Assessment of the health risks associated with heavy metal contamination in the groundwaters of the Leh district, Ladakh.

There has been a significant rise in cancer-related mortality in the Ladakh region during the past 10 years. The most common type of case is gastrointestinal cancer, which has been linked in theory by medical research to lifestyle factors, high altitude conditions, and the prevalence of Helicobacter pylori bacteria brought on by poor hygiene. Nevertheless, the precise cause of the rise in cancer cases is still unknown. Concurrently, there has been a significant change in Ladakh's water use practices due to development, improved basic utilities, and related vocational shifts. The local population has become increasingly reliant on groundwater since it provides a year-round, continuous water supply for home and agricultural uses. In this study, we assessed heavy metal contamination in groundwaters and associated human health risks. The results indicate that 46-96% of the groundwater samples have heavy metal pollution with a health hazard index > 1, which means using these groundwaters for drinking, food preparation, and agriculture is likely to result in carcinogenic and non-carcinogenic health hazards. The main heavy metal contaminants found in the groundwater of the Leh district include Cr, As, Hg, and U. According to the health risk assessment, 46-76% of the groundwater samples contain unsafe levels of Cr and As. Prolonged exposure to these levels is likely to cause gastrointestinal cancer in the local population. Acute to chronic exposure to U and Hg concentrations present in some groundwater samples is likely to result in various non-carcinogenic health risks.

Innovating Thiopurine Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis on DNA-Thioguanine Nucleotides (DNA-TG) as an Inclusive Biomarker in Thiopurine Therapy.

BACKGROUND AND OBJECTIVE: Thioguanine (TG), azathioprine (AZA), and mercaptopurine (MP) are thiopurine prodrugs commonly used to treat diseases, such as leukemia and inflammatory bowel disease (IBD). 6-thioguanine nucleotides (6-TGNs) have been commonly used for monitoring treatment. High levels of 6-TGNs in red blood cells (RBCs) have been associated with leukopenia, the cutoff levels that predict this side effect remain uncertain. Thiopurines are metabolized and incorporated into leukocyte DNA. Measuring levels of DNA-incorporated thioguanine (DNA-TG) may be a more suitable method for predicting clinical response and toxicities such as leukopenia. Unfortunately, most methodologies to assay 6-TGNs are unable to identify the impact of NUDT15 variants, effecting mostly ethnic populations (e.g., Chinese, Indian, Malay, Japanese, and Hispanics). DNA-TG tackles this problem by directly measuring thioguanine in the DNA, which can be influenced by both TPMT and NUDT15 variants. While RBC 6-TGN concentrations have traditionally been used to optimize thiopurine therapy due to their ease and affordability of measurement, recent developments in liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have made measuring DNA-TG concentrations in lymphocytes accurate, reproducible, and affordable. The objective of this systematic review was to assess the current evidence of DNA-TG levels as marker for thiopurine therapy, especially with regards to NUDT15 variants. METHODS: A systematic review and meta-analysis were performed on the current evidence for DNA-TG as a marker for monitoring thiopurine therapy, including methods for measurement and the illustrative relationship between DNA-TG and various gene variants (such as TPMT, NUDT15, ITPA, NT5C2, and MRP4). PubMed and Embase were systematically searched up to April 2024 for published studies, using the keyword "DNA-TG" with MeSH terms and synonyms. The electronic search strategy was augmented by a manual examination of references cited in articles, recent reviews, editorials, and meta-analyses. A meta-analysis was performed using R studio 4.1.3. to investigate the difference between the coefficients (Fisher's z-transformed correlation coefficient) of DNA-TG and 6-TGNs levels. A meta-analysis was performed using RevMan version 5.4 to investigate the difference in DNA-TG levels between patients with or without leukopenia using randomized effect size model. The risk of bias was assessed using the Newcastle-Ottowa quality assessment scale. RESULTS: In this systematic review, 21 studies were included that measured DNA-TG levels in white blood cells for either patients with ALL (n = 16) or IBD (n = 5). In our meta-analysis, the overall mean difference between patients with leukopenia (ALL + IBD) versus no leukopenia was 134.15 fmol TG/µg DNA [95% confidence interval (CI) (83.78-184.35), P < 0.00001; heterogeneity chi squared of 5.62, I2 of 47%]. There was a significant difference in DNA-TG levels for patients with IBD with and without leukopenia [161.76 fmol TG/µg DNA; 95% CI (126.23-197.29), P < 0.00001; heterogeneity chi squared of 0.20, I2 of 0%]. No significant difference was found in DNA-TG level between patients with ALL with or without leukopenia (57.71 fmol TG/µg DNA [95% CI (- 22.93 to 138.35), P < 0.80]). DNA-TG monitoring was found to be a promising method for predicting relapse rates in patients with ALL, and DNA-TG levels are likely a better predictor for leukopenia in patients with IBD than RBC 6-TGNs levels. DNA-TG levels have been shown to correlate with various gene variants (TPMT, NUDT15, ITPA, and MRP4) in various studies, points to its potential as a more informative marker for guiding thiopurine therapy across diverse genetic backgrounds. CONCLUSIONS: This systematic review strongly supports the further investigation of DNA-TG as a marker for monitoring thiopurine therapy. Its correlation with treatment outcomes, such as relapse-free survival in ALL and the risk of leukopenia in IBD, underscores its role in enhancing personalized treatment approaches. DNA-TG effectively identifies NUDT15 variants and predicts late leukopenia in patients with IBD, regardless of their NUDT15 variant status. The recommended threshold for late leukopenia prediction in patients with IBD with DNA-TG is suggested to be between 320 and 340 fmol/µg DNA. More clinical research on DNA-TG implementation is mandatory to improve patient care and to improve inclusivity in thiopurine treatment.

