Different mechanisms underlie compulsive alcohol self-administration in male and female rats.

BACKGROUND: Sex is an important factor in the progression and treatment of alcohol addiction, and therapeutic approaches may have to be tailored to potential sex differences. This highlights the importance of understanding sex differences in behaviors that reflect key elements of clinical alcohol addiction, such as continued use despite negative consequences ("compulsive use"). Studies in experimental animals can help provide an understanding of the role sex plays to influence these behaviors. METHODS: Large populations of genetically heterogeneous male and female Wistar rats were tested in an established model of compulsive alcohol self-administration, operationalized as alcohol responding despite contingent foot shock punishment. We also tested baseline (fixed ratio, unpunished) operant alcohol self-administration, motivation to self-administer alcohol (progressive ratio), and temporal discounting for alcohol reward. In search of predictors of compulsivity, animals were screened for novelty-induced place preference, anxiety-like behavior, pain sensitivity and corticosterone levels. The estrous cycle was monitored throughout the study. RESULTS: Unpunished self-administration of alcohol did not differ between males and females when alcohol intake was corrected for body weight. Overall, females showed higher levels of compulsive responding for alcohol. Compulsive response rates showed bimodal distributions in male but not in female rats when intermediate shock intensities were used (0.2 and 0.25 mA); at higher shock intensities, responding was uniformly suppressed in both males and females. We also found less steep discounting in females when alcohol was devalued by delaying its delivery. Males exhibited a stronger motivation to obtain alcohol under unpunished conditions, while females showed higher corticosterone levels at baseline. Factor analysis showed that an underlying dimension related to stress and pain predicted compulsivity in females, while compulsivity in males was predicted by a reward factor. We did not find differences in alcohol-related behaviors throughout the various stages of the estrous cycle. CONCLUSIONS: Our results suggest that mechanisms promoting compulsivity, a key feature of alcohol addiction, likely differ between males and females. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research, and has potential treatment implications in alcohol addiction.

Sex plays an important role in the progression and treatment of alcohol addiction. While men show a higher prevalence of alcohol addiction, women are more susceptible to the adverse effects of excessive alcohol consumption. Additionally, women often rely on heavy drinking as a maladaptive coping mechanism to alleviate stress and anxiety, driven by negative affect. On the other hand, men are more likely to report heavy drinking and relapse in response to positive emotions and social influences. These sex-based differences underline the importance of understanding how vulnerability to alcohol addiction and its treatment varies in males and females.We used genetically heterogeneous rats to explore the behavioral traits that contribute to compulsivity, a key clinical feature of alcohol addiction. We found that motivation to self-administer alcohol was higher in males, while females showed higher compulsive alcohol self-administration. In males, motivation to self-administer alcohol showed a significant correlation with compulsivity, while in females compulsivity was predicted by higher basal corticosterone levels.These findings underlie the importance of sex-specific factors in compulsive alcohol self-administration, with potential prevention and treatment implications in alcohol addiction.

Allografts use in orthopedic surgery: trend change over the past 11 years from a regional tissue bank.

Allografts are the second most transplanted tissue in medicine after blood and are now increasingly used for both primary and revision surgery. Allografts have the advantages of lower donor site morbidity, availability of multiple grafts, and shorter operative time. The Banks represents the bridge between Donor and Recipient and guarantees the quality and safety of the distributed allografts Given the increasing interest in these tissues, a retrospective analysis of data collected from the Regional Musculoskeletal Tissue Bank registry over an 11-year period (2009-2019) was conducted. The statistical analyses used were the Shapiro-Wilk normality test and a Poisson regression model. From January 2009 to December 2019, a total of 14,199 musculoskeletal tissues stored in the Regional Musculoskeletal Tissue Bank were provided for surgical allograft procedures. In 2009, the number of allografts performed was 925; this figure has steadily increased to 1599 in 2019. Epiphyses were taken as the reference tissue with an almost constant trend over the period, while a significant increase was denoted for extensor mechanism allograft, ligaments, tendons and long bone corticals (p < 0.001), processed bone tissues had no change in trend (p = 0.841). There was also a gradual decrease in the rate of microbiological positivity, as determined by bacteriological and serological tests performed on the collected tissues. This phenomenon is due to improved sampling techniques and the training of a dedicated team. Thus, we have seen how the use of allografts in orthopedic surgery has increased over the past 11 years, uniformly in terms of tissue type, except for the noticeable increase in ligamentous tissue.

Transforaminal lumbar interbody fusion with a tantalum cage: lumbar lordosis redistribution and sacral slope restoration with a modified posterior technique.

