Virological and Clinical Outcome of DAA Containing Regimens in a Cohort of Patients in Calabria Region (Southern Italy).

Background and objectives: In Italy, Hepatitis C Virus (HCV) infections are most prevalent in people older than 50 years of age, who often experience multi-morbidities, take co-medications, and have a long history of liver disease. These characteristics could potentially affect tolerability of HCV treatments and adherence in this subgroup. After achievement of sustained virological response (SVR), retention into care is very important both to detect the onset of possible complications and prevent further infections. In this study, SVR rates and retention into care of patients treated with directly acting antivirals (DAAs) of a single-center cohort in Southern Italy were evaluated. Materials and Methods: Patients treated with directly acting antivirals from 2014 to 2018 were included. Patients were stratified by age (i.e., <65 vs. ≥65 years) and by cirrhosis presence (i.e., liver stiffness >14.6 KPa or clinical/ultrasound cirrhosis vs. absence of these criteria). Primary outcome was availability of SVR at Weeks 12-24 after the end of treatment. Inter- and intra-group comparisons were performed along the follow-up for significant laboratory parameters. Results: In total, 212 patients were treated; 184 (87%) obtained SVR after the first treatment course and 4 patients after retreatment. Twenty-two (10.4%) patients were lost to follow-up before assessment of SVR, and two patients died before the end of treatment for liver decompensation. Considering only the first treatment episode, per protocol analysis (i.e., excluding patients lost to follow-up) showed the following rates of SVR: 97% (overall), 97% (older age group), 96% (age group <65 years), 94% (cirrhotics), and 100% (non-cirrhotics). By contrast, at the intention to treat analysis (i.e., patients lost were computed as failures), SVR percentages were significantly lower for patients <65 years of age (80%) and for non-cirrhotics (85%). Conclusions: High rates of SVR were obtained. However, younger patients and those without cirrhosis displayed an apparent high risk of being lost to follow-up. This may have important implications: since those who are lost may transmit HCV in case SVR is not achieved, these subpopulations should receive appropriate counselling during treatment.

Evaluation of cardiac function by global longitudinal strain before and after treatment with sofosbuvir-based regimens in HCV infected patients.

BACKGROUND: Possible cardiotoxicity of sofosbuvir in humans has not been demonstrated yet. Also, since HCV can exert deleterious effects on hearth function, it is of interest to know whether HCV eradication provides any benefits using global longitudinal strain (GLS), a measure of left ventricular function more reliable than ejection fraction (EF). METHODS: Patients eligible for treatment with the combination therapy for HCV were invited to perform a transthoracic cardiac ultrasound at four different time points: before starting treatment, after one month, at the end of treatment and, after six month. Left ventricular function was measured with both EF and GLS. RESULTS: From March 2015 to December 2016, 82 patients were enrolled. Fifty-six percent patients were males. Mean age was 66.12 (SD: 9.25) years. About 20% patients did not present any cardiovascular risk factors or comorbidities. A worsening trend of GLS was observed. Variations were not found to be statistically significant when EF was studied along the follow-up. However, when GLS was studied, its variations were found to be statistically significant indicating a worsening effect, albeit with different trends in patients who underwent treatment for three months compared to six months. Worsening of GLS was found to be statistically significant even after adjusting for body mass index and liver fibrosis, independently from treatment duration. CONCLUSIONS: Our results showed unexpected worsening of left ventricular function when measured through GLS after HCV treatment response induced by DAAs including sofosbuvir. Although this result is not proven to be clinically significant, the safety profile of sofosbuvir-based regimens needs to be studied further.

Is hand-grip another culprit for the risk of fractures in HIV-positive patients?