Frequency of Low Cardiac Output Syndrome Following on Pump Coronary Artery Bypass Grafting Surgery and it's Association with Degree of Pre-operative Left Ventricular Dysfunction.

Background Low cardiac output syndrome (LCOS) is a serious complication after coronary artery bypass grafting (CABG) surgery. It is associated with 10 times to 17 times increase in mortality and markedly increase morbidity. Objective To find out the frequency of Low cardiac output syndrome following on pump coronary artery bypass grafting surgery, to determine the association of Low cardiac output syndrome with degree of pre-operative left ventricular dysfunction and to compare in hospital outcomes of coronary bypass surgery with and without low cardiac output syndrome. Method This prospective, descriptive study enrolled 200 patients who underwent on pump coronary artery bypass grafting surgery using antegrade St Thomas blood cardioplegia. Pre-operatively grouped into two groups consisting Group A of 100 patients with pre-operative left ventricular ejection fraction (LVEF) ≥ 40% and group B of 100 patients with pre-operative left ventricular ejection fraction (LVEF) < 40%. Post-operatively frequency of low cardiac output syndrome was compared between the groups and in-hospital outcomes were studied. Result The mean age of the patients in the study was 53.50±7.57 years. Male to female ratio was 1.8:1. Results showed overall frequency of low cardiac output syndrome was 21.5%. The frequency of LCOS was 15 vs 28% (p - 0.038) in patients with preoperative LV EF ≥ 40% and < 40% respectively. The outcomes of coronary artery bypass grafting surgery were stroke (3.82 vs. 30.23%, p - 0.001), acute kidney injury (5.09 vs. 23.25%, p - 0.001), respiratory failure (6.36 vs. 34.88%, p - 0.001), ICU stay days (4.75 ± 1.28 vs. 7.44 ± 4.66, p - 0.018), hospital stay days (9.56 ± 2.40 vs. 15.22 ± 3.89, p - 0.001) and mortality (4.45 vs. 32.55%, p - 0.001) in patients without and with low cardiac output syndrome respectively. Conclusion The frequency of low cardiac output syndrome following coronary artery bypass surgery is 21.5%. Left ventricular dysfunction pre-operatively is associated with high frequency of low cardiac output syndrome following surgery. There is significantly poor outcome of coronary artery bypass surgery with low cardiac output syndrome in terms of stroke, respiratory failure, acute kidney injury, mortality and significant ICU stay, hospital stay in compare to patients without low cardiac output syndrome.

