Results from an expedited spinal nerve root block clinic at a UK tertiary neurosurgical centre.

STUDY DESIGN: Retrospective Observational Study. INTRODUCTION: Lumbar radicular pain has a prevalence of 3-5%. Level 1 evidence has demonstrated equivalence between surgical and injection treatment. We assess the outcomes from a transforaminal epidural steroid injection clinic in a tertiary neuroscience referral centre. METHODS: We performed an analysis of data from consecutive patients entered into a new internal referral database between August 2018 to May 2021. Radicular pain was classified as one of "first presentation" or "recurrence". Outcomes were obtained from follow up clinic letters and recorded in a binary manner of "positive result" or "negative result". Spinal pathology was documented from radiology reports and MRI images. RESULTS: We analysed 208 patients referred to the clinic. Excluding those who improved to a point of not requiring treatment, and those who underwent surgical intervention, 119 patients undergoing injection were included, of which 14 were lost to follow-up. 68 % of patients had a positive result from injection. Subgroup analysis demonstrated good outcomes for both hyperacute (<6 weeks) and chronic (>12 months). Contained disk pathologies had better outcomes than uncontained. There was no difference in outcomes across grades of compression, but previous same level surgery was associated with poorer response rates. CONCLUSIONS: There is a high rate of natural resolution of symptoms in patients with LSRP. In those where pain persists, TFESI is a valuable first line treatment modality. This study suggests the efficacy of TFESI is potentially independent of grade of stenosis and chronicity of symptoms. Contained disc pathologies respond better than uncontained.

Examining reuse and replacement procedures for Ipas manual vacuum aspiration and cannulae in nine countries.

OBJECTIVE: To determine how many times Ipas manual vacuum aspiration (MVA) instruments are reused, for what reasons, when the instruments are replaced and/or discarded, and what the barriers are to replacing them. METHODS: We conducted a mixed-methods cross-sectional study of health care providers who provide MVA services and key stakeholders in the supply chain to understand reuse and replacement of Ipas MVA aspirators and cannulae. Qualitative interviews focused on procurement and replacement of Ipas MVA instruments. RESULTS: The authors interviewed 352 health care providers from nine countries from 2019 to 2021. Providers reported reusing MVA instruments an average of 34.4 times (standard deviation, 45). The reuse averages ranged from one time (Democratic Republic of the Congo) to 500 times (India), with figures varying between providers within the same country. Instrument malfunctioning rather than a specific number of uses drove reuse and subsequent replacement. The decision to replace was most commonly made by the provider during use. Half of the providers said that they knew of no issues with the supply chain, and 85% said they were always able to replace Ipas MVA instruments when needed. CONCLUSION: Tracking reuse of MVA instruments was uncommon at participating providers' health facilities. Providers' estimates revealed great variability in reuse frequency and tracking procedures.

DNA methylome in pancreatic cancer identified novel promoter hyper-methylation in NPY and FAIM2 genes associated with poor prognosis in Indian patient cohort.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading cancers worldwide and has a poor survival, with a 5-year survival rate of only 8.5%. In this study we investigated altered DNA methylation associated with PDAC severity and prognosis. METHODS: Methylome data, generated using 450 K bead array, was compared between paired PDAC and normal samples in the TCGA cohort (n = 9) and our Indian cohort (n = 7). The total Indian Cohort (n = 75) was split into cohort 1 (n = 7), cohort 2 (n = 22), cohort 3 (n = 26) and cohort 4 (n = 20).Validation of differential methylation (6 selected CpG loci) and associated gene expression for differentially methylated genes (10 selected gDMs) were carried out in separate validation cohorts, using MSP, RT-PCR and IHC correlations between methylation and gene expression were observed in TCGA, GTEx cohorts and in validation cohorts. Kaplan-Meier survival analysis was done to study differential prognosis, during 2-5 years of follow-up. RESULTS: We identified 156 DMPs, mapped to 91 genes (gDMs), in PDAC; 68 (43.5%) DMPs were found to be differentially methylated both in TCGA cohort and our cohort, with significant concordance at hypo- and hyper-methylated loci. Enrichments of "regulation of ion transport", "Interferon alpha/beta signalling", "morphogenesis and development" and "transcriptional dysregulation" pathways were observed among 91 gDMs. Hyper-methylation of NPY and FAIM2 genes with down-regulated expression in PDAC, were significantly associated with poor prognosis in the Indian patient cohort. CONCLUSIONS: Ethnic variations among populations may determine the altered epigenetic landscape in the PDAC patients of the Indian cohort. Our study identified novel differentially methylated genes (mainly NPY and FAIM2) and also validated the previously identified differentially methylated CpG sites associated with PDAC cancer patient's survival. Comparative analysis of our data with TCGA and CPTAC cohorts showed that both NPY and FAIM2 hyper-methylation and down-regulations can be novel epigenetically regulated genes in the Indian patient population, statistically significantly associated with poor survival and advanced tumour stages.

Successful and unsuccessful recruitment and retainment strategies in a UK multicentre drug trial for a rare chronic pain condition which performed above target.

