Report of consensus panel 2 from the 11th international workshop on Waldenström's macroglobulinemia on the management of relapsed or refractory WM patients.

The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.

Opsoclonus in scrub typhus.

Scrub typhus is a mite borne infectious disease caused by Orientia tsutsugamushi. It is a common cause of undifferentiated febrile illness in the Indian subcontinent. We present a case of scrub typhus with a rare ophthalmic manifestation.Our patient presented with fever and opsoclonus, was diagnosed to have scrub typhus and completely improved upon treatment. Opsoclonus complicates various medical diseases, including viral infections, toxin, encephalitis, brain tumors, and paraneoplastic syndromes. There has been only one previously reported case of opsoclonus in scrub typhus. This phenomenon highlights the increasingly complex presentation of common diseases. It also indicates there is much to be discovered about the immunopathogenesis of this infectious disease.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

Early PCR-negativity after allogeneic BMT in adults with t(4;11) ALL in the absence of acute or chronic GVHD.

Acute lymphoblastic leukaemia (ALL) with the t(4;11) translocation has a very poor prognosis following conventional chemotherapy. Many patients are offered an allogeneic BMT in first remission. We report on the impact of allogeneic BMT on three patients with t(4;11) ALL in first remission. Median age was 20 years. One patient received marrow from an HLA-identical sibling and the other two from unrelated donors. All three engrafted and none of the patients developed acute or chronic GVHD. Remission status was monitored using a sensitive nested RT-PCR to detect the ALL-1/AF-4 hybrid transcript. All three were PCR-negative at 3 months post-BMT. One of the unrelated recipients died of a fungal infection 4 months post-BMT. The other two are alive and in molecular remission at 21 and 24 months post-BMT. This is the first report of longitudinal follow-up of t(4;11) ALL post-allogeneic BMT by PCR. The early attainment of molecular remission in the absence of GVHD suggests that the conditioning regimen may have been more important than a graft-versus-leukaemia effect in these patients. Follow-up of larger numbers of patients will be required to confirm these preliminary observations.

Gastrointestinal actions of buprenorphine: are different receptors involved?

The effects of buprenorphine on castor-oil-induced diarrhoea, gastrointestinal transit and ethanol-induced gastric lesions in rats were compared to the same effects of morphine. Like morphine, buprenorphine prevented castor-oil-induced diarrhoea. However, it has no effect on gastrointestinal transit per se but prevented the inhibitory action of morphine. While morphine protected against ethanol-induced gastric lesions, buprenorphine aggravated them. It is suggested that different types/subtypes of opioid receptors may be involved in the gastrointestinal actions of buprenorphine.

Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

OBJECTIVE: To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. DESIGN: A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. RESULTS: The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. CONCLUSION: Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

Clopidogrel: a novel antiplatelet agent.

Clopidogrel is a novel antiplatelet agent that has a different mechanism of action to aspirin. Clopidogrel is chemically related to ticlopidine, both of which are more effective than aspirin in preventing some thrombotic events, but it has a safer side-effect profile than ticlopidine. It is likely to add to the antithrombotic armoury and reduce vascular mortality and morbidity more than current therapies.

Multidisciplinary bedside notes: an experiment in care.

An experimental system of multidisciplinary medical records was introduced in an elderly ward at St George's Hospital, London. The new-style notes improved multidisciplinary communication in goal-setting and care-planning and, by placing the record at the foot of the patient's bed, brought the focus of patient care to the patient's bedside. Major difficulties included duplication of paperwork, refiling after discharge and the matter of confidentiality. All the members of the multidisciplinary team were in favour of continuing the system, however, and recommended its use in other wards.

Severe methemoglobinemia due to ingestion of toxicants.

BACKGROUND: Toxin-induced methemoglobinemia is seen in poisoning with oxidizing agents. We report the clinical features and outcome of patients admitted with severe methemoglobinemia due to intentional ingestion of toxicants. METHODS: In this observational case series, patients admitted with toxin-induced methemoglobinemia between September 2011 and January 2014 were identified from the institutional poisoning database. Clinical profile and outcome of patients with methemoglobin concentration greater than or equal to 49% is reported. RESULTS: Of the 824 patients admitted with poisoning, 5 patients with methemoglobin concentration greater than or equal to 49% were included. The implicated compounds were nitrobenzene, benzoylphenylurea, flubendamide and Rishab(TM). One patient refused to name the compound. All patients were managed in the intensive care unit. Altered sensorium [Glasgow coma scale (GCS) < 10] was common (80%); 2 patients presented with a GCS greater than 4. All patients manifested cyanosis, low oxygen saturation and chocolate-brown-colored blood despite supplemental oxygen therapy. The median methemoglobin concentration was 64.7% (range 49.8-91.6%); 2 patients had methemoglobin concentration greater than 70%. One patient needed inotropes. Four patients required mechanical ventilation for 4-14 days. All patients were treated with methylene blue; 4 received more than one dose. Three patients also received intravenous ascorbic acid 500 mg, once daily, for 3 days. Following treatment, there was evidence of haemolysis in all patients; 2 required blood transfusion. All patients survived. CONCLUSION: Patients with severe toxin-induced methemoglobinemia present with altered sensorium and cyanosis and may require ventilatory support and inotropes. Though methemoglobin concentrations greater than 70% are considered fatal, aggressive management with methylene blue and supportive therapy can lead to survival.

United Kingdom Myeloma Forum (UKMF) position statement on the use of bendamustine in myeloma.

Bendamustine is a unique bifunctional alkylating agent with promising activity in myeloma. Despite the increasing number of studies demonstrating its efficacy in both the upfront and relapse settings, including patients with renal insufficiency, the optimal use of bendamustine, in terms of dosage, schedule and combination with other agents, has yet to be defined. It is currently licensed for use as frontline treatment with prednisolone for patients with myeloma who are unsuitable for transplantation and who are contraindicated for thalidomide and bortezomib. Studies in relapsed/refractory patients are currently ongoing with other combinations. Given the increasing data to date, the UK Myeloma Forum believes that bendamustine with steroids alone or in combination with a novel agent could be considered for patients with multiply relapsed myeloma. This document provides guidance for the use of bendamustine for patients with myeloma until the results of definitive studies are available.

An unusual complication of an inferior dental nerve block: a case report.

Local anaesthetic drugs are commonly used in dental practice, with few complications. We describe an unusual complication of an inferior dental nerve block where, as the needle was advanced through the mucosa, the patient experienced profound numbness and skin pallor in the distribution of the infra-orbital nerve. We discuss the possible mechanism for this complication.