Risk of bone fractures in patients with HIV infection is greater than in the general population, particularly in those co-infected with hepatitis viruses. We compared bone mineral density (BMD) and muscular strength, measured by hand grip test (HG), in HIV mono-infected and co-infected patients. T-score values were lower in HIV patients co-infected with hepatitis viruses vs. mono-infected individuals. Since no significant correlations between HG and T-scores were found, we hypothesize that these factors belong, at least in part, to independent pathways, so both should be taken into account as risks for fragility fractures. Larger prospective studies are needed to confirm this hypothesis.

Challenging clinical cases in HCV infection.

We present clinical cases, which underline some difficulties in diagnosis and treatment of hepatitis C virus (HCV) infection. Case report #1 shows a patient who avoided clinical follow-up for HCV until the development of hepatocellular carcinoma. In this patient, non-invasive procedures did not allow to make a differential diagnosis between hydatidosis and hepatocellular carcinoma but diagnosis was only made with liver biopsy.

Present, old and future strategies for anti-HCV treatment in patients infected by genotype-1: estimation of the drug costs in the Calabria Region in the era of the directly acting antivirals.

BACKGROUND: In Italy, anti-HCV drugs are provided free of charge by the National Health System. Since 2011, three drug regimens including a directly acting antiviral (DAA) are considered the gold standard for HCV treatment. However, these drugs add a significant cost (roughly €26,000) to the combination of pegylated-interferon-α/ribavirin (PEG-IFN/RBV), which before DAA represented the unique treatment. To provide the National Health System potential useful information, we estimated costs to provide anti-HCV drugs to treat a population experienced for PEG-INF/RBV. METHODS: Genotype 1 HCV mono-infected or HIV/HCV co-infected individuals who were treated with PEG-IFN/RBV between 2008 and 2013 were included. The cost to treat these patients with PEG-IFN/RBV was calculated (cost 1). We also estimated costs if we had to treat these patients with a lead-in period of PEG-INF/RBV followed by PEG-IFN/RBV and a DAA in naïves (cost 2), in addition to cost 1 plus the estimated cost to re-treat with PEG-IFN/RBV and a DAA patients who had a relapse or a non response (cost 3). Moreover, all costs were normalized by SVR. Rates of foreseen response with DAA were obtained from literature data. RESULTS: The overall study population consisted of 104 patients. The rate of sustained virological response (SVR) was 55%, while it was estimated that SVR would be obtained in 75% of patients with a lead-in period with PEG-IFN/RBV followed by a DAA combination, and in 78% if this treatment is used to re-treat experienced patients with a DAA. Drug costs associated with these treatments were: €1,214,283 for cost 1, €3,474,977 for cost 2 and €3,002,095 for cost 3. Costs per SVR achieved were: €22,284 for cost 1, €44,643 for cost 2 and €38,322 for cost 3. CONCLUSIONS: Treatments including DAAs achieve a SVR in more patients than PEG-IFN/RBV but they cost around three times more than PEG-IFN/RBV alone regimens. Also, cost per SVR is almost twofold greater than PEG-IFN/RBV regimens. Therefore, it is mandatory to implement use of DAA in clinical practice, but the National Health System should allocate adequate resources to provide drugs, which challenges sustainability. Cost reduction for anti-HCV drugs should be pursued.

Epidemiology, Outcomes, and Risk Factors for Mortality in Critically Ill Women Admitted to an Obstetric High-Dependency Unit in Sierra Leone.

