Effects of tocilizumab versus hemoadsorption combined with tocilizumab in patients with SARS-CoV-2 pneumonia: Preliminary results.

OBJECTIVE: To assess the variations of Interleukin-6 (IL-6) in patients with SARS-CoV-2 infection treated with Tocilizumab (TCZ) alone or in association with hemoadsorption (HA). DESIGN: Retrospective. SETTING: An Intensive Care Unit (ICU) admitting mechanically ventilated patients with SARS-CoV-2 pneumonia. PATIENTS: Four adult patients. INTERVENTIONS: We compared the blood values of IL-6, C-reactive protein (CRP) and of other biochemical variables including the PaO2/FiO2 in two patients who received TCZ alone and in other 2 in whom it was associated with the HA (TCZ-HA) due to the presence of impending or established organ failures other than the lung. All variables were measured before, during and after the treatment. MAIN RESULTS: In all patients, the IL-6 increased during the treatment; after its termination, its values sharply decreased only in those treated also with HA; conversely, the CRP decreased in all patients; the PaO2/FiO2 increased in three patients and remained stable in the remaining one. Both the TCZ and the HA were well tolerated; all patients were weaned from the mechanical ventilation and discharged from the hospital. LIMITATIONS: Although the limited number of patients does not allow to draw firm conclusions, the increase of the IL-6 of can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ-HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with the SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators.

Kinetics of Immunoglobulins in Septic Shock Patients Treated With an IgM- and IgA-Enriched Intravenous Preparation: An Observational Study.

Objective: To assess the variations of the blood levels of immunoglobulins (Ig) in septic shock patients treated with an Ig preparation enriched in IgM and IgA (eIg). Design: The blood levels of Ig in survivors (S) and non-survivors (NS) of a group of septic shock patients were measured before the initial administration (D0) and 1 (D1), 4 (D4), and 7 (D7) days thereafter. The SAPS II score, the capillary permeability, the primary site of infection, the antibiotic appropriateness, and the outcome at 28 days were also assessed. Results: In the interval D0-D7, the IgM increased significantly only in the S while remained stable in NS; the IgA significantly increased in both groups; the IgG did not vary significantly in both groups. At D4, the capillary permeability significantly decreased in S but not in NS. Conclusions: The kinetics of the different classes of Ig after eIg were different between S and NS. This could be related either to (a) different capillary permeability in the two groups or to (b) higher Ig consumption in NS. Further studies to confirm the benefits of eIg in the treatment of sepsis syndrome and to define the specific target population and the correct eIg dose are warranted.

Correction to: Effects of the timing of administration of IgM- and IgA-enriched intravenous polyclonal immunoglobulins on the outcome of septic shock patients.

Following publication of the original article [1], we have been notified that the tagging of the author name was done incorrectly in the XML version of the paper. The correct given name is Michele Claudio, and the family name is Vassallo.

Effects of the timing of administration of IgM- and IgA-enriched intravenous polyclonal immunoglobulins on the outcome of septic shock patients.

BACKGROUND: The administration of endovenous immunoglobulins in patients with septic shock could be beneficial and preparations enriched with IgA and IgM (ivIgGAM) seem to be more effective than those containing only IgG. In a previous study Berlot et al. demonstrated that early administration of ivIgGAM was associated with lower mortality rate. We studied a larger population of similar patients aiming either to confirm or not this finding considering also the subgroup of patients with septic shock by multidrug-resistant (MDR) pathogens. METHODS: Adult patients with septic shock in intensive care unit (ICU) treated with ivIgGAM from August 1999 to December 2016 were retrospectively examined. Collected data included the demographic characteristics of the patients, the diagnosis at admission, SOFA, SAPS II and Murray Lung Injury Score (LIS), characteristics of the primary infection, the adequacy of antimicrobial therapy, the delay of administration of ivIgGAM from the ICU admission and the outcome at the ICU discharge. Parametric and nonparametric tests and logistic regression were used for statistic analysis. RESULTS: During the study period 107 (30%) of the 355 patients died in ICU. Survivors received the ivIgGAM earlier than nonsurvivors (median delay 12 vs 14 h), had significantly lower SAPS II, SOFA and LIS at admission and a lower rate of MDR- and fungal-related septic shock. The appropriateness of the administration of antibiotics was similar in survivors and nonsurvivors (84 vs 79%, respectively, p: n.s). The delay in the administration of ivIgGAM from the admission was associated with in-ICU mortality (odds ratio per 1-h increase = 1.0055, 95% CI 1.003-1.009, p < 0.001), independently of SAPS II, LIS, cultures positive for MDR pathogens or fungi and onset of septic shock. Only 46 patients (14%) had septic shock due to MDR pathogens; 21 of them (46%) died in ICU. Survivors had significantly lower SAPS II, SOFA at admission and delay in administration of ivIgGAM than nonsurvivors (median delay 18 vs 66 h). Even in this subgroup the delay in the administration of ivIgGAM from the admission was associated with an increased risk of in-ICU mortality (odds ratio 1.007, 95% CI 1.0006-1.014, p = 0.048), independently of SAPS II. CONCLUSIONS: Earlier administration of ivIgGAM was associated with decreased risk of in-ICU mortality both in patients with septic shock caused by any pathogens and in patients with MDR-related septic shock.

