Hematopoietic stem-cell transplantation in a zoo of multidrug-resistant organisms: Data from a cancer center in eastern India.

BACKGROUND: Infections by multidrug-resistant organisms (MDRO) are a major hurdle in hematopoietic stem-cell transplants (HSCTs). Conditioning regimens lead to mucosal barrier injury, which in-turn leads to transmigration of gut bacteria and sepsis. Pre-transplant stool and throat surveillance cultures can guide empirical antibiotic policy during the neutropenic period. In this paper, we document colonization with MDRO in pre-transplant surveillance cultures and the correlation with bloodstream infections in HSCT patients and analyze transplant outcomes with respect to these infections. METHODS: A single-center, retrospective study on HSCT was performed between January 2021 and December 2021. The incidence of bacterial infections, percentage of MDROs, correlation with pre-transplant stool/throat surveillance cultures, and their impact on overall 100-day and post-100-day to 6-month post-transplant survival were analyzed. RESULTS: Sixty-four patients were included in the study. Pre-transplant stool surveillance cultures were positive for MDRO in 85.9% of patients. Almost half (48.5%) of the isolates were positive for carbapenemase-producing genes (mainly New Delhi metallo-beta-lactamase-1 [NDM-1] and oxacillinase-48 [OXA-48]). Eighteen patients (18/64, 28%) had a positive blood culture for MDRO in the peri-engraftment neutropenic period. Correlation between surveillance and blood cultures was seen in 61% (11/18) of patients. All-cause mortality was 14.1% (9/64) and 25% (16/64) in patients at 100 days and 6 months post-HSCT, respectively. The 100-day and post-100-day all-cause mortality rates were higher in patients with Gram-negative MDRO bloodstream infections (p < .012 and <.008, respectively). CONCLUSION: MDRO infections can adversely affect HSCT outcomes. Pre-transplant stool and throat surveillance cultures may guide empirical antibiotic policy and lead to favorable transplant outcomes.

Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): a prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in India.

BACKGROUND: In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. METHODS: Patients 1-18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 109/L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. DISCUSSION: ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434 . Registered on 11 December 2015.

Comparison of Quality and Efficacy of Apheresis Platelets Stored in Platelet Additive Solution Vis a Vis Plasma.

PAS, by replacing part of the plasma in the platelet storage bag, reduces post transfusion allergic reactions and DHTR in the recipient. In this study we compared quality and efficacy of PAS and usual plasma stored platelets. Platelet concentration, content, MPV, pH, swirling, LDH and glucose concentration were tested in SDPs after preparation and on the day of transfusion; and compared between control (plasma-stored SDP) and study (PAS-stored SDP) groups. CCI was compared between the two groups. Transfusion reactions were also noted. In both groups quality parameters were similar except glucose [significantly decreased (p < 0.001) in plasma] and LDH [increased significantly (p: -0.005) in PAS]. CCI was similar in both groups. Transfusion reaction rate were 0.012% and 0.049% in both groups respectively. Quality and post-transfusion efficacy in both groups were similar. PAS stored platelets may be transfused in multi-transfused patients with allergic manifestations and in minor ABO incompatible transfusions.

Colistin susceptibility testing of gram-negative bacilli: Better performance of vitek2 system than E-test compared to broth microdilution method as the gold standard test.

Introduction: Unavailability of optimal susceptibility testing (ST) challenges the clinical use of colistin. Broth microdilution (BMD), which is the reference for colistin ST, is inconvenient for diagnostics. Vitek2 and E-test although technically easier, are no longer recommended. Materials and Methods: For the evaluation of Vitek2 and E-test in reference with BMD, a total of 138 Gram-negative bacilli (GNB) especially carbapenem-resistant isolates from Tata Medical Center, Kolkata, India, were included during 2017-2018. The evaluation was performed only for Enterobacteriaceae (n = 102), but not for non-fermentative GNB (n = 36) due to lack of colistin-resistant (COLR) isolates. Results and Conclusion: Of 138 isolates, meropenem, colistin and dual resistance were detected in 110 (79.7%), 31 (22.5%) and 21 (15.2%) of isolates, respectively. Using the European Committee on Antimicrobial Susceptibility Testing guidelines (susceptible, ≤2 µg/ml), Vitek2 performed better than E-test (essential agreement, 92.2% vs. 63.7%; categorical agreement, 94.1% vs. 93.1%; very major error [VME], 10% vs. 23.3%). However, Vitek2 overcalled resistance than E-test (major error, 4.2% vs. 0%). Considering Chew et al. proposed breakpoints (susceptible, ≤1 µg/ml), VMEs declined for both test (6.7% vs. 10%), but still remained unacceptable. Of eight colistin-heteroresistant isolates, two VME were categorised by Vitek2, one VME was by E-test, and two were uninterpretable. Both Vitek2 and E-test are unreliable. Further studies correlating minimum inhibitory concentrations with clinical outcome are needed to determine the accurate breakpoints for better patient management.

