Evaluation of a simple method for testing aztreonam and ceftazidime-avibactam synergy in New Delhi metallo-beta-lactamase producing Enterobacterales.

NDM-producing carbapenem-resistant bacterial infections became a challenge for clinicians. Combination therapy of aztreonam and ceftazidime-avibactam is a prudent choice for these infections. However, there is still no recommendation of a practically feasible method for testing aztreonam and ceftazidime-avibactam synergy. We proposed a simple method for testing aztreonam and ceftazidime-avibactam synergy and compared it with reference broth micro-dilution and other methods. Carbapenem-resistant Enterobacterales clinical isolates were screened for the presence of the NDM gene by the Carba R test. NDM harbouring isolates were tested for aztreonam and ceftazidime-avibactam synergy by broth microdilution (reference method), E strip-disc diffusion, double disc diffusion, and disc replacement methods. In the newly proposed method, the MHA medium was supplemented with ceftazidime-avibactam (corresponding to an aztreonam concentration of 4µg/ml). The MHA medium was then inoculated with the standard inoculum (0.5 McFarland) of the test organism. An AZT disc (30 µg) was placed on the supplemented MHA medium, and the medium was incubated overnight at 37°C. Aztreonam zone diameter on the supplemented MHA medium (in the presence of ceftazidime-avibactam) was compared with that from a standard disc diffusion plate (without ceftazidime-avibactam), performed in parallel. Interpretation of synergy was based on the restoration of aztreonam zone diameter (in the presence of ceftazidime-avibactam) crossing the CLSI susceptibility breakpoint, i.e., ≥ 21 mm. Of 37 carbapenem-resistant NDM-producing isolates, 35 (94.6%) were resistant to aztreonam and tested synergy positive by the proposed method. Its sensitivity and specificity were 97.14% and 100%, respectively. Cohen's kappa value showed substantial agreement of the reference method with the proposed method (κ = 0.78) but no other methods. The proposed method is simple, easily interpretable, and showed excellent sensitivity, specificity, and agreement with the reference method. Therefore, the new method is feasible and reliable for testing aztreonam synergy with avibactam in NDM-producing Enterobacterales.

Nitazoxanide refractory cryptosporidiosis complicating Burkitt lymphoma in a child.

Cryptosporidium species cause watery diarrhea in several vertebrate hosts, including humans. Most apparently, immunocompetent-infected individuals remain asymptomatic, whereas immunocompromised may develop severe or chronic cryptosporidiosis. We report here the case of a 6-year-old girl undergoing chemotherapy for Burkitt lymphoma who experienced multiple episodes of watery diarrhea during her hospital stay. Microscopic examination of her stool sample revealed oocysts of Cryptosporidium species. The rapid immunochromatographic test was also positive for Cryptosporidium species. She was treated with nitazoxanide for 3 weeks, which failed to provide both clinical improvement and parasitological clearance. This case highlights the importance of treatment failure in human cryptosporidiosis.

Dexamethasone-free antiemetic strategy for highly emetogenic chemotherapy: safety and efficacy-pilot study.

OBJECTIVES: Dexamethasone sparing strategies have shown success. The feasibility of a dexamethasone-free antiemetic strategy remains undetermined. A prospective, single-arm, pilot study was planned to determine the efficacy of an olanzapine-based, dexamethasone-free, three-drug antiemetic regimen. METHODS: Chemotherapy naïve, adult patients (≥18 years) who received ondansetron, aprepitant and olanzapine during the first cycle of highly emetogenic chemotherapy were enrolled. The primary endpoint was the rate of complete response (CR: no vomiting and no use of rescue medications) during the overall period (0-120 hours). RESULTS: Out of the total of 101 patients enrolled, most were women (82%) and received anthracycline cyclophosphamide (73%) combination therapy. The rate of CR for the overall period was 65% (95% CI 55.2% to 74.5%). The rate of CR for the acute and delayed period was 79% (95% CI 70% to 86.7%) and 76% (95% CI 66.7% to 84.1%). The rate of nausea control rates for the acute, delayed and overall periods were 34%, 29% and 24%, respectively. The grade I, II and III sedation rates over the 5 days were 8%, 5% and 1%, respectively. CONCLUSIONS: The dexamethasone-free antiemetic strategy showed modest efficacy with low incidence of clinically significant somnolence. There is a need to prospectively investigate the role of dexamethasone in the era of newer potent antiemetics in a randomised fashion. TRIAL REGISTRATION NUMBER: CTRI/2021/07/034813.