A better understanding of the context-specific epidemiology, outcomes, and risk factors for death of critically ill parturients in resource-poor hospitals is needed to tackle the still alarming in-hospital maternal mortality in African countries. From October 2017 to October 2018, we performed a 1-year retrospective cohort study in a referral maternity hospital in Freetown, Sierra Leone. The primary endpoint was the association between risk factors and high-dependency unit (HDU) mortality. Five hundred twenty-three patients (median age 25 years, interquartile range [IQR]: 21-30 years) were admitted to the HDU for a median of 2 (IQR: 1-3) days. Among them, 65% were referred with a red obstetric early warning score (OEWS) code, representing 1.17 cases per HDU bed per week; 11% of patients died in HDU, mostly in the first 24 hours from admission. The factors independently associated with HDU mortality were ward rather than postoperative referrals (odds ratio [OR]: 3.21; 95% CI: 1.48-7.01; P = 0.003); admissions with red (high impairment of patients' vital signs) versus yellow (impairment of vital signs) or green (little or no impairment of patients' vital signs) OEWS (OR: 3.66; 95% CI: 1.15-16.96; P = 0.04); responsiveness to pain or unresponsiveness on the alert, voice, pain unresponsive scale (OR: 5.25; 95% CI: 2.64-10.94; P ≤ 0.0001); and use of vasopressors (OR: 3.24; 95% CI: 1.32-7.66; P = 0.008). Critically ill parturients were predominantly referred with a red OEWS code and usually required intermediate care for 48 hours. Despite the provided interventions, death in the HDU was frequent, affecting one of 10 critically ill parturients. Medical admission, a red OEWS code, and a poor neurological and hemodynamic status were independently associated with mortality, whereas adequate oxygenation was associated with survival.

Cost-Utility of Intermediate Obstetric Critical Care in a Resource-Limited Setting: A Value-Based Analysis.

Background: Sierra Leone faces among the highest maternal mortality rates worldwide. Despite this burden, the role of life-saving critical care interventions in low-resource settings remains scarcely explored. A value-based approach may be used to question whether it is sustainable and useful to start and run an obstetric intermediate critical care facility in a resource-poor referral hospital. We also aimed to investigate whether patient outcomes in terms of quality of life justified the allocated resources. Objective: To explore the value-based dimension performing a cost-utility analysis with regard to the implementation and one-year operation of the HDU. The primary endopoint was the quality-adjusted life-years (QALYs) of patients admitted to the HDU, against direct and indirect costs. Secondary endpoints included key procedures or treatments performed during the HDU stay. Methods: The study was conducted from October 2, 2017 to October 1, 2018 in the obstetric high dependency unit (HDU) of Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone. Findings: 523 patients (median age 25 years, IQR 21-30) were admitted to HDU. The total 1 year investment and operation costs for the HDU amounted to €120,082 - resulting in €230 of extra cost per admitted patient. The overall cost per QALY gained was of €10; this value is much lower than the WHO threshold defining high cost effectiveness of an intervention, i.e. three times the current Sierra Leone annual per capita GDP of €1416. Conclusion: With an additional cost per QALY of only €10.0, the implementation and one-year running of the case studied obstetric HDU can be considered a highly cost-effective frugal innovation in limited resource contexts. The evidences provided by this study allow a precise and novel insight to policy makers and clinicians useful to prioritize interventions in critical care and thus address maternal mortality in a high burden scenario.

Listeria infection after treatment with alemtuzumab: a case report and literature review. Would antibiotic prophylaxis be considered?

Few cases of complicated infections with Listeria monocytogenes (LM) have been reported to date in patients with multiple sclerosis (MS) treated with alemtuzumab. Primary prevention strategies may be suggested in such patients to avoid infections. However, these may be ineffective because patients may already be carriers of LM. We report herein a case of bloodstream infection due to LM in a 25-year-old woman with MS treated with alemtuzumab. We searched the UMC/WHO Vigibase system for all reported cases of LM in patients treated with alemtuzumab and found 29 cases overall up to 21 July 2019. We also performed a literature review of MS cases with LM on alemtuzumab, in order to evaluate epidemiology, clinical characteristics, and outcome of this complication. Since the published cases (N=8) were mainly reported in recent years but more cases were found in the UMC/WHO Vigibase system (although not necessarily in patients with MS), we hypothesize that this complication is more frequent than currently believed and may become even more important in the future. Therefore, it is worth reaching a consensus on appropriate algorithms to stratify individuals by risk so as to implement targeted prevention strategies (whether primary or secondary).