How do clinicians rate patient's performance status using the ECOG performance scale? A mixed-methods exploration of variability in decision-making in oncology.

BACKGROUND: Medical decisions made by oncology clinicians have serious implications, even when made collaboratively with the patient. Clinicians often use the Eastern Clinical Oncology Group (ECOG) performance status (PS) scores to help them make treatment-related decisions. METHODS: The current study explores the variability of the ECOG score when applied to 12 predetermined specially designed clinical case vignettes presented to a group of oncology clinicians (n = 72). The quantitative analysis included evaluation of variability of ECOG PS scores and exploration of rater and patient-related factors which may influence the final ECOG rating. In-depth interviews were conducted with oncology clinicians to ascertain factors that they felt were important while making treatment-related decisions. Basic and global themes were generated following qualitative data analysis. RESULTS: Quantitative results showed that there was poor agreement in ECOG rating between raters. Overall concordance with the gold standard rating ranged between 19.4% and 56.9% for the vignettes. Moreover, patients deemed to have socially desirable qualities (p < 0.004) were rated to have better PS and women patients (p < 0.004) to have worse PS. Clinicians having international work experience had increased concordance with ECOG PS rating. Qualitative results showed that 'perceived socio-economic background of the patient', 'age of the patient', 'patient's and family's preferences' and 'past treatment response' were the major themes highlighted by respondents that influenced the treatment-related decisions made by clinicians. CONCLUSION: There is considerable variability in ECOG PS determined by clinicians. Decision-making in oncology is complex, multifactorial and is influenced by rater and patient-related factors.

Ultrasonographic assessment of altered anatomical relationship between internal jugular vein and common carotid artery with supraglottic airway in children: LMA vs i-gel™.

BACKGROUND AND AIMS: Use of ultrasound (US) during internal jugular vein (IJV) cannulation reduces the risk of associated complications in children under general anaesthesia. We studied the effect of two varieties of supraglottic airway device (SGAD), the Ambu AuraOnce™ LMA (Ambu LMA), and i-gel™ on the anatomical relationship between IJV and common carotid artery (CCA). Both these SGAD are known to have similar safety profile in paediatric age group. METHODS: A total of 62 children were randomly allocated into 2 groups. In group L: Ambu AuraOnce™ LMA (Ambu LMA) and in group I: i-gel™ was inserted. After induction of GA, US images were taken with head in neutral and 30 degrees rotated to the opposite side both before and after insertion of SGAD. The relationship between IJV and CCA was noted as lateral, anterolateral, and anterior. Degree of overlap between the two vessels was also noted. RESULTS: Lateral rotation of the head significantly alters the relationship between the IJV and CCA and also increases the degree of overlap between them. Though these changes were noted to be similar with both varieties of SGAD, but between the two varieties of SGAD, these changes were significantly higher in group I. CONCLUSION: Higher oesophageal sealing pressure exerted by i-gel™ as compared to other SGAD might cause increased distortion of the surrounding soft tissue leading to altered anatomical relationship between IJV and CCA, which makes the CCA vulnerable to puncture during IJV cannulation using landmark technique.

Cytomegalovirus reactivation and disease amongst patients with allogeneic haematopoietic stem cell transplantation in Eastern India: Epidemiology, outcome and healthcare cost.

