Plasma and Breast Milk Pharmacokinetics of Tenofovir Disoproxil Fumarate in Nursing Mother with Chronic Hepatitis B-Infant Pairs.

Tenofovir use is associated with lower risk of mother-to-infant transmission of the virus, and discontinuation of the treatment is not safe. However, the safety of the drug during pregnancy and breastfeeding is not clear. In this study, we aimed to determine the tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during the lactation period. A total of 11 mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245 mg/day for at least 1 month because of chronic hepatitis B infection. Maternal blood, breast milk, and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography-tandem mass spectrometry. The median concentrations of tenofovir in maternal plasma and breast milk samples were 88.44 (interquartile range [IQR], 62.47 to 116.17) ng/ml and 6.69 (IQR, 4.88 to 7.03) ng/ml, respectively. Tenofovir concentrations were undetectable (<4 ng/ml) in all of the infant plasma samples. The ratio of tenofovir concentration in breast milk to that in maternal plasma was 0.07. Tenofovir disoproxil fumarate passes through the breast milk in a small amount. Infants had no detectable tenofovir level in their plasma. Our study suggests that tenofovir disoproxil fumarate treatment is safe during the breastfeeding period in chronic hepatitis B patients.

Time to viral suppression is not related to achievement of SVR12 in HCV GT1-infected patients treated with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin.

High rates of sustained virologic response at post-treatment week 12 (SVR12) were achieved in six phase 3 trials of ombitasvir (OBV, an NS5A inhibitor), paritaprevir (an NS3/4A protease inhibitor) co-dosed with ritonavir (PTV/r) + dasabuvir (DSV, an NS5B RNA polymerase inhibitor) (ie, 3D regimen) with or without ribavirin (RBV) in adults with chronic genotype (GT) 1 hepatitis C virus (HCV) infection. We assessed whether time to first HCV RNA value below the lower limit of quantification in patients with and without cirrhosis was associated with achievement of SVR12. Data were analysed from GT1-infected patients enrolled in six phase 3 studies of 3D ± RBV. Patients who experienced non-virologic failure were excluded from analysis. HCV RNA was determined using the Roche COBAS TaqMan RT-PCR assay (lower limit of quantification, LLOQ =25 IU/mL). SVR12 was analysed by week of first HCV RNA suppression, defined as HCV RNA

Comparison of community-onset healthcare-associated and hospital-acquired urinary infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and antimicrobial activities.

OBJECTIVE: We aimed to compare community-onset healthcare-associated (CO-HCA) and hospital-acquired (HA) urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in terms of epidemiology, clinical outcomes and antimicrobial activities. METHODS: Patients from both groups with ESBL-producing E. coli detected by urine culture between January 2009 and January 2011 were included in this retrospective study. Relevant demographical, microbiologic and clinical data were obtained from case records. RESULTS: A total of 173 patients (mean age of 58 years, 74% female) were included, of whom 75 (43.4%) had a CO-HCA UTI and 98 (56.6%) had an HA UTI. Eighty (46.2%) patients had more than one comorbid disease, of whom 57 (32.5%) had urological problems. The most common clinical manifestations were pyelonephritis (43.9%) and urosepsis (16.2%). An age of > 65 years (p = 0.005) in addition to urinary catheterisation (p = 0.001), urosepsis (p = 0.001) and mortality (p = 0.001) were significantly more common in the HA UTI group. Acute cystitis (p = 0.027), complicated cystitis (p = 0.001) and non-urologic neoplasm (p = 0.032) were significantly more common in the CO-HCA UTI group. No isolate was resistant to carbapenems or fosfomycin. Sensitivities to nitrofurantoin, amikacin, trimethoprim sulfamethoxazole-trimoxazole and quinolones were 97.6%, 89%, 29.4% and 17.9% respectively. Both groups showed similar rates of antibiotic resistance. CONCLUSION: ESBL-producing E. coli should be taken into consideration in patients with a CO HCA UTI, not only in hospital settings but also in outpatient settings. We suggest ertapenem as a first-line empirical treatment for patients with an upper UTI and fosfomycin and nitrofurantoin for those with a lower UTI when ESBL-producing E. coli is suspected.

Predictors associated with treatment initiation and switch in a real-world chronic hepatitis B population from five European countries.

