Clinical significance of end of induction measurable residual disease monitoring in B-cell acute lymphoblastic leukemia: A single center experience.

The assessment of measurable residual disease (MRD) has emerged as a powerful prognostic tool for both pediatric and adult acute lymphoblastic leukemia (ALL). This retrospective study aimed to evaluate the prognostic relevance of the end of induction MRD in B-cell acute lymphoblastic leukemia (B ALL) patients. The study included 481 patients who underwent treatment for B ALL between August 2012 and March 2019 and had their MRD at the end of induction assessed by flow cytometry. Baseline demographic characteristics were collected from the patient's clinical records. Event free survival (EFS) and relapse free survival (RFS) were calculated using Kaplan-Meier analysis and survival estimates were compared using the log-rank test. End of induction MRD and baseline karyotype were the strongest predictors of EFS and RFS on multivariate analysis. The EFS was inversely related to the MRD value and the outcomes were similar in patients without morphological remission at the end of induction and patients in remission with MRD ≥1.0%. Even within the subgroups of ALL based on age, karyotype, BCR::ABL1 translocation and the treatment protocol, end of induction MRD positive patients had poor outcomes compared to patients who were MRD negative. The study outcome would help draft end of induction MRD-based treatment guidelines for the management of B ALL patients.

Low Serum Hepcidin Levels in Patients with Ulcerative Colitis - Implications for Treatment of Co-existent Iron-Deficiency Anemia.

Ulcerative colitis (UC) is often associated with anemia. Hepcidin, the central regulator of iron homeostasis, is known to be induced by inflammation and suppressed by anemia. It is not clear how hepcidin is affected in those with UC, when both inflammation and anemia may co-exist.Such knowledge may hold implications for treatment. Hematological and iron-related parameters, C-reactive protein (CRP), growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE) (erythroid regulators of hepcidin) levels were estimated in blood from those with UC and in control subjects. Values for hematological and iron-related parameters showed evidence of iron-deficiency and resultant anemia, in patients with UC. The presence of UC was significantly associated with inflammation. Serum levels of ERFE, but not of GDF-15, were significantly higher in patients with UC than in control patients, while hepcidin levels were significantly lower. Serum hepcidin concentrations in patients with UC correlated positively with serum iron, ferritin and GDF-15, and negatively with serum ERFE. The iron status and serum hepcidin levels in UC patients with co-existent anemia were significantly lower and serum ERFE values significantly higher than in those with UC without anemia. The effect of anemia on hepcidin predominated over that of inflammation in patients with UC, resulting in suppressed hepcidin levels. This effect is possibly mediated through erythroferrone. We suggest that a serum hepcidin-guided approach may be useful to guide use of oral iron supplements to treat co-existent iron-deficiency anemia in patients with UC and other chronic inflammatory diseases.

Effectiveness of GnRH Agonist Short Protocol Versus GnRH Antagonist Protocol in POSEIDON Groups 3 and 4: a Retrospective Cohort Study.

The aim of this study is to compare the ART (assisted reproductive technology) outcomes and cancellation rates between GnRH antagonist protocol and GnRH agonist short protocol in POSEIDON (Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number) groups 3 and 4. It is a retrospective cohort study conducted in the Department of Reproductive Medicine and Surgery of a tertiary-level hospital. Women who underwent ART treatment with either GnRH antagonist or GnRH agonist short protocol with fresh embryo transfer, between January 2012 and December 2019 belonging to POSEIDON 3 and 4 groups, were included. Among the 295 women who belonged to the POSEIDON groups 3 or 4, 138 women received GnRH antagonist and 157 women received GnRH agonist short protocol. The median total dose of gonadotropin in the GnRH antagonist protocol was not significantly different from GnRH agonist short protocol [3000, IQR (2481-3675) vs. 3175, IQR (2643-3993), p = 0.370]. There was a significant difference in the duration of stimulation between the GnRH antagonist and GnRH agonist short protocol [10, IQR (9-12) vs. 10, IQR (8-11), p = 0.002]. The median number of mature oocytes retrieved was significantly different in the cohort of women receiving GnRH antagonist protocol compared to GnRH agonist short protocol [3, IQR (2-5) vs. 3, IQR (2-4), p = 0.029]. There was no significant difference in the clinical pregnancy rate (24% vs. 20%, p = 0.503) and cycle cancellation rate (29.7% vs. 36.3%, p = 0.290) between the GnRH antagonist and agonist short protocols respectively. Live birth rate was not significantly different between the GnRH antagonist protocol (16.7%) and GnRH agonist short protocol (14.0%) [OR 1.23, 95% CI (0.56-2.68), p = 0.604]. After adjusting for the significant confounding factors, the live birth rate was not significantly associated with the antagonist protocol compared with the short protocol [aOR 1.08, 95% CI (0.44-2.63), p = 0.870]. Though GnRH antagonist protocol results in higher mature oocyte yield when compared with GnRH agonist short protocol, it does not translate into an increase in live birth in POSEIDON groups 3 and 4.

