COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT: Implications of inflammatory findings in cancer imaging

We observed several patients presenting 2-[¹⁸F]FDG uptake in the reactive axillary lymph node at PET/CT imaging, ipsilateral to the site of the COVID-19 vaccine injection. Analog finding was documented at [¹⁸F]Choline PET/CT. The aim of our study was to describe this source of false positive cases. All patients examined by PET/CT were included in the study. Data concerning patient anamnesis, laterality, and time interval from recent COVID-19 vaccination were recorded. SUVmax was measured in all lymph nodes expressing tracer uptake after vaccination. Among 712 PET/CT scans with 2-[¹⁸F]FDG, 104 were submitted to vaccination; 89/104 patients (85%) presented axillary and/or deltoid tracer uptake, related to recent COVID-19 vaccine administration (median from injection: 11 days). The mean SUVmax of these findings was 2.1 (range 1.6–3.3). Among 89 patients with false positive axillary uptake, 36 subjects had received chemotherapy due to lymph node metastases from somatic cancer or lymphomas, prior to the scan: 6/36 patients with lymph node metastases showed no response to therapy or progression disease. The mean SUVmax value of lymph nodal localizations of somatic cancers/lymphomas after chemotherapy was 7.8. Only 1/31 prostate cancer patients examined by [¹⁸F]Choline PET/CT showed post-vaccine axillary lymph node uptake. These findings were not recorded at PET/CT scans with [¹⁸F]-6-FDOPA, [⁶⁸Ga]Ga-DOTATOC, and [¹⁸F]-fluoride. Following COVID-19 mass vaccination, a significant percentage of patients examined by 2-[¹⁸F]FDG PET/CT presents axillary, reactive lymph node uptake. Anamnesis, low-dose CT, and ultrasonography facilitated correct diagnosis. Semi-quantitative assessment supported the visual analysis of PET/CT data; SUVmax values of metastatic lymph nodes were considerably higher than post-vaccine lymph nodes. [¹⁸F]Choline uptake in reactive lymph node after vaccination was confirmed. After the COVID-19 pandemic, nuclear physicians need to take these potential false positive cases into account in daily clinical practice.     

Short Article The Use of Mercury against Pediculosis in the Renaissance: The Case of Ferdinand II of Aragon,King of Naples, 1467–96

The hair samples of Ferdinand II of Aragon (1467–1496), King of Naples, whose mummy is preserved in the Basilica of San Domenico Maggiore in Naples, showed a high content of mercury, with a value of 827ppm. Furthermore, examination using a stereomicroscope and a scanning electron microscope (SEM) of head and pubic hairs of Ferdinand II, revealed a lice infestation. The reasons for the massive presence of the mercury in the king''s hair are discussed and contemporary literature regarding the use of this metal in medical therapies and in cosmetic practices is analysed. As a result, the high value of mercury in the hair of Ferdinand II can be attributed to antipediculosis therapy, applied as a topic medicament. This case represents an important finding for the history of medicine, because demonstrates that in the Renaissance mercury was applied locally not only to treat syphilis, as well attested by direct and indirect sources, but also to prevent or eliminate lice infestation.     

Concealed Automaticity From an Island of Atrial Myocardium Post Cavotricuspid Ablation

Island of Atrial Myocardium Post Cavotricuspid Ablation. We report the case of a patient with paroxysmal atrial fibrillation in whom 2 previous cavotricuspid isthmus (CTI) ablations were performed for recurrent type I counterclockwise atrial flutter. One year after the last CTI ablation, the patient underwent pulmonary vein isolation for AF and reassessment of conduction block in the CTI was performed during the procedure. While mapping the CTI, activations were documented within the CTI that were dissociated from both right atrial and ventricular activity during sinus rhythm and pacing maneuvers. This dissociated activity was confined to a region delimited by the 2 previous ablation lines, the tricuspid annulus and the inferior vena cava. These findings suggest that an island of atrial myocardium with automatic activity was created within the CTI by previous ablation lines. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1408‐1409, December 2010)     

Cesium Abolishes the Barium-Induced Pacemaker Potential and Current in Guinea Pig Ventricular Myocytes