PURPOSE: Data from developing countries about incidence, prognosis and healthcare cost of cytomegalovirus (CMV) reactivation amongst patients with allogeneic hematopoietic stem cell transplantation (AHSCT) remain scarce. The purpose of the study was to describe the epidemiology, outcome and cost implications of CMV reactivation and CMV disease amongst patients with AHSCT in cancer hospital in Eastern India. MATERIALS AND METHODS: The study design was a retrospective audit of clinical records. RESULTS: Ninety-nine per cent of patients and 94% of the donors were found to be CMV seropositive. CMV reactivation rate was 43.8% amongst patients with AHSCT (n = 130 patients). CMV reactivation occurred 118 days after AHSCT (median; range: 28-943 days). Patients with any grade of graft-versus-host disease (GVHD) had higher CMV reactivation rate than patients without GVHD. Patients with CMV reactivation had more frequent GVHD than patients without CMV reactivation. Use of steroids was associated with CMV reactivation. We found no differences in overall survival of patients with or without CMV reactivation. The cost of in-house CMV-polymerase chain reaction at our centre was USD $57 (Rs. 3650), cost for intravenous ganciclovir was USD $26 (Rs. 1665) per infusion and oral valganciclovir USD $8 (Rs. 512)/900 mg tablet. The median duration of anti-CMV therapy was 14 days (interquartile range: 14-28 days) and the average cost per patient per month directed towards CMV management ranged between USD $800 and USD $1,300 (Rs. 51,238-Rs. 83,264). Three patients (2.3%) in this series had CMV disease, all of whom died. CONCLUSION: In an increasingly globalised world, where medical tourism is common, data from developing countries regarding cost and outcome of CMV infections in AHSCT patients are of relevance.

Metastatic Involvement of Lesser Sac in Advanced Epithelial Ovarian Cancer.

OBJECTIVES: In advanced epithelial ovarian cancer (AOC), lesser sac (LS) metastasis particularly to the supragastric LS (SGLS) may be overlooked, resulting in unrecognized residual disease. We aimed to identify the frequency, distribution, and predictors of LS metastasis using laparoscopic evaluation at laparotomy and perioperative surgical complications associated with evaluation and resection/ablation. METHODS: Prospective observational study in consecutive patients with AOC undergoing laparotomy for primary or interval cytoreductive surgery in 2 centers between November 2013 and December 2016. RESULTS: Of 182 AOC patients undergoing laparotomy, 150 were eligible for metastasis distribution analysis; 96/150 (64%) had LS metastasis with 90/150 (60%) involving the SGLS, including lesser omentum (47.3%), floor (42%), upper recess (24.6%), and caudate lobe (22.6%), with 62/90 (68.8%) being less than 1 cm in dimension. Of 144 undergoing cytoreductive surgery, 92 (64%) had LS metastasis, which was completely resected/ablated in 77/92 (83.6%).The strongest multivariate predictors of LS metastasis were involvement of Morison pouch (P < 0.001) and peritoneal cancer index of 17 or greater (P < 0.001). The LS metastasis was significantly associated with diaphragmatic surgery (84% vs 54%), cholecystectomy (33% vs 2%), splenectomy (50% vs 14%), retroperitoneal nodal metastasis (75% vs 49%), and surgical complexity score of 8 or higher (75% vs 35%). Morbidity related to treatment of LS metastasis was minimal. CONCLUSIONS: Lesser sac metastasis and SGLS metastasis are present in almost two thirds of cases of AOC and often small in size. Systematic exploration is necessary to detect and treat metastases to LS to prevent unrecognized incomplete cytoreduction.

Postoperative Delirium in Indian Patients Following Major Abdominal Surgery for Cancer: Risk Factors and Associations.

Postoperative delirium (POD) is not uncommon following major abdominal surgery with its incidence ranging between five and 51%. As cancer affects disproportionately, the population older than 65 years and as delirium is more common in the elderly, surgical oncology patients are at a higher risk of developing POD. The present study was undertaken to explore the impact and associations of POD in Indian patients undergoing oncological major abdominal surgery. A retrospective review of the electronic medical records in a tertiary cancer care institution of all postoperative patients who had undergone major gastrointestinal gynaecological and urological abdominal surgery for cancer and required psycho-oncology referral was performed. Patient, surgery and postoperative outcome-related data were collected. Statistical analysis was performed using univariate and multivariate logistic regression analysis. Out of 824 patients who underwent major abdominal surgery, 33 patients (4.0%) were diagnosed with POD. In univariate analysis, older age and history of addiction were found to be statistically significantly associated with POD (p < 0.001). Among the postoperative factors, respiratory complications (p < 0.001), sepsis (p < 0.05), ICU stay > 24 h (p < 0.05) and electrolyte impairment (p < 0.05) were the significant associations with the POD. Thirty-day mortality was higher in the POD group (p < 0.05). In multivariate logistic regression analysis, advanced age, addictions, respiratory complications and sepsis were found to be significant associations with POD, p < 0.001. Postoperative delirium is associated with higher mortality. Older age, postoperative respiratory complications and sepsis are common contributory factors of postoperative delirium.