Estimation of External Contamination and Exposure Rates Due to Fission Product Release.

In the event of a radiological incident, the release of fission products into the surrounding environment and the ensuing external contamination present a challenge for triage assessment by emergency response personnel. Reference exposure rate and skin dose rate calibration data for emergency response personnel are currently lacking for cases where receptors are externally contaminated with fission products. Simulations were conducted to compute reference exposure rate coefficients and skin dose rate coefficients from photon-emitting fission products of radiological concern. To accomplish this task, simplified mathematical skin phantoms were created using surface area and height specifications from International Commission on Radiological Protection Publication 89. Simulations were conducted using Monte Carlo radiation transport code using newborn, 1-y-old, 5-y-old, 10-y-old, 15-y-old, and adult phantoms for 22 photon-emitting radionuclides. Exposure rate coefficient data were employed in a case study simulating the radionuclide inventory for a 17 × 17 Westinghouse pressurized water reactor, following three burn-up cycles at 14,600 MWd per metric ton of uranium. The decay times following the final cycle represent the relative activity fractions over a period of 0.5-30 d. The resulting data can be used as calibration standards for triage efforts in emergency response protocols.

Melanosis of bladder: A rare entity.

Melanosis of the bladder, also known as melanosis vesicae, refers to presence of pigment in bladder mucosa. A rare phenomenon, however, it can be confused with the primary or metastatic melanoma of the bladder. Therefore, knowledge of the entity can prevent over diagnosis of this benign entity. We are reporting a case of melanosis of bladder in a 69 year old male with prolonged history of LUTS and bladder diverticulae. Cystoscopic examination showed black patches and biopsy revealed pigmentation in the epithelium and underlying lamina propria. Special stains identified the pigment to be melanin. No malignant cells were identified.

Establishing a many-cytokine signature via multivariate anomaly detection.

Establishing a cytokine signature associated to some medical condition is an important task in immunology. Increasingly, large numbers of cytokines are used for signatures, via lists of reference ranges for each individual cytokine or ratios of cytokines. Here we argue that this common approach has weaknesses, especially when many different cytokines are analysed. Instead, we propose that establishing signatures can be framed as a multivariate anomaly detection problem, and hence exploit the many statistical methods available for this. In this framework, whether or not a given subject's profile matches the cytokine signature of some condition is determined by whether or not the profile is typical of reference samples of that condition, as judged by an anomaly detection algorithm. We examine previously published cytokine data sets associated to pregnancy complications, brain tumours, and rheumatoid arthritis, as well as normal healthy control samples, and test the performance of a range of anomaly detection algorithms on these data, identifying the best performing methods. Finally, we suggest that this anomaly detection approach could be adopted more widely for general multi-biomarker signatures.

Testosterone, testosterone therapy and prostate cancer.

With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer. This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed. Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer. In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.

Testosterone therapy has positive effects on anthropometric measures, metabolic syndrome components (obesity, lipid profile, Diabetes Mellitus control), blood indices, liver enzymes, and prostate health indicators in elderly hypogonadal men.

To alleviate late-onset hypogonadism, testosterone treatment is offered to suitable patients. Although testosterone treatment is commonly given to late-onset hypogonadism patients, there remains uncertainty about the metabolic effects during follow-ups. We assessed the associations between testosterone treatment and wide range of characteristics that included hormonal, anthropometric, biochemical features. Patients received intramuscular 1,000 mg testosterone undecanoate for 1 year. Patient anthropometric measurements were undertaken at baseline and at each visit, and blood samples were drawn at each visit, prior to the next testosterone undecanoate. Eighty-eight patients (51.1 ± 13.0 years) completed the follow-up period. Testosterone treatment was associated with significant increase in serum testosterone levels and significant stepladder decrease in body mass index, total cholesterol, triglycerides and glycated haemoglobin from baseline values among all patients. There was no significant increase in liver enzymes. There was an increase in haemoglobin and haematocrit, as well as in prostate-specific antigen and prostate volume, but no prostate biopsy intervention was needed for study patients during 1-year testosterone treatment follow-up. Testosterone treatment with long-acting testosterone undecanoate improved the constituents of metabolic syndrome and improved glycated haemoglobin in a stepladder fashion, with no adverse effects.

