Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study.

BACKGROUND: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). MATERIALS/METHODS: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW). RESULTS: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival. CONCLUSIONS: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.

Long-term Cannabis-based oil therapy and pain medications prescribing patterns: an Italian observational study.

OBJECTIVE: Chronic pain is one of the most common medical conditions in developed countries. The 2020 Italian National Report on Medicines shows how, in the last years, there was a light but constant increase in the prescription of pain medications. The purpose of our study was to assess the effects of long-term cannabis-based oil consumption on the distribution of patients with analgesics prescriptions for chronic pain in a Pain Medicine Unit in Northern Italy. PATIENTS AND METHODS: This is a retrospective, observational study in which patients treated with long-term medical cannabis-based oils, followed between June 2016 and July 2019, were enrolled. The effects of cannabis-based oil consumption on the distribution of patients with pain medications, before and after its long-term use, were evaluated with a Related Samples McNemar Test. Subgroups analyses were performed based on sex, age, comorbidity, duration of cannabis treatment, and condition driving cannabis prescription. RESULTS: A significant difference in opioid non-users after a long-term cannabis-based oil therapy was identified (from 32.1% to 55.4%, p = 0.0023), while no significant differences were found in the distribution of anticonvulsant, antidepressant, and benzodiazepine users. A high benzodiazepine use prevalence was revealed, while subgroup analyses showed increased antidepressant use in people over 65 years old (from 93.7% to 56.2%; p = 0.0313). CONCLUSIONS: Pain medication patterns of prescribing show how necessary it is to improve prescription practices among chronic pain patients. Opioid-sparing medications represent a crucial aspect of the pain treatment process, along with deprescribing protocols. Clinicians and clinical pharmacologists must cooperate to meet the need of a guide that can represent the most possible appropriate therapy for these patients.

The impact of the COVID-19 pandemic on healthcare-associated infections in intensive care unit patients: a retrospective cohort study.

BACKGROUND: During the intensive care units' (ICUs) reorganization that was forced by the COVID-19 emergency, attention to traditional infection control measures may have been reduced. Nevertheless, evidence on the effect of the COVID-19 pandemic on healthcare-associated infections (HAIs) is still limited and mixed. In this study, we estimated the pandemic impact on HAI incidence and investigated the HAI type occurring in COVID-19 patients. METHODS: Patients admitted to the main ICU of the Umberto I teaching hospital of Rome from March 1st and April 4th 2020 were compared with patients hospitalized in 2019. We assessed the association of risk factors and time-to-first event through multivariable Fine and Grey's regression models, that consider the competitive risk of death on the development of HAI (Model 1) or device related-HAI (dr-HAI, Model 2) and provide estimates of the sub-distribution hazard ratio (SHR) and its associated confidence interval (CI). A subgroup analysis was performed on the 2020 cohort. RESULTS: Data from 104 patients were retrieved. Overall, 59 HAIs were recorded, 32 of which occurred in the COVID-19 group. Patients admitted in 2020 were found to be positively associated with both HAI and dr-HAI onset (SHR: 2.66, 95% CI 1.31-5.38, and SHR: 10.0, 95% CI 1.84-54.41, respectively). Despite being not confirmed at the multivariable analysis, a greater proportion of dr-HAIs seemed to occur in COVID-19 patients, especially ventilator-associated pneumonia, and catheter-related urinary tract infections. CONCLUSIONS: We observed an increase in the incidence of patients with HAIs, especially dr-HAIs, mainly sustained by COVID-19 patients. A greater susceptibility of these patients to device-related infections was hypothesized, but further studies are needed.

Comparison of clinical features and outcomes in COVID-19 and influenza pneumonia patients requiring intensive care unit admission.