In Europe, healthcare systems differ between countries and different factors may influence Chronic hepatitis B (CHB) treatment choices in different counties. This analysis from a prospective, longitudinal, non-interventional study in five EU countries aimed to explore determinants associated with treatment initiation or switch in patients with CHB. A total of 1267 adult patients with compensated CHB in Germany, France, Poland, Romania and Turkey were prospectively followed for up to 2 years (March 2008-December 2010). Determinants of treatment initiation or switch were analysed using multivariate Cox proportional hazards regression. Median time since CHB diagnosis was 2.6 (0-37.7) years. Among 646 treatment-naïve patients, the probability of treatment initiation during follow-up was higher: in Germany (P = 0.0006), Poland (P < 0.0001) and Romania (P = 0.0004) compared with Turkey; in patients with alanine transaminase (ALT) 1-2 × upper limit of normal (ULN) (P = 0.0580) or >2 × ULN (P = 0.0523) compared with ALT ≤ 1 × ULN; and in patients with hepatitis B virus (HBV) DNA ≥ 2000 IU/mL (P < 0.0001) compared with HBV DNA <2000 IU/mL or undetectable. Among 567 treated patients, 87 switched treatment during follow-up. The probability of treatment switch was higher: in France (P = 0.0029), Germany (P = 0.0078) and Poland (P = 0.0329) compared with Turkey; and in patients with HBV DNA <2000 (P < 0.0001) or ≥ 2000 IU/mL (P < 0.0001), compared with undetectable. Viral load and ALT level were identified as the major drivers of treatment initiation. HBV DNA level was also a significant determinant of treatment switch. Results were statistically different across EU countries.

Coronavirus disease 2019 re-infection: first report from Turkey.

There are concerns about the possibility of SARS-CoV-2 reinfection and recently, a patient with SARS-CoV-2 re-infection (or COVID-19) confirmed by epidemiological, clinical, serological and genomic analyses have been published. We have noticed another patient with SARS-CoV-2 re-infection based on clinical and laboratory studies: A 23-year-old woman presented to her hospital with fever (39°C), chills, fatigue, cough, headache, sore throat, muscle and joint pain on April 9, 2020. On examination, oropharynx was mildly hyperemic, and chest auscultation was normal. SARS-CoV-2 PCR from nasopharyngeal specimen was ordered. She was given isotonic saline and acetaminophen and prescribed azithromycin and acetaminophen and sent home for isolation. SARS-CoV-2 PCR was reported positive and she was given hydroxychloroquine for five days. She improved in 10 days and PCR studies on April 22, and April 27 remained negative. On 4 August 2020, she was re-admitted with fever (38.7°C), chills, fatigue, loss of appetite, taste and smell loss, muscle and joint pain. On examination, oropharynx and chest auscultation were normal. SARS-CoV-2 PCR was reported positive and she was prescribed hydroxychloroquine, acetaminophen and sent home for isolation again. She improved in one week (taste-smell loss improved in 10 days) and on follow-up visit after 14 days, she was doing well. PCR was negative on 17 August 2020. Her anti-SARS-CoV-2 antibodies were negative on 17 August 2020 and slightly positive (2.14 signal-to-cutoff) on 29 August 2020. Previous report from To et al. [Clin Infect Dis. 2020;ciaa1275. doi:10.1093/cid/ciaa1275] showed that viral genomes from first and second episodes belonged to different clades/lineages. They described second episode of asymptomatic infection occurred 142 day after the first symptomatic one. Our patient is the first report, describing two symptomatic episodes 116 days apart. We conclude that as the patients recovered from COVID-19 increases, increased awareness may delineate the characteristics of re-infection.

Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers.

BACKGROUND: The effect of conventional interferon-based therapy of hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is controversial. Yet, no studies have been carried out into pegylated interferon treatment for chronic HBV/HCV coinfection. We aimed to evaluate the response rate and side effects of conventional or pegylated interferon combined with ribavirin on chronic HBV/HCV coinfection therapy. METHODS: The study included 36 chronic hepatitis patients (M/F: 28/8, mean age 47+/-12 years) who were positive for HBsAg and anti-HCV. They were tested for the presence of HBV-DNA by hybridisation assay, and the samples giving negative results were retested by polymerase chain reaction (PCR). All patients were tested for HCV-RNA using PCR, and the HCV genotype was determined. RESULTS: Nineteen patients were given standard interferon either alone or in combination with ribavirin, whereas 17 were given pegylated interferon and ribavirin combination therapy. None of the patients had HBV-DNA positivity; however, all had HCV-RNA detectable by PCR. All the patients had HCV genotype 1b. The mean alanine aminotransferase and aspartate aminotransferase levels were 118+/-65 U/l and 90+/-95 U/l respectively. Five patients in each group discontinued the treatment due to side effects. Only two patients (one from each group) reached sustained virological response. CONCLUSION: Neither pegylated nor conventional interferon based regimes were effective for HBV/HCV coinfection, in which the dominant virus was HCV. Pegylated interferon and ribavirin therapy was not superior to conventional interferon based regimes in the treatment of HBV/HCV coinfection.

Erythema nodosum: an evaluation of 100 cases.