Survival outcomes of epithelial ovarian cancer treated at a tertiary-level hospital in India.

BACKGROUND: One needs to choose wisely between primary neoadjuvant chemotherapy and primary cytoreductive surgery in ovarian cancer. The aim was to determine the recurrence free survival and overall survival after surgery for epithelial ovarian cancer and also the risk factors for recurrence and death. METHODS: Electronic medical records of 322 women operated for ovarian, fallopian or primary peritoneal cancer between 2011 and 2015table were reviewed. Descriptive statistics were used to describe patients and their clinical outcomes. Cox proportional hazard models were used for risk factor analysis. Adjusted hazard ratios were obtained for recurrence and death, adjusted for stage, primary treatment modality, residual disease and histology. Kaplan-Meier curves were drawn for probability of recurrence-free survival and overall survival. The log rank test was used to compare survival probabilities. RESULTS: The majority were stage III or stage IV (78%), serous histology (71%) and high grade (64%). Primary cytoreduction was done in 48% and interval cytoreduction in 52%. The median duration of follow up (survival) was 77 months (95% CI 72-82). There were 179 known recurrences (55.6 %). The estimated median time to recurrence was 22 (95% CI 14.5- 29.5) months. The independent risk factors for recurrence were neoadjuvant chemotherapy [HR 2.14, 95% CI 1.48-3.09], stage III/IV [HR 2.75; 95% CI 1.40-5.41], high grade serous histology [HR 1.69; 95% CI 1.12-2.54] and sub-optimal debulking [HR 3.15, 95% CI 2.19-4.55]. There were 78 known deaths (24.2 %) with a mean time to death of 24.3 (SD 16.1) months. The independent risk factors for death were sub-optimal debulking [HR 3.07; 95% CI 1.78-5.29] and stages III and IV cancer [HR 3.07; 95% CI 1.14-8.27]. CONCLUSIONS: Most ovarian cancers recur within 2 years. Risk factors for mortality are advanced stage and sub-optimal debulking. Maximal efforts at down staging and surgical resection will increase survival.

Feasibility, safety and oncological outcomes of minimally invasive oesophagectomy following neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma - Experience from a tertiary care centre.