Cesium Abolishes Barium-Induced PM Current. Introduction: The ability of cesium to block barium-induced diastolic depolarization (“Ba-DD”) and pacemaker current was tested in isolated ventricular myocytes. Because Ba-DD is due to decreasing k conductance and there is no I_f at the resting potential, this approach permits verification of whether Cs⁺ is a specific blocker of I, or if it instead also blocks a K⁺ pacemaker current. Methods and Results: Guinea pig isolated ventricular myocytes were studied by a discontinuous, single electrode, voltage clamp method. During hyperpolarizing voltage clamp steps from -80 up to -140 mV in Tyrode's solution, the inward current increased as a function of voltage but did not change us a function of time (no I_f or K⁺ depletion). Cesium (4mM) reduced the current size during the hyperpolarizing steps hut did not induce or unmask time-dependent currents. Barium (0.05 to 0.1 mM) induced diastolic depolarization, and, in its presence, depolarizing voltage clamp steps were followed by an outward tail current that reversed at -92.0 ± 1.3 mV. Outward tail currents were larger at -50 mV than at the resting potential, and inward tail currents decayed more rapidly and to a larger extent during larger hyperpolarizing steps. In the presence of Ba²⁺, Cs⁺ (4 mM) had little effect on the steady-state current but markedly reduced or abolished undershoot, Ba-DD, and time-dependent tail currents at potentials both positive and negative to the resting potential. Cs⁺ had a smaller effect on the steady-state current-voltage (I-V) relation in the presence than in the absence of Ba²⁺, as part of the I_kl channels were already blocked by Ba²⁺ and the time-dependent changes induced by Ba²⁺ were not present. Both Ba²⁺ and Cs⁺ had little blocking effect on the steady-state current positive to the negative slope region of the I-V relation. Conclusion: In ventricular myocytes, Cs⁺ abolishes the Ba²⁺-induced pacemaker current by blocking the time-dependent change in K⁺ conductance, not by blocking I_f. Because Cs⁺ can also block a decaying K⁺ pacemaker current, the abolition of a pacemaker current by Cs⁺ in other cardiac tissues cannot be taken as unequivocal proof that the blocked current is I_f     

Prevention of Sudden Cardiac Death After a First Myocardial Infarction by Pharmacologic or Surgical Antiadrenergic Interventions

Antiadrenergic Interventions and Prevention of Sudden Death after MI. Introduction: Growing evidence points to sympathetic hyperactivity as one critical trigger for life-threatening arrhythmias among postmyocardial infarction patients. Methods and Results: We have evaluated, in a placebo-controlled multicenter study, the efficacy of a β-adrenergic blocking agent (oxprenolol 160 mg) and of a selective left cardiac sympathetic denervation in preventing sudden death in patients with a first and anterior myocardial infarction. Two patient groups were studied. The high-risk group included 144 patients who survived a myocardial infarction complicated by either ventricular tachycardia or fibrillation. The relatively low-risk group included 869 patients whose myocardial infarction did not have these complications; they were allocated only to placebo or oxprenolol. Randomization took place 30 days postmyocardial infarction; mean follow-up was 22 months. In the high-risk group the sudden cardiac death (crude rate) in the placebo subgroup was indeed high (21.3%), and was strikingly reduced to 2.7% and to 3.6% by oxprenolol and by left cardiac sympathetic denervation, respectively (P < 0.05). In the low-risk group the sudden cardiac death (crude rate) in the placebo subgroup was 5.2% and was still reduced by oxprenolol to 1.6% (P < 0.05). The results for total mortality were quite similar to those for sudden death iu both groups. Conclusion: This study, unique for the populations studied and for one of the treatments used, demonstrates that pharmacologic and surgical antiadrenergic interventions significantly reduce sudden cardiac death in postmyocardial infarction patients at high and at low risk. With due consideration to the relatively small size of the high-risk group, it seems reasonable to suggest that left cardiac sympathetic denervation may be considered as a possible alternative for high-risk patients with contraindications to beta blockers. (J Cardiovasc Electrophysiol, Vol 3, pp. 2–16, February 1992)     

Structure of Connexin43 and its Regulation by pHi

pH_i Regulation of Connexin43. Electrical coupling in the heart provides an effective mechanism fur propagating the cardiac action potential efficiently throughout the entire heart. Cells within the heart are electrically coupled through specialized membrane channels called gap junctions. Studies have shown that gap junctions are dynamic, carefully regulated channels that are important for normal cardiogenesis. We have recently been interested in the molecular mechanisms by which intracellular acidification leads to gap junction channel closure. Previous results in this lab have shown that truncation of the carboxyl terminal (CT) of connexin43 (Cx43) does not interfere with functional channel expression. Further, the pH-dependent closure of C×43 channels is significantly impaired by removal of this region of the protein. Other studies have shown that the CT is capable of interacting with its receptor even when not covalently attached to the channel protein. From these data we have proposed a particle-receptor model to explain the pH-dependent closure of Cx43 gap junction channels. Detailed analysis of the CT has revealed interesting new information regarding its possible structure. Here we review the most recent studies that have contributed to our understanding of the molecular mechanisms of regulation of the cardiac gap protein C×43.     

