Teclistamab as an Effective Treatment for Pericardial Effusion in Relapsed Multiple Myeloma: Case Report and a Brief Literature Review.

Introduction: Multiple myeloma represents a malignant disorder of plasma cells. Extramedullary relapse in multiple myeloma is a rare occurrence, and pericardial involvement stands as an exceedingly uncommon manifestation. Only a few documented cases of pericardial effusion as an extramedullary relapse presentation of myeloma exist. Bispecific antibodies are emerging as a novel class of immunotherapy drugs for the treatment of relapsed refractory multiple myeloma patients who have experienced failure with four prior lines of therapy. According to a literature review, none of the reported cases with pericardial effusion relapsed myeloma have been treated with bispecific antibodies, given that these drugs have only recently gained approval. Case Presentation: We present a rare case of a patient with pericardial effusion resulting from myeloma relapse, treated with teclistamab, a bispecific antibody, and achieving an excellent response. Conclusion: Bispecific antibodies, such as teclistamab, show great effectiveness as a treatment for patients with relapsed refractory multiple myeloma, including those with extramedullary disease.

Rapid gastric emptying during pregnancy in a rat model.

BACKGROUND/AIMS: The effect of pregnancy on gastric emptying has not been established, although the predominant clinical assumption is that gastric emptying is delayed during pregnancy. We hypothesized that the rate of emptying of nutrients during pregnancy is not delayed, but is actually more rapid when compared to the non-pregnant state. The rate of gastric emptying is a major determinant of postprandial glucose elevations. MATERIALS AND METHODS: 24 female and 4 male Spague-Dawley rats were used. Female rats were randomly divided into two groups: eight rats for the control group and sixteen rats for the pregnant group. Using physiologic, non-traumatic nuclear medicine scintigraphy imaging methodology, the authors studied gastric emptying of a liquid mixed meal in pregnant rats and non-pregnant controls. Body weights, daily food ingestion, and the rate of nutrient gastric emptying were recorded in both groups at pre-pregnancy, early pregnancy, and late pregnancy. RESULTS: The authors found that pregnancy in this rat model is associated with a 37-43% increased rate of nutrient gastric emptying from the stomach in late pregnancy as compared to non-pregnant control rats and pre-pregnancy rats. CONCLUSION: These findings contradict the current clinical assumption that gastric emptying is delayed in pregnancy. If further studies confirm a more rapid gastric emptying rate during human pregnancy, new therapies aimed at slowing the rate of nutrient absorption should be considered for the prevention and treatment of pregnancy-associated nausea, gestational diabetes, and other insulin-resistant pregnancy-associated states such as pre-eclampsia.

Linking specific biological signatures to different childhood adversities: findings from the HERO project.

BACKGROUND: Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. METHODS: Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic disadvantage) early-life adversities with salivary inflammatory biomarkers (IL-1ß, IL-6, IL-8, and TNF-α) and hair HPA markers (cortisol, cortisone, and dehydroepiandrosterone) were examined in two samples of young U.S. children (N = 142; N = 145). RESULTS: Children exposed to higher SES-D had higher levels of TNF-α (B = 0.13, p = 0.011), IL-1ß (B = 0.10, p = 0.033), and DHEA (B = 0.16, p = 0.011). Higher family dysfunction was associated with higher cortisol (B = 0.08, p = 0.033) and cortisone (B = 0.05, p = 0.003). An interaction between SES-D and family dysfunction was observed for cortisol levels (p = 0.020) whereby children exposed to lower/average levels of SES-D exhibited a positive association between family dysfunction and cortisol levels, whereas children exposed to high levels of SES-D did not. These findings were partially replicated in the second sample. CONCLUSIONS: Our results indicate that these biological response systems may react differently to different forms of early-life adversity. IMPACT: Different forms of early-life adversity have varied stress signatures, and investigations of early-life adversities with inflammation and HPA markers are lacking. Children with higher socioeconomic disadvantage had higher TNF-α, IL-1ß, and DHEA. Higher family dysfunction was associated with higher hair cortisol and cortisone levels, and the association between family dysfunction and cortisol was moderated by socioeconomic disadvantage. Biological response systems (immune and endocrine) were differentially associated with distinct forms of early-life adversities.

CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment.

