When did coronavirus arrive in Europe?

The first cluster of coronavirus cases in Europe was officially detected on 21st February 2020 in Northern Italy, even if recent evidence showed sporadic first cases in Europe since the end of 2019. In this study, we have tested the presence of coronavirus in Italy and, even more importantly, we have assessed whether the virus had already spread sooner than 21st February. We use a counterfactual approach and certified daily data on the number of deaths (deaths from any cause, not only related to coronavirus) at the municipality level. Our estimates confirm that coronavirus began spreading in Northern Italy in mid-January.

Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case-control study.

BACKGROUND: Recent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients. METHODS: This case-control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR-Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin). RESULTS: The primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment (p < 0.01). The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p = 0.04). Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR-Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p = 0.04, respectively). In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13-0.87 and OR 0.43, 95% CI 0.23-0.79, respectively). CONCLUSIONS: Improved 28-day mortality was associated with the DC regimen compared with ST for severe CR-Kp infections. A randomized trial is needed to confirm these observational results. TRIAL REGISTRATION: ClinicalTrials.gov NCT03094494 . Registered 28 March 2017.

Tacrolimus-Induced Neurotoxicity After Transplant: A Literature Review.

Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used globally to prevent rejection after organ transplantation. Although it significantly improves outcomes for solid organ transplant patients, it is associated with various side effects such as nephrotoxicity and neurotoxicity. Tacrolimus-induced neurotoxicity is frequently encountered in clinical practice and can present with a variety of symptoms that may occur even at therapeutic levels. Although tacrolimus-induced neurotoxicity is well documented, there is limited literature available on pharmacologic management. Twenty-eight case reports of tacrolimus-induced neurotoxicity were identified and analyzed in addition to other literature including reviews, retrospective studies, and animal model studies. The severity of cases of tacrolimus-induced neurotoxicity reported ranged from mild symptoms that could be managed with symptomatic treatment to conditions such as posterior reversible encephalopathy syndrome and chronic inflammatory demyelinating polyradiculoneuropathy that may require more immediate intervention. This information was utilized in addition to clinical experience to compile potential management options for prevention and treatment of neurotoxic adverse events. This review is limited by the utilization of primarily retrospective studies and case reports. The available literature on the subject is largely narrative and there are no guidelines on treatment of tacrolimus-induced neurotoxicity at the time of this research. This comprehensive review may guide further studies to investigate the pathophysiology of tacrolimus-induced neurotoxicity and to define patient-specific strategies for mitigation or minimization of neurotoxicity. This is especially important given that management of tacrolimus-induced neurotoxicity can include changes to immunosuppression that can result in an increased risk of rejection.

The Efficacy of Early Osteopathic Therapy in Restoring Proper Sucking in Breastfed Infants: Preliminary Findings from a Pilot Study.

Despite the care provided, some newborns, who are perfectly healthy, show functional alterations that impair a good breast attack in the first few days. This situation often leads to the early failure of lactation. We conducted a randomized single-blind controlled trial to evaluate whether four weeks of osteopathic treatment can normalize the sucking score in a group of neonates with impaired lactation ability. Forty-two healthy full-term neonates were enrolled in this study. On the basis of the sucking score and the assessment of the infant's breastfeeding skills, infants who had intrinsic breastfeeding difficulties were selected. The inclusion criteria were healthy infants born > 37 weeks, a suction score ≤ 6, and any breast milk at enrolment. At the end of the study, the sucking score was significantly greater in the osteopathic group than in the untreated group; the median sucking score in the treated group was in the normal range, while it remained lower in the untreated group. At the end of the follow-up, the percentage of exclusively breastfeeding infants in the treatment group increased by +25%. This pilot study demonstrates the efficacy of early osteopathic intervention to relieve breastfeeding difficulties in newborns in the first few weeks of life.

Local mortality estimates during the COVID-19 pandemic in Italy.

Estimates of the real death toll of the COVID-19 pandemic have proven to be problematic in many countries, Italy being no exception. Mortality estimates at the local level are even more uncertain as they require stringent conditions, such as granularity and accuracy of the data at hand, which are rarely met. The "official" approach adopted by public institutions to estimate the "excess mortality" during the pandemic draws on a comparison between observed all-cause mortality data for 2020 and averages of mortality figures in the past years for the same period. In this paper, we apply the recently developed machine learning control method to build a more realistic counterfactual scenario of mortality in the absence of COVID-19. We demonstrate that supervised machine learning techniques outperform the official method by substantially improving the prediction accuracy of the local mortality in "ordinary" years, especially in small- and medium-sized municipalities. We then apply the best-performing algorithms to derive estimates of local excess mortality for the period between February and September 2020. Such estimates allow us to provide insights about the demographic evolution of the first wave of the pandemic throughout the country. To help improve diagnostic and monitoring efforts, our dataset is freely available to the research community. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00148-021-00857-y.

Cystic echinococcosis of the liver and lung treated by radiofrequency thermal ablation: an ex-vivo pilot experimental study in animal models.

AIM: To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs). METHODS: Infected livers and lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts were photographed, and their volume, cyst content, germinal layer adhesion status, wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80 degrees C, 7 min. Temperature was monitored inside and outside the cyst. A second needle was placed inside the cyst for pressure stabilization. After treatment, all cysts were sectioned and examined by histology. Cysts were defined as alive if a preserved germinal layer at histology was evident, and as successfully treated if the germinal layer was necrotic. RESULTS: The subjects of the study were 17 cysts (nine hepatic and eight pulmonary), who were treated with RTA. Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8); immediate volume reduction of at least 65%; layer of host tissue necrosis outside the cyst, with average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts. CONCLUSION: RTA appears to be very effective in killing hydatid cysts of explanted liver and lung. Bile duct and bronchial wall necrosis, persistence of endocyst attached to pericystium, should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration, injection and reaspiration. In vivo studies are required to confirm and validate this new therapeutic approach.