Should be a Third Dose of BNT162b2 mRNA COVID-19-Vaccine Administered in Patients with Myelofibrosis Under Ruxolitinib?

Patients with Myelobrosis (MF) are considered fragile and thus eligible in Italy for COVID-19 BNT162b2 mRNA vaccination. According to the International Prognostic Scoring System (IPSS), patients with intermediate and high MF, may receive clinical benets from ruxolitinib, the rst approved JAK1/JAK2 inhibitor. Given the potent anti-in ammatory properties of ruxolitinib against immunocompetent cells, we previously reported a lower but non-statistically absolute IgG anti-Spike humoral response in vaccinated MF patients treated with ruxolitinib. In the present report we extended the cohort of MF patients

The advancement of blood cell research by optical tweezers

Demonstration of the light radiation pressure on a microscopic level by A. Ashkin led to the invention of optical tweezers (OT). Applied in the studies of living systems, OT have become a preferable instrument for the noninvasive study of microobjects, allowing manipulation and measurement of the mechanical properties of molecules, organelles, and cells. In the present paper, we overview OT applications in hemorheological research, placing emphasis on red blood cells but also discussing OT applications for the investigation of the biomechanics of leukocytes and platelets. Blood properties have always served as a primary parameter in medical diagnostics due to the interconnection with the physiological state of an organism. Despite blood testing being a well-established procedure of conventional medicine, there are still many complex processes that must be unraveled to improve our understanding and contribute to future medicine. OT are advancing single-cell research, promising new insights into individual cell characteristics compared to the traditional approaches. We review the fundamental and practical findings revealed in blood research through the optical manipulation, stretching, guiding, immobilization, and inter-/intracellular force measurements of single blood cells

Nicotinic acetylcholine receptors assembled from the alpha7 and beta3 subunits

Intracellular recordings were performed in voltageclamped Xenopus oocytes upon injection with a mixture of cDNAs encoding the β3 and mutant α7 (L247Tα7) neuronal nicotinic acetylcholine receptor (nAChR) subunits. The expressed receptors maintained sensitivity to methyllycaconitine and to α-bungarotoxin but exhibited a functional profile strikingly different from that of the homomericL247Tα7 receptor. The heteromericL247T α7 β3 nAChR had a lower apparent affinity and a faster rate of desensitization than L247Tα7 nAChR, exhibited nonlinearity in the I-V relationship, and was inhibited by 5-hydroxytryptamine, much like wild type α7 (WT α7) nAChR. Single channel recordings in cell-attached mode revealed unitary events with a slope conductance of 19 picosiemens ans a lifetime of 5 ms, both values being much smaller than those of the homomeric receptor channel. Upon injection with a mixture of WTα7 and β3 cDNAs, clear evidence was obtained for the plasma membrane assembly of heteromeric nAChRs, although ACh could not activate these receptors. It is concluded that β3, long believed to be an orphan subunit, readily co-assembles with other subunits to form heteromeric receptors, some of which may be negative regulators of cholinergic function.</p

Cone-like resection, fistulectomy and mucosal rectal sleeve partial endorectal pull-through in paediatric Crohn's disease with perianal complex fistula

Background: Perianal abscesses and fistulae have been reported in approximately 15% of patients with paediatric Crohn's disease and they are associated with poor quality of life. Several surgical techniques were proposed for the treatment of perianal Crohn's disease, characterized by an elevated incidence of failure, incontinence, and relapse.Aim of our study was to present the technical details and results of our surgical technique in case of recurrent, persistent, complex perianal ano-rectal destroying Crohn's disease not responding to medical treatment. Methods: Data of patients who underwent surgical treatment (cone-like resection, fistulectomy, sphincter reconstruction, endorectal advancement sleeve flaps like in Soave endorectal pull-through) for complicated high-level trans, inter or suprasphincteric fistulae between January 2009 and June 2014 were retrospectively reviewed. Results: 20 surgical procedures were performed in 11 patients (males 72.7%) with transsphincteric (n= 5), intersphincteric (n= 4) and suprasphincteric (n= 2) fistulae. Three patients needed a second treatment. Two patients needed more than 2 surgeries and one temporary colostomy. No patient presented anal incontinence at 15 months' median follow-up. Conclusions: Although several procedures may be required to obtain a complete remission of perianal lesions, in our series the proposed surgical technique seemed effective and safe, preserving anal continence in all treated cases and reducing the need of faecal diversion

The impact of visceral adipose tissue on postoperative renal function after radical nephrectomy for renal cell carcinoma

