Risk factors for in-hospital mortality after emergency colorectal surgery in octogenarians: results of a cohort study from a referral center.

PURPOSE: The objective of this study was to investigate predictive factors of mortality in emergency colorectal surgery in octogenarian patients. METHODS: It is a retrospective cohort study conducted at a single-institution tertiary referral center. Consecutive patients who underwent emergency colorectal surgery between January 2015 and January 2020 were identified. The primary endpoint was 30-day mortality. Univariate and multivariate analyses were performed using a logistic regression model. RESULTS: A total of 111 patients were identified (43 men, 68 women). Mean age was 85.7 ± 3.7 years (80-96). Main diagnoses included complicated sigmoiditis in 38 patients (34.3%), cancer in 35 patients (31.5%), and ischemic colitis in 31 patients (27.9%). An ASA score of 3 or higher was observed in 88.3% of patients. The mean Charlson score was 5.9. The Possum score was 35.9% for mortality and 79.3% for morbidity. The 30-day mortality rate was 25.2%. Univariate analysis of preoperative risk factors for mortality shows that the history of valvular heart disease (p = 0.008), intensive care unit provenance (p = 0.003), preoperative sepsis (p < 0.001), diagnosis of ischemic colitis (p = 0.012), creatinine (p = 0.006) and lactate levels (p = 0.01) were significantly associated with 30-day mortality, and patients coming from home had a lower 30-day mortality rate (p = 0.018). Intraoperative variables associated with 30-day mortality included ileostomy creation (p = 0.022) and temporary laparostomy (p = 0.004). At multivariate analysis, only lactate (p = 0.032) and creatinine levels (p = 0.027) were found to be independent predictors of 30-day mortality, home provenance was an independent protective factor (p = 0.004). Mean follow-up was 3.4 years. Survival at 1 and 3 years was 57.6 and 47.7%. CONCLUSION: Emergency colorectal surgery is challenging. However, age should not be a contraindication. The 30-day mortality rate (25.2%) is one of the lowest in the literature. Hyperlactatemia (> 2mmol/L) and creatinine levels appear to be independent predictors of mortality.

First-Line Treatment of Older Patients with CLL: A New Approach in the Chemo-Free Era.

Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti-CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, patient inclusion criteria are heterogeneous across trials designed for older patients, and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events is required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies, and registry analyses provided useful information on factors predicting earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs, and the overall expenditure for new drugs in CLL is projected to increase substantially, posing an issue for sustainability. This being said, the choice of a finite-duration treatment based on venetoclax-containing regimens or treatment until progression with BTKi is today possible in high-income countries, and the therapy choice drivers are represented by coexisting medical conditions rather than age, patient expectations, logistics, and sustainability.

BL-MOL-AR Project, Preliminary Results about Liquid Biopsy: Molecular Approach Experience and Research Activity in Oncological Settings.

Background Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous. Methods The Biopsia Liquida-Molecolare-Arezzo study aims to enroll cancer patients affected by various malignancies, including pulmonary, intestinal, advanced urothelial, biliary, breast, cutaneous, and gastric malignancies. Thirty-nine patients were included in this preliminary report. At time zero, a liquid biopsy is executed, and two types of NGS panels are performed, comprising 17 genes in panel 1, which is already used in the routine tissue setting, and 52 genes in panel 2. From the 7th month after enrollment, 10 sequential liquid biopsies are performed up to the 17th month. The variant allele frequency (%) and cfDNA levels (ng/mL) are measured in every plasmatic sample. Results The NGS results obtained by different panels are similar even though the number of mutations is more concordant for lung pathologies. There are no significant differences in the actionability levels of the identified variants. Most of the molecular profiles of liquid biopsies reflect tissue data. Conclusions Preliminary data from this study confirm the need to clarify the limitations and potential of liquid biopsy beyond the lung setting. Overall, parameters related to cfDNA levels and variant allele frequency could provide important indications for prognosis and disease monitoring.

Evaluation of the SafeHeal Colovac+ anastomosis protection device after low anterior resection for rectal cancer: the safe anastomosis feasibility evaluation (SAFE) 2019 trial.

