On March 9, 2020, the Italian Prime Minister announced the lockdown, which was officially closed on May 4. This extraordinary measure was necessary to contain the COVID-19 pandemic spread in Italy. ...During this phase, a significant decrease in patients' access to Emergency Department (ED) was observed. Delayed access to treatment determined a delay in the diagnosis of acute surgical conditions, as already documented in other clinical areas, with consequences on surgical outcome and survival. Aim of this study is to provide a detailed description of abdominal urgent-emergent conditions surgically treated and surgical outcomes during the lockdown in a tertiary referral Italian hospital, compared with historical data.
A retrospective review of urgent-emergent patients surgically treated in our department was conducted in order to compare patients' characteristics and surgical outcomes during the period March 9th-May 4th, 2020 with the same period of the previous year.
152 patients were included in our study, 79 patients in 2020 group and 77 patients in 2019. We found no significant differences between the groups regarding ASA score, age, gender, and disease prevalence. Significant differences were found in symptom duration before ER access and abdominal pain as the main symptom in non-traumatic conditions. We also performed a sub-analysis on peritonitis which showed significant differences in: hospital length of stay, presence of colostomy vs. ileostomy, and fatal events in 2020. No differences were found in the use of laparoscopy.
While the overall number of ER accesses has decreased in 2020 group, the number of patients surgically treated in emergency-urgency conditions has not decreased. However, those patients waited significantly more before the hospital access. This diagnostic delay was associated with a more severe clinical condition and a consequent significantly worse prognosis.
Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. ...Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+).
This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models.
Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with 5-year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001).
HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.
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•HPV persistence correlates with an increased risk of 5-year recurrence in women undergoing cervical conization•Patients undergoing laser conization experience a slightly lower risk of recurrence in comparison to LEEP•Further evidence regarding fertility and obstetrical issues is necessary
Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead ...to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGRORF15, aiding in the correct annotation of genetic variants in online databases.
To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia.
This is a retrospective multi-institutional study. Medical records of ...consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes.
Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test).
HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.
•Overall, 10–15% of patients with high-grade cervical dysplasia are HR-HPV negative.•Patients with HR-HPV-positive lesions experience a 8-fold increase in the risk of recurrence than HPV-negative patients.•In case of HR-HPV-negative patients, achieving complete excision of the lesion the risk of recurrence is negligible.
Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before ...colectomy in comparison with biologics.
A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints.
Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio OR 1.92, 95% confidence interval CI 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00).
Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.
A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ...ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation.The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality.
This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk.
Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO
/FiO
ratio during the first 5 days of MV, respiratory system compliance (C
) lower than 40 mL/cmH
O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications.ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable.
Age, SOFA score at ICU admission, C
, PaO
/FiO
, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19.
NCT04411459.
Background and Aim
Ustekinumab is approved in Europe for the treatment of moderate to severe Crohn's disease (CD). Italian real‐life data are scarce, so the aim of this study was to assess the ...effectiveness and safety of ustekinumab in an Italian cohort of CD patients.
Methods
Data of patients with CD who started using ustekinumab were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. Primary end‐points were steroid‐free clinical remission at 8, 24, and 52 weeks of therapy and reduction of C‐reactive protein. Secondary end‐points were treatment response, treatment persistence at 12 months, and safety.
Results
A total of 131 patients (males 56%; mean age 46 years ±15) were included. All patients were biologics experienced except for one. At 24 and 52 weeks, 40% and 43% of patients achieved steroid‐free clinical remission, and 64% and 62% had clinical response, respectively. At the end of follow‐up, there was a significant reduction of steroid use (P = 0.012) and of the Harvey‐Bradshaw Index (P = 0.001). The probability of persistence in therapy with ustekinumab after 12 months of treatment was 89%. The only factor associated with discontinuation was older age.
Conclusions
Data from our real‐life cohort of treatment‐refractory CD patients suggest the satisfactory effectiveness and safety profile of ustekinumab.
We assessed one‐year effectiveness and safety of ustekinumab in an real‐life cohort of treatment‐refractory CD patients. At 52 weeks 43% of patients achieved steroid‐free clinical remission and 62% had clinical response with a persistence in therapy of 98% and a significant reduction of steroid use (p = 0.012) and of HBI (p = 0.001). Data from our cohort suggest satisfactory effectiveness and safety profile of ustekinumab.
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