Naturally occurring compounds acting as potent anti-metastatic agents and their suppressing effects on Hedgehog and WNT/ß-catenin signalling pathways.

Despite numerous remarkable achievements in the field of anti-cancer therapy, tumour relapse and metastasis still remain major obstacles in improvement of overall cancer survival, which may be at least partially owing to epithelial-mesenchymal transition (EMT). Multiple signalling pathways have been identified in EMT; however, it appears that the role of the Hedgehog and WNT/ß-catenin pathways are more prominent than others. These are well-known preserved intracellular regulatory pathways of different cellular functions including proliferation, survival, adhesion and differentiation. Over the last few decades, several naturally occurring compounds have been identified to significantly obstruct several intermediates in Hedgehog and WNT/ß-catenin signalling, eventually resulting in suppression of signal transduction. This article highlights the current state of knowledge associated with Hedgehog and WNT/ß-catenin, their involvement in metastasis through EMT processes and introduction of the most potent naturally occurring agents with capability of suppressing them, eventually overcoming tumour relapse, invasion and metastasis.

Is the daily use of vacuum erection device for a month before penile prosthesis implantation beneficial? a randomized controlled trial.

Patient concerns about penile length after penile prosthesis (PP) implantation for erectile dysfunction (ED) have significant impact on patients and their partners. In addition, corporal fibrosis is associated with difficult PP implantation. The preoperative use of vacuum erectile devices (VED) is an uncommon physical treatment for such concerns. Therefore, the current randomized controlled study assessed two outcomes: whether pre-operative VED use for a month before surgery would significantly increase flaccid stretched penile length (SPL) on the day of surgery, and facilitate easier corporal dilatation intraoperatively. Fifty-one patients scheduled for PP implantation for ED were randomized to either intervention group (pre-operative VED use; 10-15 min/day for ≥30 days; Group A; n = 25), or control group (no intervention; Group B; n = 26). A research assistant (blinded to the treatment assignments) recorded SPL at baseline (initial consultation) and on day of surgery. The surgeons performing the PP implantation (also blinded to the treatment assignments) provided subjective assessments of the ease of corporal dilatation. Baseline patient characteristics, demographics, and comorbidities were the same in both groups. Baseline measurements (SPL-1) were 10.71 ± 1.28 and 10.87 ± 1.26 cm in Group A and Group B, respectively; and the day of surgery measurements (SPL-2) were 11.50 ± 1.33 and 11.06 ± 1.34 cm in Group A and Group B, respectively. In terms of outcomes: mean SPL increase in Group A was significantly more by a mean of 0.80 ± 0.38 cm (p < 0.05) compared to Group B; and surgeons' subjective report of surgical ease indicated smoother corporal dilatation for Group A compared to Group B. VED use (10-15 min/day during the month prior to PP implantation) was associated with significantly increased SPL on day of surgery, and facilitated easier corporal dilatation intraoperatively. Future studies should examine the long-term outcomes of penile prosthesis implantation after pre-operative use of vacuum erectile devices.

Novel use of bioelectric impedence technique to detect alterations in body composition in advanced small cell lung cancer.

BACKGROUND: Malnutrition is frequent in lung cancer and is measured using various tools, including the novel bioelectric impedance technique for measuring body composition. However, the validation of this technique for assessing body composition in advanced small cell lung cancer (SCLC) is untested. METHODS: Forty-one treatment naïve patients (all males) and an equal number of age- and sex-matched controls were evaluated by anthropometric measurements of skinfold thicknesses and body composition parameters such as body fat%, fat mass, fat-free mass (FFM), and total body water (TBW). RESULTS: The mean (SD) age of the patient group was 55.7 (7.5) years, median pack-years was 20 (range, 0-80), and mean (SD) duration of symptoms was 152.6 (153.7) days. Median Karnofsky Performance Scale was 70 (range, 50-90). Majority of our patients (68.3%) were Stage IV followed by Stage III (31.7%). The percentage of patients with low, normal, and high body mass index (BMI) was 31.7%, 61%, and 7.3%, respectively. All components of body composition, i.e., body fat%, FFM, and TBW were significantly lower in patients compared to controls. However, the body composition in patients and controls with normal BMI was similar. The phenomenon of sarcopenia as a cause of cancer cachexia may explain these findings, whereas the combination of loss of body fat and lean body mass may lead to weight loss and reduced BMI. CONCLUSION: Our results indicate that body composition is markedly altered in Indian patients with advanced SCLC. The impact of these parameters on clinically relevant outcomes needs further evaluation.

