In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry.

PURPOSE: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. METHODS: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. RESULTS: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). CONCLUSION: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

Insomnia and related mental health conditions: Essential neurobiological underpinnings towards reduced polypharmacy utilization rates.

Insomnia represents a significant public health burden, with a 10% prevalence in the general population. Reduced sleep affects social and working functioning, productivity, and patient's quality of life, leading to a total of $100 billion per year in direct and indirect healthcare costs. Primary insomnia is unrelated to any other mental or medical illness; secondary insomnia co-occurs with other underlying medical, iatrogenic, or mental conditions. Epidemiological studies found a 40-50% comorbidity prevalence between insomnia and psychiatric disorders, suggesting a high relevance of mental health in insomniacs. Sleep disturbances also worsen the outcomes of several psychiatric disorders, leading to more severe psychopathology and incomplete remission, plausibly contributing to treatment-resistant conditions. Insomnia and psychiatric disorder coexistence can lead to polypharmacy, namely, the concurrent use of two or more medications in the same patient, regardless of their purpose or rationale. Polypharmacy increases the risk of using unnecessary drugs, the likelihood of drug interactions and adverse events, and reduces the patient's compliance due to regimen complexity. The workup of insomnia must consider the patient's sleep habits and inquire about any medical and mental concurrent conditions that must be handled to allow insomnia to be remitted adequately. Monotherapy or limited polypharmacy should be preferred, especially in case of multiple comorbidities, promoting multipurpose molecules with sedative properties and with bedtime administration. Also, non-pharmacological interventions for insomnia, such as sleep hygiene, relaxation training and Cognitive Behavioral Therapy may be useful in secondary insomnia to confront behaviors and thoughts contributing to insomnia and help optimizing the pharmacotherapy. However, insomnia therapy should always be patient-tailored, considering drug indications, contraindications, and pharmacokinetics, besides insomnia phenotype, clinical picture, patient preferences, and side effect profile.

Role of preoperative 3D rendering for minimally invasive parenchyma sparing liver resections.

BACKGROUND: 3D rendering (3DR) represents a promising approach to plan surgical strategies. The study aimed to compare the results of minimally invasive liver resections (MILS) in patients with 3DR versus conventional 2D CT-scan. METHODS: We performed 118 3DR for various indications; the patients underwent a preoperative tri-phasic CT-scan and rendered with Synapse3D® Software. Fifty-six patients undergoing MILS with pre-operative 3DR were compared to a similar cohort of 127 patients undergoing conventional pre-operative 2D CT-scan using the propensity score matching (PSM) analysis. RESULTS: The 3DR mandated pre-operative surgical plan variations in 33.9% cases, contraindicated surgery in 12.7%, providing a new surgical indication in 5.9% previously excluded cases. PSM identified 39 patients in both groups with comparable results in terms of conversion rates, blood loss, blood transfusions, parenchymal R1-margins, grade ≥3 Clavien-Dindo complications, 90-days mortality, and hospital stay respectively in 3DR and conventional 2D. Operative time was significantly increased in the 3DR group (402 vs. 347 min, p = 0.020). Vascular R1 resections were 25.6% vs 7.7% (p = 0.068), while the conversion rate was 0% vs 10.2% (p = 0.058), respectively, for 3DR group vs conventional 2D. CONCLUSION: 3DR may help in surgical planning increasing resectability rate while reducing conversion rates, allowing the precise identification of anatomical landmarks in minimally invasive parenchyma-preserving liver resections.

Endoscopic approach to complex or recurrent pilonidal sinus: A retrospective analysis.

Pilonidal Sinus is a benign, chronic disease that affects the hair follicles of the natal cleft of the sacrococcygeal area. Its ideal treatment is controversial, especially in complex or recurrent cases. The aim of this study is to evaluate the use of minimally invasive endoscopic approach in this setting. We enrolled patients affected by complex or recurrent sacrococcygeal pilonidal sinus from January 2015 through December 2020 who underwent Video-Assisted Ablation of Pilonidal Sinus. All patients enrolled were re-evaluated once a year with a standard physical examination. The patients included were 38. Recurrence rate at 1-, 3- and 5-years follow-ups were 28.9%, 22.2% and 38.1% respectively. Of interest, the mean (SD) distance from the most lateral orifice to the midline was higher in group of patients with recurrence and the multivariate analysis demonstrated that it was the limiting factor, which influences the recurrence rate. In complex or recurrent pilonidal sinus disease with pits off the midline the endoscopic approach should not be the first choice. This makes us think that these cases should have their own classification to be identified and guide surgeons in choosing the appropriate approach.

