Does Physical Exercise Enhance the Immune Response after Vaccination? A Systematic Review for Clinical Indications of COVID-19 Vaccine.

BACKGROUND: Stimulating protective immunity with vaccines appears to be the most promising option for providing widespread moderate to high protection against COVID-19 in people over the age of 18. Regular exercise improves the immune response, transmitting possible benefits against virus infections. The aim of this review is to study the effects of physical activity on vaccine injections, helping to develop new recommendations for COVID-19 vaccination campaigns. METHODS: A comprehensive review of the existing literature was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The internal quality of the studies was assessed according to the Physiotherapy Evidence Database (PEDro) scale. The outcomes analyzed were antibody titer, the level of lymphocytes CD4, CD8, InterLeukin 6 (IL6), leukocytes level, the visual analogue scale (VAS) for overall pain rating, arm and forearm circumferences and volume of oxygen (VO2) peak. RESULTS: Fourteen articles were selected for the analysis. The majority of studies were randomized controlled trials (RCT) (n = 8) and controlled trials (CT) (n = 6). According to PEDro, the 'fair' category (n = 7) was the most represented, followed by 'good' (n = 6) and 'excellent' (n = 1). Physical training showed a positive effect on antibody titers of the vaccine; yet, different variables seem to influence antibody titers: higher new vs. old antigen in the vaccine, higher in younger vs. older individuals, and higher in females vs. males. After exercise, when analyzing variables of direct response to the vaccine, such as the amount of CD4, IL-6 and leukocytes, higher levels were observed in the patients who performed physical exercise compared to the control group. In the same way, better results were observed in physiological variables such as VO2 and limb circumferences, or subjective variables such as pain, which showed better results than the control group. CONCLUSIONS: The immune response (antibody titers) depends on age, gender and the intensity of physical activity: long-term protocols at moderate intensity are the most recommended. All of these aspects also have to be carefully considered for the COVID-19 vaccination.

Gait robot-assisted rehabilitation in persons with spinal cord injury: A scoping review.

BACKGROUND: Many robots are available for gait rehabilitation (BWSTRT and ORET) and their application in persons with SCI allowed an improvement of walking function. OBJECTIVE: The aim of the study is to compare the effects of different robotic exoskeletons gait training in persons with different SCI level and severity. METHODS: Sixty-two studies were included in this systematic review; the study quality was assessed according to GRADE and PEDro's scale. RESULTS: Quality assessment of included studies (n = 62) demonstrated a prevalence of evidence level 2; the quality of the studies was higher for BWSTRT (excellent and good) than for ORET (fair and good). Almost all persons recruited for BWSTRT had an incomplete SCI; both complete and incomplete SCI were recruited for ORET. The SCI lesion level in the persons recruited for BWSTRT are from cervical to sacral; mainly from thoracic to sacral for ORET; a high representation of AIS D lesion resulted both for BWSTRT (30%) and for ORET (45%). The walking performance, tested with 10MWT, 6MWT, TUG and WISCI, improved after exoskeleton training in persons with incomplete SCI lesions, when at least 20 sessions were applied. Persons with complete SCI lesions improved the dexterity in walking with exoskeleton, but did not recover independent walking function; symptoms such as spasticity, pain and cardiovascular endurance improved. CONCLUSION: Different exoskeletons are available for walking rehabilitation in persons with SCI. The choice about the kind of robotic gait training should be addressed on the basis of the lesion severity and the possible comorbidities.

Gait rehabilitation in persons with spinal cord injury using innovative technologies: an observational study.

