children with nonalcoholic steatohepatitis (NASH), simple hepatic steatosis, overweight and obese children without hepatic steatosis.Materials and methods. The study included 170 patients aged 6 to 17 years. The mean age of patients was (12.15 ± 2.51) years. According to the presence of steatosis, steatohepatitis, overweight and obesity, patients were divided into 4 groups: the 1st group consisted of 37 patients with NASH, the 2nd group – 53 patients with simple steatosis, the 3rd group – 65 overweight and obese patients without hepatic steatosis, the 4th group (control) – 15 patients with normal weight without steatosis. Biochemical hepatogram, carbohydrate metabolism investigation, as well as CK18 enzyme-linked immunosorbent assay, were conducted with the MACK-3 calculation.Results. The average level of CK18 in children with NASH increased by 1.6 times (P <0.05) compared with children of the control group. The median CK18 level in patients with NASH was by 1.6 times (P < 0.05) and 2.0 times (P < 0.05) higher than in groups 2 and 3, respectively. T he threshold level of CK18 for the diagnosis of NASH was 87.4 U/l: its sensitivity was 81.8 %, specificity 70 %, AUROC 0.736 (P ˂ 0.05). Calculated index MACK-3 revealed a significant increase in children with NASH compared with other groups (P < 0,05). Threshold level of MACK-3 for the diagnosis of NASH was 0.053: sensitivity – 90.9 %, specificity – 81.6 %, AUROC 0.958 (P ˂ 0.05).Conclusions. Thus, in children with NASH, a significant increase in the CK18 level was found, which can be used for early non-invasive diagnosis of NASH in children. The advantage of the calculated index MACK-3 is the increase in diagnostic accuracy and the possibility of its use to stratify the risk of the progressive course of NAFLD, which will streamline the selection of patients for active therapeutic intervention.

Preclinical Activity of PI3K Inhibitor Copanlisib in Gastrointestinal Stromal Tumor.

KIT or PDGFRA gain-of-function mutations are the primary drivers of gastrointestinal stromal tumor (GIST) growth and progression throughout the disease course. The PI3K/mTOR pathway is critically involved in the transduction of KIT/PDGFRA oncogenic signaling regardless of the type of primary and secondary mutations, and therefore emerges as a relevant targetable node in GIST biology. We evaluated in GIST preclinical models the antitumor activity of copanlisib, a novel pan-class-I PI3K inhibitor with predominant activity against p110α and p110δ isoforms, as single-agent and in combination with first-line KIT inhibitor imatinib. In vitro studies undertaken in one imatinib-sensitive (GIST-T1) and two imatinib-resistant (GIST-T1/670 and GIST430/654) GIST cell models showed that single-agent copanlisib effectively suppressed PI3K pathway activation leading to decreased cell viability and proliferation in both imatinib-sensitive and -resistant cells irrespective of the type of primary or secondary KIT mutations. Simultaneous PI3K and KIT inhibition with copanlisib and imatinib resulted in enhanced impairment of cell viability in both imatinib-sensitive and -resistant GIST cell models, although apoptosis was mostly triggered in GIST-T1. Single-agent copanlisib inhibited GIST growth in vivo, and conjoined inhibition of PI3K and KIT was the most active therapeutic intervention in imatinib-sensitive GIST-T1 xenografts. IHC stain for cleaved-caspase 3 and phospho-S6 support a predominant antiproliferative effect of copanlisib in GIST. In conclusion, copanlisib has single-agent antitumor activity in GIST regardless KIT mutational status or sensitivity to imatinib. Effective KIT inhibition is necessary to achieve synergistic or additive effects with the combination of imatinib and any given PI3K/mTOR pathway inhibition.

Transarterial (chemo)embolisation versus no intervention or placebo for liver metastases.