BACKGROUND: Little is known in distinguishing clinical features and outcomes between coronavirus disease-19 (COVID-19) and influenza (FLU). MATERIALS/METHODS: Retrospective, single-centre study including patients with COVID-19 or FLU pneumonia admitted to the Intensive care Unit (ICU) of Policlinico Umberto I (Rome). Aims were: (1) to assess clinical features and differences of patients with COVID-19 and FLU, (2) to identify clinical and/or laboratory factors associated with FLU or COVID-19 and (3) to evaluate 30-day mortality, bacterial superinfections, thrombotic events and invasive pulmonary aspergillosis (IPA) in patients with FLU versus COVID-19. RESULTS: Overall, 74 patients were included (19, 25.7%, FLU and 55, 74.3%, COVID-19), median age 67 years (58-76). COVID-19 patients were more male (p = 0.013), with a lower percentage of COPD (Chronic Obstructive Pulmonary Disease) and chronic kidney disease (CKD) (p = 0.001 and p = 0.037, respectively) than FLU. SOFA score was higher (p = 0.020) and lymphocytes were significantly lower in FLU than in COVID-19 [395.5 vs 770.0 cells/mmc, p = 0.005]. At multivariable analysis, male sex (OR 6.1, p < 0.002), age > 65 years (OR 2.4, p = 0.024) and lymphocyte count > 725 cells/mmc at ICU admission (OR 5.1, p = 0.024) were significantly associated with COVID-19, whereas CKD and COPD were associated with FLU (OR 0.1 and OR 0.16, p = 0.020 and p < 0.001, respectively). No differences in mortality, bacterial superinfections and thrombotic events were observed, whereas IPA was mostly associated with FLU (31.5% vs 3.6%, p = 0.0029). CONCLUSIONS: In critically ill patients, male sex, age > 65 years and lymphocytes > 725 cells/mmc are related to COVID-19. FLU is associated with a significantly higher risk of IPA than COVID-19.

Prescribing cascades and medications most frequently involved in pain therapy: a review.

OBJECTIVE: The aging of the population and chronic pain represents topical issues in developed countries. These often translate into polypharmacy, inappropriate medications, and adverse drug events, with the risk of misinterpreting these latter with new medical conditions, generating what is referred to prescribing cascade. Prescribing cascades may lead to the prescription of new drugs, which could cause new potential side effects and unnecessary costs for individuals and healthcare systems. Therefore, the purpose of our review was to collect a good deal of prescribing cascades examples involving pain therapy medicines, to help clinicians minimize drug-related clinical outcomes. MATERIALS AND METHODS: We search in MEDLINE database through PubMed, including 31 studies and 80 different examples of prescribing cascades. RESULTS: The medications most commonly resulting in the initial drug therapy prescribed were represented by psychoanaleptics (27/80, 33.7%). Among adverse drug events, the most common one, misinterpreted as a new medical condition, was represented by tremor and extrapyramidal symptoms (20/80, 25%). As regards the new drug therapies prescribed for adverse drug events, the therapeutic subgroups most commonly resulting in the new drug therapy prescribed were represented by psycholeptics (12/80, 15%), and by anti-Parkinson drugs (12/80, 15%). CONCLUSIONS: This study provides a list of several examples of prescribing cascades in pain medicine and is essential to raise awareness of the potential dangers they could involve in all patient populations. Collaboration between clinicians and clinical pharmacologists may lead to more appropriate polypharmacy schemes.

Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae: a case series and review of the literature.

INTRODUCTION: The novel coronavirus SARS-CoV-2 has spread all over the world causing a global pandemic and representing a great medical challenge. Nowadays, there is limited knowledge on the rate of co-infections with other respiratory pathogens, with viral co-infection being the most representative agents. Co-infection with Mycoplasma pneumoniae has been described both in adults and pediatrics whereas only two cases of Chlamydia pneumoniae have been reported in a large US study so far. METHODS: In the present report, we describe a series of seven patients where co-infection with C. pneumoniae (n = 5) or M. pneumoniae (n = 2) and SARS-CoV-2 was detected in a large teaching hospital in Rome. RESULTS AND CONCLUSION: An extensive review of the updated literature regarding the co-infection between SARS-CoV-2 and these atypical pathogens is also performed.

Preliminary risk assessment of workplace violence in hospital emergency departments.