STUDY DESIGN: Prospective, quasi-experimental study, pre- and post-design, single arm study. OBJECTIVES: Investigate whether persons affected by SCI can safely experience walking function using Robotic Exoskeletons and Functional Electrical Stimulation (FES). SETTING: Inpatient METHODS: 52 persons with SCI were recruited (36 completed the protocol) and assigned to one of two groups based on their Lower Limb Motor Scores (LEMS): Group A: LEMS ≥ 10 and Group B: LEMS < 10. Participants in Group A (n = 19) underwent 20 sessions of Robot-Assisted Gait Training (RAGT) on a treadmill followed by 20 sessions of FES during Overground Gait (FES-OG). Participants in Group B (n = 17) received 20 sessions of FES-cycling followed by 20 sessions of overground RAGT. The main outcome measures were: WISCI-II, 10MWT, 6MWT, TUG and SCIM-II. RESULTS: 36 persons completed the study with no complications; only 4 of the 16 dropped out because of mild complications during the RAGT. Participants in Group A exhibited significant improvements in WISCI-II, 10MWT, 6MWT and TUG (p < 0.05), while those in Group B did not significantly improve their gait function but their walking velocity and resistance with the assistance of the robotic exoskeleton increased. SCIM-II scores increased followed therapy only in Group A. CONCLUSIONS: Persons affected by SCI can safely experience their walking function with RAGT and FES therapy; only few mild complications were observed. Our data provides initial evidence of the potential value of these technologies, especially in persons with SCI having LEMS > 10.

Elevated platelet count is a negative predictive and prognostic marker in locally advanced rectal cancer undergoing neoadjuvant chemoradiation: a retrospective multi-institutional study on 965 patients.

BACKGROUND: In patients with locally advanced rectal cancer treated by neoadjuvant chemoradiation, pathological complete response in the surgical specimen is associated with favourable long-term oncologic outcome. Based on this observation, nonoperative management is being explored in the subset of patients with clinical complete response. Whereas, patients with poor response have a high risk of local and distant recurrence, and appear to receive no benefit from standard neoadjuvant chemoradiation. Therefore, in order to develop alternative treatment strategies for non responding patients, predictive and prognostic factors are highly needed. Accumulating clinical observations indicate that elevated platelet count is associated with poor outcome in different type of tumors. In this study we investigated the predictive and prognostic impact of elevated platelet count on pathological response and long-term oncologic outcome in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation. METHODS: A total of 965 patients were selected from prospectively maintained databases of seven Centers within the SICO Colorectal Cancer Network. Patients were divided into two groups based on a pre-neoadjuvant chemoradiation platelet count cut-off value of 300 × 109/L identified by receiver operating characteristic curve considering complete pathological response as the outcome. RESULTS: Complete pathological response rate was lower in patients with elevated platelet count (12.8% vs. 22.1%, p = 0.001). Mean follow-up was 50.1 months. Comparing patients with elevated platelet count with patients with not elevated platelet count, 5-year overall survival was 69.5% vs.76.5% (p = 0.016), and 5-year disease free survival was 63.0% vs. 68.9% (p = 0.019). Local recurrence rate was higher in patients with elevated platelet count (11.1% vs. 5.3%, p = 0.001), as higher was the occurrence of distant metastasis (23.9% vs. 16.4%, p = 0.007). At multivariate analysis of potential prognostic factors EPC was independently associated with worse overall survival (HR 1.40, 95% CI 1.06-1.86), and disease free survival (HR 1.37, 95% CI 1.07-1.76). CONCLUSIONS: In locally advanced rectal cancer elevated platelet count before neoadjuvant chemoradiation is a negative predictive and prognostic factor which might help to identify subsets of patients with more aggressive tumors to be proposed for alternative therapeutic strategies.

Robotic versus laparoscopic distal pancreatectomy: an up-to-date meta-analysis.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) reduces postoperative morbidity, hospital stay and recovery as compared with open distal pancreatectomy. Many authors believe that robotic surgery can overcome the difficulties and technical limits of LDP thanks to improved surgical manipulation and better visualization. Few studies in the literature have compared the two methods in terms of surgical and oncological outcome. The aim of this study was to compare the results of robotic (RDP) and laparoscopic distal pancreatectomy. METHODS: A systematic review and meta-analysis was conducted of control studies published up to December 2016 comparing LDP and RDP. Two Reviewers independently assessed the eligibility and quality of the studies. The meta-analysis was conducted using either the fixed-effect or the random-effect model. RESULTS: Ten studies describing 813 patients met the inclusion criteria. This meta-analysis shows that the RDP group had a significantly higher rate of spleen preservation [OR 2.89 (95% confidence interval 1.78-4.71, p < 0.0001], a lower rate of conversion to open OR 0.33 (95% CI 0.12-0.92), p = 0.003] and a shorter hospital stay [MD -0.74; (95% CI -1.34 -0.15), p = 0.01] but a higher cost than the LDP group, while other surgical outcomes did not differ between the two groups. CONCLUSION: This meta-analysis suggests that the RDP procedure is safe and comparable in terms of surgical results to LDP. However, even if the RDP has a higher cost compared to LDP, it increases the rate of spleen preservation, reduces the risk of conversion to open surgery and is associated to shorter length of hospital stay.

