Ipsilateral mid-third clavicle fracture with grade V acromioclavicular joint dislocation

We report the case of a 20-year-old man with an ipsilateral mid-third clavicle fracture with grade V acromioclavicular joint (ACJ) dislocation. The combination of these two injuries is rare. A literature search produced various treatment algorithms. In this case, the patient was successfully treated with a Bosworth screw.This work was carried out in the Department of Orthopaedics, William Harvey Hospital, Ashford, Kent, UK     

Susceptibility of colistin-resistant pathogens to predatory bacteria

The increase in multidrug-resistant Gram-negative bacterial infections has forced the reintroduction of antibiotics such as colistin. However, the spread of the plasmid-borne mcr-1 colistin resistance gene have moved us closer to an era of untreatable Gram-negative infections. To evaluate whether predatory bacteria could be used as a potential therapeutic to treat this upcoming threat, the ability of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus to prey on several clinically relevant mcr-1-positive, colistin-resistant isolates was evaluated. No change in the ability of the predators to prey on free swimming and biofilms of prey cells harboring mcr-1 was measured, as compared to their mcr-1 negative strain.     

Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19

How to cite this article: Kumar A, Kumar N, Lenin D, Kumar A, Ahmad S. Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19. Indian J Crit Care Med 2021;25(4):474–475.

Sir,Itolizumab, an anti-CD6 humanized IgG1 monoclonal antibody, binds to domain-1 of CD-6 that is responsible for priming, activation, and differentiation of T-cells.^[1] It significantly reduces T-cell proliferation along with substantial downregulation of the production of cytokines/chemokines.¹ It was approved for moderate to severe chronic plaque psoriasis in 2013. However, it has recently been approved by the Drug Controller General of India for emergency use in India for the treatment of cytokine release syndrome in moderate to severe acute respiratory distress syndrome patients due to COVID-19.² Here, we report a case of life-threatening infusion-related hypersensitivity reaction of itolizumab.A 65-year-old male COVID-19 patient got admitted to the intensive care unit (ICU) with complaints of shortness of breath and cough without any history of known disease. However, the baseline electrocardiogram (ECG) done in the ICU was suggestive of left bundle branch block (LBBB) (Fig. 1A). The patient was supported through noninvasive ventilation (NIV) and was started on remdesivir, dexamethasone, low-molecular-weight heparin, antibiotics, and other supportive treatment as per our institutional standard protocol. The patient was maintaining on continuous positive airway pressure mode of NIV with a fraction of inspired oxygen (FiO₂) of 0.5 on the third day of ICU admission. Among the laboratory markers, the total leucocyte counts were raised (12,000/μL) with decreased lymphocytes (3.2%) and increased inflammatory markers (CRP, 320 mg/L; D dimer >20 μg/mL; LDH, 1694 U/L; IL6, 329 pg/mL). Serum electrolytes, renal function tests, liver function tests, and arterial blood gases were within acceptable limits. The patient was hemodynamically stable with a respiratory rate of 30 to 35/minute and a PO₂/FiO₂ ratio of 140. After taking informed written consent, inj. itolizumab was planned in this patient because of the increasing severity of the disease along with increased inflammatory markers. Inj. hydrocortisone 100 mg IV and inj. pheniramine 30 mg IV were given 30 minutes before itolizumab infusion. And 100 mg of itolizumab (Alzumab-L, Biocon Biologics) was diluted to 250 mL with normal saline and was started at 25 mL/hour. After about 20 minutes of infusion, the patient started complaining of shivering, sweating, and impending doom. The patient had sudden bronchospasm, and oxygen saturation dropped to 90%. ECG showed second-degree AV nodal block with an increased blood pressure of 180/110 mm Hg (Fig. 1B). The drug was immediately withdrawn and the patient was given a repeat dose of hydrocortisone and pheniramine along with other supportive measures. After sometime patients became alert and their respiratory symptoms were relieved. However, the second-degree heart block in ECG was persistent. ECHO was normal and troponin I was within normal limits while there was a slight increase in CPK-MB. The patient was observed closely and the ECG reverted to its previous state only after 24 hours. The patient was weaned from the ventilator in due course of time and put on face mask on the eighth day of stay.Open in a separate windowFigs 1A and B(A) Baseline ECG showing LBBB; (B) ECG showing second-degree AV nodal block after infusion reactionMost infusion reactions related to monoclonal antibodies are IgE mediated and are mild (grade 1 or 2) in nature.³ The incidence of severe (grade 3 or 4) reactions is generally low. The reported infusion-related reactions to itolizumab are chills/rigors (common), nausea, flushing, urticaria, cough, hypersensitivity, pruritus, rash, wheezing, dyspnea, oxygen desaturation, dizziness, headache, and hypertension. In our case, itolizumab infusion leads to a grade 4 reaction causing a persistent second-degree heart block for about 24 hours. Among the monoclonal antibodies, rituximab is most notorious for causing infusion reactions.⁴ There are only a few reports of cardiac arrhythmias (monomorphic VT, supraventricular tachycardia, trigeminy, and irregular pulse) during therapeutic infusion of rituximab,⁵ and there is no reported case of cardiac arrhythmia during itolizumab infusion. In our case, the patient was having LBBB and was on a QT prolonging drug (remdesivir), which might be a predisposing factor for the occurrence of second-degree heart block during infusion reaction. Premedications (e.g., antipyretics, antihistamines, and steroids) are recommended before the administration of some chemotherapeutic agents and monoclonal antibodies. These drugs should never be given as IV bolus and should always be given slowly in an infusion. Baseline assessments including vital signs and cognition should be documented carefully before the start of treatment and all the emergency equipment and drugs should be kept ready. Grade 3 and 4 reactions should be managed promptly with epinephrine, antihistaminics, and steroids along with other symptomatic supportive measures. As itolizumab is approved for emergency use in COVID-19, risk-benefit ratio should be assessed before prescribing this and should be explained before taking consent for infusion.The patient provided written informed consent for the publication.     

