Comparing Different Donor Sites After Vascularized Lymph Node Transfer to the Lymphedematous Upper Limb: A Systematic Review and Meta-analysis of Clinical Outcomes.

BACKGROUND: Vascularized lymph node transfer (VLNT) involves the microvascular transplantation of functional lymph nodes from a donor site into a limb affected by lymphedema to restore the normal flow of lymphatic fluid. Despite the increasing clinical experience with VLNT, there remains insufficient data to support its routine use in clinical practice. Here, we aim to evaluate the effectiveness and safety of VLNTs for upper limb lymphedema and compare clinical outcomes when using different donor sites. METHODS: We carried out a systematic search of the literature through PubMed and Scopus databases for studies on VLNT for upper limb lymphedema. Primary and secondary outcomes included circumference reduction rate (CRR) and infection reduction rate by postoperative cellulitis episodes for the efficacy and safety of VLNT. Pooled analysis was performed using the inverse variance weighting meta-analysis of single means using the meta package in R software. Subgroup analyses were performed for donor and recipient sites, age groups, follow-ups, and symptom durations. Quality assessment was performed using the Newcastle-Ottawa Scale for nonrandomized studies. RESULTS: A total of 1089 studies were retrieved from the literature, and 15 studies with 448 upper limb lymphedema patients who underwent VLNT were included after eligibility assessment. The mean CRR was 34.6 (18.8) and the mean postoperative cellulitis episodes per year was 0.71 (0.7). The pooled analysis of CRR was 28.4% (95% confidence interval, 19.7-41.1) and postoperative cellulitis episodes showed a mean of 0.59 (95% confidence interval, 0.36-0.95) using the random-effect model. Subgroup analyses showed significant group differences in recipient site for CRR and postoperative cellulitis episodes with the wrist comprising the highest weights, and patients younger than 50 years showing a lower postoperative infection. CONCLUSIONS: Vascularized lymph node transfer using gastroepiploic flaps at the wrists has shown a significant difference in reductions of limb circumference and cellulitis episodes in upper limb lymphedema patients when compared with other donor sites. However, further prospective studies are needed to consolidate this finding.

Quantum Mechanical Aspects in the Pathophysiology of Neuropathic Pain.

Neuropathic pain is a challenging complaint for patients and clinicians since there are no effective agents available to get satisfactory outcomes even though the pharmacological agents target reasonable pathophysiological mechanisms. This may indicate that other aspects in these mechanisms should be unveiled to comprehend the pathogenesis of neuropathic pain and thus find more effective treatments. Therefore, in the present study, several mechanisms are chosen to be reconsidered in the pathophysiology of neuropathic pain from a quantum mechanical perspective. The mathematical model of the ions quantum tunneling model is used to provide quantum aspects in the pathophysiology of neuropathic pain. Three major pathophysiological mechanisms are revisited in the context of the quantum tunneling model. These include: (1) the depolarized membrane potential of neurons; (2) the cross-talk or the ephaptic coupling between the neurons; and (3) the spontaneous neuronal activity and the emergence of ectopic action potentials. We will show mathematically that the quantum tunneling model can predict the occurrence of neuronal membrane depolarization attributed to the quantum tunneling current of sodium ions. Moreover, the probability of inducing an ectopic action potential in the axons of neurons will be calculated and will be shown to be significant and influential. These ectopic action potentials are generated due to the formation of quantum synapses which are assumed to be the mechanism behind the ephaptic transmission. Furthermore, the spontaneous neuronal activity and the emergence of ectopic action potentials independently from any adjacent stimulated neurons are predicted to occur according to the quantum tunneling model. All these quantum mechanical aspects contribute to the overall hyperexcitability of the neurons and to the pathogenesis of neuropathic pain. Additionally, providing a new perspective in the pathophysiology of neuropathic pain may improve our understanding of how the neuropathic pain is generated and maintained and may offer new effective agents that can improve the overall clinical outcomes of the patients.

GABA Receptors Can Depolarize the Neuronal Membrane Potential via Quantum Tunneling of Chloride Ions: A Quantum Mathematical Study.

GABA (gamma-aminobutyric acid) receptors represent the major inhibitory receptors in the nervous system and their inhibitory effects are mediated by the influx of chloride ions that tends to hyperpolarize the resting membrane potential. However, GABA receptors can depolarize the resting membrane potential and thus can also show excitatory effects in neurons. The major mechanism behind this depolarization is mainly attributed to the accumulation of chloride ions in the intracellular compartment. This accumulation leads to increase in the intracellular chloride concentration and depolarize the Nernst potential of chloride ions. When the membrane potential is relatively hyperpolarized, this will result in a chloride efflux instead of influx trying to reach their depolarized equilibrium potential. Here, we propose different mechanism based on a major consequence of quantum mechanics, which is quantum tunneling. The quantum tunneling model of ions is applied on GABA receptors and their corresponding chloride ions to show how chloride ions can depolarize the resting membrane potential. The quantum model states that intracellular chloride ions have higher quantum tunneling probability than extracellular chloride ions. This is attributed to the discrepancy in the kinetic energy between them. At physiological parameters, the quantum tunneling is negligible to the degree that chloride ions cannot depolarize the membrane potential. Under certain conditions such as early neuronal development, gain-of-function mutations, stroke and trauma that can lower the energy barrier of the closed gate of GABA receptors, the quantum tunneling is enhanced so that the chloride ions can depolarize the resting membrane potential. The major unique feature of the quantum tunneling mechanism is that the net efflux of chloride ions is attained without the need for intracellular accumulation of chloride ions as long as the energy barrier of the gate is reduced but still higher than the kinetic energy of the chloride ion as a condition for quantum tunneling to take place.