Esperanza Merino

Increasing Incidence of Hepatocellular Carcinoma in HIV-Infected Patients in Spain

BACKGROUND To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. METHODS All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. RESULTS Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. CONCLUSIONS HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.

Functional status determined by Barthel Index predicts community acquired pneumonia mortality in general population

BACKGROUND Barthel Index (BI) measures functional status. Our aim was to analyze if BI and other factors not included in Pneumonia Severity Index (PSI) predict mortality in general population with community acquired pneumonia (CAP). METHODS Prospective observational study including all patients with CAP diagnosed in 2006. Endpoint of study: 30-day mortality. Variables not included in PSI as BI were analyzed. Strength of association was determined by odds ratio (OR) with 95% confidence interval. RESULTS 550 patients, mean age of 60.3 ± 20.8, were included. 32 were lost during follow-up and 518 patients were finally analyzed. 44 (8.5%) patients died in the first 30 days after CAP diagnosis. In bivariate analysis, mortality was significantly more frequent in patients with PSI ≥ IV (19.2% vs 1.9%), BI≤80 points (23.9% vs 2.9%), multilobar infiltrate (20% vs 6%), diabetes mellitus (14.9% vs 6.5%), influenza vaccination (11.9% vs 6.6%) and pneumococcal vaccination (16.7% vs 6%). In multivariate analysis, mortality independently associated factors were: BI ≤80, OR: 3.9(CI95% 1.4-10.5; p < 0.001); PSI ≥ IV OR: 3.9(1.2-12.7; p < 0.05); and multilobar infiltrate OR: 2.9(1.1-7.3; p = 0.05). CONCLUSION A BI score ≤80 is associated with a higher mortality in patients with CAP independently of the PSI. BI can be a useful tool to predict CAP mortality in general population.

HIV/hepatitis C virus-coinfected patients who achieved sustained virological response are still at risk of developing hepatocellular carcinoma.

Objective:To describe the frequency and the characteristics of hepatocellular carcinoma (HCC) cases that appeared in HIV/hepatitis C virus (HCV)-coinfected patients with previous sustained virological response (SVR) and to compare these cases to those diagnosed in patients without SVR. Methods:All HIV/HCV-coinfected patients diagnosed with HCC in 26 hospitals in Spain before 31 December 2012 were analyzed. Comparisons between cases diagnosed in patients with and without previous SVR were made. Results:One hundred and sixty-seven HIV/HCV-coinfected patients were diagnosed with HCC in the participant hospitals. Sixty-five (39%) of them had been previously treated against HCV. In 13 cases, HCC was diagnosed after achieving consecution of SVR, accounting for 7.8% of the overall cases. The median (Q1–Q3) elapsed time from SVR to diagnosis of HCC was 28 (20–39) months. HCC was multicentric and was complicated with portal thrombosis in nine and six patients, respectively. Comparisons with HCC cases diagnosed in patients without previous SVR only yielded a significantly higher proportion of genotype 3 infection [10 (83%) out of 13 cases versus 34 (32%) out of 107; P = 0.001)]. The median (Q1–Q3) survival of HCC was 3 (1–39) months among cases developed in patients with previous SVR, whereas it was 6 (2–20) months in the remaining individuals (P = 0.7). Conclusion:HIV/HCV-coinfected patients with previous SVR may develop HCC in the mid term and long term. These cases account for a significant proportion of the total cases of HCC in this setting. Our findings reinforce the need to continue surveillance of HCC with ultrasound examinations in patients with cirrhosis who respond to anti-HCV therapy.

