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We thank Dr Buckley1 for the interest in our report on interleukin-6 receptor blockade with subcutaneous tocilizumab in patients with severe COVID-19 pneumonia receiving supplemental oxygen without mechanical ventilation and hyperinflammation.2 We acknowledge that the recently published results from the RECOVERY trial showed reduced mortality in patients treated with dexamethasone (6 mg daily up to 10 days) in addition to usual care, with the benefits being greater in critically ill patients receiving mechanical ventilation (41% vs 29%), while considerably reduced in severe patients on supplemental oxygen without mechanical ventilation (18% vs 14%).3 We also read with interest the results of the CHIC study showing that high-dose intravenous tocilizumab (8 mg/kg body weight, single infusion) may increase the benefits of high-dose methylprednisolone (250 mg on day 1, followed by 80 mg on days 2–5) in patients with severe COVID-19 pneumonia and cytokine storm syndrome requiring supplemental oxygen, mostly through nasal cannulas or mask.4 It is therefore of utmost …

Objectives We evaluated how the Severe Acute Respiratory disease from Coronavirus 2 (SARS‐CoV‐2) epidemic impacted transfusion services, transfusion support required by Covid‐19 patients and their clinical outcome. Background In Italy, the first confirmed case of SARS‐CoV‐2 infection was registered on 21 February 2020. As of 20 April, about 250 000 cases were registered, 1143 of which were in the province of Pescara. Methods We compared transfusion services provided by the blood centre of Pescara between 1 March and 20 April 2019 and between 1 March and 20 April 2020. We assessed the number and type of blood components donated, those transfused in the various hospital departments and those transfused to Covid‐19 patients. Results Compared to 2019, we documented a decrease of 32% in the number of donations. The number of transfusions increased by 139% in the infectious diseases department (IDD), dedicated to Covid‐19 patients, and by 76% in the intensive care unit (ICU), whereas it markedly decreased in the other departments. Of 299 patients with Covid‐19, 60 were transfused (20.1%). Transfused patients in the ICU were significantly younger than those in IDD and had a lower number of lymphocytes, lower post‐transfusion increment of haemoglobin levels and higher D‐dimer and C reactive protein values. Mortality rate was 60.7% among transfused patients in the ICU and 39.0% among those in the IDD (p = 0.02). Conclusion The Covid‐19 epidemic had a profound impact on transfusion activities. The important blood demand for Covid‐19 patients was satisfied because of the reduction in activities in other hospital wards. Covid‐19‐positive transfused patients showed a very poor prognosis.

Background Monocyte Distribution Width (MDW), a simple proxy marker of innate monocyte activation, can be used for the early recognition of sepsis along with Procalcitonin. This study explored the added value of MDW as an early predictor of ensuing sepsis in patients hospitalised in an Intensive Care Unit. Methods We performed an observational prospective monocentric study to estimate the analytical performance of MDW in detecting ensuing sepsis in a sample of consecutive patients assisted in an Intensive Care Unit for > 48 h for any reason. Demographic and clinical characteristics, past medical history and other laboratory measurements were included as potential predictors of confirmed sepsis in multivariate logistic regression. Results A total of 211 patients were observed, 129 of whom were included in the final sample due to the suspect of ensuing sepsis; of these, 74 (57%) had a confirmed diagnosis of sepsis, which was best predicted with the combination of MDW > 23.0 and PCT > 0.5 ng/mL (Positive Predictive Value, PPV: 92.6, 95% CI: 82.1–97.9). The best MDW cut-off to rule out sepsis was ≤20.0 (Negative Predictive Value, NPV: 86.4, 95% CI: 65.1–97.1). Multivariate analyses using both MDW and PCT found a significant association for MDW > 23 only (OR:17.64, 95% CI: 5.53–67.91). Conclusion We found that values of MDW > 23 were associated with a high PPV for sepsis, whereas values of MDW ≤ 20 were associated with a high NPV. Our findings suggest that MDW may help clinicians to monitor ICU patients at risk of sepsis, with minimal additional efforts over standard of care.

Background Early recognition of patients hospitalized for sepsis at higher risk of poor clinical outcome is a mandatory task and many studies suggested that indicators of the immune status may be useful for this purpose. We performed a retrospective, monocentric cohort study to evaluate whether lymphocyte subsets may be useful in predicting in-hospital mortality of septic patients. Methods Data of all consecutive patients with a diagnosis of sepsis at discharge and an available peripherical blood lymphocyte subset (CD4, CD8, CD16/CD56 and CD19) analysis at hospital entry were retrospectively collected between January 2015 and August 2018. Clinical characteristics of patients, past medical history and other laboratory parameters were also considered. Results Two-hundred-seventy-eight septic patients, 171 (61.5%) males, mean age 63.2 ± 19.6 years, were enrolled. Total counts of lymphocytes, CD4 T cells, CD8 T cells and B cells were found significantly lower in deceased than in surviving patients. At univariate analyses, CD4 T cells/µL (OR 0.99 for each incremental unit, 95%CI 0.99–1.10, p Conclusions In adjunct to biomarkers routinely determined for the prediction of prognosis in sepsis, CD4 T lymphocytes, measured at hospital entry, may be useful in identifying patients at higher risk of in-hospital death.