Monitoring for multidrug-resistant Plasmodium falciparum isolates and analysis of pyrimethamine resistance evolution in Uige province, Angola.

OBJECTIVES: To assess the extent of drug resistance in Uige through molecular genetic analysis and to test whether the dhfr triple mutant alleles present in Angola are of southeast Asian origin. METHODS: Seventy-one samples of blood from children admitted to the Pediatric Emergency Unit of Uige Provincial Hospital in 2004 were screened for resistance mutations at pfcrt, pfmdr1, pfdhfr, pfdhps and pfATPase6. RESULTS: Mutations in pfcrt (codon76), pfmdr1 (codon86), pfdhfr (codons 51, 59, 108) and pfdhps (codons 436, 437) were common. Among the 66 isolates for which we were able to determine complete genetic information 13.7% carried all seven of these mutations. Flanking microsatellite analysis revealed the triple mutant pfdhfr was derived from the southeast Asian lineage, while the N51I+S108N double mutant pfdhfr alleles are a local origin. pfATPase6 mutations were rare and S769N was not found. CONCLUSION: The parasite population of Uige Angola has high frequency mutations in pfcrt, dhfr and dhps associated with resistance to chloroquine and sulphadoxine pyrimethamine, reflecting past reliance on these two drugs which were the mainstay of treatment until recently. Our findings show that drug resistance in Uige has occurred through a combination of local drug pressure and the regional and international dispersal of resistance mutant alleles.

Discussion on critical points for a tailored therapy to cure hepatitis C virus infection.

Hepatitis C virus (HCV) infects around 71 million people worldwide and in 2018 it is still a major health problem. Since 2011, anti-HCV therapy with availability of direct-acting antiviral drugs has revolutionized the clinical response and paved the way to eradication strategies. However, despite the high rate of sustained virological response, treatment failure may occur in a limited percentage of patients, possibly due to resistance-associated substitutions (RASs), either emergent or pre-existent even in minority viral populations. Clearly this problem may impair success of eradication strategies. With this background, several questions marks still exist around HCV treatment, including whether pan-genotypic treatments with complete effectiveness in any clinical conditions really exist outside clinical trials, the actual cost-effectiveness of genotyping testing, and utility of RAS detection in viral quasispecies by next generation sequencing approach. In this review, we describe these critical points by discussing recent literature data and our research experience.

Clinical, Virological Characteristics, and Outcomes of Treatment with Sofosbuvir/Ledipasvir in Two Pediatric Patients Infected by HCV Genotype 4.

Direct-acting antiviral drugs to cure infections with Hepatitis C virus (HCV) achieve a sustained virological response (SVR) in more than 90% of adult patients. At present, clinical trials are ongoing and real-life data are still limited in children. Herein, we report two cases of pediatric patients treated with fixed-dose combination of sofosbuvir/ledipasvir, already approved to treat HCV4 genotype. Both young girls achieved SVR even though HCV4 isolates carried L28M and M31L NS5A resistance-associated substitutions (RASs). Therefore, possible effects of these RASs merit further study, especially in children.

Impact of Ebola outbreak on reproductive health services in a rural district of Sierra Leone: a prospective observational study.