Acalculous Cholecystitis Associated with Plasmodium falciparum Malaria

SIR—We read with interest the report by Dylewski and AlAzragi [1] that describes a patient with acalculous cholecystitis (AC) and Plasmodium falciparum malaria, which has not been previously described. We present another patient with the same condition and comment on the pathogenesis of AC and P. falciparum malaria, an underdiagnosed condition. A 24-year-old Spanish woman was admitted to the hospital because of a 1-week history of diarrhea and fever after a 15day tourist visit to Punta Cana, Dominican Republic. On admission, she was lethargic, her temperature was 397C, her pulse 105/min, and her blood pressure 90/50 mm Hg. A general physical examination showed tenderness in the right upper abdominal quadrant without any other abnormalities. Laboratories studies disclosed the following values: hemoglobin, 8.9 g/dL; leukocytes, 6200/mm; platelets, 11.000/mm; prothrombin time, 22 s; partial thromboplastin time, 120 s; fibrinogen, 80 mg/dL; antithrombin III, 36%; total bilirubin, 6.9 mg/dL (direct bilirubin, 6.5 mg/dL); lactate dehydrogenase, 928 U/L; aspartate aminotransferase, 214 U/L; alanine aminotransferase, 254 U/L; and alkaline phosphatase, 423 U/L. A test for fibrin degradation products was positive. Other routine laboratory data and the chest x-ray were normal. Abdominal ultrasonography revealed a stone-free gallbladder with a thickened wall surrounded by a thin layer of fluid. A diagnosis of AC cholecystitis was made. Examination of 3 blood smears for parasites was negative. A hematological study revealed anemia with normal iron metabolism, a negative Coombs test, and absence of hemolysis signs. Freshly frozen plasma was administered for the severe coagulation abnormalities, and empirical therapy with ceftriaxone and metronidazole was initiated. Cultures of blood, stool specimen, and urine were negative. Two serologic studies separated by 1 week were negative for Salmonella, Yersinia, amoeba, Leptospira, and HIV. After 1 week of antibiotic treatment, although the fever continued, abdominal symptoms had improved, and the gallbladder ultrasonography was normal. A thoracic and abdominal CT showed a moderate splenomegaly. On day 21, the patient became apyretic; the antibiotics were stopped, and she was discharged. Four days later, the clinical symptoms reappeared. On readmission, 1 of 3 blood cultures grew Shigella sonnei, whereas stool cultures remained negative. Again therapy with ceftriaxone was begun. Despite a normal abdominal ultrasonography, the patient had a persistent fever, anemia, hyperbilirubinemia, and increased levels of lactate dehydrogenase without hemolysis. A second set of blood smears revealed infestation with ring trophozoites typical of Plasmodium falciparum and merozoites. Several days later, a positive serology of P. falciparum at a titer of 1:360 was received. A diagnosis of imported malaria was made, and treatment with quinine and doxicycline was started, with resolution of the diarrhea and fever, as well as normalization of the laboratory data. An enteric fever was initially suspected, despite negative cultures and serology. The patient had recently traveled to the Caribbean islands, her clinical features were compatible, and she had developed an AC and had a good response to ceftriaxone. During the second admission to the hospital, the patient’s fever and diarrhea relapsed and, although S. sonnei was isolated in a blood culture, specific treatment failed, and symptoms persisted until malaria treatment was administered. The clinical presentation with AC and the concept that Punta Cana in the Altagracia province of the Dominican Republic was not a malaria area led to the delay of the diagnosis. On 22 December 1999, the Centers for Disease Control and Prevention reported in its travel web page (www.cdc.gov/travel/blusheet.htm) an outbreak of P. falciparum malaria in the Altagracia province. This outbreak involved 1250 cases during 1999 and has been associated with climatic changes induced by Hurricane George. It has also been associated with worker emigration, usually illegal and without sanitary control, from endemic areas (Haiti) to tourist zones in the Dominican Republic. The pathogenesis of AC [2] involves a combination of bile stasis and ischemia. As in Dylewski’s patient, our patient presented hypotension that probably contributed to gallbladder damage. Etiology of AC [2] includes trauma, vascular diseases (polyarteritis nodosa), and infectious agents, such as Salmonella, cytomegalovirus, Cryptosporidium, and microsporidium. To the best of our knowledge, S. sonnei has never been associated with AC. The S. sonnei bacteremia was probably related to a transient immunosuppression induced by malaria [3]. The contribution of malaria to AC in this patient seems evident, but secondary bacterial infections are common in malaria. It remains to be determined whether AC is directly related to malaria or to a secondary gallbladder bacterial infection that could not be identified. We agree with Dylewski and Al-Azragi that malaria, although the pathogenesis remains controversial, should be included among the differential diagnoses of AC, especially in endemic zones of malaria.

Nosocomial outbreak of scabies clinically resistant to lindane.

To the Editor: Scabies is a cutaneous parasitosis transmitted mainly by skin contact. Delayed diagnosis because of atypical presentation facilitates dissemination. Crusted (Norwegian) scabies particularly is likely to lead to epidemics, because patients are infested by thousands of mites and thus are extremely contagious. Several nosocomial scabies outbreaks with secondary cases among the relatives of patients and staff have been noted in recent years.1,2 Here we report such an outbreak that was very difficult to eradicate due to clinical resistance to 1% lindane, which had been our standard treatment for scabies. In late November 1994, a patient with acquired immunodeficiency syndrome and psoriatic erythroderma with severe itching was admitted to our infectious disease unit and received topical treatment, involving frequent manipulation of the lesions and changes of dressings. When symptoms persisted, crusted scabies was suspected, proven by skin biopsy on December 14, and treated with lindane. In the following 19 weeks, six cases of scabies were diagnosed among healthcare workers, five among their family members, and five among patients with no prior contact with the index patient. Lindane treatment and prophylaxis showed no effect. An intervention program was designed by our Preventive Medicine Department and was implemented in the 20th week of 1995. All of our facilities and the fomites (including beds and wheelchairs) were cleaned intensely and fumigated, 5% permethrin was used prophylactically on every patient in the ward, all the staff, and the families of both the staff and the patients. The same day, we instituted a nurse protocol directed to pruritus. Every patient admitted to our unit was questioned systematically about itching. If pruritus was detected and it affected other relatives, appeared mainly at night, or was located in areas suggesting scabies, the patient was placed in cutaneous isolation, treated with an emulsion of 5% permethrin, and kept in cutaneous isolation until scabies had been definitely excluded. From that intervention on, no more cases of scabies were diagnosed either in the staff or in their families, and no further nosocomial transmission of scabies was observed. Control of a scabies outbreak requires good disinfestation of fomites, paying special attention to beds and wheelchairs, and simultaneous treatment of all potentially affected individuals (patients and staff) in the facility and their families.3 This may require treatment of over 500 people and expenditure of more than