We thank Jain and Sharma1 for their interest in our recent report on interleukin-6 (IL-6) receptor blockade with subcutaneous tocilizumab (324 mg, given in two concomitant 162 mg doses) in patients with severe COVID-19 pneumonia and hyperinflammation.2 Jain and Sharma bring up an important point regarding the safety profile of subcutaneous tocilizumab in patients with COVID-19 at risk of concomitant bacterial infections.1 As already concisely described, in our case–control series, only relatively young patients with severe COVID-19 pneumonia, requiring oxygen support through nasal cannulas or masks, hyperinflammation (C-reactive protein >20 mg/dL) and no contraindications to tocilizumab, including suspected concomitant bacterial infection, were included.2 Well aware of the potential adverse effects of tocilizumab, our screening protocol to rule out concomitant bacterial infection was based on medical history, collected at the time of and during hospitalisation in advance of tocilizumab administration, absolute white blood cell, neutrophil and lymphocyte counts, serial procalcitonin (PCT) values, which were persistently

Many patients with severe COVID-19 rapidly progress to critical disease with refractory hypoxemia requiring invasive mechanical ventilation (IMV).1 Elevated levels of C reactive protein (CRP) and interleukin-6 (IL-6), reflecting an hyperinflammatory response, identify patients at risk of progression to refractory hypoxemia and death.2 Recent evidences suggested that high-dose intravenous tocilizumab (TCZ), a humanised anti-IL-6 receptor antibody, may rapidly reduce fever and inflammatory markers, and improve oxygenation in severe to critical COVID-19.3–5 Data on the safety and efficacy of subcutaneous TCZ, already approved for the treatment of rheumatoid arthritis, are limited. The aim of this study was to compare the clinical course and outcomes of patients treated with subcutaneous TCZ on top of standard of care (SOC) with those of patients receiving SOC only. In this retrospective case–control study, we treated with TCZ 324 mg, given as two concomitant subcutaneous injections, all consecutive patients at Pescara General Hospital, Italy between 28 March and 21 April 2020, with laboratory-confirmed COVID-19 pneumonia (involving ≥20% of lung parenchyma on chest CT), hyperinflammation (CRP ≥20 mg/dL), hypoxemia (oxygen saturation

Background: Gram-negative Multi-Drug-Resistant Organisms (GNMDROs) cause an increasing burden of disease in Intensive Care Units (ICUs). We deployed a multifaceted intervention to control selection and transmission of GNMDROs and to estimate at which rate GNMDROs would decline with our interventional bundle. Methods: Interventions implemented in 2015: in-ward Antimicrobial-Stewardship-Program for appropriate management of antimicrobial prescription; infection monitoring with nasal/rectal swabs and repeated procalcitonin assays; 24 h microbiological support (since 2016); prevention of catheter-related infections, VAPs and in-ward GNMDROs transmission; education of ICU personnel. In May 2017, epidemiological, clinical and microbiological data were collected and retrospectively analyzed. Rates of resistance in Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, as well as percentages of resistance among all Gram-negative bacteria were compared during the study period. Results: Of 668 patients, at least one isolate was obtained from 399 patients. The proportions of patients with infection and with Gram-negative isolates were even across the 5 semesters (p = 0.8). For Klebsiella pneumoniae, the number of strains resistant to carbapenems fell from 94% to 6% (p

Background and objectives Operative laparoscopy is generally performed under general anesthesia. Local anesthesia and conscious sedation may be useful in select short procedures. In the present study, we evaluated safety and efficacy of operative laparoscopy under conscious sedation. Methods Retrospective observational study evaluating patients undergoing gynecologic laparoscopy. Laparoscopy under conscious sedation was performed for each patient with umbilical direct insertion of a 12-mm port, followed by 2 ancillary ports at 1 cm medially to the anterior superior iliac spine. Conversion to conventional laparoscopy or laparotomy was recorded. Conscious sedation was obtained using Remifentanil and Propofol, administered by an infusion system based on pharmacokinetic and pharmacodynamic models. Local anesthesia was administered at port insertion sites and for paracervical block. Pain intensity was evaluated with the Visual Analog Scale (VAS). Adverse events and drug concentrations throughout the procedure were retrieved. Results Our study population included 166 patients. They underwent laparoscopic unilateral versus bilateral salpingo-oophorectomy, ovarian cystectomy, bilateral salpingo-oophorectomy and omentectomy for a borderline ovarian tumor, myomectomy; or underwent surgery for unexplained infertility evaluation, pelvic pain, staging of ovarian cancer. Mean duration of pneumoperitoneum was 22.3 ± 7.2 min. Rate of conversion to laparoscopy under general anesthesia was 17/166 (10.2%) and there were only 3 cases of patients with low tolerability to the procedure. No severe adverse events occurred. Hospital discharge occurred in all unconverted cases after 6 to 18 h. Conclusions Operative laparoscopy under conscious sedation and local anesthesia appears to be a feasible technique in gynecologic surgery with no adverse patient outcomes.