PURPOSE: Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting the need for novel therapies specifically targeting this subset of tumor-driving cells. Here, we identify CD70 as a potential therapeutic target for recurrent GBM CSCs. EXPERIMENTAL DESIGN: In the current study, we identified the relevance and functional influence of CD70 on primary and recurrent GBM cells, and further define its function using established stem cell assays. We use CD70 knockdown studies, subsequent RNAseq pathway analysis, and in vivo xenotransplantation to validate CD70's role in GBM. Next, we developed and tested an anti-CD70 chimeric antigen receptor (CAR)-T therapy, which we validated in vitro and in vivo using our established preclinical model of human GBM. Lastly, we explored the importance of CD70 in the tumor immune microenvironment (TIME) by assessing the presence of its receptor, CD27, in immune infiltrates derived from freshly resected GBM tumor samples. RESULTS: CD70 expression is elevated in recurrent GBM and CD70 knockdown reduces tumorigenicity in vitro and in vivo. CD70 CAR-T therapy significantly improves prognosis in vivo. We also found CD27 to be present on the cell surface of multiple relevant GBM TIME cell populations, notably putative M1 macrophages and CD4 T cells. CONCLUSION: CD70 plays a key role in recurrent GBM cell aggressiveness and maintenance. Immunotherapeutic targeting of CD70 significantly improves survival in animal models and the CD70/CD27 axis may be a viable polytherapeutic avenue to co-target both GBM and its TIME.

Artificial intelligence-based radiotherapy machine parameter optimization using reinforcement learning.

PURPOSE: To develop and evaluate a volumetric modulated arc therapy (VMAT) machine parameter optimization (MPO) approach based on deep-Q reinforcement learning (RL) capable of finding an optimal machine control policy using previous prostate cancer patient CT scans and contours, and applying the policy to new cases to rapidly produce deliverable VMAT plans in a simplified beam model. METHODS: A convolutional deep-Q network was employed to control the dose rate and multileaf collimator of a C-arm linear accelerator model using the current dose distribution and machine parameter state as input. A Q-value was defined as the discounted cumulative cost based on dose objectives, and experience-replay RL was performed to determine a policy to minimize the Q-value. A two-dimensional network design was employed which optimized each opposing leaf pair independently while monitoring the corresponding dose plane blocked by those leaves. This RL approach was applied to CT and contours from 40 retrospective prostate cancer patients. The dataset was split into training (15 patients) and validation (5 patients) groups to optimize the network, and its performance was tested in an independent cohort of 20 patients by comparing RL-based dose distributions to conformal arcs and clinical intensity modulated radiotherapy (IMRT) delivering a prescription dose of 78 Gy in 40 fractions. RESULTS: Mean ± SD execution time of the RL VMAT optimization was 1.5 ± 0.2 s per slice. In the test cohort, mean ± SD (P-value) planning target volume (PTV), bladder, and rectum dose were 80.5 ± 2.0 Gy (P < 0.001), 44.2 ± 14.6 Gy (P < 0.001), and 43.7 ± 11.1 Gy (P < 0.001) for RL VMAT compared to 81.6 ± 1.1 Gy, 51.6 ± 12.9 Gy, and 36.0 ± 12.3 Gy for clinical IMRT. CONCLUSIONS: RL was applied to VMAT MPO using clinical patient contours without independently optimized treatment plans for training and achieved comparable target and normal tissue dose to clinical plans despite the application of a relatively simple network design originally developed for video-game control. These results suggest that extending a RL approach to a full three-dimensional beam model could enable rapid artificial intelligence-based optimization of deliverable treatment plans, reducing the time required for radiotherapy planning without requiring previous plans for training.

A semiautomatic segmentation method for interstitial needles in intraoperative 3D transvaginal ultrasound images for high-dose-rate gynecologic brachytherapy of vaginal tumors.

PURPOSE: The purpose of this study was to evaluate the use of a semiautomatic algorithm to simultaneously segment multiple high-dose-rate (HDR) gynecologic interstitial brachytherapy (ISBT) needles in three-dimensional (3D) transvaginal ultrasound (TVUS) images, with the aim of providing a clinically useful tool for intraoperative implant assessment. METHODS AND MATERIALS: A needle segmentation algorithm previously developed for HDR prostate brachytherapy was adapted and extended to 3D TVUS images from gynecologic ISBT patients with vaginal tumors. Two patients were used for refining/validating the modified algorithm and five patients (8-12 needles/patient) were reserved as an unseen test data set. The images were filtered to enhance needle edges, using intensity peaks to generate feature points, and leveraged the randomized 3D Hough transform to identify candidate needle trajectories. Algorithmic segmentations were compared against manual segmentations and calculated dwell positions were evaluated. RESULTS: All 50 test data set needles were successfully segmented with 96% of algorithmically segmented needles having angular differences <3° compared with manually segmented needles and the maximum Euclidean distance was <2.1 mm. The median distance between corresponding dwell positions was 0.77 mm with 86% of needles having maximum differences <3 mm. The mean segmentation time using the algorithm was <30 s/patient. CONCLUSIONS: We successfully segmented multiple needles simultaneously in intraoperative 3D TVUS images from gynecologic HDR-ISBT patients with vaginal tumors and demonstrated the robustness of the algorithmic approach to image artifacts. This method provided accurate segmentations within a clinically efficient timeframe, providing the potential to be translated into intraoperative clinical use for implant assessment.