The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of people; therefore, other treatments have to be considered. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents, and can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. This can also be performed without chemotherapy, which is called bland transarterial embolisation (TAE). To assess the beneficial and harmful effects of TAE or TACE compared with no intervention or placebo in people with liver metastases. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and four more databases (December 2019). We also searched two trials registers and the US Food and Drug Administration database (September 2019). Randomised clinical trials assessing beneficial and harmful effects of TAE or TACE compared with no intervention or placebo for liver metastases. We followed standard Cochrane methodological procedures. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of evidence with GRADE. We resolved disagreements by discussion. We included one randomised clinical trial with 61 participants (43 male and 18 female) with colorectal cancer with liver metastases: 22 received transarterial embolisation (TAE; hepatic artery embolisation), 19 received transarterial chemoembolisation (TACE; 5-fluorouracil hepatic artery infusion chemotherapy with degradable microspheres), and 20 received 'no active therapeutic intervention' as a control. Most tumours were synchronous, unresectable metastases involving up to 75% of the liver. Participants were followed for a minimum of seven months. The trial was at high risk of bias. Very-low-certainty evidence found inconclusive results for mortality at 44 months between the TAE and TACE versus no intervention groups (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06; 61 participants). Local recurrence was reported in 10 participants without any details about the group allocation. Very-low-certainty evidence found little or no difference in mortality between the TAE and no intervention groups (RR 0.91, 95% CI 0.75 to 1.10; 42 participants). Median survival was 7 months from trial entry (range 2 to 44 months) in the TAE group and 7.9 months (range 1 to 26 months) in the control group, and 8.7 months after diagnosis (range 2 to 49 months) in the TAE group and 9.6 months (range 1 to 27 months) in the control group. The trial authors reported the differences were not statistically significant. There were no reported side effects in the control group. In the TAE group, 18 participants experienced short-term symptoms of 'post-embolisation syndrome', which were relieved with symptomatic treatment; one participant also had a local puncture site haematoma. Very-low-certainty evidence found little or no difference in mortality between the TACE and no intervention groups (RR 0.83, 95% CI 0.65 to 1.07; 39 participants). Median survival in the TACE group was 10.7 months (range 3 to 38 months) from trial entry, and 13.0 months (range 3 to 38 months) after diagnosis. The trial authors reported that differences between groups were not statistically significant. All participants experienced short-term nausea, with or without vomiting, immediately after treatment; one participant developed a wound infection, and one developed deep vein thrombosis. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Cancer Research Campaign, a non-profit organisation, provided a grant for the trial; Pharmacia Ltd. delivered the Port-a-Cath arterial delivery systems and degradable starch microspheres. We identified one ongoing trial comparing TACE plus chemotherapy versus chemotherapy alone in people with unresectable colorectal liver metastases who failed with first-line chemotherapy (NCT03783559). Based on one, small randomised trial at high risk of bias, the evidence is very uncertain about the effect of TAE or TACE versus no active therapeutic intervention on mortality for people with liver metastases as the true effect may be substantially different. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Short-term, minor adverse events were recorded in the intervention groups only. Large trials, following current standards of conduct and reporting, are required to explore the benefits and harms of TAE or TACE compared with no intervention or placebo in people with resectable and unresectable liver metastasis.

Effect of Normal Saline Injections on Lateral Epicondylitis Symptoms: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Background: Lateral epicondylitis, or tennis elbow, is a painful degenerative disorder that commonly occurs in adults between 40 and 60 years of age. Normal saline (NS) injections have been used as placebo through a large number of randomized controlled trials (RCTs) focused on the treatment of lateral epicondylitis. Purpose: This meta-analysis of RCTs aimed to assess the therapeutic effect of NS injections on lateral epicondylitis symptoms and compare results with established minimal clinically important difference criteria. Study Design: Systematic review and meta-analysis. Methods: MEDLINE, Embase, Web of Science, and Scopus databases were searched for clinical trials reporting pain and joint function with the visual analog scale, Patient-Rated Tennis Elbow Evaluation, and Disabilities of the Arm, Shoulder and Hand in patients with lateral epicondylitis. The meta-analysis was conducted with a random effects model and generic inverse variance method. Heterogeneity was tested with the I2 statistic index. Results: A total of 15 RCTs included in this meta-analysis revealed a significant improvement in pain (mean difference, 3.61 cm [95% CI, 2.29-4.92 cm]; P < .00001; I2 = 88%; visual analog scale) and function (mean difference, 25.65 [95% CI, 13.30-37.99]; P < .0001; I2 = 82%; Patient-Rated Tennis Elbow Evaluation / Disabilities of the Arm, Shoulder and Hand) after NS injection (≥6 months). Conclusion: NS injections yielded a statistically significant and clinically meaningful improvement in pain and functional outcomes in patients with lateral epicondylitis. New research should focus on better methods to diminish the potential confounders that could lead to this effect because NS injections could mask the real effect of an active therapeutic intervention in RCT. Registration: CRD42019127547 (PROSPERO).

Successful treatment of a female pediatric patient with carbamazepine-induced toxic epidermal necrolysis: Active wound care and systemic therapy.