Enterotomy Closure after Minimally Invasive Distal Gastrectomy with Intracorporeal Anastomosis: A Multicentric Study.

INTRODUCTION: Despite progressive improvements in technical skills and instruments that have facilitated surgeons performing intracorporeal gastro-jejunal and jejuno-jejunal anastomoses, one of the big challenging tasks is handsewn knot tying. We analysed the better way to fashion a handsewn intracorporeal enterotomy closure after a stapled anastomosis. METHODS: All 579 consecutive patients from January 2009 to December 2019 who underwent minimally invasive partial gastrectomy for gastric cancer were retrospectively analysed. Different ways to fashion intracorporeal anastomoses were investigated: robotic versus laparoscopic approach; laparoscopic high definition versus three-dimensional versus 4K technology; single-layer versus double-layer enterotomies. Double-layer enterotomies were analysed layer by layer, comparing running versus interrupted suture; the presence versus absence of deep corner suture; and type of suture thread. RESULTS: Significantly lower rates of bleeding (p = 0.011) and leakage (p = 0.048) from gastro-jejunal anastomosis were recorded in the double-layer group. Barbed suture thread was significantly associated with reduced intraluminal bleeding and leakage rates both in the first (p = 0.042 and p = 0.010) and second layer (p = 0.002 and p = 0.029). CONCLUSIONS: Double-layer sutures using barbed suture thread both in first and second layer to fashion enterotomy closure result in lower intraluminal bleeding and anastomotic leak rates.

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.

Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30-40% of patients, and characterized by serious cognitive deficits and functional impairment. In the present systematic review, we address with a direct and reverse translational perspective the efficacy of D-amino acids, including D-serine, D-aspartate, and D-alanine, in poor responders. The impact of these molecules on the synaptic architecture is also considered in the light of dendritic spine changes reported in schizophrenia and antipsychotics' effect on postsynaptic density proteins. Moreover, we describe compounds targeting D-amino acid oxidase and D-aspartate oxidase enzymes. Finally, other drugs acting at NMDAR and proxy of D-amino acids function, such as D-cycloserine, sarcosine, and glycine, are considered in the light of the clinical burden of TRS, together with other emerging molecules.

Systematic review, meta-analysis and single-centre experience of the diagnostic accuracy of intraoperative near-infrared indocyanine green-fluorescence in detecting pancreatic tumours.

BACKGROUND: During pancreatic resections assessing tumour boundaries and identifying the ideal resection margins can be challenging due to the associated pancreatic gland inflammation and texture. This is particularly true in the context of minimally invasive surgery, where there is a very limited or absent tactile feedback. Indocyanine green (ICG) fluorescence imaging can assist surgeons by simply providing valuable real-time intraoperative information at low cost with minimal side effects. This meta-analysis summarises the available evidence on the use of near-infrared fluorescence imaging with ICG for the intraoperative visualization of pancreatic tumours (PROSPERO ID: CRD42021247203). METHODS: MEDLINE, Embase, and Web Of Science electronic databases were searched to identify manuscripts where ICG was intravenously administered prior to or during pancreatic surgery and reporting the prevalence of pancreatic lesions visualised through fluorescence imaging. RESULTS: Six studies with 7 series' reporting data on 64 pancreatic lesions were included in the analysis. MINOR scores ranged from 6 to 10, with a median of 8. The most frequent indications were pancreatic adenocarcinoma and neuroendocrine tumours. In most cases (67.2%) ICG was administered during surgery. ICG fluorescence identified 48/64 lesions (75%) with 81.3% accuracy, 0.788 (95%CI 0.361-0.961) sensitivity, 1 (95%CI 0.072-1) specificity and positive predictive value of 0.982 (95%CI 0.532-1). In line with the literature, ICG fluorescence identified 5/6 (83.3%) of pancreatic lesions during robotic pancreatic resections performed at our Institution. CONCLUSION: This meta-analysis is the first summarising the results of ICG immunofluorescence in detecting pancreatic tumours during surgery, showing good accuracy. Additional research is needed to define optimal ICG administration strategies and fluorescence intensity cut-offs.

The Role of Indocyanine Near-Infrared Fluorescence in Colorectal Surgery.