OBJECTIVES: To assess the trends concerning utilisation of maternal and child health (MCH) services before, during and after the Ebola outbreak, quantifying the contribution of a reorganised referral system (RS). DESIGN: A prospective observational study of MCH services. SETTING: Pujehun district in Sierra Leone, 77 community health facilities and 1 hospital from 2012 to 2017. MAIN OUTCOME MEASURES: MCH utililization was evaluated by assessing: (1) institutional deliveries, Cesarean-sections, paediatric and maternity admissions and deaths, and major direct obstetric complications (MDOCs), at hospital level; (2) antenatal care (ANC) 1 and 4, institutional delivery and family planning, at community level. Contribution of a strengthened RS was also measured. RESULTS: At hospital level, there is a significant difference between trends Ebola versus pre-Ebola for maternal admissions (7, 95% CI 4 to 11, p<0.001), MDOCs (4, 95% CI 1 to 7, p=0.006) and institutional deliveries (4, 95% CI 2 to 6, p=0.001). There is also a negative trend in the transition from Ebola to post-Ebola for maternal admissions (-7, 95% CI -10 to -4, p<0.001), MDOCs (-4, 95% CI -7 to -1, p=0.009) and institutional deliveries (-3, 95% CI -5 to -1, p=0.001). The differences between trends pre-Ebola versus post-Ebola are only significant for paediatric admissions (3, 95% CI 0 to 5, p=0.035). At community level, the difference between trends Ebola versus pre-Ebola and Ebola versus post-Ebola are not significant for any indicators. The differences between trends pre-Ebola versus post-Ebola show a negative difference for institutional deliveries (-7, 95% CI -10 to -4, p<0.001), ANC 1 (-6, 95% CI -10 to -3, p<0.001), ANC 4 (-8, 95% CI -11 to -5, p<0.001) and family planning (-85, 95% CI -119 to -51, p<0.001). CONCLUSIONS: A stronger health system compared with other districts in Sierra Leone and a strengthened RS enabled health facilities in Pujehun to maintain service provision and uptake during and after the Ebola epidemic.

Utility of Molecular Identification and Quantitation of Bartonella Species with Species-Specific Real-Time PCR for Monitoring Treatment Response: A Case Series.

BACKGROUND: Bartonella species are intracellular bacteria capable of producing several diseases in humans. The three most common and wellknown diseases are cat scratch disease (CSD), caused by B. henselae, trench fever, caused by B. quintana and Carrion's Disease, caused by B. bacilliformis. Signs and symptoms are very different and aspecific: Fatigue, fever, headache, lymphadenopathy, malaise, loss of weight. No data exist to support guidelines' recommendations to decide which drugs should be optimally used and how long they should be administered. Therefore, a marker of treatment response is needed to guide treatment strategies. METHODS: We report herein three cases in which a species specific Reverse-Transcriptase Polymerase-Chain-Reaction (RT PCR) developed in-house was performed and compared to serology in order to make diagnosis and to evaluate treatment response. RESULTS: Our species-specific RT PCR seemed to play a fundamental role both in diagnosis and treatment. Moreover, a discrepancy with the serology results was found. CONCLUSION: Further studies are necessary to validate these results and elucidate what is the best treatment for this pleomorphic disease. However, in absence of clear guidelines, RT PCR may be useful to orientate kind of treatment ad its duration.

Prevalence of parasitic infections in migrants: do official symptom-driven guidelines apply to the current situation?

In recent years, migration has become a significant challenge in Western countries. Migrant populations, coming from hyper-endemic areas, may present parasitic infections that remain latent and asymptomatic even for years, eventually leading to severe complications. Italian guidelines have been established to perform screening guided by the presence of symptoms and/or hypereosinophilia. Parasitological screening was conducted in a migrant population to carry out preventative measures. All migrants were asked to report any symptoms suggesting parasitic infections and list any previous treatment received. Travel data were recorded. Parasitological examination of stools and urine were conducted in all patients regardless of symptoms. In all, 208 consecutive patients were enrolled in our outpatient clinic from November 2016 to August 2017. Thirty-four patients were excluded due to the previous assumption of albendazole or because they did not exhibit suitable samples. Prevalence of parasitic infections was 33/174 (18.9%). A statistically significant difference for the prevalence of parasitic infections was not found between patients who were asymptomatic and without hypereosinophilia compared to those who presented symptoms and/or hypereosinophilia (27/151 [17.9%] vs. 6/23 [26.0%]; p=0.39). By contrast, a statistically significant difference was found for the length of time between arrival in Italy and parasitological examinations (4/51 [7.8%] migrants who arrived in Italy more than six months prior to screening vs. 29/123 [23.6%] migrants who arrived within six months; p= 0.016). Our results did not demonstrate any significant differences in prevalence of parasitic infections between symptomatic or hypereosinophilic and asymptomatic migrants. Thus we feel it inappropriate to support recent guidelines recommending parasitological examinations only in migrants with symptoms and/or hypereosinophilia. By contrast, it would appear important to perform parasitological screening in migrants as soon as possible after their arrival. Since such infestations, if untreated, could result in chronic diseases and complications, and could be transmitted in the host countries, our results have potential implications for public health.

