Timely HAART initiation may pave the way for a better viral control

<p>Abstract</p> <p>Background</p> <p>When to initiate antiretroviral therapy in HIV infected patients is a diffcult clinical decision. Actually, it is still a matter of discussion whether early highly active antiretroviral therapy (HAART) during primary HIV infection may influence the dynamics of the viral rebound, in case of therapy interruption, and overall the main disease course.</p> <p>Methods</p> <p>In this article we use a computational model and clinical data to identify the role of HAART timing on the residual capability to control HIV rebound after treatment suspension. Analyses of clinical data from three groups of patients initiating HAART respectively before seroconversion (very early), during the acute phase (early) and in the chronic phase (late), evidence differences arising from the very early events of the viral infection.</p> <p>Results</p> <p>The computational model allows a fine grain assessment of the impact of HAART timing on the disease outcome, from acute to chronic HIV-1 infection. Both patients' data and computer simulations reveal that HAART timing may indeed affect the HIV control capability after treatment discontinuation. In particular, we find a median time to viral rebound that is significantly longer in very early than in late patients.</p> <p>Conclusions</p> <p>A timing threshold is identified, corresponding to approximately three weeks post-infection, after which the capability to control HIV replication is lost. Conversely, HAART initiation occurring within three weeks from the infection could allow to preserve a significant control capability. This time could be related to the global triggering of uncontrolled immune activation, affecting residual immune competence preservation and HIV reservoir establishment.</p

Estimate of overdiagnosis of breast cancer due to mammography after adjustment for lead time. A service screening study in Italy

INTRODUCTION: Excess of incidence rates is the expected consequence of service screening. The aim of this paper is to estimate the quota attributable to overdiagnosis in the breast cancer screening programmes in Northern and Central Italy. METHODS: All patients with breast cancer diagnosed between 50 and 74 years who were resident in screening areas in the six years before and five years after the start of the screening programme were included. We calculated a corrected-for-lead-time number of observed cases for each calendar year. The number of observed incident cases was reduced by the number of screen-detected cases in that year and incremented by the estimated number of screen-detected cases that would have arisen clinically in that year. RESULTS: In total we included 13,519 and 13,999 breast cancer cases diagnosed in the pre-screening and screening years, respectively. In total, the excess ratio of observed to predicted in situ and invasive cases was 36.2%. After correction for lead time the excess ratio was 4.6% (95% confidence interval 2 to 7%) and for invasive cases only it was 3.2% (95% confidence interval 1 to 6%). CONCLUSION: The remaining excess of cancers after individual correction for lead time was lower than 5%

Modeling lymphocyte homing and encounters in lymph nodes

International audienceBackgroundThe efficiency of lymph nodes depends on tissue structure and organization, which allow the coordination of lymphocyte traffic. Despite their essential role, our understanding of lymph node specific mechanisms is still incomplete and currently a topic of intense research.ResultsIn this paper, we present a hybrid discrete/continuous model of the lymph node, accounting for differences in cell velocity and chemotactic response, influenced by the spatial compartmentalization of the lymph node and the regulation of cells migration, encounter, and antigen presentation during the inflammation process.ConclusionOur model reproduces the correct timing of an immune response, including the observed time delay between duplication of T helper cells and duplication of B cells in response to antigen exposure. Furthermore, we investigate the consequences of the absence of dendritic cells at different times during infection, and the dependence of system dynamics on the regulation of lymphocyte exit from lymph nodes. In both cases, the model predicts the emergence of an impaired immune response, i.e., the response is significantly reduced in magnitude. Dendritic cell removal is also shown to delay the response time with respect to normal conditions

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)

Background Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. Methods This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo &gt; 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed &gt;= 12, and proximal and distal free resection margins length &gt;= 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. Results A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to infinity). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to infinity). Conclusions Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection

Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme

In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model

A prospective cohort analysis of the prevalence and predictive factors of delayed discharge after laparoscopic cholecystectomy in Italy: the DeDiLaCo Study

Background: The concept of early discharge ≤24 hours after Laparoscopic Cholecystectomy (LC) is still doubted in Italy. This prospective multicentre study aims to analyze the prevalence of patients undergoing elective LC who experienced a delayed discharge &gt;24 hours in an extensive Italian national database and identify potential limiting factors of early discharge after LC. Methods: This is a prospective observational multicentre study performed from January 1, 2021 to December 31, 2021 by 90 Italian surgical units. Results: A total of 4664 patients were included in the study. Clinical reasons were found only for 850 patients (37.7%) discharged &gt;24 hours after LC. After excluding patients with nonclinical reasons for delayed discharge &gt;24 hours, 2 groups based on the length of hospitalization were created: the Early group (≤24 h; 2414 patients, 73.9%) and the Delayed group (&gt;24 h; 850 patients, 26.1%). At the multivariate analysis, ASA III class ( P &lt;0.0001), Charlson's Comorbidity Index (P=0.001), history of choledocholithiasis (P=0.03), presence of peritoneal adhesions (P&lt;0.0001), operative time &gt;60 min (P&lt;0.0001), drain placement (P&lt;0.0001), pain ( P =0.001), postoperative vomiting (P=0.001) and complications (P&lt;0.0001) were independent predictors of delayed discharge &gt;24 hours. Conclusions: The majority of delayed discharges &gt;24 hours after LC in our study were unrelated to the surgery itself. ASA class &gt;II, advanced comorbidity, the presence of peritoneal adhesions, prolonged operative time, and placement of abdominal drainage were intraoperative variables independently associated with failure of early discharge

Changes in surgicaL behaviOrs dUring the CoviD-19 pandemic. The SICE CLOUD19 Study

BACKGROUND: The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic.METHODS: The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March-May 2020), II (June-September 2020), and III (October-December 2020).RESULTS: Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (>200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency (<20 procedures: 43.3%, 27.1%, 36.5% in the three phases, respectively) surgical activity. The use of laparoscopy also had a setback in phase I (25.8% performed less than 20% of elective procedures through laparoscopy). 60.6% of the respondents used a smoke evacuation device during laparoscopy in phase I, 61.6% in phase II, and 64.2% in phase III. Almost all responders (82.8% vs. 93.2% vs. 92.7%) in each analyzed period did not modify or reduce the use of high-energy devices.CONCLUSION: This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic

Delayed colorectal cancer care during covid-19 pandemic (decor-19). Global perspective from an international survey

Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care