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF), a commonly used procedure in spine surgery, has the advantage of a lower incidence of nerve lesions compared to the posterior lumbar interbody fusion (PLIF) technique. The intersomatic arthrodesis has always been carried out with a single tantalum cage normally used for PLIF. Tantalum is a metal that is particularly used in orthopedic surgery. It has a modulus of elasticity similar to marrow and leads to high primary stability of the implant. MATERIALS AND METHODS: Our study was a retrospective monocentric observational study evaluating clinical and radiological outcomes of tantalum cages in a modified TLIF technique with posterior instrumentation and autologous and/or homologous posterolateral bone grafting. The aim of the study was to evaluate clinical outcomes and the increase in or redistribution of lumbar lordosis. The intersomatic arthrodesis was always carried out with a single tantalum cage normally used for PLIF to reduce the neurological risk. We retrospectively studied 105 patients who were treated with a modified unilateral TLIF approach by two surgeons between 2013 and 2018. We evaluated the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) for back pain, global lumbar lordosis, lordosis of L4-sacrum, segmental lordosis of functional motion units that underwent arthrodesis, pelvic tilt, pelvic incidence, and the sacral slope in 77 patients. All patients were suffering from grade III or IV Pfirrmann, instability, or foraminal post-laminectomy stenosis and/or grade I-II degenerative spondylolisthesis or low-grade isthmic spondylolisthesis. They had no significant sagittal imbalance, with a sagittal vertical axis (SVA) of < 5 mm. The average follow-up duration was 30 months. RESULTS: We achieved excellent clinical results, with only four cases of failure (5.2%). Moreover, we noticed a statistically significant redistribution of lumbar lordosis, with an average percentage increase in L4-S1 lordosis equal to 19.9% (P < 0.001), an average increase in the L4-S1/Lumbar lordosis (LL) ratio from 0.53 to 0.63 (P < 0.001), and a mean percentage increase in sacral slope equal to 7.6% (P < 0.001). CONCLUSION: Thanks to the properties of tantalum, our modified single-portal TLIF technique is a valid surgical solution to obtain a solid arthrodesis and restore the correct lumbar lordosis distribution while reducing neurological complications and the number of failures. LEVEL OF EVIDENCE: 4 Trial registration statement: retrospective observational study, no trial registration.

What Is the Role of Traction Test Radiographs in the Preoperative Planning of Adolescent Idiopathic Scoliosis?

Lower instrumented vertebra (LIV) selection is critical to avoid complications like adding-on. This study aims to determine the usefulness of the traction test (TR) in selecting the LIV during surgery for adolescent idiopathic scoliosis (AIS). We analyzed 42 AIS patients with Lenke 1 curves who had preoperative, postoperative, and at least 12-month follow-up X-rays, as well as preoperative side bending (SB) and TR radiograms. Neutral vertebra (NV), stable vertebra (SV), lower instrumented vertebra (LIV), and Cobb angles were identified and compared on all radiographic images. In 23 cases, the TR resulted in SV proximalization compared to the preoperative X-rays, while in 8 cases, SV-TR was more distal. This distalization occurred in 50% of Lenke 1C curves, where a greater correction of the distal curve was found. NV-TR was proximal to NV-preop in 9 cases, while NV-SB was proximal in 22 cases. LIV was proximal to SV-TR in 8 cases, while it was proximal to SV-preop in 22. One patient with LIV proximal to SV-TR developed adding-on. In conclusion, the TR is crucial in AIS preoperative planning as it provides information distinct from that of standard X-rays and SB: (1) it better assesses gravitational stability than rotational stability; and (2) choosing LIV equal to or proximal to SV-TR may prevent adding-on, except in 'flexible' Lenke 1C curves where LIV should be equal or distal to SV-preop.

Paraparesis and congenital severe hyperkyphosis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: A rare deformity management during the Sars-Cov-2 pandemic.

Introduction: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) syndrome can be classified into two types: type I (isolated) without extragenital abnormalities; type II (associated) with the presence of extragenital dimorphisms. Skeletal abnormalities are the second most frequent extragenital manifestations. Research question: Association between MRKH and congenital scoliosis has been described; on the contrary, hyperkyphosis is very rare and sparsely described in the medical literature. Here we report our experience in the management of thoracolumbar hyperkyphosis in 16-year-old patient diagnosed with MRKH syndrome with an acute neurological impairment due to T11-T12 disc herniation. Material and methods: Clinical and radiological images of the case were retrieved from the medical notes, operative records and imaging system. Results: Posterior surgical correction was proposed to treat the severe spinal deformity; however, surgery was delayed because of SARS-CoV2 pandemic outbreak. During the pandemic, the patient had a major clinical and radiological deterioration with development of paraparesis. Complete clinical resolution of the paraparesis and restoration of balance was achieved with a two stage surgical approach, with a first anterior stage followed by a delayed posterior approach aimed at deformity correction. Discussion: Congenital kyphosis are rare deformities that can progress rapidly leading to severe neurological deficits and worsening of the deformity. When patient has neurological deficit the surgical strategy to address the neurological problem first and plan the more complex and demanding corrective surgery remains a valid strategy that must be consider. Conclusion: This is the first reported case of hyperkyphosis in Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) syndrome surgically treated.

Does Risser Casting for Adolescent Idiopathic Scoliosis Still Have a Role in the Treatment of Curves Larger Than 40°? A Case Control Study with Bracing.