Pharmacology and psychiatry at the origins of Greek medicine: The myth of Melampus and the madness of the Proetides.

Melampus is a seer-healer of Greek myth attributed with having healed the young princesses of Argos of madness. Analysis of this legend and its sources sheds light on the early stages of the "medicalizing" shift in the history of ancient Greek medicine. Retrospective psychological diagnosis suggests that the descriptions of the youths' madness rose from actual observation of behavioral and mental disorders. Melampus is credited with having healed them by administering hellebore. Pharmacological analysis of botanical specimens proves that Helleborus niger features actual neurological properties effective in the treatment of mental disorders. The discussion aims at examining the rational aspects of the treatment of mental conditions in Greco-Roman antiquity.

Long-Term Outcome of Rectal Cancer With Clinically (EUS/MRI) Metastatic Mesorectal Lymph Nodes Treated by Neoadjuvant Chemoradiation: Role of Organ Preservation Strategies in Relation to Pathologic Response.

BACKGROUND: Organ preservation strategies are under investigation for patients with locally advanced rectal cancer (LARC) who achieve a complete pathologic response in the primary tumor (ypT0) after neoadjuvant chemoradiation therapy (CRT). This study explored the value of this approach for cN+ patients. METHODS: Data were retrieved from our institutional prospective rectal cancer database. Tumors with mesorectal lymph nodes larger than 5 mm shown on endorectal ultrasonography, pelvic magnetic resonance imaging, or both were staged as cN+. RESULTS: The study population comprised 226 patients (142 men and 84 women; median age, 64 years) with LARC who underwent CRT followed by surgery including total mesorectal excision (TME) (n = 179) and full-thickness local excision (LE) (n = 47) between 1996 and 2013. At staging, 123 patients (54.4 %) were cN+. In 65 cases (28.7 %), ypCR was observed. Metastatic mesorectal lymph nodes (ypN+) were detected in 41.6 % of the cN+ patients and in 2.8 % of the cN0 patients (P < 0.01). Among the cN+ patients, 16 % of the ypT0 cases were ypN+ compared with 51.8 % of the no-ypT0 cases (P < 0.01). Among the cN+ patients who underwent TME, the 5-year disease-specific survival (DSS) and disease-free survival (DFS) rates were respectively 100 and 91.6 % for the ypT0 patients compared with 71.2 and 58.0 % for the no-ypT0 patients (P = 0.01). Among the ypN+ patients, the 5-year DSS and DFS rates were both 100 % for the ypT0 cases compared with 59.1 and 43.3 % for the no-ypT0 patients. Among the cN+ and ypT0 patients, the 5-year DSS and DFS were respectively 100 and 85.7 % for the TME patients compared with 100 and 91.6 % for the LE patients. In the multivariate analysis, ypT0 was the only independent prognostic factor. CONCLUSIONS: Protocols aimed at organ preservation in LARC that achieve ypT0 after CRT can be offered also to cN+ patients.

Reliability of forced internal rotation and active internal rotation to assess lateral instability of the biceps pulley.