Leber hereditary optic neuropathy—new insights and old challenges

Graefe's Archive for Clinical and Experimental Ophthalmology - Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) disorder with the majority of...     

Chemometric Models for Quantification of Carbamazepine Anhydrous and Dihydrate Forms in the Formulation

Carbamazepine (CBZ) exists in anhydrous and dihydrate forms. These forms differ in their solubility, dissolution rate, and subsequently in their oral bioavailability. The objective of this study is to develop multivariate chemometric models for estimation of the low level of carbamazepine dihydrate (CBZ-DH) in the CBZ formulations containing excipients of the commercial formulation. The selected excipients were mixed in proportions to make sample matrices ranging from 0% to 50% CBZ-DH. Fourier transform infrared (FTIR), near infrared (NIR), and hyperspectral imaging data were mathematically pretreated before the development of partial least square and principal component analysis regression models. The developed partial least squares regression and principal component analysis models demonstrated predictability of CBZ and CBZ-DH by multiple scattering correction and standard normal variate processing methods. Among the spectroscopic techniques used the model performance parameters such as root-mean-square error, standard error, and bias were found to be low for NIR compared to FTIR. The treated data have shown better model fitting than without treatment, which was demonstrated by correlation coefficient of 0.9778, 0.9824, and 0.9852 for FTIR, NIR, and hyperspectral imaging, respectively. Furthermore, the predicted values were found to be very close to the selected low level of independent samples having 5% CBZ-DH in tablet formulation.     

Both homo and heterodimers of Marek's disease virus encoded Meq protein contribute to transformation of lymphocytes in chickens

Marek' disease virus serotype-1, also know as Gallid herpesvirus 2 (GaHV-2), elicits T-cell lymphomas in chickens. The GaHV-2 genome encodes an oncoprotein, Meq, with similarity to the Jun/Fos family of proteins. We have previously shown that Meq homodimers are not sufficient to induce lymphomas in chickens. In this study, we investigated the role of Meq heterodimers in the pathogenicity of GaHV-2 by generating a chimeric meq gene, which contains the leucine zipper region of Fos (meqFos). A recombinant virus containing the meqFos gene in place of parental meq, rMd5-MeqFos, was not capable of transforming chicken lymphocytes, indicating that heterodimerization of Meq alone is not sufficient for transformation. In addition, the recovery of the oncogenic phenotype by a recombinant virus encoding one copy each of MeqGCN (homodimer) and MeqFos (heterodimer) conclusively demonstrates that both homo and heterodimerization of Meq are required for oncogenesis.     

Mitigation of free radical toxicity in hyperoxaluric condition by a novel derivative eicosapentaenoate-lipoate

Lipoic acid (LA) and eicosapentaenoic acid (EPA) have been shown to ameliorate the changes associated with hyperoxaluria. This prompted us to study the effect of EPA-LA, a new derivative, in experimental urolithiatic condition. Foreign body implantation method followed by supplementation of ammonium oxalate was adopted to induce stone formation in the bladder. Significant depletion in the antioxidant status was observed in the kidney and bladder of stone-forming animals, associated with increased lipid peroxidation. The present observations provide supporting evidence to the hypothesis that free radicals might be involved in causing toxicity in hyperoxaluric condition. The three drugs, namely LA, EPA and EPA-LA had reversed the above changes, but the effect was more pronounced in EPA-LA-treated stone formers. These features highlight the beneficial effect of EPA-LA wherein the potency of two drugs has been combined. The practical outcome of these findings is that the cellular antioxidant defence can be increased by the supplementation of lipoate and its derivative EPA-LA.     

A simple K-wire cap

The authors describe a simple technique to cap sticking K-wires using plastic syringes readily available in the hospitals, that has not been described before.