Effect of different postoperative flexion regimes on the outcomes of total knee arthroplasty: randomized controlled trial.

PURPOSE: A consistent limb position strategy could be an attractive and easier alternative to reduce blood loss and increase range of motion following total knee arthroplasty. The aim of this study was to understand the proper amount of flexion required to improve functional outcomes with limited patients' discomfort. METHODS: Eighty-five patients undergoing total knee arthroplasty were randomly assigned to receive mild (30° of knee flexion) or high-flexion protocol (70° of knee flexion), 48 h after surgery. The same daily rehabilitation scheme was followed. Total blood loss, hidden blood loss, haemoglobin and haematocrit levels, fixed flexion deformity, range of motion and limb circumference at the superior patellar pole were evaluated preoperatively and 7 days after surgery. RESULTS: Demographics, blood parameters and preoperative range of motion did not show any significant difference between the two groups. No complications were recorded in both groups. High-flexion group had greater rate of dropout due to excessive patients' discomfort. A significantly lower Hb at day 1 was found in the high-flexion group. No differences were recorded regarding the remaining parameters. CONCLUSION: No significant differences were found between the high-flexion and mild-flexion protocols; however, mild-flexion protocol was better tolerated by patients. We therefore recommend a 30° flexion protocol to be routinely used 48 h postoperatively after total knee arthroplasty. This is an easy strategy to improve functional outcomes, which is a fundamental issue considering the steady increase in knee prostheses utilization. LEVEL OF EVIDENCE: Randomized controlled trial, Level II.

Small bowel intussusception from renal cell carcinoma metastasis: a case report and review of the literature.

BACKGROUND: Renal cell carcinoma is the most frequent malignant neoplasia of the kidney accounting for 90 % of all renal solid tumors. Metastases from renal cell carcinoma are rarely located in the small bowel and generally their clinical presentation includes bleeding and obstruction. Intussusception in adults is an extremely rare pathological condition and only 30 to 35 % of small bowel intussusceptions are derived from malignant lesions. CASE PRESENTATION: We report here a clinical case of a 75-year-old white man hospitalized for anemia and subocclusion. An abdominal ultrasound and computed tomography showed a small bowel intussusception. During a surgical exploration, a polypoid lesion was found to be the lead point of the intussusception. His small intestine was resected and a functional side-to-side anastomosis was performed. The histological features of the surgical specimen confirmed the diagnosis of metastatic renal cell carcinoma. CONCLUSIONS: Small bowel intussusception from renal cell carcinoma metastasis should always be considered in the setting of unexplained intestinal subocclusion in patients with a history of renal cell carcinoma.

Psychosocial impact of presymptomatic genetic testing for transthyretin amyloidotic polyneuropathy.

Presymptomatic genetic testing of an untreatable disease raises clinical, ethical, legal and psychosocial questions. Investigations in specific disorders are needed to help in understanding the motivation for and the impact of genetic testing in the lives of persons at risk for these diseases. Here, we performed a longitudinal study to investigate the psychological consequences of presymptomatic genetic testing on people at risk for transthyretin-related familial amyloidotic polyneuropathy (TTR-FAP). The aim of the present study was to provide possible guidelines for genetic counselling and psychosocial support. Impact of Event Scale Revised (IES-R), Hospital Anxiety and Depression Scale (HADS) and SF-36 questionnaires were administered to 18 asymptomatic subjects before, immediately after communication of the genetic test result and after 3, 6 and 26 months. Our findings showed evidence of anxiety, depression, avoidance of the disease, and psychological distress, especially for women, including those with a negative genetic test result ("survivor guilt"). A psychological support has to be provided before and continued at long term after presymptomatic genetic testing for TTR-FAP in people with positive result as well as in those with negative result.

Unilateral cerebellar stroke disrupts movement preparation and motor imagery.

OBJECTIVE: To assess motor cortex excitability, motor preparation and imagery in patients with unilateral cerebellar stroke with damage of the dentate nucleus by using transcranial magnetic stimulation (TMS). METHOD: Eight patients with unilateral cerebellar lesions due to tromboembolic stroke and 10 age matched healthy subjects were enrolled. Resting (RMT) and active (AMT) motor threshold, cortical and peripheral silent period, evaluation of motor imagery, reaction time and premovement facilitation of motor evoked potential (MEP) were tested bilaterally using TMS. RESULTS: The RMT and AMT were found to be increased contra lateral to the affected cerebellar hemisphere while the cortical silent period was prolonged. In addition the amount of MEP facilitation during motor imagery and the pre-movement facilitation were reduced in the motor cortex contra lateral to the affected cerebellar hemisphere. The reaction time, performed with the symptomatic hand, was slower. CONCLUSIONS: On the whole, our data confirm a role for the cerebellum in maintaining the excitability of primary motor area. Furthermore, patients with unilateral cerebellar stroke exhibit lateralized deficit of motor preparation and motor imagery. SIGNIFICANCE: Our results add to evidence that cerebellum contributes to specific aspects of motor preparation and motor imagery.