Unusual Male Breast Involvement in Burkitt Lymphoma Detected on Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Burkitt lymphoma (BL) is a poorly differentiated, aggressive form of B-cell non-Hodgkin's lymphoma. The clinical presentation of this disease is varied and may be nodal, extranodal, or both. BL of the breast, either primary or secondary, with bilateral breast involvement, is extremely rare. Herein, we present a case of BL in a 27-year-old male with unusual bilateral breast involvement.

Characteristics & outcomes of cancer patients with COVID-19: A multicentre retrospective study from India.

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

Oral metronomic chemotherapy is a cost effective alternative to pazopanib in advanced soft tissue sarcoma.

INTRODUCTION: Soft tissue sarcoma(STS) is a rare and heterogeneous group of disorders with dismal outcomes in metastatic setting. Pazopanib and oral metronomic chemotherapy (OMT) have been evaluated as therapeutic options in this cohort. MATERIALS AND METHODS: We conducted a retrospective, single center study evaluating 45 patients with unresectable and/or metastatic STS, who received pazopanib or oral metronomic regimen as per instituitonal protocol between January 2013 and December 2019. An informal cost minimisation analysis was conducted for both OMT and pazopanib arms, considering equivalent outcomes for both (PFS and OS). RESULTS: Median PFS in OMT and Pazopanib groups was 4.13 months and 3.53 months,respectively (HR1.31, 95% CI:0.68-2.51, p = 0.41) Only one patient in the OMT group achieved an objective response (partial response) and no objective response was noted in the pazopanib group. The incidence of grade III/IVtoxicities was higher with pazopanib than with OMT (p = 0.08). There were no toxicity related deaths noted in either arm. CONCLUSIONS: Our study demonstrates that OMT have a similar progression free survival (PFS) and overall survival (OS) in metastatic STS. This study raises the possibility that OMT might be an equally efficacious and less toxic alternative to pazopanib, without compromising survival outcome especially in LMIC.

Pazopanib in rare histologies of metastatic soft tissue sarcoma.

BACKGROUND: Uncommon histopathological subtypes account for less than 5% cases of soft tissue sarcoma (STS) and unclassified STSs comprise another 16%, these are often chemotherapy-resistant, with a dismal outcome in unresectable/metastatic disease. Prospective studies on the use of pazopanib in this cohort of patients are lacking in the literature. Here, we describe the safety and efficacy of pazopanib in rare histologies of advanced STS. MATERIALS AND METHODS: We conducted a retrospective study at two tertiary cancer centres in India, evaluating 33 cases of rare subtypes of STS, who received pazopanib as per institutional protocol between January 2013 and December 2019. Patients who received pazopanib for unresectable/metastatic disease were enrolled in this study for clinicopathologic features, treatment outcome and evaluation of prognostic factors. RESULTS: Out of 33 patients, there were seven cases of undifferentiated pleomorphic sarcoma, four cases each of myxofibrosarcoma, epithelioid sarcoma and malignant peripheral nerve sheath tumour, three cases each of haemangiopericytoma and spindle cell sarcoma, two cases of haemangioendothelioma and a case each of clear cell sarcoma, retroperitoneal sarcoma, angiosarcoma and pleomorphic rhabdomyosarcoma-adult type. The objective response rate was 27%. Most of the patients (67%) received pazopanib in second or subsequent lines of therapy. The majority (70%) were started at a lower dose of 400/600 mg and only 43% of these (10/23) could be escalated to a full dose of 800 mg based on tolerance. On univariate analysis, pazopanib's starting dose didn't predict progression-free survival (PFS)/overall survival (OS)/response rate. At a median duration of follow-up of 18.8 months (range 1.9-150.4 months), the median PFS and median OS were 10.3 months (95% confidence interval (CI): 5.9-14.8) and 17.8 months (95% CI: 10.7-29.3), respectively. 27% of the patients experienced grade ¾ toxicities, 12% required dose modification of pazopanib and 21% needed permanent discontinuation due to toxicity. CONCLUSION: Our study shows that pazopanib is active in rare subtypes of STS.

Utility and safety of maintenance chemotherapy in advanced non-small cell lung cancer across various performance status categories: real-world experience.