An Australian Response to the COVID-19 Pandemic and Its Implications on the Practice of Neurosurgery.

OBJECTIVE: This study was designed to assess the impact of public health policy in Australia in response to the coronavirus disease identified in 2019 (COVID-19) pandemic on the delivery of neurosurgical services. Being essential services, we postulated that there would not be a decrease in elective and emergency neurosurgical presentations and surgeries. METHODS: This is a prospective, observational, epidemiologic study in strict adherence to the "STROBE" (Strengthening The Reporting of OBservational studies in Epidemiology) guidelines. It is a cross-sectional, multicentric study involving 5 tertiary neurosurgical centers to capture all public neurosurgical admissions in Queensland during the past 3 months (February-April, 2020) of significant public health policy changes to combat COVID-19. RESULTS: An analysis of the 1298 admissions for the Queensland population of 5.07 million Australians demonstrated a decrease in the number of elective and emergency admissions. The decline in elective admissions, particularly degenerative spine, benign neoplasms, and vascular pathologies, was a direct response of government strategy to curb activity to urgent surgical interventions only. Moreover, a trend toward fewer emergency admissions was also noted, partly explained by less trauma and also a decline in vascular pathologies including subarachnoid hemorrhage. CONCLUSIONS: In comparison with Europe and North America, this study demonstrates the impact of proactive public health measures in Australia that successfully flattened the COVID-19 curve while facilitating ongoing care of acutely unwell neurosurgical patients.

Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated into solid lipid nanoparticles and polymeric nanocapsules / Avaliação das alterações retinais no coelho após injeção intravítrea de sunitinib encapsulado em nanoparticulas lípidas sólidas e nanocapsulas polímeros

ABSTRACT Purpose: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. Methods: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. Results: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. Conclusions: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.

RESUMO Objetivos: O presente estudo teve por objetivo avaliar a segurança da injeção intravítrea de 0,1 ml de sunitinibe em duas concentrações (1 mg/ml e 10 mg/ml), 0,1 ml de dispersão contendo nanopartículas lipídicas sólidas sem droga e 0,1 ml de dispersão contendo nanocápsulas poliméricas livre de drogas analisando os possíveis efeitos tóxicos à retina de coelhos albinos detectados pela eletrofisiologia e histologia por microscopia óptica. Métodos: Um estudo controlado experimental foi rea­lizado com 20 olhos de coelhos albinos. Foram realizadas injeções intravítrea de duas concentrações diferentes de suniti­nibe, uma dispersão contendo nanopartículas lipídicas sólidas e uma dispersão contendo nanocápsulas. O olho contralateral não recebeu tratamento e foi utilizado como controle. Resultados: Não foram observadas alterações eletrorretinográficas nos grupos do sunitinibe (1 mg/ml e 10 mg/ml) e no grupo das nanopartículas lipídicas sólidas. No grupo das nanocápsulas, houve alterações significativas tanto na morfologia, quanto na amplitude e tempo das ondas do eletrorretinograma. Ao estudo histológico, somente o grupo das nanocápsulas apresentou al­terações degenerativas (núcleos tumefeitos) com acentuado edema e formação de vacúolos citoplasmáticos, sugerindo toxidade retiniana. Conclusões: As injeções intravítreas de sunitinibe e nanopartículas lipídicas sólidas não foram tóxicas para a retina. No entanto, nanocápsulas mostraram ser tóxicas para a retina. Sendo assim, a possibilidade de poder combinar o potencial de uma droga que possui a capacidade de inibir duas importantes vias da angiogênese, às vantagens de liberação controlada das nanopartículas lipídicas sólidas, pode ser um importante recurso terapêutico para doenças vasoproliferativas oculares.

Unusual complication of a tattoo in an immunosuppressed patient.