Background: Neoadjuvant chemoradiotherapy (nCRT) has improved the resectability and survival of operable oesophageal squamous cell carcinoma (OSCC). We aimed to study if nCRT for OSCC makes minimally invasive oesophagectomy (MIO) technically more challenging and if the peri-operative and oncological outcomes are acceptable for MIO following nCRT. Materials and Methods: A retrospective review of patients with OSCC (cT1-2N1-2, cT3-4aN0-2) treated with nCRT and MIO between 2013 and 2019 was performed. The operative details including the technical difficulty in tumour dissection and lymphadenectomy, the post-operative complications and oncological outcomes were studied. Results: Seventy-five patients (male:female - 50:25; mean [range] age - 55.49 ± 8.43 [22-72] years; stage II - 34.7%; stage III - 37.3%; stage IVA - 28.0%) were enrolled. The concurrent chemotherapy course was completed by 25.3% of patients and the most common reason limiting the completion of chemotherapy was neutropaenia (66.0%). A thoraco-laparoscopic (n = 60) or hybrid (n = 15) McKeown's oesophagectomy with a two-field lymphadenectomy was performed. The increased surgical difficulty was reported in 41 (54.7%) patients, particularly for mid-thoracic tumours and tumours exhibiting incomplete response. The 30-day overall and major complication rate was 48.0% and 20.0%, respectively, and there was no mortality. The rate of R0 resection, pathological complete response and median lymph nodal yield were 93.3%, 48% and 8 (range: 1-25), respectively. The mean overall survival (OS) was 62.2 months (95% confidence interval [CI]: 52.6-71.8) and recurrence-free survival (RFS) was 53.5 months (95% CI: 43.5-63.5). The 1-, 2- and 3-year OS and RFS were 89.5%, 78.8% and 64.4% and 71.1%, 61.3% and 56.6%, respectively. Conclusion: Minimally invasive McKeown's oesophagectomy is feasible and safe in patients with OSCC receiving nCRT. The radiation component of nCRT increases the degree of operative difficulty, especially in relation to the supracarinal dissection and lymphadenectomy. However, this drawback did not adversely affect the short-term surgical or the long-term oncological outcomes.

The clinical demand and supply of blood in India: A National level estimation study.

BACKGROUND: Estimating the clinical demand for blood and components arising in a health facility is crucial to ensure timely availability of blood. This study aims to estimate disease-specific clinical demand, supply and utilization of whole blood and components in India. METHODS: We conducted a national level cross-sectional study in five randomly selected states from five regions of the country. We included 251 public and private facilities representing primary, secondary and tertiary care facilities. We collected annual disease-specific demand, supply and utilization of blood and components using a structured tool. We estimated the national demand by extrapolating the study data (demand and beds) to the total number of estimated beds in the country. FINDINGS: According to the study, the total clinical demand of 251 health facilities with 51,562 beds was 474,627 whole blood units. Based on this, the clinical demand for India was estimated at 14·6 million whole blood units (95 CI: 14·59-14·62), an equivalent of 36·3 donations per 1,000 eligible populations, which will address whole blood and component requirement. The medicine specialty accounted for 6·0 million units (41·2%), followed by surgery 4·1 million (27·9%), obstetrics and gynecology 3·3 million (22·4%) and pediatrics 1·2 million (8·5%) units. The supply was 93% which is equivalent to 33·8 donations against the demand. CONCLUSION: The study indicated a demand and supply gap of 2.5 donations per 1,000 eligible persons which is around one million units. The gap emphasises the need for sustained and concerted efforts from all stakeholders and for increasing the awareness about repeat voluntary non-remunerated blood donation (VNRBD); optimizing the availability of blood components through efficient blood component separation units; promoting modern principles of patient blood management and strengthening capacities of human resources in the blood transfusion system in India.

Diagnostic Accuracy of Fluorescein Sodium for Targeted Cervical Biopsies.

BACKGROUND: Visual inspection methods for cervical cancer screening are widely used in low resource settings. Fluorescent sodium could improve accuracy of cancer screening. This study aimed to assess diagnostic accuracy of fluorescein sodium (FNa) to detect cervical neoplasia. METHODS: Seventy consecutive patients referred for colposcopy were enrolled prospectively. Acetic acid, Lugol's iodine, and FNa were used sequentially. Biopsies were taken from all abnormal areas. If there was no obvious abnormality, two random biopsies and endocervical curettage were done. Reference standard was the highest grade lesion on cervical biopsy with a threshold of CIN2+. The patterns of each staining agent were recorded as absent, faint, or distinct. Diagnostic accuracy estimates with 95% confidence intervals were calculated. Correlation between the various tests were also determined using the kappa statistic. RESULTS: There were 27 cases of CIN2+ (38.6%). The sensitivity of any fluorescence for CIN2+ was 82% (62, 94) and for distinct fluorescence was 59% (39, 78). The specificity was 65% (49, 79) for any fluorescence and 95% (84, 99) for distinct fluorescence, the same as for Swede score > 7. For any fluorescence, the positive likelihood ratio was 2.34 (1.5, 3.65) and the negative likelihood ratio was 0.28 (0.13, 0.65). For distinct fluorescence, the positive likelihood ratio was 12.74 (3.18, 51.1) and the negative likelihood ratio was 0.43 (0.27, 0.68). There was moderate correlation between FNa and the other tests. CONCLUSION: Distinct fluorescence with FNa was very specific, low cost, and easy to perform and may contribute to confirm CIN2+ disease.