We describe a 6‐year‐old female patient who developed carbamazepine‐associated toxic epidermal necrolysis. With active wound care, systemic methylprednisolone and intravenous immunoglobulin pulse therapies and multidisciplinary supportive care, the patient improved significantly. This case indicates that improving the management of Stevens‐Johnson syndrome/Toxic epidermal necrolysis patients requires attention not only to the process of wound management but also to individual supportive care and active therapeutic intervention. Only through this can standardized care, including muco‐cutaneous and visceral wound care, be delivered to provide high‐quality care with improved clinical prognosis and quality of life.

Incidence and risk factors for anastomotic leakage after anterior resection for rectal cancer

To assess the incidence and independent risk factors for clinical anastomotic leakage (AL) in patients undergoing anterior resection(AR) or low anterior resection, (LAR) for rectal cancer. This was a retrospective case-control study of 550 patients with rectal cancer who underwent AR or LAR from April 2007 to March 2017 in Beijing Friendship Hospital, Capital Medical University. The relationship between the incidence of AL and clinicopathological manifestations was analyzed by Chi-squared test and Fisher exact test, and the independent risk factors of AL were analyzed using logistic regression analysis. AL is defined as a defect (including necrosis or abscess formation) of the intestinal wall at the anastomotic site, leading to a communication between the intra- and extra-luminal compartments. AL can be divided into three grades. Grade A anastomotic leakage results in no change in the management of patients, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy. AL was noted in 32(5.8%) of 550 patients with rectal cancer who underwent AR or LAR, including 15(46.9%), 4(12.5%), and 13 patients (40.6%) with Grades A, B, and C, respectively. Five patients(0.9%, 5/550) died peri-operatively. AL- and non-AL-related deaths occurred in 3 (9.4%, 3/32, all cases were Grade C) and 2 patients(0.4%, 2/518), respectively, with the two mortality rates being significant difference(P=0.002). Chi-squared test or Fisher exact test showed that the incidence of AL was associated with neoadjuvant chemoradiotherapy (P=0.011), intraoperative bleeding(≥100 ml)(χ2=11.980, P=0.001), and tension-reducing suture of anastomosis(P=0.015). The results of logistic regression analysis showed that the independent risk factors of AL were neoadjuvant chemoradiotherapy(OR=2.402, 95%CI: 1.004-5.749, P=0.049), intraoperative bleeding(≥100 ml)(OR=2.971, 95%CI: 1.269-6.957, P=0.012) and tension-reducing suture of anastomosis(OR=2.304, 95%CI: 1.008-5.263, P=0.048). The incidence of AL in patients undergoing AR for rectal cancer is 5.8%. The high-risk factors for AL are neoadjuvant chemoradiotherapy, intraoperative bleeding (≥100 ml), and tension-reducing suture of anastomosis. Patients with these three risk factors have a high risk of AL rate, and a defunctioning stoma should be performed.

Can we expect long-term survival in patients with extrahepatic metastasis of hepatocellular carcinoma?

251 Background: Hepatocellular carcinoma presenting metastases has been considered detrimental situation. However, it is not infrequent observing long term survivors following active therapeutic intervention in selected patients. In this study, we investigated whether long term survival could be real as well as its common clinical features. Methods: From november 2005 to december 2014, among 1020 HCC patients with extrahepatic metastasis, 75 patients survived over 2 years. The patient and tumor characteristics were examined involving the site, number of metastatic lesions, liver function, and other factors. Treatment methods for liver and metastatic lesions were also reviewed with subgroup survival analysis according to the treatment strategies. Results: We observed survival over 2 years in 7.3 % with median survival of 41 months. The most common sites of extrahepatic metastasis were lung, bone, adrenal gland and lymph nodes in order of frequency. Of 75 survivors, 72 (96%) had single organ metastasis, and 46 (64%) had four or less countable metastatic lesions. Child-Pugh score was within 5 to 7 points for 71 patients when extrahepatic metastasis first occurred. More than two-thirds of patients (52 patients, 69.3%) received local treatments such as surgery or radiotherapy showing significantly higher survival than systemic treatment only (23 patients, 30.7 %) group; 3 year survival 65.7 % versus 21.7 % for the group with and without local treatment respectively (p = 0.001). For patients with a viable tumor in the liver, the application of local treatments such as transarterial treatment or radiotherapy showed a significant survival benefit (3-year survival 46.6 % versus 31.3%, p = 0.045). Conclusions: The long-term survivors presented limited number of extrahepatic metastasis (oligometastasis) and received local treatment for their metastatic lesions. Local treatments to metastatic lesions will increase the survival of advanced HCC patients who have proper liver function and a small number of metastases in a single organ. This study suggests the application of individually tailored therapeutic strategies for advanced HCC patients with extrahepatic metastasis.

Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity

The asymptomatic phase of type 1 diabetes is recognised by the presence of beta cell autoantibodies in the absence of hyperglycaemia. We propose that an accurate description of this stage is provided by the name ‘Autoimmune Beta Cell Disorder’ (ABCD). Specifically, we suggest that this nomenclature and diagnosis will, in a proactive manner, shift the paradigm towards type 1 diabetes being first and foremost an immune-mediated disease and only later a metabolic disease, presaging more active therapeutic intervention in the asymptomatic stage of disease, before end-stage beta cell failure. Furthermore, we argue that accepting ABCD as a diagnosis will be critical in order to accelerate pharmaceutical, academic and public activities leading to clinical trials that could reverse beta cell autoimmunity and halt progression to symptomatic insulin-requiring type 1 diabetes. We recognize that there are both opportunities and challenges in the implementation of the ABCD concept but hope that the notion of ‘asymptomatic autoimmune disease’ as a disorder will be widely discussed and eventually accepted.

Reference Change Values for Sodium Are Ignored by the American and European Treatment Guidelines for Hyponatremia

Updated revised expert panel recommendations on the evaluation and treatment of hyponatremia were published in the United States in 2013 (1). In 2014, a separate set of guidelines were issued by a group representing the European Society of Intensive Care Medicine, the European Society of Endocrinology, and the European Renal Association–European Dialysis and Transplant Association represented by European Renal Best Practice (2). The recommended rates of correction of chronic hyponatremia from the US group are 4–8 mmol/L per day for patients at low risk of osmotic demyelinating syndrome (ODS)4 and 4–6 mmol/L per day if that risk is high. The limits not to exceed are 8 mmol/L in any 24-h period when the ODS risk is high, and when the ODS risk is low, 10–12 mmol/L in any 24-h period and 18 mmol/L in any 48-h period. If 8 mmol/L is exceeded in a 24-h period, there should be no active therapeutic intervention for the next 24 h (1). Regarding frequency of sodium analysis, serum sodium should be measured at 4- to 6-h intervals until mildly hyponatremic concentrations ≥125 mmol/L have been reached. The section on counteracting overcorrection of chronic hyponatremia by >6–8 mmol/L in the first 24 h of therapy discusses the uses of 2–4 μg desmopressin with repeated 3-mL/kg infusions of 5% dextrose in water administered over 1 h combined with the measurement of serum sodium after each infusion, i.e., hourly until the therapeutic target for the patient has been reached when the starting serum sodium is <120 mmol/L. When using vasopressin receptor antagonists (vaptans) and when treating diuretic-induced hyponatremia, measurements of serum sodium are set at a 6- to 8-h minimum until a stable sodium value >125 mmol/L has been reached. When diuretics have caused hyponatremia-induced seizures, hypertonic saline is recommended to raise the …

Use of transanastomotic double-pigtail stents in the management of grade B colorectal leakage: a pilot feasibility study.

Anastomotic leakage (AL) is a major complication of colorectal surgery. The leakage is classified as grade B when the patient's clinical condition requires an active therapeutic intervention but does not require further surgery. The management of grade B AL commonly includes administration of antibiotics and/or the placement of a pelvic drainage performed under radiological guidance or transanal drain. The objective of this study was to evaluate the feasibility and the efficacy of endoscopic transanastomotic drainage using double-pigtail stents (DPSs) in the management of grade B AL in colorectal surgery. Between September 2011 and December 2014, 650 patients underwent a colorectal procedure in our university hospital; 8.7% presented with AL, including 42.8% with grade B. Fourteen patients required endoscopic management and constituted the study population. The study's primary objective was to assess the feasibility and efficacy of DPS placement for the treatment of grade B AL after colorectal surgery. The secondary endpoints were the requirement for radiological drainage, the DPS placement failure rate, the rate of stoma closure and, lastly, feasibility of chemotherapy (if indicated). DPS placement was feasible in 92.8% of the 14 patients (n=13). The overall success rate for endoscopic management was 78.5% (n=11). The median length of hospitalization after DPS placement was 5days (3-17). The average duration of drainage through a DPS was 62days (28-181). Five patients (35.7%) also underwent drainage with radiological guidance. Of the 10 patients with stoma, closure occurred in 80%. All patients that required adjuvant chemotherapy were able to receive it. The treatment of AL requires multidisciplinary collaboration to save the anastomosis. DPS placement under endoscopic control is associated with AL healing, good clinical tolerance and the ability to undergo chemotherapy and is an alternative to repeat laparotomy when radiological drainage is unfeasible or inefficient.