Background In critically ill patients with colonization/infection of multidrug-resistant organisms, source control surgery is one of the major determinants of clinical success. In more complex cases, the use of different tools for sepsis management may allow survival until complete source control. Case presentation A 42-year-old white man presented with traumatic hemorrhagic shock. Unstable pelvic fractures led to emergency stabilization surgery. Fever ensued with diarrhea, followed by septic shock. Two weeks later, an abdominal computed tomography scan revealed suprapubic and ischiatic abscesses at surgical sites, as well as dilated bowel. Debridement of both surgical sites, performed with vacuum-assisted closure therapy, yielded isolates of carbapenem and colistin-resistant Klebsiella pneumoniae. Antibiotic treatment was de-escalated after 21 days; 4 days later fever, leukocytosis, hypotension and acute renal failure relapsed. Blood purification techniques were started, for the removal of endotoxin and inflammatory mediators, with sequential hemodialysis. Clinical improvement ensued; blood cultures yielded Candida albicans and multidrug-resistant Acinetobacter baumannii; panresistant carbapenemase-producing Klebsiella pneumoniae grew from wound swabs. In spite of shock reversal, our patient remained febrile, with diarrhea. Control blood cultures yielded Candida albicans, Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae. His abdominal pain increased, paralleled by a right flank palpable mass. Colonoscopy revealed patchy serpiginous ulcers. At exploratory laparotomy, an inflammatory post-traumatic pseudotumor of his right colon was removed. Blood cultures turned negative after surgery. Septic shock, however, relapsed 4 days later. A blood purification cycle was repeated and combination antimicrobial therapy continued. Surgical wounds and blood cultures were persistently positive for carbapenem-resistant Klebsiella pneumoniae. Removal of pelvic synthesis media was therefore anticipated. Three weeks later, clinical, microbiological, and biochemical evidence of infection resolved. Conclusions High quality intensive assistance for sepsis episodes needs a clear plan of cure, aimed to complete infection source control, in a complex multidisciplinary interplay of specialists and intensive care physicians.

Extensively drug resistant Pseudomonas aeruginosa (XDR-PA) strains with limited or absent residual antimicrobial susceptibility cause a growing burden of difficult-to treat infections. Treatment options are even more limited for patients with central nervous system (CNS) involvement, as colistin-based regimens are hampered by poor blood brain barrier penetration, being often associated with insufficient clinical and microbiological success. New treatment options are awaited, but evidence from prospective evidence-based evaluations is still lacking. Here we report a case of breakthrough otogenous meningitis caused by XDR-PA in a young patient treated with meropenem and colistin for XDR-PA bloodstream infection and pneumonia after a car-crash polytrauma. The patient was treated with off-label, high-dose ceftolozane-tazobactam and high-dose fosfomycin after characterization of CNS XDR-PA isolates, with rapid clinical and microbiological resolution of meningitis. Our experience, although based on a single case, lands preliminary support to the concept that rescue regimens including ceftolozane-tazobactam and fosfomycin may be considered for XDR-PA CNS infections in patients without alternative therapeutic options. Keywords: Ceftolozane-tazobactam, Fosfomycin, XDR, Pseudomonas aeruginosa, Meningitis, Rescue therapy

Introduction: Conscious sedation has traditionally been used for laparoscopic tubal ligation. General anesthesia with endotracheal intubation may be associated with side effects, such as nausea, vomiting, cough, and dizziness, whereas sedation offers the advantage of having the patient awake and breathing spontaneously. Until now, only diagnostic laparoscopy and minor surgical procedures have been performed in patients under conscious sedation. Case Description: Our report describes 5 cases of laparoscopic salpingo-oophorectomy successfully performed with the aid of conventional-diameter multifunctional instruments in patients under local anesthesia. Totally intravenous sedation was provided by the continuous infusion of propofol and remifentanil, administered through a workstation that uses pharmacokinetic–pharmacodynamic models to titrate each drug, as well as monitoring tools for levels of conscious sedation and local anesthesia. We have labelled our current procedure with the acronym OLICS (Operative Laparoscopy in Conscious Sedation). Four of the patients had mono- or bilateral ovarian cysts and 1 patient, with the BRCA1 gene mutation and a family history of ovarian cancer, had normal ovaries. Insufflation time ranged from 19 to 25 minutes. All patients maintained spontaneous breathing throughout the surgical procedure, and no episodes of hypotension or bradycardia occurred. Optimal pain control was obtained in all cases. During the hospital stay, the patients did not need further analgesic drugs. All the women reported high or very high satisfaction and were discharged within 18 hours of the procedure. Discussion and Conclusion: Salpingo-oophorectomy in conscious sedation is safe and feasible and avoids the complications of general anesthesia. It can be offered to well-motivated patients without a history of pelvic surgery and low to normal body mass index.