Non Infectious Complications Related to Blood Transfusion: An 11 year Retrospective Analysis in a Tertiary Care Hospital

In India transmission of transfusion transmissible infections (TTI) has shown a relative decrease as a result of mandatory screening of donated blood for TTI’s. However, reducing the incidence of non infectious complications poses a major challenge, mainly due to the fact that a number of adverse reactions go unreported. Blood transfusion reaction, can be categorized based on the time interval between transfusion of blood products and the presentation of adverse reactions as acute i.e. those presenting during or within 24 h and as delayed i.e. those presenting anytime after 24 h. Transfusion reactions can further be classified as immune and non immune or infectious and non infectious based on the pathophysiology. In this retrospective study which was undertaken with an aim to determine the type and frequency of non infectious complications due to transfusion of blood and blood products recorded the incidence of febrile non hemolytic transfusion reactions (FNHTR) 51.40 %, allergic reactions 40.14 %, non immune hemolytic reactions 4.22 %, hypothermia 2.81 %, anaphylaxis 0.70 % and iron overload 0.70 %. FNHTR which was found to be the most common complication in this study can certainly be minimized, if not completely eliminated by adopting a policy of universal leucodepletion, the implementation of which solely depends on the financial and infrastructure resources available. This study also reiterates the importance of hemovigilance as a tool to improve the safety of blood transfusion.     

Paraganglioma of the Oropharynx

Paraganglioma is a rare tumor in head and neck region. A 35 years male presented with huge swelling of tonsillar region occupying a large portion of oropharynx. Tumor had been dissected out transorally. HPE showed extra-adrenal paraganglioma. It is being reported because of its rare clinical presentation and unusual surgical approach.     

Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu

Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies, including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.     

Beverage-induced enhanced bioavailability of carbamazepine and its consequent effect on antiepileptic activity and toxicity

The present study was undertaken to investigate the food–drug interaction of carbamazepine (CBZ). Common fruit juices [grapefruit juice (GFJ), lime juice (LJ)], known to inhibit the enzyme cytochrome P450 3A4 (CYP3A4), and some widely consumed beverages [milk (M), black tea (BT)] were involved in this study in the presence of CBZ, as might happen during clinical therapy. The effects of the beverages on the pharmacokinetics and drug-induced toxicity of CBZ was observed after concomitant administration for a period of 28 days. Accordingly, the influence of altered bioavailability of CBZ on its antiepileptic activity was investigated. A significant shift in the C_max as well as T_max of CBZ was observed in the presence of LJ and GFJ. This increase in bioavailability significantly enhanced hepatotoxicity and delayed the onset of tremor and piloerection against pentylene tetrazole (PTZ)-induced seizure in experimental animals. However, increased toxicity of CBZ was found to be absent with BT. Thus, from our observation, LJ or GFJ in the presence of CBZ significantly increased the bioavailability of CBZ, which might lead to increased toxicity and antiepileptic activity of the drug.     

2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells

2-Methoxyestradiol (2ME2) an estrogen derivative, induces growth arrest and apoptosis in leukemic cells and is also antiangiogenic. In this study, we demonstrate that 2ME2 inhibits growth and induces apoptosis in multiple myeloma (MM) cell lines and patient cells. Significantly, 2ME2 also inhibits growth and induces apoptosis in MM cells resistant to conventional therapies including melphalan (LR-5), doxorubicin (Dox-40 and Dox-6), and dexamethasone (MM.1R). In contrast to its effects on MM cells, 2ME2 does not reduce the survival of normal peripheral blood lymphocytes. Moreover, 2ME2 enhances Dex-induced apoptosis, and its effect is not blocked by interleukin-6 (IL-6). We next examined the effect of 2ME2 on MM cells in the bone marrow (BM) milieu. 2ME2 decreases survival of BM stromal cells (BMSCs), as well as secretion of vascular endothelial growth factor (VEGF), and IL-6 triggered by the adhesion of MM cells to BMSCs. We show that apoptosis induced by 2ME2 is mediated by the release of mitochondrial cytochrome-c (cyto-c) and Smac, followed by the activation of caspases-8, -9, and -3. Finally, 2ME2 inhibits MM cell growth, prolongs survival, and decreases angiogenesis in a murine model. These studies, therefore, demonstrate that 2ME2 mediates anti-MM activity directly on MM cells and in the BM microenvironment. They provide a framework for the use of 2ME2, either alone or in combination with Dex, to overcome drug resistance and to improve outcome in MM.     