BACKGROUND: The risk assessment of workplace violence in emergency departments represents a global challenge for both healthcare organizations and workers. Recent studies have revealed increased rates of workplace violence towards physicians and nurses employed in emergency departments and have shown that type II is the most common typology of workplace violence among the four types of workplace violence defined by the National Institute for Occupational Safety and Health. The present study aimed to develop a methodological technique for a preliminary assessment of type II workplace violence risk in emergency departments. METHODS: The Delphi method was used to develop a questionnaire entitled Emergency Department Workplace Violence-Questionnaire which was composed of two sections: 1) sentinel events, and 2) risk factors. The authors used the Emergency Department Workplace Violence-Questionnaire to evaluate the workplace violence risk among physicians and nurses employed in a hospital emergency department. RESULTS: The Emergency Department Workplace Violence-Questionnaire was composed of 21 items. The sentinel events section consisted of three company indicators related to workplace violence and identified three areas of risk. The risk factors section identified 18 organizational and environmental factors associated with workplace violence occurrence. The assessment of workplace violence risk in the targeted hospital emergency departments, obtained through the use of the Emergency Department Workplace Violence-Questionnaire, showed a medium risk of workplace violence for both physicians (score=18) and nurses (score=19.5); the analysis found objective risk factors associated with workplace violence and led us to suggest organizational and environmental interventions for reducing the sources of risk among healthcare workers and to prioritize the interventions targeted at the problematical issues detected by the Emergency Department Workplace Violence-Questionnaire. The corrective interventions were focused on an engineering level (i.e. absence of areas for patients/clients to de-escalate, absence of alarm systems) and regarding the organizational environment (i.e. absence of a Workplace Violence Task Force to assess workplace violence risk and develop solutions, working alone). CONCLUSION: The proposed questionnaire proved to be a valid, structured, and reliable tool for assessing the risk of workplace violence in the targeted emergency departments and allowed for the identification of improvement actions targeted at specific critical issues which could be minimized through strategic interventions.

Fashioning enterotomy closure after totally laparoscopic ileocolic anastomosis for right colon cancer: a multicenter experience.

BACKGROUND: Laparoscopic right hemicolectomy is a commonly performed procedure. Little is known on how to perform the enterotomy closure after stapled side-to-side intracorporeal anastomosis. METHOD: A multicentric case-controlled study has been designed to compare different ways to fashion enterotomy closure: double layer versus single layer, sewn versus stapled, and robotic versus laparoscopic approach. Furthermore, additional characteristics including sutures' materials, interrupted versus running suture and the presence of deep corner suture has been investigated. RESULTS: We collected data for 1092 patients who underwent right hemicolectomy at ten centers. We analyzed 176 robotic against 916 laparoscopic anastomosis: no significant differences were found in terms of bleedings (p = 0.455) and anastomotic leak (p = 0.405). We collected data from 126 laparoscopic sewn single-layer versus 641 laparoscopic sewn double-layer anastomosis: a significant reduction was recorded in terms of leaks in double-layer group (p = 0.02). About double-layer characteristics, we found a significant reduction of bleedings (p = 0.008) and leaks (p = 0.017) with a running suture; similarly, a reduction of bleedings (p = 0.001) and leaks (p = 0.005) was observed with the usage of deep corner closure. The presence of a barbed suture thread seemed to significantly reduce both bleedings (p = 0.001) and leaks (p = 0.001). We found no significant differences in terms of bleedings (p = 0.245) and anastomotic leak (p = 0.660) comparing sewn versus stapled anastomosis. CONCLUSIONS: Fashioning a stapled ileocolic intracorporeal anastomosis, we can recommend the adoption of a double-layer enterotomy closure using a running barbed suture in the first layer. Totally, stapled closure and robotic assistance have to be considered a non-inferior alternative.

The ERAS Protocol is at the forefront of the peri-operative pathway in colorectal surgery: monocentric clinical study.

INTRODUCTION: Colon cancer is one of the most common neoplastic diseases, with onset in old age; the benefits of the ERAS protocol were evaluated in the peri-operative treatment of patients affected by this neoplasm. METHODS: We studied 90 cases of colorectal neoplasia observed at the General Surgery UOC of the San Camillo de Lellis Hospital between September 2014 and April 2016, undergoing laparoscopic surgery and to which the ERAS protocol was applied; key points were the preoperative oral feeding, the epidural anesthesia, the reduced or failed hydro-electrolytic overload, the early mobilization and recovery of the feeding, the non-use of drainage. The most important parameers considered were the reduced duration of the operating hospital stay, the lower occurrence of early and distant complications. RESULTS: 85 surgical procedures were performed with laparoscopic technique (94.4%) and 5 with traditional open technique (5.6%). The conversion rate was 5.8% (5/85). 29 surgical procedures of right hemicolectomy (32.2%) and 26 of anterior resection of the rectum (28.9%) were performed; in another 29 patients (32.2%) an intervention with an open traditional technique was performed. A balanced anesthesia was performed in 41 patients (45.6%); epidural anesthesia in 32 cases (35.6%); the Tap Block in 17 subjects (18.9%). The average volume of liquid infusion was 1664cc ± 714; the average post-operative hospital stay of 4.3 ± 0.9 days. CONCLUSIONS: The ERAS protocol reduces the duration of the post-operative hospitalization, involves a lower incidence of precocious and remote complications, in particular if associated with a minimally invasive surgical method; it is easily applicable and reproducible in a hospital environment, with a marked reduction in healthcare management costs.

