Background: Fatigue significantly affects health-related quality of life (HRQoL) in patients with immune thrombocytopenia (ITP). However, the interplay between fatigue and cytokines in ITP remains poorly understood. Methods: This study included 100 patients with persistent or chronic ITP who had not received ITP-directed therapy in the previous 8 weeks and 50 age-matched healthy controls. Fatigue and HRQoL were assessed using the Functional Assessment of the Chronic Illness Therapy (FACIT) scale. Concurrently, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, and interferon-gamma (IFN-γ) were measured via enzyme-linked immunosorbent assay (ELISA). Results: ITP patients had significantly lower total FACIT scores [median 146 (range 59–160]) and fatigue subscale scores [median 45 (range 9–52]) than controls [155 (149–159) and 49 (44–52), respectively; both p < 0.001]. IL-12 levels were significantly elevated in patients (313.2 vs. 95.5 pg/mL; p < 0.001) and showed a significant negative correlation with FACIT scores (Spearman’s ρ = –0.272, p = 0.007). Multivariate analysis revealed that female sex, longer disease duration among patients with chronic ITP (> 24 months), and elevated IL-12 levels were independently associated with greater fatigue and poorer HRQoL. Conclusions ITP is associated with significant fatigue and HRQoL impairment, with IL-12 emerging as a potential immunological marker linked to this symptom burden.

This study highlights the use of levobupivacaine as a substitute for lignocaine in the treatment of two patients with documented adverse reactions to lignocaine. Lignocaine, the most widely used local anesthetic, can trigger allergies and other adverse effects.Allergic reactions can be mild, ranging from urticaria, erythema, and pruritus, to severe reactions in the form of angioedema and bronchospasm. In patients with a documented allergy to lignocaine, options for analgesia during nonsurgical rejuvenation include other amide-based local anesthesia, light sedation, or general anesthesia. Two patients with documented allergies to lignocaine underwent nonsurgical rejuvenation with levobupivacaine as the local anesthetic and reconstitution agent for Ellanse M. Levobupivacaine, chosen for its lower central nervous system and cardiovascular toxicity compared to those of racemic bupivacaine, has dual functions: local anesthesia and reconstitution of Ellanse. Ellanse is a collagen stimulator composed of polycaprolactone microspheres embedded in carboxymethylcellulose (CMC) gel distributed by Sinclair Pharmaceutical. It produces a natural aesthetic result through collagen stimulation. The 2 patients tolerated levobupivacaine as the choice of local anesthesia, with no adverse events. The reconstituted Ellanse was treated using a 27 G needle as well as a 25 G 50 mm cannula. The extrusion force was uniform and no needle or cannula jams were found. During 1-month assessment, the injected Ellanse volume decreased owing to resorption of the CMC gel, and during 3-month assessment, neocollagenesis was observed. Levobupivacaine is a suitable alternative to lignocaine as it enables patients with lignocaine allergies to undergo nonsurgical facial rejuvenation with Ellanse. Levobupivacaine offers comparable efficacy and safety profiles, making it a valuable option for anesthesia and reconstitution in such cases.Level of Evidence: Level V (Case Series)

Background/Aims: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. Results: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively. Conclusions Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Background/Aims: Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods: This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results: Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P= 0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P= 0.046) predicted response to EEN. Conclusions EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.

Background/Aims: Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods: This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results: Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P= 0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P= 0.046) predicted response to EEN. Conclusions EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.

The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread “prion like” via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.
Animals ; Anti-Bacterial Agents ; Biopsy ; Brain ; Brain Stem ; Cytokines ; Deglutition Disorders ; Dysbiosis ; Enteric Nervous System ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; In Vitro Techniques ; Inflammation ; Mesencephalon ; Mice ; Microbiota ; Neuroglia ; Neurons ; Parkinson Disease ; Probiotics ; Vagus Nerve