Comparison of Clinical Outcomes With Drug Coated Balloons Versus Plain Balloon Angioplasty In Chronic Limb-Threatening Ischemia.

OBJECTIVE: The use of drug coated balloon (DCB) for angioplasty has shown superior efficacy against plain balloons for treating complex infrainguinal arterial disease. We report and compare the clinical outcomes following application of DCB(Paclitaxel) and plain angioplasty (POBA) in our tertiary care centre. METHODS: A retrospective, single centre analysis of 301 patients with chronic limb-threatening ischemia involving the infrainguinal segment was conducted between September 2014 and September 2018, after approval from the Institutional review board. We analyzed clinical outcomes by measuring postoperative ABI improvement, restenosis requiring reintervention procedure, minor and major amputations at the end of 18 months. . To find the association between the group variables (POBA and DCB) and other risk variables, Chi-square test/Fisher's exact test was used. Multivariable logistic regression analysis was used. RESULTS: Patients who underwent treatment with plain balloon (POBA) and DCB(Paclitaxel) angioplasty were 246(81.7%) and 55(18.3%) respectively. Our study group was predominantly male (Male: Female = 6.7:1), most patients were more than 50 years of age (n = 251, 83.4%). Smoking (n = 199, 66.1%) and diabetes (n = 210, 69.8%) were the most common atherosclerotic risk factors. Postoperative Ankle Brachial Pressure Index (ABI) improvement were similar in both groups (POBA = 57.7%; DCB = 69.8%; p = 0.103). Minor and major amputations following POBA were 26% and 22%; and DCB were 12.7% and 16.4% respectively. Re-stenosis requiring a re-interventional procedure within 18 months was 15%, (n = 37) following POBA; and 12.7% (n = 7) following DCB (p = 0.661). CONCLUSIONS: This retrospective study shows similar clinical limb related outcomes following POBA and DCB at 18 months. However, our comparative analysis between the POBA and DCB groups was totally unadjusted and not adjusted for common confounders such as age and sex. Hence, for one to draw definitive conclusions leading to changes in clinical practice; a randomized, prospective study with a larger patient cohort is needed.

A national level estimation of population need for blood in India.

BACKGROUND: The population need for blood is the total volume required to transfuse all the individuals who need transfusion in a defined population over a defined period. The clinical demand will arise when people with a disease or condition who require transfusion, access healthcare services, and subsequently the clinicians request blood. Essentially, the conversion of need to demand must be maximum to avoid preventable mortality and morbidity. The study estimated the population need for blood in India. METHODS: The methodology included a comprehensive literature review to determine the diseases and conditions requiring transfusion, the population at risk, and prevalence or incidence; and Delphi method to estimate the percentage of people requiring transfusion, and the quantum. RESULTS: The estimated annual population need was 26.2 million units (95% CI; 17.9-38.0) of whole blood to address the need for red cells and other components after the separation process. The need for medical conditions was 11.0 million units (95% CI:8.7-14.7), followed by surgery 6.6 million (95% CI:3.8-10.0), pediatrics 5.0 million (95% CI:3.5-7.0), and obstetrics and gynecology 3.6 million units (95% CI:1.9-6.2). The gap between need and demand which depends upon the access and efficiency of healthcare service provision was estimated at 13 million units. CONCLUSION: The study brings evidence to highlight the gap between need and demand and the importance of addressing it. It cannot be just the responsibility of blood transfusion or health systems, it requires a multi-sectoral approach to address the barriers affecting the conversion of need to clinical demand for blood.

