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Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high morbidity and mortality rates in haematopoietic cell transplantation (HCT) recipients. Factors like mucositis, neutropenia, prolonged hospital stay, and frequent use of prophylactic antimicrobials make HCT recipients especially susceptible to CRE infections. Low culture positivity rates, delay in microbiological diagnosis, and resistance to empirical antimicrobial therapy for febrile neutropenia are responsible for high mortality rates in HCT recipients infected with CRE. In this review we discuss the epidemiology, diagnosis, and management of CRE infections with particular emphasis on patients undergoing HCT. We emphasise the need for preventive strategies like multidisciplinary antimicrobial stewardship, and pre-emptive screening for CRE colonisation in prospective HCT patients as measures to mitigate the adverse impact of CRE on HCT outcomes. Newer diagnostic tests like polymerase chain reaction and matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) assay that enable earlier and better identification of CRE isolates are discussed. Antimicrobial agents available against CRE, including newer agents like ceftazidime-avibactam and meropenem-vaborbactam, have been reviewed. We also discuss the data on promising experimental treatments against CRE: phage therapy and healthy donor faecal microbiota transplant. Finally, this review puts forth recommendations as per existing literature on diagnosis and management of CRE infections in blood and marrow transplant (BMT) unit.

Paroxysmal nocturnal hemoglobinuria (PNH) presents with intravascular hemolysis, bone marrow failure and thrombosis. Various studies have reported geographic and ethnic variation in prevalence of thrombosis in PNH. There is limited data on thrombosis in PNH from the Indian subcontinent. In this study we describe disease burden and risk factors for thrombosis in 18 Indian PNH patients. We studied markers of thrombin generation (Thrombin-antithrombin complexes; TAT and D-Dimer), endothelium and platelet activation (soluble P-selectin) and inflammation (interleukin-6; IL-6) in PNH patients and compared their levels with healthy controls. Thrombosis was identified in 17% of PNH patients. TAT, sP-selectin and D-Dimer levels were significantly elevated in PNH patients (TAT: 5.06 ± 1.08 ng/ml; sP-selectin: 80.57 ± 19.5 ng/ml; D-Dimer mean: 936 ng/ml 95% CI 559, 1310) compared to control population (TAT: 3.39 ± 0.769 ng/ml P = 0.016; sP-selectin: 44.67 ± 5.17 ng/ml P = 0.002). Using Youden’s J statistic, the cut-off values for TAT and sP-selectin in our cohort of PNH patients were 2.90 ng/ml and 58.41 ng/ml respectively. TAT, sP-selectin and D-Dimer levels were elevated beyond the cut-off values in PNH patients with thrombosis compared to those without thrombosis. A positive correlation was noted between TAT, sP-selectin and D-Dimer levels. Increased TAT, sP-selectin, and D-Dimer levels may indicate impending thrombosis in PNH.

A 50-year-old woman presented with a right-sided isolated third cranial nerve palsy. MRI brain showed a mass lesion arising from the right clivus with extension into the cavernous sinus. Blood investigations and bone marrow biopsy were suggestive of multiple myeloma with hypercalcaemia and renal dysfunction. It was unclear at first if the intracranial lesion was due to myelomatous involvement or a separate disease entirely. The patient declined consent for a biopsy and cerebrospinal fluid analysis was inconclusive. She was treated with bortezomib based chemotherapy and the palsy resolved by day 6, which helped clinch the rare diagnosis of central nervous system (CNS) involvement by multiple myeloma. Most patients with CNS myeloma have a dismal survival of under 6 months but she is on therapy for relapse 26 months after diagnosis. While placed under the umbrella of CNS myeloma, patients with osteodural myeloma have better outcomes, perhaps due to their distinct aetiopathogenesis.