BACKGROUND: The objective of this study was to evaluate the usefulness of pre-operative visceral (VAT) and subcutaneous adipose tissue (SAT) evaluation in the prediction of acute kidney injury (AKI) and decrease of eGFR at 12 months after radical nephrectomy (RN).METHODS: We relied on 112 patients who underwent RN between January 2010 and March 2017 at a single institution. Images from the pre-operatory CT scan were analyzed and both SAT and VAT assessments were carried out on a cross-sectional plane. eGFR was measured before surgery, at 7 days, and 12 months after surgery. ROC analysis was used to compare the diagnostic value of BMI, VAT ratio, and abdominal circumference in predicting AKI. Logistic regression models were fitted to predict the new onset of AKI, and the progression from chronic kidney disease (CKD) stage 1-3a to CKD stage 3b or from 3b to 4 at 12 months follow-up. Two logistic regression models were also performed to assess the predictors for AKI and CKD stage progression. The predictive accuracy was quantified using the receiver operating characteristic-derived area under the curve.RESULTS: Sixty-six patients (58.9%) had AKI after RN. Thirty-five (31.3%) patients were upgraded to CKD IIIb or from CKD stage IIIb to CKD IV. In the ROC analysis, VAT% performed better than the BMI and abdominal circumference (AUC=0.66 vs. 0.49 and 0.54, respectively). At multivariable analyses, VAT reached an independent predictor status for AKI (OR: 1.03) and for CKD stage at 12-month follow-up (OR: 1.05). Inclusion of VAT% into the multivariable models was associated with the highest accuracy both for AKI (AUC=0.700 vs. 0.570) and CKD stage progression (AUC=0.848 vs. 0.800).CONCLUSIONS: In patients undergoing RN, preoperative visceral adipose tissue ratio significantly predicts AKI incidence and is significantly predictive of 12-month CKD stage worsening

Morbidity and risk factors of laparoscopic-assisted ileostomies in children with ulcerative colitis

Introduction: Laparoscopic-assisted ileostomy (LAI) represents a cornerstone for the staged approach to ulcerative colitis (UC). The aim is to determine stoma morbidity in a series of pediatric patients and possibly identify specific risk factors. Methods: All of the patients who underwent LAI for UC between January 2008 and December 2014 were included. The following data were collected: patient demographics, preoperative medical treatment, body mass index (BMI) at surgery, Pediatric UC Index (PUCAI), and stoma-related complications. In this series of patients, a staged approach has been adopted (subtotal colectomy + ileostomy; restorative proctocolectomy with J-pouch ileo-rectal anastomosis + ileostomy; ileostomy closure). Results: Seventy-two LAIs were fashioned in 37 pediatric patients with UC. Median age at surgery was 12 years (range 5-14.8 years). Boy to girl ratio was 0.85:1. Mortality was zero. Complications occurred after 8 procedures after a median of 31 days postoperatively (range 8-60 days). Those were significantly more frequent in the case of BMI-z score &gt;-0.51 (deleted in revised manuscript, ie, relatively overweight patients) and in the case of preoperative azathioprine administration. Pediatric UC Index score, sex, number of preoperative medications, and other preoperative parameters did not correlate with the incidence of complications. Conclusions: Our study suggests to keep a prudent behavior in the case of patients with a BMI-z score &gt;-0.51 and received preoperative azathioprine administration. Parents should be adequately acknowledged on this regard

Patients with Chronic Lymphocytic Leukemia Have a Very High Risk of Ineffective Response to the BNT162b2 Vaccine

Patients with CLL have high rates of either severe disease or death from COVID-19 and a low response rate after COVID-19 vaccination has been reported. We conducted a single-center study with the main objective to evaluate the immunogenicity of the BNT1162b2 mRNA vaccines in 42 patients affected by CLL with the assessment of antibody response after the second and the third dose. After the second dose of vaccine, 13 patients (30%) showed an antibody response. The presence of hypogammaglobulinemia and the use of steroids or IVIG were the main factors associated with poor response. After the third dose, 5/27 (18%) patients showed an antibody response while in non-responders to the second dose, only 1 patient (4%) showed an elicitation of the immune response by the third dose, with no statistically significant difference. Our data, despite the small size of our cohort, demonstrate that patients with CLL have a low rate of effective response to the BNT162b2 vaccine. However, the effective role of a subsequent dose is still unclear, highlighting the need for alternative methods of immunization in this particularly fragile group of patients