Hepatic microabscesses during CMV reactivation in a multiple sclerosis patient after alemtuzumab treatment.

The anti-CD52 monoclonal antibody alemtuzumab is a highly active treatment for multiple sclerosis (MS) causing rapid depletion of B and T lymphocytes with nadir one month after last infusion. Opportunistic Cytomegalovirus (CMV) infections have been reported in MS patients treated with this drug. We report one patient who developed a CMV reactivation with hepatic involvement three weeks after the first cycle of alemtuzumab. This patient, promptly diagnosed and treated, achieved a complete recovery with valganciclovir. The possibility of this treatable opportunistic infection should be considered by neurologists in febrile patients with hepatic markers alteration after treatment with alemtuzumab.

Evolution of glomerular filtration rates and neutrophil gelatinase-associated lipocalin during treatment with direct acting antivirals.

Background/Aims: Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection. METHODS: A retrospective cohort study evaluated eGFR modification during treatment with DAA. Subgroup analysis on serum NGAL was conducted in those receiving sofosbuvir/ledipasvir, with complete follow-up until week 12 after the end of treatment (FU-12). RESULTS: In the 102 enrolled patients, eGFR reduction was observed (from 86.22 mL/min at baseline to 84.43 mL/min at FU-12, P=0.049). Mean NGAL increased in 18 patients (from 121.89 ng/mL at baseline to 204.13 ng/mL at FU-12, P=0.014). At FU-12, 38.8% (7/18) of patients had a plasmatic NGAL value higher than the normal range (36-203 ng/mL) compared with 11.1% (2/18) at baseline (χ 2 =3,704; P=0.054). In contrast, eGFR did not change significantly over the follow-up in this subgroup. Conclusions: In conclusion, compared to a negligible eGFR decline observed in the entire cohort analyzed, a significant NGAL increase was observed after HCV treatment with DAA in a small subgroup. This could reflect tubular damage during DAA treatment rather than glomerular injury.

Patterns of multi-drug resistant bacteria at first culture from patients admitted to a third level University hospital in Calabria from 2011 to 2014: implications for empirical therapy and infection control.

Surveillance of antimicrobial drug resistance is fundamental to guide empirical treatment. However, the European Antimicrobial Resistance Surveillance Network provides a general picture, which might not be applicable to clinical settings that are excluded from this survey. We evaluated resistance patterns of ESKAPE isolates over a four-year period in a third level University hospital in the province of Catanzaro (Southern Italy). In this retrospective study, we evaluated the frequency of ESKAPE isolates with different resistance patterns (group 1=low-resistant bacteria; group 2=multi-drug and extremely drug-resistant bacteria; group 3=pan-resistant bacteria), stratified by year (2011, 2012, 2013 and 2014), hospital units (intensive care units, medical and surgical units) and by sample type (urine, blood, wound swabs, respiratory samples, other samples). Chi square test was applied to find differences between isolates with different resistance patterns by hospital unit and by organs and systems. Cochran-Armitage trend test was applied to assess the trend in resistance patterns during the four years analyzed. Amongst 2385 isolates, Escherichia coli (38%) was the most frequent, followed by Pseudomonas aeruginosa (15%), Klebsiella pneumoniae (14%), Staphylococcus aureus (13%), Acinetobacter baumannii (9%), Enterococcus faecalis (8%) and Enterococcus faecium (3%). From 2011 to 2014, frequency of isolates in group 2 plus 3 decreased from 23% to 14% (chi square=55.093; p<0.0001), particularly for E. coli and K. pneumoniae, but the trend increased for S. aureus (from 5% in 2011 to 10% in 2014), and remained stable for the other species. Frequency of isolates in group 2 plus 3 was higher in intensive care units for K. pneumoniae (chi square =32.292; p<0.0001), A. baumannii (chi square =6.947; p<0.0001) and S. aureus (chi square =22.079; p<0.0001). It was also higher from blood than from different sources for most species.