Purposes: The aim of this study was to evaluate the importance of Indocyanine Green in control of anastomosis perfusion and on anastomotic leakage rates during laparoscopic and robotic colorectal procedures. Methods: A retrospective review of patients who underwent elective minimally invasive surgery for colorectal cancer from 1 January 2018 to 31 December 2020 was performed. All patients underwent Near-Infrared Fluorescence-Indocyanine Green system in two moments: before performing the anastomosis and after completing the anastomotic procedure. Primary outcomes were the rate of intraoperative change in the surgical resection due to an inadequate vascularization and the rate of postoperative anastomotic leakage. Secondary outcomes were the postoperative complications, both medical and surgical (intra-abdominal bleeding, anastomotic leakage). Results: Our analysis included 93 patients. Visible fluorescence was detected in 100% of the cases. In 7 patients (7.5%), the planned site of resection was changed due to inadequate perfusion. The mean extension of the surgical resection in these 7 patients was 2.2 ± 0.62. Anastomotic leakage occurred in 2 patients (2.1%). Other complications included 8 postoperative bleedings (8.6%) and 1 pulmonary thromboembolism. Conclusions: The intraoperative use of Near-Infrared Fluorescence-Indocyanine Green in colorectal surgery is safe, feasible, and associated with a substantial reduction in postoperative anastomotic leakage rate.

Surgical stress and metabolic response after totally laparoscopic right colectomy.

No clear consensus on the need to perform an intracorporeal anastomosis (IA) after laparoscopic right colectomy is currently available. One of the potential benefits of intracorporeal anastomosis may be a reduction in surgical stress. Herein, we evaluated the surgical stress response and the metabolic response in patients who underwent right colonic resection for colon cancer. Fifty-nine patients who underwent laparoscopic resection for right colon cancer were randomized to receive an intracorporeal or an extracorporeal anastomosis (EA). Data including demographics (age, sex, BMI and ASA score), pathological (AJCC tumour stage and tumour localization) and surgical results were recorded. Moreover, to determine the levels of the inflammatory response, mediators, such as C-reactive protein (CRP), tumour necrosis factor (TNF), interleukin 1ß (IL-1ß), IL-6, IL-10, and IL-13, were evaluated. Similarly, cortisol and insulin levels were evaluated as hormonal responses to surgical stress. We found that the proinflammatory mediator IL-6, CRP, TNF and IL-1ß levels, were significantly reduced in IA compared to EA. Concurrently, an improved profile of the anti-inflammatory cytokines IL-10 and IL-13 was observed in the IA group. Relative to the hormone response to surgical stress, cortisol was increased in patients who underwent EA, while insulin was reduced in the EA group. Based on these results, surgical stress and metabolic response to IA justify advocating the adoption of a totally laparoscopic approach when performing a right colectomy for cancer.This trial is registered on ClinicalTrials.gov (ID: NCT03422588).

Hepatocellular carcinoma in patients with chronic renal disease: Challenges of interventional treatment.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, recognized as the fourth most common cause of cancer related death. Many risk factors, leading to liver cirrhosis and associated HCC, have been recognized, among them viral hepatitis infections play an important role worldwide. Patients suffering from chronic kidney disease (CKD), especially those on maintenance dialysis, show a higher prevalence of viral hepatitis than the general population what increases the risk of HCC onset. In addition, renal dysfunction may have a negative prognostic impact on both immediate and long-term outcomes after malignancy treatment. Several interventional procedures for the treatment of HCC are currently available: thermal ablation, transcatheter arterial chemoembolization, liver surgery or even liver transplantation. The Barcelona Clinic Liver Cancer system provides an evidence-based treatment algorithm to address different categories of patients to the most-effective treatment in consideration of the extension of disease, liver function and performance status. Liver resection and transplantation are usually reserved to patients with early stage HCC and acceptable performance status, while the other treatments are more indicated in case of impaired liver function or locally advanced or unresectable tumors. However, there is no validated treatment algorithm for HCC in CKD patients, mainly due to the rarity of reports in this cohort of patients. Hereby we discuss the available evidences on interventional HCC treatments in CKD patients, and briefly report up-to-date pharmacological therapy for HCC patients affected by viral hepatitis.

Conversions related to adhesions in abdominal surgery. Robotic versus laparoscopic approach: A multicentre experience.

BACKGROUND: An advantage of robotic surgery over laparoscopy is the lower rate of unplanned conversion. One of the implicated reasons for conversion is adhesions from previous abdominal surgeries (PASs). METHODS: A comparative analysis of 98 patients with history of open PAS treated by laparoscopic or robotic surgery was performed. Primary endpoint was the rate of conversion to open surgery related to adhesiolysis. Secondary endpoints were short-term outcomes and complications. RESULTS: Conversion rate specifically related to adhesiolysis was significantly lower in robotic group (13 for laparoscopic group vs. 2 for robotic group; p = 0.046). Conversions occurred during adhesiolysis were significantly related to severity of adhesions expressed by peritoneal adhesion index (PAI) score (p < 0.001), number of abdominal areas involved by adhesions (p < 0.001) and severity of PAI into the target area of surgical intervention (p = 0.021). CONCLUSIONS: Benefits of robotic surgery are more noticeable in performing procedures with increasing technical difficulties.