Context RHOAG17V mutation has been implicated in peripheral T-cell lymphomas (PTCL), characteristically angioimmunoblastic T-cell lymphomas (AITL). However, the association of the dominant-negative control with clinicopathological profile of the neoplasm is yet not clear. Objective To study the impact of RHOAG17V on the clinicopathological presentation and prognostication of T-follicular helper (TFH) cell-derived PTCL and PTCL-NOS. Design This was an ambispective study over six years (2015–2020), including 88 patients with diagnoses of PTCL-NOS (44), AITL (37), PTCL-TFH phenotype (P-TFH; 6), and follicular T-cell lymphoma (1) from the archives of Department of Pathology (AIIMS, New Delhi). Mutational analysis was performed using allele-specific polymerase chain reaction (PCR), validated by the sequencing of cloned products, along with conventional Sanger sequencing. Detailed clinicopathological correlation was done. Main Outcome Measures The association between the presence of mutation and diagnosis, clinical factors (demographics, performance status, organomegaly, IPI/PIT score, stage, marrow involvement), histologic and immunophenotypic presentation (pattern, high endothelial venules [HEV], immunopositivity for TFH markers [CD10, ICOS, PD1, BCL6, and others], CD30, and EBER ISH), and survival (overall and progression-free survival) was analyzed. Results RHOAG17V mutation was present in association with diagnosis of AITL (51.35%) in comparison to PTCL-NOS (25%) and P-TFH (16.67%; p-value=0.027). Sanger sequencing of conventional PCR did not yield any mutations, and the results were based on allele-specific PCR. Mutant cases of AITL had an overall worse performance status at presentation (p-value=0.045), along with a diffuse pattern of nodal involvement (p-value=0.046). Two diffuse large B-cell lymphoma-transformed cases harbored the mutation. Amongst the PTCL-NOS patients, immunopositivity for ICOS (p-value=0.045), along with the presence of increased HEV (p-value=0.035), was noted. None of these factors showed any association with P-TFH. On multivariate analysis, wild-type status predicted an inferior OS (p-value=0.029) in AITL, whereas no significant difference was noted in PFS. Mutation did not confer a survival advantage in PTCL-NOS or P-TFH. Conclusions RHOAG17V mutation, though not specific, shows an association with diagnosis of AITL and has been studied as a lineage-assigning marker for the TFH phenotype, as implicated by ICOS immunopositivity and HEVs in PTCL-NOS. Low variant allelic frequency could lead to false-negative results with conventional PCR products. Mutant status can have prognostic implications with translational relevance and requires larger cohorts for validation. Funding Thanks to Science Engineering Research Board and AIIMS Research section (SERB-EEQ/2016/402, AIIMS A-653).

The SARS-CoV-2 (COVID-19) pandemic is a worldwide public health emergency with widespread impact on health care delivery. Unforeseen challenges have been noted during administration of usual haematology care in these unusual COVID-19 times. Medical services have been overstretched and frontline health workers have borne the brunt of COVID-19 pandemic. Movement restrictions during lockdown prevented large sections of population from accessing health care, blood banks from holding blood drives, and disrupted delivery of diagnostic hematology services. The disruption in hematology care due to COVID-19 pandemic in India has been disproportionately higher compared to other subspecialities as hematology practice in India remains restricted to major cities. In this review we chronicle the challenges encountered in caring for hematology patients during the COVID-19 pandemic in India and put forth recommendations for minimizing their impact on provision of hematology care with special emphasis on hematology practice in lower and middle income countries (LMICs).

Despite improvements in leukemia therapy, acute myeloid leukemia (AML) remain a difficult disease to treat with a majority of patients having disease relapse without an allogeneic stem cell transpl...

The objective of this paper was to report on a case of steroid-responsive chorea in a patient with κ light-chain monoclonal gammopathy. In addition to subacute-onset generalized chorea, evidence of peripheral neuropathy in this elderly gentleman led us to investigate for paraproteinemia. We treated the patient with intravenous steroids in view of elevated κ light-chain assay and bone marrow biopsy, suggestive of monoclonal gammopathy of undetermined significance. There was a remarkable improvement of paresthesias and chorea at 6 months follow-up with no evidence of evolution to malignancy at 1 year. Autoimmune chorea is a treatable condition if identified and treated timely.