BACKGROUND: Protective ileostomy (PI) is the current standard of care to protect the anastomosis after low anterior resection (LAR) for rectal cancer, but is associated with significant morbidity. Colovac is an anastomosis protection device designed to shield the anastomosis from fecal content. A second version (Colovac+) was developed to limit the migration risk during the implantation period. The objective of this clinical trial was to evaluate the preliminary efficacy and safety of the Colovac+. METHODS: This was a prospective, multicenter, pilot study aiming to enroll 15 patients undergoing LAR with Colovac+ placement. After 10 days, a CT scan was performed to evaluate the anastomosis and the Colovac+ was retrieved endoscopically. During the 10-day implantation and 3-month follow-up period, we collected data regarding predefined efficacy and safety endpoints. The primary endpoint was the rate of major (Clavien-Dindo III-V) postoperative complications related to the Colovac+ or LAR procedure. RESULTS: A total of 25 patients were included (68% male), of whom 15 were consecutively treated with the Colovac+ and Vacuum Loss Alert System. The Colovac+ was successfully implanted in all 15 patients. No major discomfort was reported during the implantation period. The endoscopic retrieval was performed in 14/15 (93%) patients. The overall major postoperative morbidity rate was 40%, but none of the reported complications were related to the Colovac+. A device migration occurred in 2 (13%) patients, but these were not associated with AL or stoma conversion. Overall, Colovac+ provided effective fecal diversion in all 15 patients and was able to avoid the PI in 11/15 (73%) patients. CONCLUSIONS: Colovac+ provides a safe and effective protection of the anastomosis after LAR, and avoids the PI in the majority (73%) of patients. The improved design reduces the overall migration rate and limits the clinical impact of a migration.

Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: a nationwide registry study from the Italian Medicines Agency.

In this analysis we describe the effectiveness of first-line ibrutinib in 747 patients with chronic lymphocytic leukemia (CLL) and TP53 aberrations in a nationwide study with a 100% capture of patients who received the study drug. Median age was 71 years (range 32-95). An estimated treatment persistence rate of 63.4% (95% CI 60.0%-67.0%) and survival rate of 82.6% (95% CI 79.9-85.4%) were recorded at 24 months. Disease progression or death were the reasons for discontinuation in 182/397 patients (45.8%). A higher risk of treatment discontinuation was found to be associated with age, ECOG-PS and pre-existing heart disease, whereas ECOG ≥ 1, age ≥ 70 years and male sex were associated with an increased risk of death. Median post-progression overall survival (OS) was 12.2 months (95% CI 9.2-22.0). Post-discontinuation median OS in patients who discontinued ibrutinib for other reasons was not reached (95% CI 42.3 months - NA). Ibrutinib was an effective first-line treatment for CLL and TP53 aberrations in patients treated at large academic centers and community practice hospitals. Clinical characteristics at baseline may influence the effectiveness of ibrutinib, whereas the experience of prescribing centers and multi-hit or single-hit TP53 aberrations had no impact on outcome in this high-risk population.

Laparoscopy-assisted vs open total gastrectomy with D2 lymphadenectomy for advanced gastric cancer: results of a retrospective, multicenter study.

The aim of this study was to retrospectively compare the results of laparoscopy-assisted total gastrectomy (LATG) with those of open total gastrectomy (OTG) for advanced gastric cancer. Patients undergoing total gastrectomy for a T4a, N0-3a-b, M0 gastric adenocarcinoma were divided into two groups. Patients in group A (n = 122) underwent LAG, whereas patients in group B (n = 109) underwent OTG. Mean length of follow-up was 39 months. Primary study's endpoints were postoperative mortality and morbidity, overall late survival (OS) and disease-free survival (DFS). Secondary endpoints were the number of retrieved lymph nodes, operating time, intraoperative blood loss, postoperative length of stay (LOS) and the incidence of local recurrence. Twenty-four patients in group A (19.6%) required conversion into OTG. Postoperative mortality was absent in both groups. Postoperative morbidity was 19% in group A and 11% in group B [p = 0.19]. OS was 34% in group A and 42% in group B [p = 0.21]. DFS was 29% in group A and 33% in group B [p = 0.49]. Mean number of retrieved lymph nodes was 29 in group A and 34 in group B [p < 0.01]. Mean intraoperative blood loss was 230 ml in group A and 180 ml in group B [p = 0.02]. Mean postoperative LOS was 9 days in group A and 11 days in group B [p = 0.09]. Local recurrence was 19% in group A and 13% in group B [p = 0.20]. For advanced gastric cancer, OTG favorably compares with LATG.