Maintenance chemotherapy (MC) with pemetrexed is a commonly used strategy in nonsquamous non-small cell lung cancer. However, most of the available evidence is from subjects with good performance status (PS), while data on the real-world utility and safety of this strategy in subjects with various categories of PS is limited. We performed a retrospective analysis of multicentric data of 3 centers from India. All patients with advanced nonsquamous non-small cell lung cancer who received MC with pemetrexed after induction chemotherapy were included. Subjects were divided into 2 groups based on baseline Eastern Cooperative Oncology Group score before initiation of induction chemotherapy as good PS (<2) and poor PS (≥2). Progression-free survival, overall survival, and toxicity were assessed in the study population. A total of 290 subjects were included in the study, of whom a significant proportion (n = 104, 35.9%) had poor PS. Survival was better in subjects with good PS as compared to those with poor PS (1-year progression-free survival: 43.5% vs 29.8%, P = 0.021; 1-year overall survival: 61.8% vs 48.1%, P = 0.023). Grade 3/4 toxicity was observed in 14.5% of subjects during MC and was not different between both groups (P = 0.287). Renal dysfunction was more common in subjects who received ≥10 cycles of MC (10.7% vs 4.2%, P = 0.040). MC with pemetrexed appeared to be beneficial and safe in the real-world setting regardless of the baseline PS. However, survival benefit was more pronounced in subjects with good PS at baseline. Renal dysfunction was more frequently encountered in subjects who received prolonged MC.

High-dose chemotherapy followed by autologous stem cell transplant for multiple myeloma: Predictors of long-term outcome.

Background & objectives: Survival of patients with multiple myeloma (MM) has improved in the past two decades following use of novel agents and autologous stem cell transplantation. To determine predictors of long-term outcome, data of MM patients who underwent autologous stem cell transplantation (ASCT) at a tertiary care centre in north India were retrospectively analyzed. Methods: Between 1995 and 2016, 349 MM patients underwent ASCT. Patients' median age was 52 yr, ranging from 29 to 68 yr, 68.2 per cent were males. Thirty three per cent patients had international staging system (ISS) Stage III and 68.5 per cent had received novel agents-based induction. High-dose melphalan (200 mg/m2) was used for conditioning; patients with renal insufficiency (estimated glomerular filtration rate <40 ml/min) received melphalan 140-150 mg/m2. Results: Post-transplant, 317 of 349 (90.8%) patients responded; complete [complete response (CR)] -213 (61%)], very good partial response (VGPR) -62 (17.8%) and PR in 42 (12%)]. Induction with novel agents, pre-transplant chemosensitive disease, transplant in first remission and serum albumin (≥3.5 g/dl) were predictors of significant response. At a median follow up of 73 months, median overall survival (OS) was 90 months [95% confidence interval (CI) 70.8-109.2], and progression-free survival (PFS) was 41 months (95% CI 33.0-49.0). On multivariate analysis, achievement of CR post-transplant, transplant in first remission, ISS Stages I and II (vs. III), absence of extramedullary disease and serum albumin ≥3.5 g/dl were predictors of prolonged OS. For PFS, achievement of post-transplant CR and transplant in first remission were predictors of superior outcome. Interpretation & conclusions: Treatment with novel agents, achievement of complete remission post-transplant, ISS Stages I and II, absence of extramedullary disease and transplant in first remission were predictors of long-term survival for patients with MM.

A Rare Occurrence of Simultaneous Venous and Arterial Thromboembolic Events - Lower Limb Deep Venous Thrombosis and Pulmonary Thromboembolism as Initial Presentation in Acute Promyelocytic Leukemia.

The development of acute myeloid leukemia has been attributed to various factors, including hereditary, radiation, drugs, and certain occupational exposures. The association between malignancy and venous thromboembolism events is well established. Here, we present a case of a 70-year-old Indian man who had presented with arterial and venous thrombosis, and the patient was later diagnosed with acute promyelocytic leukemia (APL). In our case, the patient presented with right lower limb deep venous thrombosis and pulmonary thromboembolism four months prior to the diagnosis of APL. Although thromboembolic event subsequent to the diagnosis of malignancy, and especially during the chemotherapy has been widely reported, this prior presentation with simultaneous occurrence of both venous and arterial thromboembolism has rarely been reported. We take this opportunity to state the significance of a complete medical evaluation in cases of recurrent or unusual thrombotic events.