An acute febrile outbreak in a refugee community of an Italian asylum seeker center: lessons learned.

OBJECTIVES: The management of infectious outbreaks in closed settings represents an important public health issue. An outbreak of acute febrile syndrome affecting 22 refugees resident at the Asylum Seekers Centre of Castelnuovo di Porto in Rome has been reported, and the preventive and control measures adopted have been described as an example of public health safety. METHODS: Pharyngeal swab and whole-blood samples were collected from 22 cases observed and analyzed for standard bacterial cultures and respiratory and herpesviruses by qualitative CLART PneumoVir2 and Entherpex microarray. RESULTS: A possible respiratory-transmitted etiology and a concomitant reactivation of multiple herpesviruses have been evidenced. The epidemiological investigation showed that the spread of the epidemic was promoted because patients were hosted in neighboring rooms or in the same room, facilitating the rapid spread of infectious disease. CONCLUSIONS: The potential way of transmission was supposed, and preventive measures for infection control were adopted. The measures adopted are an example of best practice for outbreak management, and the microbiological surveillance is recommended for public health improvement.

Preliminary assessment of rotating shiftwork risk in a twenty-four hours hospital department.

BACKGROUND: The safety and health of healthcare workers employed in twenty-four-hour hospital wards and exposed to rotational shiftwork (RS), including night shift, is an hot topic of international literature; in fact shift workers incur increased rates of burnout, accidents and injuries, absenteeism and, consequently, reduced work efficiency than non-shift workers. The aims of the present study were: 1) to analyze the occupational risk associated with RS in healthcare sector and 2) to detect the consequent interventions effective in minimizing RS risk. METHODS: The authors designed a questionnaire entitled Rotating Shiftwork Questionnaire (RSQ) which is made up of two sections: 1) Sentinel Events; 2) Risk Factors. The authors used the RSQ to evaluate the RS-Risk among homogeneous groups employed in a twenty-four-hour hospital department. RESULTS: Results. The authors found a medium level of risk among all homogeneous groups. The analysis led to suggest organizational interventions for reducing the sources of RS-risk among healthcare workers. CONCLUSION: The proposed questionnaire revealed effective in approaching the assessment of RS-risk; the findings were also useful in prioritizing and implementing strategic interventions aimed to moderate the occupational risk related to RS.

Acute low back pain among registered nurses. Organizational implications for practice management.

BACKGROUND: To date there is a lack of evidence about the impact of shiftwork on the occurrence of acute low back pain among registered nurses working non-traditional shifts, including nights and 12-hour shifts. The objectives of the present study were: 1) to investigate the impact of shiftwork, physical activity and body mass index on the occurrence of acute low back pain among female shift-registered nurses; 2) to suggest preventive interventions. METHODS: The author conducted a cross-sectional nested case-control analysis of data concerning acute low back pain and staffing data for female registered nurses employed in hospital wards. RESULTS: The analysis found a relationship between acute low back pain and nightshift, extended shifts, obesity; the adoption of forward rotating schedules proved to be effective in minimizing the frequency of acute low back pain. CONCLUSIONS: The findings showed that the prevention of acute low back pain should consider interventions aimed at minimizing not only physical ergonomic factors, but also organizational risks and lifestyle factors.

Role of biomarkers in adult sepsis and their application for a good laboratory practice: a pilot study.

This study measured Procalcitonin (PCT), Presepsin (PRE-S) and pro-Adrenomedullin (pro-ADM) in intensive care unit (ICU) patient’s blood to assess their contribution to accurate diagnosis of sepsis and potential predictive impact on prognosis. The final aim was to improve the use of infection biomarkers for optimizing the impact of laboratory medicine on clinical outcomes, focusing on the good management of resources designed to produce maximum effectiveness and efficiency. Sixty-four adult patients were studied during their hospitalization in ICU; blood samples were collected and categorized according to their clinical diagnosis and illness severity, and sepsis marker levels were measured on automated immunoassay platforms. PCT, PRE-S and pro-ADM infection markers were significantly lower in controls than in sepsis or septic shock groups. The area under the curve, by ROC curve analysis, was 0.945 for PCT, 0.756 for PRE-S and 0.741 for pro-ADM. Sepsis diagnostic accuracy was not improved by combining PCT, PRE-S and pro-ADM measures. Preliminary data demonstrated that, despite PRE-S and pro-ADM being able to differentiate between septic and non-septic patients with accuracy, PCT remains the most reliable marker available. The results obtained still do not allow us to consider a combination of markers, because it would merely increase laboratory costs without improving diagnostic performance. Furthermore, the results confirm a possible prognostic role of pro-ADM in septic states, but no correlation between biomarker levels and survival at 48 h was detected. Hence PCT, PRE-S, nor pro-ADM can be used to predict short-term prognosis.

Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae.

The aim of this study was to identify factors associated with mortality in intensive care unit patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) septic shock. A retrospective analysis of intensive care unit patients with KPC-Kp infection and septic shock observed in a large teaching hospital from November 2010 to December 2014 was performed. A total of 111 patients were included in the study. The most frequent source of infection was unknown-focus bacteraemia in 53 patients (47.7%). The rate of resistance to colistin was 51.3%; 30-day mortality was reported for 44 patients (39.6%). Surviving patients were more frequently treated with an initial therapy (within 24 hours) including two or more antibiotics displaying in vitro activity against the isolated KPC-Kp strain (41.8 vs. 18.1%, p 0.01) and were also more likely to receive a definitive therapy including two or more in vitro active antibiotics (85.1 vs. 15.9%, p <0.001). Cox regression analysis revealed that a colistin-containing antibiotic regimen (hazard ratio (HR) 0.21, confidence interval (CI) 95% 0.05-0.72, p <0.001), use of two or more in vitro active antibiotics as definite therapy (HR 0.08, CI 95% 0.02-0.21, p <0.001) and control of removable source of infection (HR 0.14, CI 95% 0.04-0.25, p <0.001) were associated with favourable outcome; colistin resistance (HR 8.09, CI 95% 3.14-11.23, p 0.001) and intra-abdominal source of infection (HR 2.92, CI 95% 2.11-4.12, p 0.002) were associated with death. In conclusion, use of a definitive therapy with at least two antibiotics displaying in vitro activity against the KPC-Kp isolates was the most important determinant of favourable outcome, whilst isolation of colistin-resistant strains was associated with death in septic patients with KPC-Kp infection.

Renal cavernous hemangioma: robot-assisted partial nephrectomy with selective warm ischemia. Case report and review of the literature.

Renal hemangioma is a relatively rare benign tumor with a wide range of clinical and radiological presentation, not easy to differentiate preoperatively from a renal cancer. Due to its benign nature complete surgical resection is the recommended therapy and is considered curative. A 73-year old male patient followed-up for a lung carcinoma and a chronic renal failure underwent a CT scan showing a 35-mm mass of the inferior pole of the left kidney. The patient underwent robot-assisted partial nephrectomy with left inferior pole selective warm ischemia. The outcome was favorable and no repercussions on the renal reserve were observed postoperatively. Histopathological characteristics of the surgical specimen were consistent with renal cavernous hemangioma. A robot-assisted operation allows the fine dissection required to carry out a bloodless nephron-sparing surgery without a complete warm ischemia. The use of robot could be noteworthy for nephron-sparing surgery in cases of concomitant chronic renal failure.

Laparoscopic ventral/incisional hernia repair: updated Consensus Development Conference based guidelines

BACKGROUND: The Executive board of the Italian Society for Endoscopic Surgery (SICE) promoted an update of the first evidence-based Italian Consensus Conference Guidelines 2010 because a large amount of literature has been published in the last 4 years about the topics examined and new relevant issues. METHODS: The scientific committee selected the topics to be addressed: indications to surgical treatment including special conditions (obesity, cirrhosis, diastasis recti abdominis, acute presentation); safety and outcome of intraperitoneal meshes (synthetic and biologic); fixing devices (absorbable/non-absorbable); abdominal border and parastomal hernia; intraoperative and perioperative complications; and recurrent ventral/incisional hernia. All the recommendations are the result of a careful and complete literature review examined with autonomous judgment by the entire panel. The process was supervised by experts in methodology and epidemiology from the most qualified Italian institution. Two external reviewers were designed by the EAES and EHS to guarantee the most objective, transparent, and reliable work. The Oxford hierarchy (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence") was used by the panel to grade clinical outcomes according to levels of evidence. The recommendations were based on the grading system suggested by the GRADE working group. RESULTS AND CONCLUSIONS: The availability of recent level 1 evidence (a meta-analysis of 10 RCTs) allowed to recommend that not only laparoscopic repair is an acceptable alternative to the open repair, but also it is advantageous in terms of shorter hospital stay and wound infection rate. This conclusion appears to be extremely relevant in a clinical setting. Indications about specific conditions could also be issued: laparoscopy is recommended for the treatment of recurrent ventral hernias and obese patients, while it is a potential option for compensated cirrhotic and childbearing-age female patients. Many relevant and controversial topics were thoroughly examined by this consensus conference for the first time. Among them are the issue of safety of the intraperitoneal mesh placement, traditionally considered a major drawback of the laparoscopic technique, the role for the biologic meshes, and various aspects of the laparoscopic approach for particular locations of the defect such as the abdominal border or parastomal hernias.(AU)