Endoscopic Anterior Transposition of Ulnar Nerve (EATUN) for Treatment of Tardy Ulnar Nerve Palsy.

BACKGROUND: Tardy ulnar nerve palsy is the development of late onset ulnar nerve dysfunction and is usually treated by open anterior transposition of ulnar nerve. Open technique is done using a longitudinal incision about 6-8 inch. in length with chances of development of medial antebrachial cutaneous nerve neuromas. PURPOSE: In this study, we describe the technique of Endoscopic Anterior Transposition of Ulnar Nerve (EATUN procedure) to treat tardy ulnar nerve palsy and analyze the results. METHODS: Seven patients diagnosed to have tardy ulnar nerve palsy was treated by EATUN. The humerus-elbow-wrist angle (HEW), pre- and post-operative intrinsic muscle power and sensory assessment, Dellon scores, and the Q-DASH was analyzed. RESULTS: The minimum follow-up was 12 months (Mean 27.4 months, Range 12-36 months). Improvement in Dellon and Q-DASH scores following EATUN procedure was statistically significant. There was objective improvement of intrinsic muscle power and sensation on follow-up, though not statistically significant. No instance of neuroma of the medial cutaneous nerve of forearm was noted. CONCLUSIONS: The endoscopic anterior transposition of the ulnar nerve is a good option in surgical management of tardy ulnar nerve palsy. LEVEL OF EVIDENCE: Therapeutic Level IV. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43465-021-00366-w.

Myoepithelial Tumors of Salivary Gland: A Clinicopathologic and Immunohistochemical Study of 15 Patients with MIB-1 Correlation.

Myoepithelial neoplasms are rare tumors of the salivary glands with predominant myoepithelial differentiation and a broad histologic spectrum. Their histological features, immunohistochemical profile and biological behavior are not well characterized and pose a diagnostic challenge. A total of 15 myoepithelial tumors, diagnosed during 2012 and 2019 were subcategorized and correlated with MIB-1 labeling index (LI) and various histological parameters. Immunohistochemical stains for MIB-1 and other antibodies were performed. Statistical analysis was done by chi-square test, Fisher's exact test and Kaplan Meier curve. Nine patients were male and six were female with the median age of 44 years (range 21-83 years). Of the 15 patients, 6 cases were classified as myoepithelioma (ME) and 9 cases as myoepithelial carcinoma (MECA). Parotid gland was the most common site (46.7%) followed by the palate. MEs showed well circumscribed tumor borders whereas MECAs exhibited focal capsular to extensive invasion into adjacent tissues. Epithelioid cell morphology was most common followed by mixed cell morphology. MIB-1 LI was significantly associated with invasive tumor borders, necrosis and high mitosis. Increased frequency of recurrence was noted with high MIB-1 LI, though it was not statistically significant. MIB-1 LI was high in nearly all MECAs with focal capsular to extensive invasion while low in MEs. Myoepithelial tumor with multinodular growth pattern and focal capsular invasion may have an indolent behavior if mitotic activity and MIB-1 LI is low. Early diagnosis and treatment of MECAs significantly improves the patient's survival and prognosis.

Management of relapse in acute promyelocytic leukaemia treated with up-front arsenic trioxide-based regimens.

The standard of care for patients with acute promyelocytic leukaemia (APL) relapsing after front-line treatment with arsenic trioxide (ATO)-based regimens remains to be defined. A total of 67 patients who relapsed after receiving ATO-based up-front therapy and were also salvaged using an ATO-based regimen were evaluated. The median (range) age of patients was 28 (4-54) years. While 63/67 (94%) achieved a second molecular remission (MR) after salvage therapy, three (4·5%) died during salvage therapy. An autologous stem cell transplant (auto-SCT) was offered to all patients who achieved MR, 35/63 (55·6%) opted for auto-SCT the rest were administered an ATO + all-trans retinoic acid maintenance regimen. The mean (SD) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received auto-SCT versus those who did not was 90·3 (5·3)% versus 58·6 (10·4)% (P = 0·004), and 87·1 (6·0)% versus 47·7 (10·3)% (P = 0·001) respectively. On multivariate analysis, failure to consolidate MR with an auto-SCT was associated with a significantly increased risk of relapse [hazard ratio (HR) 4·91, 95% confidence interval (CI) 1·56-15·41; P = 0·006]. MR induction with ATO-based regimens followed by an auto-SCT in children and young adults with relapsed APL who were treated with front-line ATO-based regimens was associated with excellent long-term survival.