Context: Peripheral T-cell lymphomas derived from the mature T-cells are a heterogeneous group with varying biological and clinical behaviour. Objective: We analysed the epidemiological, clinical, histomorphological, immunophenotypic, and mutational characteristics of PTCLs in our centre. Design: This was a retrospective study including all cases of PTCL from 2015 to 2019 retrieved from the archive of Department of Pathology, AIIMS, New Delhi. The cases were reclassified according the WHO 2016 classification. Additional immunohistochemistry (PD1, ICOS, Bcl6 and CD10), EBERish, and mutational studies for IDHR172 and RHOA G17V) were done in cases diagnosed as PTCL-NOS and AITL. The clinical profile was correlated with the above factors and the prognostication index. Results: Of the total 441 lymphoma cases diagnosed of T-cell lineage, 35.37% were of the precursor type, and the rest were mature T-cell lymphomas. A male predominance was noted. PTCL-NOS was the most common subtype among the mature type (n=76; 17.23%) followed by ALCL, ALK+ (n=70; 15.87%), extranodal NK-/T-cell lymphomas (n=58, 13.15%), and AITL (n=16; 3.63%). They were dominant in the adult age (19–65 years, n=207), followed by pediatric and adolescents (n=43) and elderly (n=35) populations. The primary site of involvement was a mixture of nodal (n=138) and extranodal (n=147). The patients presented in advanced stages with a mean IPI score of 3/5. High LDH levels with direct Coombs test positivity was noted among AITL patients. With the help of immunohistochemistry, a few of the diagnosed PTCL-NOS were reclassified as AITL, and one of the diagnosed AITL was reclassified as PTCL with TFH phenotype. A few of the diagnosed AITL cases immunonegative for EBV-LMP1 proved their causal relationship with EBERish positivity. An overall mean survival of 20 months was noted among 30 cases with a maximal follow up of 3 years. Conclusions: A higher prevalence of immature cell neoplasm and ALCL was noted among the Indian population. Though morphologically there may be an overlap in the diagnosis among the various PTCL subtypes, immunohistochemistry and molecular studies can help in reaching the definite diagnosis. Funding: Thanks to the Science Engineering Research Board (EEQ/2016/402, ECR /2015/452) and All India Institute of Medical Science Research Section (A-653).

Introduction: Because of its functional and cosmetic importance, facial injuries, especially bony fractures are clinically very significant. Missed and maltreated fractures might result in malocclusion and disfigurement of the face, thus making accurate diagnosis of the fracture very essential. In earlier times, conventional radiography along with clinical examination played a major role in diagnosis of maxillofacial fractures. However, it was noted that the overlapping nature of bones and the inability to visualise soft tissue swelling and fracture displacement, especially in face, makes radiography less reliable and useful. Computed tomography (CT), also called as X-ray computed radiography, has helped in solving this problem. This clinical study is to compare three-dimensional (3D) CT reconstruction with conventional radiography in evaluating the maxillofacial fractures preoperatively and effecting the surgical management, accordingly. Materials and Methods: Fifty patients, with suspected maxillofacial fractures on clinical examination, were subjected to conventional radiography and CT face with 3D reconstruction. The number and site of fractures in zygoma, maxilla, mandible and nose, detected by both the methods, were enumerated and compared. The final bearing of these additional fractures, on the management protocol, was analysed. Results: CT proved superior to conventional radiography in diagnosing additional number of fractures in zygoma, maxilla, mandible (subcondylar) and nasal bone. Coronal and axial images were found to be significantly more diagnostic in fracture sites such as zygomaticomaxillary complex, orbital floor, arch, lateral maxillary wall and anterior maxillary wall. Conclusion: 3D images gave an inside out picture of the actual sites of fractures. It acted as mind’s eye for pre-operative planning and intra-operative execution of surgery. Better surgical treatment could be given to 33% of the cases because of better diagnostic ability of CT.