Electrophysiology of the Right Anterior Approach to the Atrioventricular Node:

Electrophysiology of Anterior AVN Input. Introduction: Previous reports have described electrophysiologic properties and rate-dependent responses in the transitional cell zone of the posterior AV nodal input (slow pathway). The purpose of this study was to investigate the electrophysiology of the anterior transitional cell zone (fast pathway) in vivo and in a Langendorff preparation perfused with a nonblood solution containing butanedionemonoxime to inhibit contraction. Methods and Results: In five anesthetized dogs, the His-bundle electrogram recorded from the aortic root included atrial activity in close proximity to the anterior limbus of the fossa ovalis. During decremental atrial pacing, the atrial potential exhibited amplitude alternans at a pacing cycle length (CL) of 135 ± 14 msec. In ten isolated pertused canine hearts, a bipctlar electrode catheter was positioned with its tip against the right anterior interatrial septum just superior to the tendon of Todaro. The AV Wenckebach CL (WCL) averaged 262 ± 21 msec. During further decreases in pacing CL, the bipolar atrial potential developed a 2:1 amplitude alternans (9/10 dogs) at CL = 168 ± 15 msec and then split into two components with subsequent 2:1 block between these components (10/10 dogs) at CL = 152 ± 19 msec. Radiofrequency ablation at this site in six dogs prolonged the stimulus to HB interval from 113 ± 19 to 151 ± 30 msec (P < 0.01) without changing the WCL, consistent with ablation of the fast AV nodal pathway. In six other isolated perfused canine hearts, an octapolar catheter (2-mm spacing) was positioned along the anterior limbus of the fossa ovalLs with the tip electrode located over the anterior portion (apex) of the triangle of Koch. The aforementioned 2:1 amplitude alternans occurred at a longer CL in the distal electrodes located at the tendon of Todaro than in the proximal electrodes at farther distances from the tendon of Todaro (185 ± 25 vs 171 ± 20 msec, P < 0.05), as did the 2:1 block between the two components (161 ± 18 vs 150 ± 18 msec, P < 0.05). Microelectrode recordings obtained adjacent to the catheter demonstrated 2:1 alternans and block patterns in the action potentials of transitional cells but not in atrial cells, which exhibited 1:1 conduction at all CL. Conclusions: The transitional cell zone in the anterior interatrial septum exhibits a specific rate-dependent, spatial gradient of conduction block, which can be recorded in bipolar electro-grams as well as microelectrode recordings. Electrophysiologic changes induced by radiofrequency ablation of this anterior atrial/transitional cell zone (corroborated by histology) provide strong presumptive evidence that this area constitutes all or a major part of the fast AV nodal pathway.     

CD3-induced T-cell activation in the bone marrow of myeloma patients: major role of CD4+ cells

Summary. A large expansion of activated T cells (CD3⁺CD25⁺) with the potential to act as anti-tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3-activated T cells. On day 6, most T cells coexpressed the CD1 la, CD18, CD54, CD45R0 antigens and consisted of activated (CD25⁺) CD4⁺ and CD8⁺ cells in nearly equal proportions. Kinetics studies showed that CD4⁺CD25⁺ cells proliferated more rapidly and peaked earlier than CD8⁺CD25⁺ cells. When experiments were performed with purified subpopulations by removing CD4⁺ cells (resulting in CD8⁺ BMMCs) or by removing CD8⁺ cells (resulting in CD4⁺ BMMCs), T-cell activation and autologous plasma cell decrease were observed in CD4⁺ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8⁺ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the supernatants of CD4⁺ BMMCs cultures, whereas no secretion of IL-4 was detected, indicating a Thl-like profile of CD3-activated CD4⁺ cells.
These data indicate that CD4⁺ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4⁺ cells is therefore essential in any strategy aiming to recover T-cell-mediated immunity in MM.