Treatment of Partial Thickness Rotator Cuff Tears in Overhead Athletes

Purpose of Review

To review the etiology, classification, presentation, evaluation, treatment strategy, and outcomes in overhead athletes with partial thickness rotator cuff tears.

Recent Findings

Despite advances in surgical repair techniques, return to play following surgical repair of partial rotator cuff tears remains modest at best.

Summary

Overhead athletes may be particularly prone to rotator cuff pathology due to the supraphysiological strains within the tendon during the throwing motion, as well as mechanical stress with contact between the undersurface of the rotator cuff and the glenoid. The true prevalence of partial tears may be underestimated given the high incidence of asymptomatic tears. Both dynamic ultrasound and enhanced contrast MRI have improved our understanding of this pathology. For most overhead athletes, nonoperative management is the most common course. Despite advances in imaging, diagnosis, and surgical techniques, our ability to return these patients to their elite level is modest at best when nonoperative management fails and surgical treatment is performed. If a surgical route is needed, debridement alone is the most frequent procedure given concerns of over constraint and poor return to play with surgical repair of the partial thickness rotator cuff tear.

     

The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

     

Structural elucidation of NASICON (Na3Al2P3O12) based glass electrolyte materials: effective influence of boron and gallium

Understanding the conductivity variations induced by compositional changes in sodium super ionic conducting (NASICON) glass materials is highly relevant for applications such as solid electrolytes for sodium (Na) ion batteries. In the research reported in this paper, NASICON-based NCAP glass (Na_2.8Ca_0.1Al₂P₃O₁₂) was selected as the parent glass. The present study demonstrates the changes in the Na⁺ ion conductivity of NCAP bulk glass with the substitution of boron (NCABP: Na_2.8Ca_0.1Al₂B_0.5P_2.7O₁₂) and gallium (NCAGP: Na_2.8Ca_0.1Al₂Ga_0.5P_2.7O₁₂) for phosphorus and the resulting structural variations found in the glass network. For a detailed structural analysis of NCAP, NCABP and NCAGP glasses, micro-Raman and magic angle spinning-nuclear magnetic resonance (MAS-NMR) spectroscopic techniques (for ³¹P, ²⁷Al, ²³Na, ¹¹B and ⁷¹Ga nuclei) were used. The Raman spectrum revealed that the NCAP glass structure is more analogous to the AlPO₄ mesoporous glass structure. The ³¹P MAS-NMR spectrum illustrated that the NCAP glass structure consists of a high concentration of Q⁰ (3Al) units, followed by Q⁰ (2Al) units. The ²⁷Al MAS-NMR spectrum indicates that alumina exists at five different sites, which include AlO₄ units surrounded by AlO₆ units, Al(OP)₄, Al(OP)₅, Al(OAl)₆ and Al(OP)₆, in the NCAP glass structure. The ³¹P, ²⁷Al and ¹¹B MAS-NMR spectra of the NCABP glass revealed the absence of B–O–Al linkages and the presence of B₃–O–B₄–O–P₄ linkages which further leads to the formation of borate and borophosphate domains. The ⁷¹Ga MAS-NMR spectrum suggests that gallium cations in the NCAGP glass compete with the alumina cations and occupy four (GaO₄), five (GaO₅) and six (GaO₆) coordinated sites. The Raman spectrum of NCAGP glass indicates that sodium cations have also been substituted by gallium cations in the NCAP glass structure. From impedance analysis, the dc conductivity of the NCAP glass (∼3.13 × 10⁻⁸ S cm⁻¹) is slightly decreased with the substitution of gallium (∼2.27 × 10⁻⁸ S cm⁻¹) but considerably decreased with the substitution of boron (∼1.46 × 10⁻⁸ S cm⁻¹). The variation in the conductivity values are described based on the structural changes of NCAP glass with the substitution of gallium and boron.

Understanding the conductivity variations induced by compositional changes in sodium super ionic conducting (NASICON) glass materials is highly relevant for applications such as solid electrolytes for sodium (Na) ion batteries.