We report a 14-year-old girl who presented with subdural hematoma and a deranged coagulation profile suggestive of an inhibitor. Investigations revealed prothrombin deficiency along with positivity for antiphospholipid antibodies, which improved with steroid therapy. Bleeding diathesis in children and adolescents commonly results from thrombocytopenia, platelet function disorders, or coagulation factor deficiency; whereas bleeding because of coagulation factor inhibitors are extremely rare in this age group. This case also highlights the uncommon presentation of antiphospholipid antibody syndrome, as they often present with thrombosis or pregnancy complications rather than bleeding.

Acute monoblastic leukemia (AMoL) is a rare hematopoietic neoplasm, and simultaneous occurrence of acute monoblastic leukemia with chronic lymphocytic leukemia is very rare and only a few cases have been reported in the literature. We here report a rare case of dual hematological malignancy in an 85-year-old male. The peripheral blood and bone marrow examination revealed dual population of atypical cells, comprising large cells with opened-up chromatin having monocytic appearance and small mature-appearing lymphocytes. Flowcytometric immunophenotyping confirmed the monocytic lineage of cells, whereas small lymphocytes showed the immunophenotype consistent with chronic lymphocytic leukemia (CLL). The final diagnosis was made as acute monoblastic leukemia with associated CLL. This is a rare case scenario, and this highlights the importance of careful morphological examination and flowcytometric immunophenotyping in the exact characterization of hematopoietic malignancies.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal stem cell disorder. Eculizumab and bone marrow transplantation are disease-modifying treatments for PNH but may not be readily available in resource-constrained settings. Of 52 pediatric patients with PNH, 20 had classical PNH and 32 had PNH/aplastic anemia (PNH/AA). Median time to diagnosis was 30 months in classical PNH patients. Renal failure was present in four patients (20%). Six (30%) achieved complete response, 10 (50%) achieved partial response with androgens in classical PNH. Two underwent allogenic stem cell transplantation. In the PNH/AA group, 16 (50%) were in CR and seven (21%) were in PR with anti-thymocyte globulin ± cyclosporine.

We report a case of a 15-year old boy who was managed as a case of B cell lymphoblastic leukaemia with the modified BFM 90 protocol. During the induction phase, he developed febrile neutropenia with sino-pulmonary fungal infection confirmed on histopathology. He developed left sided hemiparesis during in-hospital management of febrile neutropenia. Neuroimaging revealed 9.6 × 8.4 mm round well defined aneurysm arising from right cortical artery in distal middle cerebral artery territory. He underwent fronto-temporo-parietal craniectomy with evacuation of the hematoma and excision of the aneurysm. Histopathological examination of excised aneurysmal specimen grew same species of fungus as was cultured from nasal scraping. He recovered fully in next 6 months with minimal residual focal neurological deficits. Presently he is in maintenance phase chemotherapy. We presented this case to illustrate a rare complication of ALL therapy with mycotic aneurysm secondary to invasive fungal infection treated successfully.