PURPOSE: the aim of this study was to investigate the relationship between positive painful forced internal rotation (FIR) and lateral pulley instability in the presence of a pre-diagnosed posterosuperior cuff tear. The same investigation was conducted for painful active internal rotation (AIR). METHODS: a multicenter prospective study was conducted in a series of patients scheduled to undergo arthroscopic posterosuperior cuff repair. Pain was assessed using a visual analog scale (VAS) and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) was administered. The VAS score at rest, DASH score, and presence/absence of pain on FIR and AIR were recorded and their relationships with lesions of the lateral pulley, cuff tear patterns and shape of lesions were analyzed. RESULTS: the study population consisted of 115 patients (mean age: 55.1 years) recruited from 12 centers. The dominant arm was affected in 72 cases (62.6%). The average anteroposterior extension of the lesion was 1.61 cm. The mean preoperative VAS and DASH scores were 6.1 and 41.8, respectively. FIR and AIR were positive in 94 (81.7%) and 85 (73.9%) cases, respectively. The lateral pulley was compromised in 50 cases (43.4%). Cuff tears were partial articular in 35 patients (30.4%), complete in 61 (53%), and partial bursal in 19 (16.5%). No statistical correlation between positive FIR or AIR and lateral pulley lesions was detected. Positive FIR and AIR were statistically associated with complete lesions. Negative FIR was associated with the presence of partial articular tears. CONCLUSIONS: painful FIR in the presence of a postero-superior cuff tear does not indicate lateral pulley instability. When a cuff tear is suspected, positive FIR and AIR are suggestive of full-thickness tear patterns while a negative FIR suggests a partial articular lesion. LEVEL OF EVIDENCE: level I, validating cohort study with good reference standards.

Ratio between metastatic and examined lymph nodes is an independent prognostic factor after D2 resection for gastric cancer: analysis of a large European monoinstitutional experience.

BACKGROUND: In view of the lack of consensus on the level and number of lymph nodes to be examined for accurate staging of patients with gastric cancer, our aim was to evaluate the prognostic significance of lymph node status in a large European monoinstitutional experience. METHODS: A review was made of our prospective database from 1980 to 2000, when 314 of 445 patients operated for gastric adenocarcinoma underwent radical resection (R0) with D2 lymphadenectomy. Survival was determined by the Kaplan-Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression. RESULTS: In 277 evaluable patients, 5-year survival was 57% (median follow-up, 48 months; range, 2-251). A total of 7668 lymph nodes were examined (median, 27; range, 11-62). The 5-year survivals according to the metastatic/examined lymph nodes ratio (N ratio) were 14%, 50%, 61%, and 82% in the group of patients with N ratio >25%, 11%-25%, 1%-10%, and 0%, respectively (P <.0001). At multivariate analysis, the N ratio was the best single independent prognostic factor (P =.000). CONCLUSIONS: After R0 resection for gastric cancer, the N ratio is a potent prognostic factor. It should therefore be considered in the clinical decision making process.

Lymphadenectomy in patients with gastric cancer. A critical review.

BACKGROUND: Surgical resection is still the main treatment for patients with gastric cancer. However, while surgical procedures for the treatment of the primary tumor have been standardized, there has been no worldwide consensus as yet on the extent of lymphadenectomy. The aim of the present study was therefore to evaluate the outcome following extended lymphadenectomy, and the prognostic significance of lymph node status, in a group of patients who underwent radical resection for gastric cancer. METHODS: Among 445 consecutive patients operated on for gastric adenocarcinoma between 1980 and 2000 at Clinica Chirurgica II of the Padua University, 314 underwent radical resection (R0). A D2 lymphadenectomy was performed in 293/314 cases (93.3%), and a D1 in 21/314 (6.7%). The rate of postoperative morbidity was 22% (69/314 patients), and the postoperative mortality (within 30 days of surgery), 4.1% (13/314 patients). Survival was determined using the Kaplan Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression. RESULTS: Of 301 valuable patients, a total of 7991 lymph nodes were examined (mean, 27.18; range, 9-62) and the total number of metastatic lymph nodes was 1343 (mean, 4.5; range, 1-47). After a median follow-up of 49 months (range, 2-251), the overall 5-year survival was 57%. At multivariate analysis of all 301 patients, factors retained were depth of invasion (P < 0.001), age (P = 0.027), number of lymph node metastasis (P = 0.029), and metastatic/examined lymph node ratio (P < 0.0001). CONCLUSIONS: D2 dissection can be performed without incurring high mortality and morbidity rates. At least 15 lymph nodes must be removed to achieve an accurate disease staging. As confirmed at multivariate analysis, a metastatic/examined lymph node ratio greater than 25% is an independent negative prognostic factor.