Prognostic plasma biomarkers of early complications and graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplantation.

Early complications post hematopoietic stem cell transplantation (HSCT) such as sinusoidal obstruction syndrome (SOS) and graft versus host disease (GVHD) can be life threatening. Although several biomarkers have been identified to correlate with these complications and their response to treatment, these are yet to be used in clinical practice. Here, we evaluated circulating endothelial cells (CECs) (n = 26) and plasma biomarkers (ST2, REG3α, VCAM1, ICAM1, TIM3) (N = 210) at early time points, to determine their association with early complications post-HSCT. Elevated CEC counts at the end of conditioning was associated with GVHD, indicating endothelial damage during HSCT. Plasma levels of REG3α, VCAM1, ICAM1, and TIM3 on day 14 (D14) and D14 ICAM1 and D28 ST2 were significantly higher in patients with SOS and aGVHD, respectively. Upon sub-group analysis, D28 ST2, D14/D28 REG3α, and D14ICAM1 levels were significantly higher in patients with gastrointestinal GVHD, while D28ST2 was higher in those with skin/liver GVHD. High ST2 levels on D28 was significantly associated with non-relapse mortality (NRM) and overall survival. Our results suggest that elevated ST2 levels on D28 could predict the likelihood of developing aGVHD and could influence NRM and OS.

Regular Low-Dose Oral Metronidazole Is Associated With Fewer Vesicovaginal and Rectovaginal Fistulae in Recurrent Cervical Cancer: Results From a 10-Year Retrospective Cohort.

PURPOSE: Anaerobic necrosis in cervical cancer can lead to malodor, fistulae, and treatment abandonment. In this retrospective cohort study, we examined the association between maintenance metronidazole and the incidence of malignant fistulae in recurrent cervical cancer. METHODS: We screened all cervical cancer records registered between 2007 and 2016 in the local palliative care database at Christian Medical College, Vellore, India. There were 208 eligible patients with post-treatment residual/recurrent pelvic disease. Among them, 76 had received oral maintenance metronidazole 200 mg once per day for 2 to 86 weeks (interquartile range, 4-16 weeks). RESULTS: Seventy-two patients developed at least one fistula. Forty-nine had vesicovaginal fistulae, 10 had rectovaginal fistuale, and 13 developed both types of fistulae. Patients on maintenance metronidazole had fewer fistulae (22.4% v 41.7%; P = .005), a longer median fistula-free survival (42.9 months v 14.1 months; P < .001), and a postrecurrence survival of 11.5 months versus 8.7 months (P = .112). We performed Cox multivariable proportional hazards regression analysis on the data from the subset of 146 patients observed until death. Bladder/rectal infiltration had a higher risk of fistula (HR, 5.24; P = .011), whereas distant metastases (HR, 2.46; P = .012) and Eastern Cooperative Oncology Group performance status greater than 1 (HR, 1.64; P = .008) were associated with a higher risk of death. Maintenance metronidazole was associated with a lower risk of fistula (hazard ratio [HR], 0.33; 95% CI, 0.16 to 0.67; P = .002) and a lower risk of death (HR, 0.56; 95% CI, 0.39 to 0.81; P = .002). CONCLUSION: Our data indicate that there is a significant inverse association between oral maintenance metronidazole and malignant fistulae in locally recurrent cervical cancer. The impact of this simple intervention on pelvic symptoms, fistulae, and survival should be evaluated in prospective studies.