Background: Neutropenic sepsisis a major cause of induction mortality in acute leukemia. The estimated incidence in various series ranges from 12% to 36% 1-2. Carbapenem resistant enterobacteriaceae (CRE) colonization of the gut can increase the incidence of neutropenic sepsis to 50%3-4. In the present study we report the prevalence of CRE gut colonization and its impact on outcomes of remission induction chemotherapy in patients with acute leukemias. Primary Outcome: To compare induction mortality in patients with acute leukaemia who have CRE colonization of the gut at admission with a cohort of Non-CRE colonizer patients of acute leukemia receiving induction chemotherapy at our centre. Secondary Outcomes: Compare the durations of febrile period, antibiotic use and chemotherapy interruptions in CRE colonizers vs. Non-CRE colonizers. Methods: This is a prospective observational study. Institute ethics clearance was taken. Patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia(ALL) and mixed-phenotype acute leukemia(MPAL) who were admitted to our centre for remission induction chemotherapy from January 2017 to February 2018 were enrolled in our study. Perianal swab for diagnosing CRE colonization was taken at the time of admission. CRE were identified as per the Centre for Diseases Control (CDC) guidelines. On the basis of surveillance culture results patients were divided into cohorts of CRE-colonizers and Non-CRE-colonizers. These cohorts were followed up prospectively and parameters mentioned in primary and secondary outcome were recorded. Patients with probable and proven fungal infections as per EORTC criteria were excluded from our analysis. This was done in order to better dilineate the attributable cause of death to CRE infections. Results:A total of 136 patients with acute leukemia were enrolled in our study. Almost half of the patients (67) had acute myeloid leukemia (49%), sixty four (47%) patients had acute lymphoblastic leukemia and four (3%) patients had mixed-phenotype acute leukmeia. 61% of patients had CRE colonization of the gut at the time of admission. There was no significant difference with regards to median age at presentation, sex and the underlying disease (AML, ALL, MPAL) between the CRE colonizers and non-CRE colonizers. Escherichia coli (E.coli) was the most prevalent bacteria among CRE colonizers and non-CRE colonizers (63% vs. 71%, P=0.42). More patients in the CRE colonizer cohort did not receive remission induction chemotherapy due to life threatening sepsis at the time of presentation (15% vs. 5%, P=0.07). Chemotherapy interruptions due to life threatening sepsis were seen in a significantly higher numebr of CRE colonizers compared to non-CRE colonizers (32% vs. 18%, P=0.02). Induction deaths in CRE colonizers were almost double that seen in non-CRE colonizers (40% vs. 21%, P=0.01). There was no significant difference in duration of fever, duration of antibiotic use and blood culture positivity between the two cohorts. Conclusion:More than half of the patients with acute leukemia had CRE colonization of the gut at the time of presentation. Chemotherapy interruptions and deaths during induction were seen in a significantly higher number of patients colonized with CRE at the time of presentation. Patients with acute leukemia should be screened for CRE colonization of the gut prior to induction chemotherapy. This assumes importance is centres with high prevalence of CRE colonization as CRE colonisation of the gut is a predictor for induction mortality. References:J. de Naurois, I. Novitzky-Basso, M.J. Gill etal, Management of febrile neutropenia ESMO guidelines. Annals of Oncology, (2010) 21 (suppl_5): v252-v256Collin BA, Leather HL, Wingard JR etal, Evolution, incidence, and suspecitibility of bacterial blood stream isolates from 519 bone marrow transplant patients. Clin Ifect Dis. 2001:33(7):947-53Neil Gupta, Brandi M, Limbago et al, Carbapenem-Resistant Enterobacteriaceae: Epidemiology and Prevention, Healthcare Epidemiology, CID 2011:53 (1 July)Mathews, V., Srivastava, A., George, B., Korula, A., Perumalla, S., Abubacker, F. N., N, N. P., Devasia, A., Abraham, A., Balaji, V., & Lakshmi, K. M. (2016).Multi-Drug Resistant Organisms Are Common in Fecal Surveillance Cultures and Do Not Predict Bacteremia but Correlate with Poorer Outcomes in Patients Undergoing Allogeneic Stem Cell Transplants. Blood, 128(22), 3406 Disclosures Seth: Shire: Honoraria.

Hemicrania continua (HC)-like headache has been described with various intra- and extracranial pathologies. We describe a female patient with HC-like headache of 6-year duration with an epidermoid in cerebello-pontine angle, in whom indomethacin was successfully withdrawn after surgery. We also review the reports of various other symptomatic HC and compare with primary HC.

Dizziness and vertigo are frequently reported by patients with migraine. In migrainous vertigo (MV), vertigo is causally related to migraine. Patients of MV usually have an attenuated or absent headache with their vertigo as compared with their usual headache of migraine. Here we report three female patients of MV in which administration of triptan was associated with induction (two patients) or exacerbation (one patient) of headache with disappearance of vertigo. We suggest that headache and vertigo of migraine may be inversely related to each other and suppression of one may induce or aggravate the other.