Comparison of ultrasound imaging in transverse median and parasagittal oblique planes for thoracic epidurals: A pilot study.

BACKGROUND AND AIMS: The use of ultrasound (US) scanning to assess the depth of epidural space to prevent neurological complications is established in current practice. In this study, we hypothesised that pre-puncture US scanning for estimating the depth of epidural space for thoracic epidurals is comparable between transverse median (TM) and paramedian sagittal oblique (PSO) planes. METHODS: We performed pre-puncture US scanning in 32 patients, posted for open abdominal surgeries. The imaging was done to detect the depth of epidural space from skin (ultrasound depth [UD]) and needle insertion point, in parasagittal oblique plane in PSO group and transverse median plane in TM group. Subsequently, epidural space was localised through the predetermined insertion point by 'loss of resistance' technique and needle depth (ND) to the epidural space was marked. Correlation between the UD and actual ND was calculated and concordance correlation coefficient (CCC) was used to determine the degree of agreement between UD and ND in both the planes. RESULTS: The primary outcome, i.e., the comparison between UD and ND, done using Pearson correlation coefficient, was 0.99 in both PSO and TM groups, and the CCC was 0.93 (95% confidence interval [95% CI]: 0.81-0.97) and 0.90 (95% CI: 0.74-0.96) in PSO and TM groups respectively, which shows a strong positive association between UD and ND in both groups. CONCLUSION: The use of pre-puncture US scanning in both PSO and TM planes for estimating the depth of epidural space at the level of mid- and lower-thoracic spine is comparable.

Correlation of clinicopathological outcomes with changes in IHC4 status after NACT in locally advanced breast cancers: do pre-NACT ER/PR status act as better prognosticators?

BACKGROUND: Following neoadjuvant chemotherapy (NACT) for breast cancer, changes in estrogen receptor (ER), progesterone receptor (PR), HER2 status, and Ki-67 index (IHC4 status) and its correlation with pathological complete response (pCR) or relapse-free survival (RFS) rates could lead to better understanding of tumor management. PATIENTS AND METHODS: Pre- and post-NACT IHC4 status and its changes were analyzed in 156 patients with breast cancer. Associations between pCR, RFS rates to IHC4 status pre- and post-NACT were investigated. RESULTS: pCR was found in 25.3% patients. Both ER and PR positive tumors had the lowest (14.3%) pCR compared to ER and PR negative (29%) or either ER-/PR-positive (38.6%) tumors. PR positivity was significantly associated with less likelihood of pCR (15% versus 34%). The pCR rate was low for luminal A subtype (13.68%) compared to 24.36%, 26.31%, and 33.33% for luminal B, HER2-enriched, and triple-negative subtypes, respectively. There was significant reduction in ER expression and Ki-67 index post-NACT. RFS of patients in whom the hormonal status changed from positive to negative was better compared to those of patients in whom the hormonal status changed from negative to positive. CONCLUSION: Although changes in IHC4 occurred post-NACT, pre-NACT hazard ratio status prognosticated RFS better. pCR and RFS rates were lower in PR-positive tumors.

Evaluation of the pneumatic tube system for transportation of packed red cell units.

BACKGROUND: Pneumatic tube system (PTS) is commonly used in hospital settings to transport blood samples to diagnostic laboratories. At our blood center, we receive blood requisitions via the PTS, but units are carried to the ward by human courier. Recently we considered using the PTS for transporting blood units. Since, there are reports of hemolysis in blood samples sent through the PTS, we evaluated this system for transporting red cell units. AIMS: The aim was to assess the effect of PTS transport on the quality of packed red cell units. MATERIALS AND METHODS: A total of 50 red blood cells units (RBC), (25 non-irradiated and 25 irradiated) were subjected to transportation through the PTS. The control arm in the study was age-matched RBC units not subjected to PTS transport. Each RBC unit was evaluated for hemoglobin (Hb), lactate dehydrogenase, potassium and plasma hemoglobin (Hb). The paired t-test was used to compare these parameters, and the P value was calculated. RESULTS AND CONCLUSION: The percentage of hemolysis after transportation through PTS was below the recommended guidelines. Delivery of the blood unit to the wrong station, bags lying unattended at the destination were few of the problems that had to be addressed. To conclude, though the PTS is a safe means of transporting blood products with reduction in the turn-around-time, it must be validated before use.