Combined surgical and negative pressure therapy to treat multiple enterocutaneous fistulas and abdominal abscesses: A case report.

INTRODUCTION: We report the case of a successful management with combined aggressive surgery and negative pressure therapy, to treat a severely ill-septic patient, affected by multiple chronic enterocutaneous fistulas. PRESENTATION OF CASE: A 26-year-old female patient presented with multiple pelvic and intra-abdominal abscesses, enterocutaneous fistulas and central venous catheter-related bacteraemia in extremely poor general conditions.The patient underwent both an abdominal CT which showed multiple digestive loops stuck and apparently fistulised and an abdominal-pelvic MRI, confirming the CT findings, and demonstrating a third fistula involving the Pouch and responsible for a pelvic and retroperitoneal chronic abscess.Given the patient's septic condition, despite several attempts of conservative therapies, an aggressive surgical approach was adopted.After temporary abdominal wall closure, the patient underwent Vacuum Assisted Closure therapy in order to close the abdominal wall and drain the residual abscess. The patient was discharged at the 35th post-operative day in good general conditions. DISCUSSION: This case is about a complex, long-lasting clinical scenario, progressively leading a young woman to death despite several attempts of conservative therapy, sometimes allowed to treat enterocutaneous fistulas. The use of negative pressure therapy to manage open abdomen is still controversial. Patients affected by enterocutaneous fistulas are in need of adequate nutritional support due to their hypercatabolic state, secondary both to the fluid loss and the concomitant inflammatory status. CONCLUSION: When conservative management fails and the patient shows septic complications, a multidisciplinary aggressive approach, including surgery, negative-pressure therapy and hyperbaric oxygen therapy is required to treat this life-threatening condition.

Hepatic function assessment to predict post-hepatectomy liver failure: what can we trust? A systematic review.

Post hepatectomy liver failure (PHLF) could occur even though an adequate liver volume is preserved. Liver function is not strictly related to the volume and the necessity to pre-operatively predict the future liver remnant (FLR) function is emerging, together with the wide spreading of techniques, aiming to optimize the FLR. The aim of this study was to systematically review all the available tests, to pre-operatively assess the liver function and to estimate the risk of PHLF. A systematic literature research of Medline, Embase, Scopus was performed in accordance to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, to identify all the studies available for pre-operative liver function tests to assess the risk of PHLF and/or complications. From the 1122 references retrieved, 79 were included in the review. Dynamic functional tests, such as indocyanine green test (ICG), could evaluate only global liver function, with no definition of functional capacity of the remnant. Magnetic resonance imaging (MRI) with liver-specific contrast agents enables both liver function and volume evaluation; the absence of ionizing radiation showed a better patient's compliance. Nuclear imaging studies as hepatobiliary scintigraphy (HBS) present the unique ability to allow a precise evaluation of the segmental liver function of the remnant liver. Liver volume could overestimate liver function. Several liver function tests are available to evaluate the risk of PHLF in the pre-operative setting. However, no single test alone could accurately predict PHLF. Pre-operative combination between a dynamic quantitative test, such as ICG, with MRI or HBS, should enable a more complete functional evaluation. Functional tests to predict PHLF should be chosen according to patient's characteristics, disease, and center experience.

Long-term results of a randomized clinical trial comparing endoscopic versus conventional treatment of pilonidal sinus.

BACKGROUND: In the new era of minimally invasive surgery, recent studies encouraged the adoption of endoscopic approaches as the most effective way to treat (pilonidal sinus disease) PSD but little is known about long-term results of minimally invasive procedures. MATERIALS AND METHODS: A total of 145 patients with chronic non recurrent pilonidal sinus were enrolled for this randomized controlled trial. The follow-up rate was 97% at 5 years for a total of 74 patients assigned to the minimally invasive treatment group and 67 patients assigned to the conventional Bascom cleft lift treatment group. We evaluated the following outcomes: long-term recurrence rate, patients' satisfaction, cosmetic outcome and cost-effectiveness results. RESULTS: Long-term data confirm that the recurrence rate was similar in both groups and, in minimally invasive patients, there were a higher satisfaction and better cosmetic results. Costs analysis revealed improved outcome in favour of VAAPS with a much lower mean global cost. CONCLUSION: Minimally invasive treatment has all the characteristics of an ideal approach to PSD with advantages including minimal patient inconveniences, high satisfaction and good aesthetics results. It was also more cost effective to carry out the treatment.