Monocyte distribution width and the fighting action to neutralize sepsis (FANS) score for sepsis prediction in emergency department.

BACKGROUND AND AIMS: The aim of this study was to evaluate the diagnostic accuracy of sepsis markers and to develop a multiparametric score, using demographic and clinical variables as well as laboratory parameters to predict sepsis in patients admitted in the ED with suspected symptoms. MATERIALS AND METHODS: Patients with clinical presentation of suspected sepsis were enrolled in the ED of San Donato Hospital in Arezzo between September 2019 and May 2020. Anagraphic, anamnestic, clinical and laboratory data were collected for all subjects. PCT, MDW, WBC, MPV and BT were utilised to formulate FANS score. RESULTS: The AUC of the FANS score, PCT, MDW and CRP was 0.87, 0.80, 0.77 and 0.71, respectively, when used to predict sepsis in all 308 subjects. Instead, the AUC of the FANS (Fighting Action To Neutralize Sepsis) score, PCT, MDW and CRP was 0.93, 0.84, 0.83 and 0.77, respectively, when used to predict sepsis excluding subjects with infection (clinically classified as the Infections group). CONCLUSIONS: The results obtained with PCT, PCR and MDW confirm the results of these markers for the identification of sepsis obtained from other studies. The multiparametric approach, obtained from the statistical study of the parameters using binary logistic regression, identified those PCT, WBC, MPV, BT and MDW as the most significant and effective clinical classifiers for diagnosing sepsis.

A Cost Analysis of Healthcare Episodes Including Day-Case Bariatric Surgery (Roux-en-Y Gastric Bypass and Sleeve Gastrectomy) Versus Inpatient Surgery.

BACKGROUND: Assessing the medico-economic outcomes of a healthcare pathway including day-case bariatric surgery versus the conventional pathway. METHODS: This economical evaluation is a prospective cohort study with historical controls. Between March 2019 and December 2020, 30 patients eligible for bariatric surgery were considered in the day-case group. Surgical procedures included sleeve gastrectomy and Roux-en-Y gastric bypass. The day-case pathway included patient education, post-discharge follow-up by a community nurse twice-daily and standardized communications to surgeons. Day-case patients were paired with 30 inpatients, based on the type of intervention, age, and ASA status. The primary outcome was the cost of care episodes from the preoperative visit to the 30-day postoperative visit. Micro-costing methodology and activity-based costing were used. Secondary outcomes included length of hospital stay, rate of unanticipated events, and patient' satisfaction assessment. RESULTS: Male-to-female ratio was 1/2. In the day-case versus inpatient group, age, number of associated medical conditions, and BMI (42.9 ± 4.9 versus 42.6 ± 4.6, p > 0.05) were similar. In the day-case group, there were 7 overnight stays (23.3%), 3 readmissions (10%), and 4 unscheduled consultations (13.3%). The overall length of hospital stay was significantly shorter (0.65 ± 0.33, versus 2.9 ± 0.4 days, p < 0.0001). The complication rate was 6.6% in both groups. The cost of the care episode was € 4272.9 ± 589.7 for the day-case group versus € 4993.7 ± 695.6 for inpatients, corresponding to a 14.4% cost reduction (p = 0.0254). CONCLUSIONS: Day-case bariatric surgery appears to be safe and beneficial in terms of costs. It involves a specific organization with postdischarge follow-up. TRIAL REGISTRATION: ClinicalTrial.gov: NCT04423575.

Evaluation of the SafeHeal Colovac+ Anastomosis Protection Device: A Preclinical Study.