INTRODUCTION: Recruitment into trials in rare chronic pain conditions can be challenging, so such trials consequently are underpowered or fail. METHODS: Drawing from our experience in conducting, to date, the largest academic trial in a rare chronic pain condition, complex regional pain syndrome, we have identified recruitment and retention strategies for successful trial conduct. RESULTS: We present 13 strategies grouped across the categories of 'setting the recruitment rate', 'networking', 'patient information', 'trial management' and 'patient retention'. Moreover, six recruitment risks are also discussed. A conservative recruitment estimate, based on audits of newly referred patients to the trial centres without taking into account availability of 'old' patients or recruitment from outside centres, and assuming a 55% patient refusal rate yielded accurate numbers. CONCLUSION: Appreciation of these identified recruitment challenges and opportunities may contribute to supporting prospective investigators when they design clinical trials for chronic pain patient population groups where it has been historically difficult to conduct high-quality and robust clinical trials.

A novel hotspot and rare somatic mutation p.A138V, at TP53 is associated with poor survival of pancreatic ductal and periampullary adenocarcinoma patients.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5-2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now. METHODS: Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured. RESULTS: Among the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients. CONCLUSION: Detection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.

Differential methylation landscape of pancreatic ductal adenocarcinoma and its precancerous lesions.

BACKGROUND: Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality. In addition to having genetic causes, cancer can also be considered an epigenetic disease. DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor. In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma (PDAC), the epigenetic changes play a significant role. DATA SOURCES: Relevant studies for this review were derived via an extensive literature search in PubMed via using various keywords such as pancreatic ductal adenocarcinoma, precancerous lesions, methylation profile, epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest. The literature search was intensively done considering a time frame of 20 years (1998-2018). RESULT: In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions (pancreatic intra-epithelial neoplasia, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm and chronic pancreatitis) and PDAC along with the potential biomarkers. We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC. A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC (ppENK, APC, p14/5/16/17, hMLH1 and MGMT) are also documented. We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy. Epigenetic inactivation occurs by hypermethylation of CpG islands in the promoter regions of tumor suppressor genes. We listed all hyper- and hypomethylation of CpG islands of several genes in PDAC including its precancerous lesions. CONCLUSIONS: The concept of the review would help to understand their biological effects, and to determine whether they may be successfully combined with other epigenetic drugs. However, we need to continue our research to develop more specific DNA-demethylating agents, which are the targets for hypermethylated CpG methylation sites.

Drain in laparoscopic cholecystectomy in acute calculous cholecystitis: a randomised controlled study.

BACKGROUND: There is paucity of evidence regarding the role of drain in laparoscopic cholecystectomy (LC) in acute calculous cholecystitis (ACC), and surgeons have placed the drains based on their experiences, not on evidence-based guidelines. This study aims to assess the value of drain in LC for ACC in a randomised controlled prospective study. PATIENTS AND METHODS: All patients with mild and moderate ACC undergoing LC were assessed. Preoperatively, patients with choledocholithiasis, Mirizzi syndrome and biliary stent were excluded. Intraoperatively or postoperatively, patients with complications, partial cholecystectomies and malignancies were excluded. Patients were randomised using computer-generated random numbers into two groups at the end of cholecystectomy before closure. Requirement of radiologically guided (ultrasonography () or CT) percutaneous aspiration/drainage of symptomatic intra-abdominal collection or reoperation; continuation of parenteral antibiotics beyond 24 hours or change in antibiotics empirically or based on peritoneal fluid culture sensitivity; requirement of postoperative USG or CT scan based on postoperative clinical course; wound infection rates; postoperative pain using numeric rating scale at 6 and 24 hours; and the duration of hospital stay in both groups were noted. RESULTS: Forty-two out of 50 consecutive patients were randomised into two equal groups. Pain score at 6 and 24 hours was less in patients without drain. All other complication rates and duration of stay were similar in both groups. CONCLUSIONS: Drains should not be placed routinely after LC in ACC as it increases pain and does not help in detecting or decreasing complications.

Surgical Management of Cystic Duct Stump Stone or Gall Bladder Remnant Stone.

Retained calculi in the cystic duct or gall bladder remnant can present as a post-cholecystectomy problem. Increased suspicion is necessary to diagnose this condition in a symptomatic post-cholecystectomy patient. Ultrasonography usually detects this condition, but magnetic resonance cholangiopancreatography is the test of choice for diagnosis as well as for surgical planning. Laparoscopic re-excision of the stump in most cases is feasible and safe. It is increasingly becoming the treatment of choice.

Angiographic management of pseudoaneurysms of gastroduodenal artery following endoscopic sphincterotomy.

Gastrointestinal bleeding follows endoscopic sphincterotomy in 1 % to 10 % of patients. We report two cases of bleeding from pseudoaneurysms of the gastroduodenal artery occurring as a complication of endoscopic sphincterotomy.

Associations Between Abortion Services and Acceptance of Postabortion Contraception in Six Indian States.