Background: The most common conservative treatment for Adolescent Idiopathic Scoliosis (AIS) is bracing. However, several papers questioned the effectiveness of bracing for curves between 40° and 50° Cobb: the effectiveness in preventing curve progression could be as low as 35%. Seriate casting is considered a standard approach in early onset scoliosis; however, in the setting of AIS, cast treatment is seldom utilized, with only few studies reporting on its effectiveness. Aim of the study: The main aim of the study is to determine whether a seriate casting with Risser casts associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. Furthermore, the secondary endpoints were: (1) is there a difference in effectiveness of casting between Thoracic (T) and Thoracolumbar/Lumbar (TL/L) curves? (2) Does the 'in cast' correction predicts the treatment outcome? (3) What is the effect on thoracic kyphosis of casting? Methods: This is a retrospective monocentric case−control study; through an Institutional Database search we identified all the patients treated at our institution between 1 January 2017 and 31 December 2020, with a diagnosis of AIS, Risser grade between 0 and 4 at the beginning of the treatment, at least one curve above 40° Cobb and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Standing full spine X-rays in AP and LL are obtained before and after the cast treatment; only AP standing full spine X-rays 'in-cast' are obtained for each cast made. Patients were stratified according to the curve behavior at the end of treatment (Risser 5): progression was defined as ≥6° increase in the curve magnitude or fusion needed; stabilization is defined as a change in curve by ±5°; and improvement was defined as ≥6° reduction in the curve. Results: For the final analysis, 55 compliant patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 27 (4 M, 23 F, mean age 13.6 ± 1.6) in the CG. Eight (14.5%) patients in the SG failed the conservative treatment while 14 (51.3%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1, 3−2.6, p = 0.001), and the Number Needed to Treat was 2,4. No significant difference was found between the T and TL/L curves concerning the 'progressive' endpoint (z-score 0.263, p = 0.79). The mean percentage of 'in cast' curve reduction was 40.1 ± 15.2%; no significant correlation was found between the percentage of correction and the outcome (Spearman Correlation Coefficient 0.18). Finally, no significant differences between baseline and end of FU TK were found (32° ± 16.2 vs. 29.6 ± 15.8, p = ns). Discussion: Seriate Risser casting for AIS with larger curves (>40° Cobb) is effective in reducing curve progression when compared with full time bracing alone in treatment compliant patients. The treatment is equally effective in controlling T and TL/L curves; furthermore, a slight but non-significant decrease in TK was observed in patients treated with casting. This type of treatment should be considered for AIS patients who present with large curves to potentially reduce the percentage of surgical cases. Short Abstract: The aim of the study is to determine whether seriate Risser casting associated with bracing is more effective in preventing curve progression than bracing alone in curves larger than 40°. This is a retrospective monocentric case−control study; we identified all the patients treated at our institution with a diagnosis of AIS, Risser grade 0−4 at the beginning of the treatment, at least one curve above 40° Cobb (35° if treated with bracing alone) and treatment with either seriate Risser casting and bracing (Study Group, SG) or bracing alone (Control Group, CG). Fifty-five patients (12 M, 43 F, mean age 13.5 ± 1.6) were included in the SG and 30 (5 M, 25 F, mean age 13.9 ± 1.7) in the CG. Eight (14,5%) patients in the SG failed the conservative treatment while fifteen (50%) failed in the CG. Consequently, the Relative Risk for progression in the Efficacy Analysis was 1.8 (95% CI 1.3−2.6, p = 0.001), and the Number Needed to Treat was 2,4. Seriate Risser casting for AIS with larger curves (>40°) is effective in reducing curve progression when compared with full time bracing alone. This type of treatment should be considered for AIS patients who present with large curves.

Apical vertebral derotation and translation (AVDT) for adolescent idiopathic scoliosis using screws and sublaminar bands: a safer concept for deformity correction.

PURPOSE: To assess the efficacy and safety of a new deformity correction philosophy treatment for AIS called apical vertebral derotation and translation (AVDT). METHODS: It is a retrospective study of prospectively collected data concerning two different scoliosis correction techniques used in our department. A total of 81 patients (22M, 59F) with a mean age of 15.5 years and minimum follow-up of 2 years were reviewed. Patients were divided into two groups according to the correction technique: 36 patients underwent single-rod derotation using all screws construct (AS), while 45 patients underwent apical vertebral derotation and translation using screws and sublaminar bands (SB). RESULTS: The mean improvement of the MT curve was 70% in the AS group and 60.6% in the SB group, while the mean improvement of the TL/L curve was 65.5 and 72.4%, respectively. PT increased in both groups after surgery with a mean amount of 2.5° in the AS group and only 1° in the SB group. We observed also a greater amount of cervical lordosis reduction in the AS group (4.5°) compared with the SB group (only 1°). The SB group had less operative time and less blood loss. CONCLUSION: There was no significant difference between the two groups at the final follow-up and both techniques led to an excellent correction in the frontal plane; in the sagittal plane, the AVDT technique seemed to give less sagittal imbalance with better cervical profile; the surgical procedure is easy with less operative time, less blood loss and less risk of potential complications. These slides can be retrieved under Electronic Supplementary Material.