BackgroundThe protective ostomy is the current standard of care to protect a low colorectal anastomosis from leakage, but exposes patients to complications requiring an alternative strategy. The Colovac+ is a vacuum-based intraluminal bypass device designed to shield the anastomosis from fecal content, preventing the clinical outcomes of anastomotic leakage. The objective of this study was to evaluate the preliminary efficacy, safety, and technical feasibility of the Colovac+ in a porcine model. Methods: Twelve pigs received a colorectal anastomosis with Colovac+ implantation. The device was left in situ for 10 days and then retrieved endoscopically. Six pigs were to be sacrificed immediately after device retrieval and the other 6 were to be sacrificed on day 38. Clinical, endoscopic, and histopathological examinations were performed to evaluate the following endpoints: prevention of contact between the anastomosis and fecal content, device migration, feasibility of the implantation and retrieval procedure, collateral damage to the colonic wall, colon healing after device retrieval, and systemic toxicity related to the device. Results: Eleven pigs completed the study. One pig died prematurely due to a surgical complication unrelated to the device (bladder damage with uroperitoneum). There was no evidence of contact between the anastomosis and fecal content, none of the pigs developed symptomatic anastomotic leakage, there were no significant device migrations, and there was no evidence of systemic toxicity. Colovac+ implantation was easily performed in all cases except 1 (due to an inappropriate lubricant). Colovac+ retrieval was achieved successfully in all cases. Postretrieval examinations on day 10 revealed ulcerations at the anchoring site in 4 cases indicating mechanical damage caused by the stent. However, in the recovery group, no ulcerations were observed on day 38, and the colonic wall had properly healed in all animals. Conclusions: The Colovac+ is a technically feasible, safe, and efficient device for the protection of a colorectal anastomosis in a porcine model. The device holds promise for clinical use and warrants further research.

Spontaneously reversible adrenal nodules in primary diffuse large B-cell testicular lymphoma mimicking an extranodal involvement: A case report.

In the staging of cancer patients, transient and spontaneously reversible bilateral adrenal hypertrophy may mimic a secondary localization of the disease. We discuss the case of an 82-year-old male patient with suspected testicular neoplasia in which abdominal CT examination reveals the onset of a bilateral macronodular adrenal enlargement, suggesting the diagnostic hypothesis of primary testicular neoplasia with secondary adrenal localization. The subsequent 18FDG-PET/CT study showed hyper-metabolism of the testicular mass, while the adrenal glands, surprisingly, did not show increased uptake of the radiotracer. After right orchifunicolectomy, primary testicular diffuse large B-cell lymphoma was diagnosed. The subsequent staging PET/CT study with iodine contrast medium, three months after the first CT examination, showed spontaneous complete regression of the adrenal hypertrophy without any use of drug therapy. The differential diagnosis of this finding considered the lack of hypermetabolism and the densitometric characteristics of the adrenal glands, the absence of possible pharmacological interactions throughout the time of the diagnostic procedures, and the available clinical-laboratory data. By excluding the main causes of adrenal hypertrophy, the most likely diagnostic hypothesis was transient adrenal hypertrophy due to stress induced by testicular lymphoma, meaning by stress a disturbance not only emotional but also an alteration of organic homeostasis. Our case suggests that the analysis of adrenal lesions appeared in cancer patients should take into account non-metastatic conditions that must be studied with a multimodal approach and with serial investigations.

Indications and Long-Term Outcomes of Conversion of Sleeve Gastrectomy to Roux-en-Y Gastric Bypass.

PURPOSE: Long-term results on sleeve gastrectomy (SG) with more than 10 years report patients needing sleeve revision for weight loss failure, de novo gastroesophageal reflux (GERD), or sleeve complications. The aim of this study was to analyze the results of laparoscopic conversion of failed SG to Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: Retrospective review of a prospectively institutional maintained database to identify patients who underwent conversion of SG to RYGB between 2012 and June 2020. RESULTS: Sixty patients(50 females) underwent conversion to RYGB. Average time to conversion was 5.6 years (2-11). Mean %WL and TWL after SG were respectively 26±8.8% and 33.2±14.1kg. Mean BMI at the time of RYGB was 38.1±7.1 kg/m2. Mean follow-up was 30.4±16.8 months (6-84). Available patients at each time of follow-up: 1 year 59 (98.3%); 2 years 47 (78.3%); 3 years 39 (71.6%); and 5 years 33 (55%). Patients were divided according to indication for revision in weight regain/insufficient weight loss (30 patients) group 1 and GERD/complications (25 patients) group 2. Percentage of excess weight loss at 1, 3, and 5 years follow-up after bypass was for group 1 40.3±17.6, 34.3±19.5, and 23.2±19.4 and for group 2 90.4±37, 62.6±28.2, and 56±35.02. Total weight loss at last follow-up since sleeve was respectively 31kg in group 1 and 46.7kg in group 2 (p=0.002). No mortality was observed. Thirty-day complication rate was 3.3%. CONCLUSION: RYGB after SG is a safe and effective revisional procedure to manage weight regain and de novo GERD, to address complications, and to improve comorbidities.