Tattooing for decorative body art is becoming more popular and, as a result, so are tattoo-related complications. Patients are unlikely to discuss tattoos with medical professionals, even though these might be relevant. Long-term immunosuppressed patients are often young adults who may wish to consider tattooing. It is well recognised that immunosuppressed patients are at increased risk of infection including cutaneous mycobacterial infections. They therefore represent a group that is at a potentially higher risk of tattoo-related complications and warrant special consideration.We present the first documented case of inflammatory myopathy as a complication following tattooing in an immunosuppressed individual. This unusual case presented as distal thigh and medial knee pain and it was only after some time that a link to the tattoo was made. This serves as a reminder to consider tattoo-related complications in the differential diagnosis of unusual atraumatic musculoskeletal pain, especially in immunosuppressed individuals.

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study.

BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.

Accuracy and variability of high-dose-rate prostate brachytherapy needle tip localization using live two-dimensional and sagittally reconstructed three-dimensional ultrasound.

PURPOSE: To measure the accuracy and variability of manual high-dose-rate (HDR) prostate brachytherapy (BT) needle tip localization using sagittally reconstructed three-dimensional (3D) transrectal ultrasound (TRUS) augmented with live two-dimensional (2D) sagittal TRUS. METHODS AND MATERIALS: Ten prostate cancer patients underwent HDR-BT during which the sagittally assisted sagittally reconstructed (SASR) segmentation technique was completed in parallel with commercially available sagittally assisted axially reconstructed (SAAR) TRUS for comparison. The SASR technique makes use of live 2D ultrasound intraoperatively and allows needle tip updates using the final 3D image in the absence of image artifacts. These updates were repeated offline twice by two separate users. Needle end-length measurements were used to calculate insertion depth errors (IDEs) for each technique. RESULTS: Images of 147 needles were analyzed. For the SASR technique, both users were confident in tip positions on the final 3D image within 3 mm for 52% of needles, so these tip positions were updated. For the remaining 48% of needles, the tip positions from the live 2D images were used. This SASR technique enabled the localization of all needles with IDEs within ±3 mm for 84% of needles and IDE range of [-6.2 mm, 5.9 mm], compared with 57% and [-8.1 mm, 7.7 mm] when using the commercially available SAAR technique. CONCLUSIONS: The SASR technique mitigates the impact of 3D TRUS image artifacts on HDR-BT needle tip localization by incorporating live 2D sagittal TRUS intraoperatively and provides a statistically significant reduction in IDE variance compared with the routine SAAR technique.

ANG1 treatment reduces muscle pathology and prevents a decline in perfusion in DMD mice.

Vascular endothelial growth factor (VEGF) and other pro-angiogenic growth factors have been investigated to enhance muscle tissue perfusion and repair in Duchenne muscular dystrophy (DMD). Current understanding is limited by a lack of functional data following in vivo delivery of these growth factors. We previously used dynamic contrast-enhanced computed tomography to monitor disease progression in murine models of DMD, but no study to date has utilized this imaging technique to assess vascular therapy in a preclinical model of DMD. In the current study, we locally delivered VEGF and ANG1 alone or in combination to dystrophic hind limb skeletal muscle. Using functional imaging, we found the combination treatment as well as ANG1 alone prevented decline in muscle perfusion whereas VEGF alone had no effect compared to controls. These findings were validated histologically as demonstrated by increased alpha-smooth muscle actin-positive vessels in muscles that received either VEGF+ANG1 or ANG1 alone compared to the sham group. We further show that ANG1 alone slows progression of fibrosis compared to either sham or VEGF treatment. The findings from this study shed new light on the functional effects of vascular therapy and suggest that ANG1 alone may be a candidate therapy in the treatment of DMD.

Simultaneous automatic segmentation of multiple needles using 3D ultrasound for high-dose-rate prostate brachytherapy.

PURPOSE: Sagittally reconstructed 3D (SR3D) ultrasound imaging shows promise for improved needle localization for high-dose-rate prostate brachytherapy (HDR-BT); however, needles must be manually segmented intraoperatively while the patient is anesthetized to create a treatment plan. The purpose of this article was to describe and validate an automatic needle segmentation algorithm designed for HDR-BT, specifically capable of simultaneously segmenting all needles in an HDR-BT implant using a single SR3D image with ~5 mm interneedle spacing. MATERIALS AND METHODS: The segmentation algorithm involves regularized feature point classification and line trajectory identification based on the randomized 3D Hough transform modified to handle multiple straight needles in a single image simultaneously. Needle tips are identified based on peaks in the derivative of the signal intensity profile along the needle trajectory. For algorithm validation, 12 prostate cancer patients underwent HDR-BT during which SR3D images were acquired with all needles in place. Needles present in each of the 12 images were segmented manually, providing a gold standard for comparison, and using the algorithm. Tip errors were assessed in terms of the 3D Euclidean distance between needle tips, and trajectory error was assessed in terms of 2D distance in the axial plane and angular deviation between trajectories. RESULTS: In total, 190 needles were investigated. Mean execution time of the algorithm was 11.0 s per patient, or 0.7 s per needle. The algorithm identified 82% and 85% of needle tips with 3D errors ≤3 mm and ≤5 mm, respectively, 91% of needle trajectories with 2D errors in the axial plane ≤3 mm, and 83% of needle trajectories with angular errors ≤3°. The largest tip error component was in the needle insertion direction. CONCLUSIONS: Previous work has indicated HDR-BT needles may be manually segmented using SR3D images with insertion depth errors ≤3 mm and ≤5 mm for 83% and 92% of needles, respectively. The algorithm shows promise for reducing the time required for the segmentation of straight HDR-BT needles, and future work involves improving needle tip localization performance through improved image quality and modeling curvilinear trajectories.