The Risk of Hepatocellular Carcinoma After Directly Acting Antivirals for Hepatitis C Virus Treatment in Liver Transplanted Patients: Is It Real?

INTRODUCTION: Since directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) were introduced, conflicting data emerged about the risk of hepatocellular carcinoma (HCC) after interferon (IFN)-free treatments. We present a case of recurrent, extra-hepatic HCC in a liver-transplanted patient soon after successful treatment with DAAs, along with a short review of literature. CASE PRESENTATION: In 2010, a 53-year old man, affected by chronic HCV (genotype 1) infection and decompensated cirrhosis, underwent liver resection for HCC and subsequently received orthotopic liver transplantation. Then, HCV relapsed and, in 2013, he was treated with pegylated-IFN plus ribavirin; but response was null. In 2014, he was treated with daclatasvir plus simeprevir to reach sustained virological response. At baseline and at the end of HCV treatment, computed tomography (CT) scan of abdomen excluded any lesions suspected for HCC. However, alpha-fetoprotein was 2.9 ng/mL before DAAs, increasing up to 183.1 ng/mL at week-24 of follow-up after the completion of therapy. Therefore, CT scan of abdomen was performed again, showing two splenic HCC lesions. CONCLUSIONS: Overall, nine studies have been published about the risk of HCC after DAAs. Patients with previous HCC should be carefully investigated to confirm complete HCC remission before starting, and proactive follow-up should be performed after DAA treatment.

Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

AIM: To evaluate neutrophil gelatinase associated lipocalin (NGAL) in patients infected by hepatitis C virus (HCV) before and during treatment with directly acting antivirals (DAAs). METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate (eGFR). Then, NGAL and eGFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for non-parametric data. Differences in dichotomous variables were evaluated through χ (2) test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four (FIB-4), AST to platelet ratio index (APRI), and eGFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with eGFR < 60 mL/min vs patients with eGFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/dL were compared with those of NGAL ≤ 118.11 ng/dL, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis (P > 0.05). Linear correlation was found between NGAL and both age (P = 0.0475) and eGFR (P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for eGFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline (P = 0.0239). CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

A hospital-centered approach to improve emergency obstetric care in South Sudan.

OBJECTIVE: To assess provision of emergency obstetric care (EmOC) in Greater Yirol, South Sudan, after implementation of a hospital-centered intervention with an ambulance referral system. METHODS: In a descriptive study, data were prospectively recorded for all women referred to Yirol County Hospital for delivery in 2012. An ambulance referral system had been implemented in October 2011. Access to the hospital and ambulance use were free of charge. RESULTS: The number of deliveries at Yirol County Hospital increased in 2012 to 1089, corresponding to 13.3% of the 8213 deliveries expected to have occurred in the catchment area. Cesareans were performed for 53 (4.9%) deliveries, corresponding to 0.6% of the expected number of deliveries in the catchment area. Among 950 women who delivered a newborn weighing at least 2500 g at the hospital, 6 (0.6%) intrapartum or very early neonatal deaths occurred. Of 1232 women expected to have major obstetric complications in 2012 in the catchment area, 472 (38.3%) received EmOC at the hospital. Of 115 expected absolute obstetric indications, 114 (99.1%) were treated in the hospital. CONCLUSION: A hospital-centered approach with an ambulance referral system effectively improves the availability of EmOC in underprivileged remote settings.