In chronic lymphocytic leukaemia, SLAMF1 deregulation is associated with genomic complexity and independently predicts a worse outcome.

In a series of 349 patients with chronic lymphocytic leukaemia (CLL), we found lower levels of signalling lymphocytic activation molecule family member 1 (SLAMF1) expression in cases with highly complex karyotypes, as defined by the presence of five or more chromosomal abnormalities (CK5; P < 0·001) and with major chromosomal structural abnormalities (P < 0·001). SLAMF1 downregulation was significantly associated with advanced Binet Stage (P = 0·001), CD38 positivity (P < 0·001), high ß2 -microglobulin levels (P < 0·001), immunoglobulin heavy chain variable region gene (IGHV) unmutated status (P < 0·001), 11q deletion (P < 0·001), tumour protein p53 (TP53) disruption (P = 0·011) and higher risk CLL International Prognostic Index categories (P < 0·001). Multivariate analysis showed that downregulated SLAMF1 levels had independent negative prognostic impact on time-to-first treatment (P < 0·001) and overall survival (P < 0·001).

Computer-assisted quantification and visualization of bowel perfusion using fluorescence-based enhanced reality in left-sided colonic resections.

BACKGROUND: Fluorescence-based enhanced reality (FLER) is a computer-based quantification method of fluorescence angiographies to evaluate bowel perfusion. The aim of this prospective trial was to assess the clinical feasibility and to correlate FLER with metabolic markers of perfusion, during colorectal resections. METHODS: FLER analysis and visualization was performed in 22 patients (diverticulitis n = 17; colorectal cancer n = 5) intra- and extra-abdominally during distal and proximal resection, respectively. The fluorescence signal of indocyanine green (0.2 mg/kg) was captured using a near-infrared camera and computed to create a virtual color-coded cartography. This was overlaid onto the bowel (enhanced reality). It helped to identify regions of interest (ROIs) where samples were subsequently obtained. Resections were performed strictly guided according to clinical decision. On the surgical specimen, samplings were made at different ROIs to measure intestinal lactates (mmol/L) and mitochondria efficiency as acceptor control ratio (ACR). RESULTS: The native (unquantified) fluorescent signal diffused to obvious ischemic areas during the distal appreciation. Proximally, a lower diffusion of ICG was observed. Five anastomotic complications occurred. The expected values of local capillary lactates were correlated with the measured values both proximally (3.62 ± 2.48 expected vs. 3.17 ± 2.8 actual; rho 0.89; p = 0.0006) and distally (4.5 ± 3 expected vs. 4 ± 2.5 actual; rho 0.73; p = 0.0021). FLER values correlated with ACR at the proximal site (rho 0.76; p = 0.04) and at the ischemic zone (rho 0.71; p = 0.01). In complicated cases, lactates at the proximal resection site were higher (5.8 ± 4.5) as opposed to uncomplicated cases (2.45 ± 1.5; p = 0.008). ACR was reduced proximally in complicated (1.3 ± 0.18) vs. uncomplicated cases (1.68 ± 0.3; p = 0.023). CONCLUSIONS: FLER allows to image the quantified fluorescence signal in augmented reality and provides a reproducible estimation of bowel perfusion (NCT02626091).

Comparison of serologic and molecular SARS-CoV 2 results in a large cohort in Southern Tuscany demonstrates a role for serologic testing to increase diagnostic sensitivity.