Kidney disease in HIV-infected patients.

The introduction of highly active antiretroviral therapy (HAART) has reduced mortality and improved life expectancy of HIV-positive patients. However, increased survival is associated with increased prevalence of comorbidities, such as cardiovascular disease, hepatic and renal disease. Kidney disease, including HIV-associated nephropathy, acute renal failure and chronic kidney disease, represents one of the main causes of morbidity and mortality, especially if associated to other risk factors, i.e. hypertension, diabetes, older age, black race and hepatitis C coinfection. Careful evaluation of renal function may help identifying kidney disease in its early stages. In addition, proper management of hypertension and diabetes is recommended. Even if HAART has changed the natural course of HIV-associated nephropathy, reducing the risk of End-stage Renal Disease (ERDS), some antiretroviral regimens have been related with the development of acute or chronic kidney disease. Further studies are needed to optimize the management of renal disease among HIV-infected patients.

Vitamin D deficiency in HIV infection: an underestimated and undertreated epidemic.

Hypovitaminosis D is a very common disorder, regarding both Western and developing countries. A growing amount of data over the last years have shown vitamin D deficiency to be high prevalent among HIV-positive subjects. In addition to "classic" risk factors, such as female sex, low dietary intake, dark skin pigmentation and low sun exposure, HIV-related factors, including immune activation and antiretroviral adverse effects, may affect vitamin D status. Even if both protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been associated with low vitamin D levels, available evidences have failed to univocally associate hypovitaminosis D with specific antiretroviral class effects. Low vitamin D is known to have a negative impact not only on bone health, but also on neurocognitive, metabolic, cardiovascular and immune functions. Similarly to the general population, several studies conducted on HIV-infected subjects have associated hypovitaminosis D with a greater risk of developing osteopenia/osteoporosis and fragility fractures. Analogously, vitamin D deficiency has been described as an independent risk factor for cardiovascular disease and metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. Last EACS guidelines suggest to screen for hypovitaminosis D every HIV-positive subject having a history of bone disease, chronic kidney disease or other known risk factors for vitamin D deficiency. Vitamin D repletion is recommended when 25-hydroxyvitamin D levels are below 10 ng/ml. Furthermore, it may be indicated in presence of 25OHD values between 10 and 30 ng/ml, if associated with osteoporosis, osteomalacia or increased parathyroid hormone levels. The optimal repletion and maintenance dosing regimens remain to be established, as well as the impact of vitamin D supplementation in preventing comorbidities.

High-Frequency Vibration Treatment of Human Bone Marrow Stromal Cells Increases Differentiation toward Bone Tissue.

In order to verify whether differentiation of adult stem cells toward bone tissue is promoted by high-frequency vibration (HFV), bone marrow stromal cells (BMSCs) were mechanically stimulated with HFV (30 Hz) for 45 minutes a day for 21 or 40 days. Cells were seeded in osteogenic medium, which enhances differentiation towards bone tissue. The effects of the mechanical treatment on differentiation were measured by Alizarin Red test, (q) real-time PCR, and protein content of the extracellular matrix. In addition, we analyzed the proliferation rate and apoptosis of BMSC subjected to mechanical stimulation. A strong increase in all parameters characterizing differentiation was observed. Deposition of calcium was almost double in the treated samples; the expression of genes involved in later differentiation was significantly increased and protein content was higher for all osteogenic proteins. Lastly, proliferation results indicated that stimulated BMSCs have a decreased growth rate in comparison with controls, but both treated and untreated cells do not enter the apoptosis process. These findings could reduce the gap between research and clinical application for bone substitutes derived from patient cells by improving the differentiation protocol for autologous cells and a further implant of the bone graft into the patient.