Vitamin D insufficiency and subclinical atherosclerosis in non-diabetic males living with HIV

20,000. Good coordination is essential. It is imperative that treatment be given to the entire group. The medications have to be distributed and all participants given careful directions regarding the importance of following the instructions completely. Factors contributing to the persistence of epidemics include patients with unrecognized infestations because of atypical or minimally symptomatic lesions, patients with crusted (Norwegian) scabies, carriage of scabies mites by infested staff members before they have symptoms, treatment failure due to improper use of scabicides or bad compliance, and lindane failure.4 When an epidemic proves difficult to control and scabies persists as a chronic problem over a period of months or even years, this often leads to staff demoralization. Frustration and anger are common among staff, patients, and families. An accurate information policy is very useful in allaying fears and achieving the cooperation needed to resolve the outbreak.

Infección crónica por el virus de la hepatitis C y enfermedad hepática asociada en una prisión española

Vitamin D insufficiency (VDI) has been associated with increased cardiovascular risk in the non‐HIV population. This study evaluates the relationship among serum 25‐hydroxyvitamin D [25(OH)D] levels, cardiovascular risk factors, adipokines, antiviral therapy (ART) and subclinical atherosclerosis in HIV‐infected males.

Polyostotic osteitis in secondary syphilis in an HIV-infected patient.

OBJECTIVE The objective of this study was to determine the prevalence and genotype distribution of chronic hepatitis C virus (HCV) infection in a penitentiary population. The secondary objective was to describe histological findings in liver of the biopsied population, and identify risk factors associated with liver fibrosis and inflammatory activity. METHODS Among 800 inmates, 730 accepted HCV antibody screening and PCR confirmation. Sociodemographic, behavioral, and incarceration-related variables were analyzed. Liver biopsy was offered to individuals with chronic HCV infection. Advanced liver disease was defined as fibrosis 3 and/or an inflammatory activity index score 8). RESULTS HCV antibodies were found in 279 inmates. PCR confirmed HCV infection in 250 inmates, yielding a prevalence of 34.2% (95% confidence interval [CI]: 30.8-37.8). Intravenous drug use was independently associated with HCV infection, odds ratio (OR) 51.7 (95% CI: 31-86). Genotypes were 1a 32.9%, 3 29.7%, 1b 18.4% and 4 17.1%. Fifty-one liver biopsies were performed; advanced liver disease was found in 7 patients (13.7%) based on fibrosis and in 31 patients (60.7%) based on the inflammatory activity index. High AST and ALT levels were associated with advanced liver disease established on both fibrosis and inflammatory activity (P<.05). Lengthy intravenous drug use was associated with inflammatory activity (P=.02; OR 1.2; 95% CI: 1.03-1.7). CONCLUSIONS Persistent HCV infection is highly prevalent among prison inmates and is associated with intravenous drug abuse. HCV genotype diversity is higher in prison inmates than in the general population. Higher transaminase levels are associated with advanced liver disease.

Evaluation of the Sepsis Flow Chip assay for the diagnosis of blood infections

We herein describe a case of secondary syphilis in a patient with HIV infection that presented with an unusually diffuse polyostotic osteitis with skull involvement. Syphilis has to be added to the differential diagnosis of extensive inflammatory bone pain in patients at risk, especially if pain worsens at night.

Prediction of recurrent clostridium difficile infection at the bedside: the GEIH-CDI score.

Background Blood infections are serious complex conditions that generally require rapid diagnosis and treatment. The big challenge is to reduce the time necessary to make a diagnosis with current clinical microbiological methods so as to improve the treatment given to patients. Methods In this study, we assess for the first time the Sepsis Flow Chip assay, which is a novel diagnostic assay for simultaneous rapid-detection of the vast majority of bloodstream pathogens, including Gram-positive and Gram-negative bacteria and fungi, in the same assay, and for the detection of most common antibiotic resistance genes. The SFC assay is based on multiplex PCR and low density DNA arrays. Results Positive blood cultures from 202 consecutive bacteremia patients were analyzed by SFC assay and the results were compared with the results obtained by the gold standard methodology used in clinical microbiology diagnostic laboratories (EUCAST guidelines). SFC assay overall sensitivity and specificity for bacterial identification were 93.3% and 100% respectively and sensitivity and specificity for the identification of antibiotic genetic resistance determinants were 93.6% and 100% respectively. Conclusions This is the first evaluation of SFC assay in clinical samples. This new method appears to be very promising by combining the high number of distinct pathogens and genetic resistance determinants identified in a single assay. Further investigations should be done to evaluate the usefulness of this assay in combination with clinical multidisciplinary groups (stewardship), in order for the results to be applied appropriately to the management of patients`infectious processes.