BACKGROUND: Since February 2020, Italian hospitals registered COVID-19 (COronaVIrus Disease 19) cases more often than the rest of the Europe. During this epidemic, health authorities requested swab tests, while seeking new patient paths. METHODS: A dual laboratory approach was evaluated, consisting of patient care reports for viral RNA detection on swabs and rapid serological tests in 516 patients (192 symptomatic or paucisymptomatic and 324 asymptomatic). RESULTS: We found the molecular positive fraction equal to 12% (23/192) among symptomatic/paucisymptomatic (S/P) and 15.4% (50/324) in asymptomatic (As) sets. Among subsets, we observed serologically positive results, corresponding to 35% (8/23) for S/P and 38% (19/50) for As. Among molecular negative cases, we detected specific Immunoglobulin G or M (Ig G or Ig M) positivity in the S/P cohort equal to 6.6% (11/167) and 6% (15/246) in As cases. For indeterminate molecular results, we found S/P serological positivity equal to 100% (1/1) and 54% (13/24) in As patients. We found higher (p < 0.05) seropositivity in older patients (n = 8) among symptomatic and positives for viral RNA (n.23). CONCLUSIONS: It has been observed that a dual approach of serological and molecular tests detects a higher absolute number of disease cases in a pandemic context,which could improve monitoring and health surveillance efficacy. The age-related seropositivity frequency in this study, if confirmed, could enhance the validity of serological tests, especially in older patients.In these subjects, molecular positivity accompanied by serological positivity (distinct for M and G immunoglobulins) should help determine disease status and support decisions related to patient management.

6-Month Gastrointestinal Quality of Life (QoL) Results after Endoscopic Sleeve Gastroplasty and Laparoscopic Sleeve Gastrectomy: A Propensity Score Analysis.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is currently the most commonly performed bariatric procedure. Endoscopic sleeve gastroplasty (ESG) is a promising new bariatric technique which is less invasive in its approach. To date no study has compared quality of life (QoL) outcomes between LSG and ESG. The aim of this study is to compare QoL after ESG and LSG using a propensity score analysis. METHODS: QoL was evaluated by means of Gastrointestinal Quality of Life Index (GIQLI) questionnaire before and 6 months after the procedure. Patients were matched for age, sex, preoperative weight, and comorbidities. RESULTS: Propensity score matching resulted in 23 pairs of patients homogeneous for age (p = 0.3), preoperative BMI (p = 0.3), sex (p = 0.74), and comorbidities (p = 0.9). Post-ESG patients, despite a less important %EWL (39.9 (17.5-58.9)vs 54.9 (46.2-65); p = 0.01) and %TWL (13.4 (7.8-20.9) vs 18.8 (17.6-21.8); p = 0.03), presented better QoL (14 [3-24] vs 13 (- 1-23) ΔGIQLI score; p = 0.79) with clear advantage for the gastrointestinal symptoms subdomain (66.5 (61-70.5) vs 59 (55-63); p = 0.001), while post-LSG patients presented a worsening of GERD symptoms (30.7% vs 0%) and an increased use of PPI therapy (p = 0.004). Resolution or improvement of comorbidities was similar (ESG 53% vs LSG 45.8%; p = 0.79) in both groups. CONCLUSION: LSG may significantly affect QoL and results in worsening of gastrointestinal symptoms including GERD. ESG is a promising less invasive bariatric endoscopic procedure that demonstrated a positive impact on both QoL and comorbidities, which could lead to greater patient acceptance earlier in their disease or at a younger age.

Intraluminal flexible sheath for the protection of low anastomosis after anterior resection: results from a First-In-Human trial on 15 patients.

BACKGROUND: Defunctioning ostomy is commonly used to protect patients from anastomotic leakage complications after low anterior resection, but is fraught with its own deleterious effects. This first-in-human study examines the safety and preliminary efficacy of Colovac, an anastomosis protection device. The Colovac consists of a flexible bypass sheath, placed in the lumen of colon and anchored above the anastomosis using a vacuum stent. METHODS: 15 patients underwent anterior resection (AR) with anastomosis protection by Colovac at 3 European centers. After 14 days, the anastomosis integrity was examined by CT scan and endoscopy. The device was then endoscopically removed. Data regarding demographics, surgical details, 30 day post-operative complications, and patient satisfaction were collected prospectively. RESULTS: 15 patients (10 male) underwent laparoscopic AR with Colovac placement. Preoperative neoadjuvant therapy was administered to 54% of patients. Device placement was uneventful in all patients with a median duration of 7 min and placement was judged as easy or very easy in 93% of the cases. Patients did not report major discomfort during the 14 days. Endoscopic removal (10 min) was judged as easy or very easy in 87% of the cases. Absence of feces below the Colovac anchoring site was observed in 100% of the cases. 4 anastomotic leakages were observed (including 3 device migrations). Overall 5 patients (33%) required a planned stoma creation. At 3 months, 1 had already been closed. CONCLUSION: Colovac provides a minimally invasive protection of the anastomosis during the healing process by avoiding the need for a diverting ostomy for two-thirds of patients who will not experience anastomotic complications and allowing safe conversion to the standard of care for patients requiring extended anastomotic protection. A larger study is ongoing to confirm these results.