Robotic approach to the liver: Open surgery in a closed abdomen or laparoscopic surgery with technical constraints?

The application of the minimally invasive approach has shown to be safe and effective for liver surgery and is in constant growth. The indications for laparoscopic surgery are steadily increasing across the field. In the early 2000s, robotic surgery led to some additional improvements, such as tremor filtration, instrument stability, 3D view and more comfort for the surgeon. These techniques bring in some advantages compared to the traditional OLR: less blood loss, shorter admissions, fewer adhesions, and a faster postoperative recovery and better outcomes in case of further hepatectomy for tumor recurrence has been shown. Concerning which is the best minimally invasive approach between laparoscopic and robotic surgery, the evidence is still conflicting. The latter shows good potential, since the endo-wristed instruments work similarly to the surgeon's hands, even with an intact abdominal wall. However, the technique is still under development, burdened by important costs, and limited by the lack of some instruments available for the laparoscopic approach. The paucity of universally accepted and proven data, especially concerning long-term outcomes, hampers drawing univocal acceptance at present. Furthermore, the number of variables related both to the patient and the disease further complicates the decision leading to a treatment tailored to each patient with strict selection. This review aims to explore the main differences between laparoscopic and robotic surgery, focusing on indications, operative technique and current debated clinical issues in recent literature.

Home Parenteral Nutrition in Patients with Intestinal Failure: Possible Undetected Complications.

BACKGROUND: Septic pulmonary embolism (SPE) may be a frequently undetected complication of central venous catheter (CVC)-related bloodstream infections (CRBSIs). MATERIALS AND METHODS: The incidence of SPE was evaluated in a cohort of non-oncological patients on home parenteral nutrition (HPN) who were hospitalized for a CRBSI from January 2013 to December 2017. The main clinical, microbiological, and radiological features and the therapeutic approach were also described. RESULTS: Twenty-three infections over 51,563 days of HPN therapy were observed, corresponding to an infection rate of 0.45/1000. In 10 out of the 23 cases (43.5%), pulmonary lesions compatible with SPE were identified. CONCLUSION: Our results demonstrated that a CRBSI can produce asymptomatic SPE with lung infiltrates in 43.5% of the cases, suggesting the need to check for secondary lung infections to choose the most appropriate antimicrobial therapy.

Deep tissue biopsy vs. superficial swab culture, including microbial loading determination, in the microbiological assessment of Skin and Soft Tissue Infections (SSTIs).

Thirty-two patients affected by SSTIs including DFIs were enrolled between 2013 and 2014. Superficial swab was obtained before and after cleansing with sterile saline, and after ultrasonic debridement; deep tissue biopsy was obtained from ulcer base. Samples were diluted with 1 mL of saline, serial 10-fold dilutions to 10-6 were made and 50 µL of each dilution was plated onto appropriate media. Bacteria were identified by Vitek II system. Microbial load was expressed as CFU/mL. Statistical analysis was performed by χ2. Incidence of Gram positives was higher than Gram negatives (S. aureus and P. aeruginosa being the most frequent); concordance (same bacteria isolated before and after debridement) never exceeded 60%. Ultrasonic debridement significantly reduced bacterial load or even suppressed bacterial growth. While reliability of superficial swab is poor for microbiological diagnosis of SSTIs, swabbing after ultrasonic debridement and biopsy of the ulcer base may be equally reliable.

Diagnostic and therapeutic appropriateness in bone and joint infections: results of a national survey.

The impact of infectious diseases (ID) specialist consultation in the management of many types of bacterial infections has been fully demonstrated but not for bone and joint infections (BJIs). Nineteen ID Italian centres collected of data from June 2009 to May 2012. Italian guidelines (2009) were used to determine the appropriateness of the diagnostic and therapeutic process of BJIs before and after consulting an ID specialist. Data on 311 patients were collected: 111 cases of prosthetic joint infection, 99 osteomyelitis, 64 spondylodiscitis and 37 fixation device infection. A significant increase of microbiological investigations, imaging techniques and blood inflammation markers were noted after consulting the ID specialist. Moreover, inappropriateness of treatment duration, dosage, and number of administrations significantly decreased after consultation. Infectious disease specialist intervention in the management of BJIs significantly increases the appropriateness both in performing instrumental and laboratory analysis, but especially in determining the correct therapy.