Indian folklore medicine in managing men's health and wellness.

India is a home for a large variety of plants with remarkable medicinal and pharmacological value. Traditional medicine in the form of Ayurveda, Siddha and Unani has used many of these plants since ancient days for treating and curing various ailments of the body. When it comes to issues related to reproductive health, people still hesitate to discuss and/or accept it openly and hence look for alternate and natural remedies. The various tribal populations distributed across different parts of the country still use these plant extracts in various formulations for maintenance of good health. The medical utilities of several of these plants have been documented; however, there are many more, whose potential is yet to be explored. This review discusses the role of various plants grown in the Indian subcontinent that have been widely used in maintaining various aspects of reproductive health in men such as infertility, aphrodisiac, contraception, libido, sexually transmitted infections and reproductive tract cancers as well as in treating chronic disorders.

Comparison of nickel doped Zinc Sulfide and/or palladium nanoparticle loaded on activated carbon as efficient adsorbents for kinetic and equilibrium study of removal of Congo Red dye.

In this study, the efficiency of nickel doped Zinc Sulfide nanoparticle loaded on activated carbon (Ni-ZnS-NP-AC) and palladium nanoparticles loaded on activated carbon (Pd-NP-AC) for the removal of Congo Red (CR) from aqueous solution was investigated. These materials were fully identified and characterized in term of structure, surface area and pore volume with different techniques such XRD, FE-SEM and TEM analysis. The dependency of CR removal percentage to variables such as pH, contact time, amount of adsorbents, CR concentration was examined and optimum values were set as: 0.03g Ni-ZnS-NP-AC and 0.04g of Pd-NP-AC at pH of 3 and 2 after mixing for 22 and 26min for Ni-ZnS-NP-AC and Pd-NP-AC, respectively. Subsequently, it was revealed that isotherm data efficiency can be correlated Langmuir with maximum monolayer adsorption capacities of 286 and 126.6mgg(-1) at room temperature for Ni-ZnS-NP-AC and Pd-NP-AC, respectively. Investigation of correlation between time and rate of adsorption reveal that the CR adsorption onto both adsorbents followed pseudo second order and interparticle diffusion simultaneously.

Comparison of nickel oxide and palladium nanoparticle loaded on activated carbon for efficient removal of methylene blue: kinetic and isotherm studies of removal process.

Palladium nanoparticles (Pd-NPs) and nickel oxide nanoparticles (NiO-NPs) were synthesized and loaded on activated carbon (AC). This novel material successfully used for the removal of methylene blue (MB) dye from aqueous medium. Full characterization of both material using X-ray diffraction, transmission electron microscopy, scanning electron microscopy and Brunauer-Emmet-Teller analyses for Pd-NP show their high surface area (>1340 m(2)/g) and low pore size (<20 Å) and average particle size lower than 45 Å and for NiO-NP show their high surface area (>1316.1554 m(2)/g) and low pore size (<20 Å) and average particle size lower than 46 Å in addition to high reactive atom and presence of various functional groups. These unique properties make them possible for efficient removal of MB. In batch experimental set-up, optimum conditions for maximum removal of MB by both adsorbents were attained following searching effect of variables such as central composite design. The Langmuir isotherm was found to be highly recommended for fitting the experimental equilibrium data. The kinetic of adsorption of MB on both adsorbents strongly can be fitted by a combination of pseudo-second order and intraparticle diffusion pathway. The experimental result achieved in this article shows the superiority of Pd-NP-AC for MB removal than NiO-NP-AC, so the maximum adsorption capacities of Pd-NP-AC and NiO-NP-AC were 555.5 mg/g and 588.2 mg/g, respectively.