Autonomic nervous system responses to strength training in top-level weight lifters.

In athletes, spectral analysis of HR variability (HRV) has been shown capable to detect the adaptational changes in sympatho-vagal control attending physical training. So far, studies investigated autonomic nervous system (ANS) changes occurring with endurance training, whereas adaptations to markedly different exercise modes, for example, strength training, have never been investigated. We assessed the changes in cardiac ANS parameters during long-term training in weight lifters of the Italian team preparing for the European Championship, where athletes competed for obtaining the pass for Olympic Games. We investigated nine athletes. Subject trained 3 sessions/day, 6 days a week. The intensity of strength exercises varied from 70% to 95% 1 RM. Training load (TL) was calculated as: volume (min) × intensity (%1RM).All ANS parameters were significantly and highly correlated on an individual basis to the dose of exercise with a second-order regression model (r2 ranged from 0.96 to 0.99; P < 0.001). The low-frequency (LF) component of HRV and LF/HF ratio showed an initial increase with the progression of TL and then a decrease, resembling a bell-shaped curve with a minimum at the highest TL. The high-frequency (HF) component of HRV and R-R interval showed a reciprocal pattern, with an initial decrease with progression of TL followed by an increase, resembling an U-shaped curve with a maximum at the highest TL. These adaptations were at the opposite to those previously reported in endurance athletes. These results suggest that in Olympic weight lifters, ANS adaptations to training are dose-related on individual basis and that ANS adaptations are mainly sport-specific.

Response to Ibrutinib of a Refractory IgA Lymphoplasmacytic Lymphoma Carrying the MYD88 L265P Gene Mutation.

In 2014 a 66-year-old woman presented with anemia and an IgAk monoclonal spike. Bone marrow (BM) biopsy showed 80% lymphocytes and lymphoplasmacytoid cells. Computed Tomography (CT) scan documented neither adenopathy nor splenomegaly. Diagnosis of IgA lymphoplasmacytic lymphoma was made. After three lines of treatment, progressive disease with adenopathies, splenomegaly, and ascites were documented on a CT scan. Our patient developed thrombocytopenia, transfusion-dependent anemia, and clinical deterioration. We performed genetic studies of peripheral blood lymphocytes with the NGS approach. Given the identification of MYD88 L265P mutation, in February 2018 our patient started ibrutinib off-label. Hb and PLT improved from day +35. In July 2018 no ascites and 50% reduction of adenopathies and spleen were shown on a CT scan. In April 2019 the patient was still on ibrutinib with transfusion independence and good performance status.

Biological significance and prognostic/predictive impact of complex karyotype in chronic lymphocytic leukemia.

The complex karyotype (CK) is an established negative prognostic marker in a number of haematological malignancies. After the introduction of effective mitogens, a growing body of evidence has suggested that the presence of 3 or more aberrations by conventional banding analysis (CBA) is associated with an unfavorable outcome in chronic lymphocytic leukemia (CLL). Thus, the importance of CBA was recognized by the 2018 guidelines of the International Workshop on CLL, which proposed the introduction of CBA in clinical trials to validate the value of karyotype aberrations. Indeed, a number of observational studies showed that cytogenetic aberrations and, particularly, the CK may have a negative independent impact on objective outcome measures (i.e. time to first treatment, progression free survival, time to chemorefractoriness and overall survival) both in patients treated with chemoimmunotherapy and, possibly, in patients receiving novel mechanism-based treatment. Here, we set out to present the scientific evidence supporting the significance of CK as a prognostic marker in CLL and to discuss the biological basis showing that the CK is a consequence of genomic instability.