A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction.

Rapid and stable control of pupil size in response to light is critical for vision, but the neural coding mechanisms remain unclear. Here, we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically photosensitive retinal ganglion cells (ipRGCs), a critical relay in the control of pupil size. We show that transient and sustained pupil responses are mediated by distinct photoreceptors and neurotransmitters. Transient responses utilize input from rod photoreceptors and output by the classical neurotransmitter glutamate, but adapt within minutes. In contrast, sustained responses are dominated by non-conventional signaling mechanisms: melanopsin phototransduction in ipRGCs and output by the neuropeptide PACAP, which provide stable pupil maintenance across the day. These results highlight a temporal switch in the coding mechanisms of a neural circuit to support proper behavioral dynamics.

Three-dimensional transrectal ultrasound guided high-dose-rate prostate brachytherapy: A comparison of needle segmentation accuracy with two-dimensional image guidance.

PURPOSE: Conventional transrectal ultrasound guided high-dose-rate prostate brachytherapy (HDR-BT) uses an axially acquired image set for organ segmentation and 2D sagittal images for needle segmentation. Sagittally reconstructed 3D (SR3D) transrectal ultrasound enables both organ and needle segmentation and has the potential to reduce organ-needle alignment uncertainty. This study compares the accuracy of needle tip localization between the conventional 2D sagittally assisted axially reconstructed (SAAR) and SR3D approaches. METHODS AND MATERIALS: Twelve patients underwent SAAR-guided HDR-BT, during which SR3D images were acquired for subsequent segmentation and analysis. A total of 183 needles were investigated. Needle end-length measurements were taken, providing a gold standard for insertion depths. Dosimetric impact of insertion depth errors (IDEs) on clinical treatment plans was assessed. RESULTS: SR3D guidance provided statistically significantly smaller IDEs than SAAR guidance with a mean ± SD of -0.6 ± 3.2 mm and 2.8 ± 3.2 mm, respectively (p < 0.001). Shadow artifacts were found to obstruct the view of some needle tips in SR3D images either partially (12%) or fully (10%); however, SR3D IDEs had a statistically significantly smaller impact on prostate V100% than SAAR IDEs with mean ± SD decreases of -1.2 ± 1.3% and -6.5 ± 6.7%, respectively (p < 0.05). CONCLUSIONS: SR3D-guided HDR-BT eliminates a source of systematic uncertainty from the SAAR-guided approach, providing decreased IDEs for most needles, leading to a significant decrease in dosimetric uncertainty. Although imaging artifacts can limit the accuracy of tip localization in a subset of needles, we identified a method to mitigate these artifacts for clinical implementation.

Regional anesthesia for management of acute pain in the intensive care unit.

Pain is a major problem for Intensive Care Unit (ICU) patients. Despite numerous improvements it is estimated that as many as 70% of the patients experience moderate-to-severe postoperative pain during their stay in the ICU. Effective pain management means not only decreasing pain intensity, but also reducing the opioids' side effects. Minimizing nausea, vomiting, urinary retention, and sedation may indeed facilitate patient recovery and it is likely to shorten the ICU and hospital stay. Adequate postoperative and post-trauma pain management is also crucial for the achievement of effective rehabilitation. Furthermore, recent studies suggest that effective acute pain management may be helpful in reducing the development of chronic pain. When used appropriately, and in combination with other treatment modalities, regional analgesia techniques (neuraxial and peripheral nerve blocks) have the potential to reduce or eliminate the physiological stress response to surgery and trauma, decreasing the possibility of surgical complications and improving the outcomes. Also they may reduce the total amount of opioid analgesics necessary to achieve adequate pain control and the development of potentially dangerous side effects.