No abstract available.
Lung* ; Lymphoma*

PURPOSE: To compare the dose distribution of three-dimensional conformal radiation therapy (3DCRT) with intensity-modulated radiation therapy (IMRT) for post-mastectomy radiotherapy (PMRT) to left chest wall. MATERIALS AND METHODS: One hundred and seven patients were randomised for PMRT in 3DCRT group (n = 64) and IMRT group (n = 43). All patients received 50 Gy in 25 fractions. Planning target volume (PTV) parameters—Dnear-max (D2), Dnear-min (D98), Dmean, V95, and V107—homogeneity index (HI), and conformity index (CI) were compared. The mean doses of lung and heart, percentage volume of ipsilateral lung receiving 5 Gy (V5), 20 Gy (V20), and 55 Gy (V55) and that of heart receiving 5 Gy (V5), 25 Gy (V25), and 45 Gy (V45) were extracted from dose-volume histograms and compared. RESULTS: PTV parameters were comparable between the two groups. CI was significantly improved with IMRT (1.127 vs. 1.254, p < 0.001) but HI was similar (0.094 vs. 0.096, p = 0.83) compared to 3DCRT. IMRT in comparison to 3DCRT significantly reduced the high-dose volumes of lung (V20, 22.09% vs. 30.16%; V55, 5.16% vs. 10.27%; p < 0.001) and heart (V25, 4.59% vs. 9.19%; V45, 1.85% vs. 7.09%; p < 0.001); mean dose of lung and heart (11.39 vs. 14.22 Gy and 4.57 vs. 8.96 Gy, respectively; p < 0.001) but not the low-dose volume (V5 lung, 61.48% vs. 51.05%; V5 heart, 31.02% vs. 23.27%; p < 0.001). CONCLUSIONS: For left sided breast cancer, IMRT significantly improves the conformity of plan and reduce the mean dose and high-dose volumes of ipsilateral lung and heart compared to 3DCRT, but 3DCRT is superior in terms of low-dose volume.
Breast Neoplasms ; Heart ; Humans ; Lung ; Mastectomy, Modified Radical ; Radiometry ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Thoracic Wall ; Thorax ; Unilateral Breast Neoplasms

BACKGROUND/AIMS: The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed. METHODS: This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated). RESULTS: Of 69 patients (22 ulcerative colitis/47 Crohn’s disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5–48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0–84.5 weeks) of IFX. Of these 8 patients’ none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn’s disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation. CONCLUSIONS: There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX.
Colitis, Ulcerative ; Crohn Disease ; Follow-Up Studies ; Humans ; Incidence ; India* ; Inflammatory Bowel Diseases* ; Infliximab* ; Interferon-gamma Release Tests ; Latent Tuberculosis ; Male ; Mass Screening* ; Retrospective Studies ; Thorax ; Tuberculosis* ; Ulcer

BACKGROUND/AIMS: Familial occurrence of inflammatory bowel disease (IBD) is well documented. Reports from Western countries have shown a higher familial occurrence of ulcerative colitis (UC) in first- and second-degree relatives than that in the Asian UC population. No data are currently available from the Indian subcontinent in this regard. We present our data on the familial aggregation of UC. METHODS: Records of patients with UC followed at the Inflammatory Bowel Disease Clinic at the All India Institute of Medical Sciences, New Delhi from August 2004 to January 2016 were reviewed. Details regarding the prevalence of family history and characteristics of these patients were recorded. Affected family members were contacted and disease characteristics were noted for assessment of familial aggregation. RESULTS: Of the 2,058 UC patients included in the analysis, a positive family history of IBD was confirmed in 31 patients (1.5%), 24 (77.4%) of whom had only first-degree relatives affected. All the affected relatives had UC and none had Crohn's disease. Among first-degree relatives, siblings were found to have the highest prevalence of IBD (53.3%), followed by parents (26.7%). CONCLUSIONS: The probability of occurrence of IBD in family members of affected North Indian UC patients is lower than that reported in Western populations.
Asian Continental Ancestry Group ; Colitis, Ulcerative* ; Crohn Disease ; Humans ; India ; Inflammatory Bowel Diseases* ; Medical History Taking ; Parents ; Prevalence ; Siblings ; Ulcer*