Women receiving induced abortions or postabortion care are at high risk of subsequent unintended pregnancy, and intervals of less than six months between abortion and subsequent pregnancy may be associated with adverse outcomes. This study highlights the prevalence and attributes of postabortion contraceptive acceptance from 2,456 health facilities in six major Indian states, among 292,508 women who received abortion care services from July 2011 through June 2014. Eighty-one percent of the women accepted postabortion contraceptive methods: 53 percent short-term, 11 percent intrauterine devices, and 16 percent sterilization. Postabortion contraceptive acceptance was highest among women who were aged 25 years and older, received first-trimester services, received induced abortion, attended primary-level health facilities, and had medical abortions. Doctors receiving post-training support were more likely to offer contraceptives, but no association was observed between such support and acceptance of IUDs or sterilization. Comprehensive service-delivery interventions, including ensuring availability of skilled providers and contraceptive commodities, offering clinical mentoring for providers, identifying and addressing provider bias, and improving provider counseling skills, can increase postabortion contraceptive acceptance and reduce unintended pregnancy.

Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms.

Anandamide is a ligand of the endocannabinoid system. Animals show a depletion following repeated Δ(9)-tetrahydrocannabinol (THC) administration but the effect of cannabis use on central nervous system levels of endocannabinoids has not been previously examined in humans. Cerebrospinal fluid (CSF) levels of the endocannabinoids anandamide, 2-arachidonoylglycerol (2-AG) and related lipids were tested in 33 volunteers (20 cannabis users). Lower levels of CSF anandamide and higher levels of 2-AG in serum were observed in frequent compared with infrequent cannabis users. Levels of CSF anandamide were negatively correlated with persisting psychotic symptoms when drug-free. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use.

Quality of life in patients with lower limb ischemia; revised suggestions for analysis.

BACKGROUND: Quality of life (QoL) is a crucial outcome measure in patients with lower limb ischemia (LLI). The Short Form 36 (SF36) has been proposed as the gold standard instrument for generic QoL analysis in patients with LLI. The Short Form 8 (SF8) was developed from the SF36 and we aim to compare these two instruments in terms of validity, reliability, and responsiveness. METHODS: One hundred ninety-three patients, 135 men and 58 women, median age 66 (range, 44-84) years with LLI completed the SF36 and the SF8. Disease severity was graded according to International Society of Cardiovascular Surgery (ISCVS) suggested reporting standards. Correlation between the two instruments' like domains and non-like domains reflects convergent and divergent validity respectively. A subgroup of 58 patients (44 men) completed two sets of questionnaires, with an intervening period of 2 weeks. Correlation between these two sets of questionnaires was used to analyze test/retest reliability. Spearman's rank correlation was used to analyze validity and reliability. Responsiveness of the individual domains across the whole group was analyzed using the Kruskall-Wallis analysis of variance (ANOVA) test, while responsiveness between the groups of patients with varying severity of LLI was analyzed using the Mann-Whitney U test. RESULTS: There was greater correlation between like domains of SF36 and the SF8 than the non-like domains suggesting good convergent-divergent validity. Test/retest reliability was significant for both instruments (r(s) > 0.7). Increasing LLI resulted in a statistically significant deterioration in all eight domains of both instruments. The time taken was significantly shorter and less assistance was required to complete the SF8 than the SF36. CONCLUSION: The SF8 is a valid and reliable QoL instrument in patients with LLI, and as it is simpler and quicker to complete, we suggest it may challenge the SF36 as the gold standard generic QoL analysis instrument in LLI.

Nurse-led risk assessment/management clinics reduce predicted cardiac morbidity and mortality in claudicants.

Nurse-led assessment/management of risk factors is effective in many chronic medical conditions. We aimed to evaluate whether this finding was true for patients with intermittent claudication and to analyze its impact on patient-reported quality of life and predicted mortality due to coronary heart disease. We prospectively studied a series of 78 patients (51 men; median age, 65 years [IQR: 56-74 years]), diagnosed with intermittent claudication and referred to a nurse-led risk assessment/management clinic (NLC) from a consultant-led vascular surgical clinic. The NLC used clinical care pathways to manage antiplatelet medication, smoking cessation, hyperlipidemia, hypertension, and diabetes and to provide exercise advice. All patients were reassessed at a 3 months. Medication compliance, smoking status, fasting lipid profiles, blood pressure, and HbA1c were recorded. Disease-specific quality of life was assessed using King's College VascuQoL and predicted cardiac morbidity and mortality were calculated using the PROCAM and Framingham risk scores. We found that NLC enrollment produced an antiplatelet and a statin compliance of 100%, a smoking cessation rate of 17% (9 patients) and significant improvements in total cholesterol (median, 5.2-4.5 mmol/l), LDL (median, 3.1-2.5 mmol/l) and triglyceride (median, 1.7-1.4 mmol/l) levels. Significant disease-specific quality of life improvements and significant reduction in both the PROCAM (14% to 10%) and Framingham (14% to 11%) coronary risk scores were observed. Providing care at NLCs for claudicants is effective in assessing and managing risk factors, improves disease-specific quality of life and reduces predicted morbidity and mortality due to coronary heart disease.