Immuno-pathomechanism of liver fibrosis: targeting chemokine CCL2-mediated HIV:HCV nexus.

Even in the era of successful combination antiretroviral therapy (cART), co-infection of Hepatitis C virus (HCV) remains one of the leading causes of non-AIDS-related mortality and morbidity among HIV-positive individuals as a consequence of accelerated liver fibrosis and end-stage liver disease (ESLD). The perturbed liver microenvironment and induction of host pro-inflammatory mediators in response to HIV and HCV infections, play a pivotal role in orchestrating the disease pathogenesis and clinical outcomes. How these viruses communicate each other via chemokine CCL2 and exploit the liver specific cellular environment to exacerbate liver fibrosis in HIV/HCV co-infection setting is a topic of intense discussion. Herein, we provide recent views and insights on potential mechanisms of CCL2 mediated immuno-pathogenesis, and HIV-HCV cross-talk in driving liver inflammation. We believe CCL2 may potentially serve an attractive target of anti-fibrotic intervention against HIV/HCV co-infection associated co-morbidities.

Successful immunotherapy of autoimmune cholangitis by adoptive transfer of forkhead box protein 3(+) regulatory T cells.

Treatment of primary biliary cirrhosis (PBC) has lagged behind that of other autoimmune diseases. In this study we have addressed the potential utility of immunotherapy using regulatory T cells (Treg ) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8(+) T cells from the dominant negative form of transforming growth factor beta receptor type II (dnTGF-ßRII) mice to recombination-activating gene (Rag)1(-/-) recipients. We then used this robust established adoptive transfer system and co-transferred CD8(+) T cells from dnTGF-ßRII mice with either C57BL/6 or dnTGF-ßRII forkhead box protein 3 (FoxP3(+) ) T cells. Recipient mice were monitored for histology, including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57BL/6 but not dnTGF-ßRII mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of action that explains the differential ability of C57BL/6 Treg versus dnTGF-ßRII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GARP), CD73, CD101 and CD103 and a functionally significant increase in interleukin (IL)-10 in Treg from C57BL/6 compared to dnTGF-ßRII mice. Our data reflect the therapeutic potential of wild-type CD4(+) FoxP3(+) Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC.

Autologous stem cell transplantation in severe treatment-resistant Crohn's disease: long-term follow-up of UK patients treated on compassionate basis.

BACKGROUND: Although autologous stem cell transplantation (ASCT) may achieve disease control in severe treatment-resistant Crohn's disease (CD), relapse is frequent, and there is little information regarding long-term outcomes in terms of response to subsequent treatments and complications of ASCT. DESIGN: Retrospective evaluation of UK patients treated on a compassionate basis from three UK tertiary centres. METHODS: We summarize long-term outcomes of six previously unreported patients with severe treatment-resistant CD treated with ASCT according to international guidelines between 2003 and 2009. Median duration of CD before ASCT was 14 (7-22) years. Following stem cell mobilization, patients were treated with high-dose cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (7.5 mg/kg) followed by ASCT. RESULTS: All patients tolerated ASCT with routine toxicities and no treatment-related mortality and are alive at 50-123 months post-ASCT. Clinical and endoscopic remissions of CD were confirmed at 3 months post-ASCT in five patients, although median time to next treatment for inflammatory disease was 10 months (range: 3-16 months). Subsequently, disease control was achieved with previously ineffective and newer treatments, with surgery performed predominantly for pre-existing fibrotic strictures. Two patients became independent of home total parenteral nutrition (TPN). Reported late complications of ASCT included hypothyroidism and ovarian failure. CONCLUSION: Long-term follow-up supports the safety and feasibility of ASCT as a means of achieving short-term control of severe CD whilst potentially re-sensitizing the disease to medical therapy and reducing requirements for surgery and TPN. Given the inevitability of relapse, pre-emptive salvage and/or maintenance treatments post-ASCT should be the focus of future trials.