OBJECTIVES: In this study, we investigated the clinical features, etiology, and also predictive factors of secondary erythema nodosum (EN) in patients with EN. METHODS: A total of 100 patients (mean age: 37 years) diagnosed with EN between 1993 and 2004 in our clinic were included in the study prospectively. A skin biopsy was performed in 46 of the patients. Patients were considered to have secondary EN when an underlying condition was found, and to have primary EN when no such condition was found. For the diagnosis of the underlying diseases, the pertinent diagnostic criteria and/or diagnostic methods were used. Categorical and continuous variables were compared by using chi-square and Mann-Whitney U tests respectively. Multiple regression analysis was applied to the significantly different variables. RESULTS: The majority of the patients were female (female/male: 6/1) and nearly half (47%) of the cases had a determined etiology. The leading etiology was poststreptococcal (11%), followed in decreasing order by primary tuberculosis (10%), sarcoidosis (10%), Behçet's syndrome (BS) (6%), drugs (5%), inflammatory bowel diseases (IBD) (3%), and pregnancy (2%). Fifteen (15%) patients complained of cough; the diagnosis was primary tuberculosis in eight cases and sarcoidosis in seven. Four patients with arthritis were diagnosed as having BS (in 3) and Crohn's disease (in 1). All the patients were followed for a mean duration of 4.5 years. The nodosities relapsed annually in 62% (33/53) of idiopathic EN patients but in only one (BS) in the secondary EN group. The histology was consistent with EN in all biopsied patients. Our study revealed that fever, leukocytosis, elevated CRP level, accelerated ESR, presence of cough, sore throat, diarrhea, arthritis, and pulmonary pathology were predictors of secondary EN. Recurrence in EN significantly predicted primary EN. All of the patients had bed rest and the majority was given an anti-inflammatory agent (naproxen sodium). The outcomes were usually favorable within 7 days. The patients with an underlying disease were given the specific treatment. CONCLUSION: EN has been associated with numerous diseases. In order to reduce cost and duration of diagnosis, every centre should determine its own most frequent etiologic factors. Predictive variables for secondary EN should also be determined and an optimum management for such patients should be clarified. Our study revealed streptococcal pharyngitis, primary tuberculosis, sarcoidosis, IBD, and BS as the main etiologies of EN.

Is laparotomy necessary in the diagnosis of fever of unknown origin?

Fever of unknown origin (FUO) is a diagnostic challenge for the practising physician. Detailed medical history, physical examination, non-invasive laboratory tests, and radiologic examinations compose the first level in the diagnostic approach to the FUO. When a diagnosis cannot be established with these procedures, some invasive diagnostic techniques and finally exploratory laparotomy are performed. Although advanced diagnostic measures and imaging-guided less invasive procedures have decreased the need, laparotomy remains as a final diagnostic method for FUO cases. In this study we evaluate the role and importance of laparotomy in the diagnosis of our FUO cases. In 17 out of 126 patients (8 male, 9 female, the median age 35.8 years) hospitalized in our clinic between 1982 and 2002 with the diagnosis of FUO, the diagnosis was established by laparotomy. The diagnosis was made directly in 13 patients, and indirectly (by excluding other diseases) in 2 patients. In several FUO series, the contribution of laparotomy to the diagnosis of FUO was reported as 27-100%. This rate was found to be 88% in the present study. During laparotomy on 17 cases, tissue samples were taken from spleen, liver, intra-abdominal and mesenteric lymph nodes. Pathologic examination of these tissue samples revealed miliary tuberculosis in 4; non-Hodgkin's lymphoma in 3; Hodgkin's lymphoma in 3; liver tumour in 1; hairy cell leukemia in 1; peritonitis carcinomatosis in 1. In the patients with miliary tuberculosis, the liver (3) and/or spleen (2), and/or lymph node (3) revealed caseating granulomas. Laparotomy diagnosed 3 of 5 cases whose abdominal ultrasonography and computerized tomography were normal. In conclusion, although advanced diagnostic methods decreased the need for laparotomy in FUO, if non-invasive and invasive diagnostic measures fail, laparotomy may contribute to the diagnosis. The selection of the patient and the timing are important for laparotomy.

Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe.

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

Fever of unknown origin: a review of 20 patients with adult-onset Still's disease.

In this study we aimed to investigate the findings in patients with adult-onset Still's disease (AOSD) admitted with fever of unknown origin (FUO) during the last 18 years in our unit, in order to discover the ratio of such patients to all patients with FUO during the same period, and to determine the clinical features of AOSD in FUO. The number and the aetiologies of the patients with FUO diagnosed between 1984 and 2001, and the clinical features of those with AOSD, were taken from the patient files. The diagnosis of AOSD was reanalysed according to the diagnostic criteria of Cush et al. [11]. The presumed diagnoses before a diagnosis of AOSD was established were also noted. The chi(2) and Fisher's exact tests were used for statistical analysis. We studied 130 patients with a diagnosis of FUO, 36 (28%) of whom had collagen vascular diseases. Of these 36 patients, 20 (56%, 12 female, 8 male, mean age 34 years, range 16-65) had AOSD. Clinical and laboratory findings were as follows: fever (100%), arthralgia (90%), rash (85%), sore throat (75%), arthritis (65%), myalgia (60%), splenomegaly (40%), hepatomegaly (25%), lymphadenopathy (15%), anaemia (65%), neutrophilic leukocytosis (90%), increased erythrocyte sedimentation rate (100%), elevated transaminase levels (65%), a negative RF (100%), and a negative FANA (80%). Antibiotics had been prescribed in 18 (90%) of cases. The presumed infectious diagnoses were streptococcal tonsillitis/pharyngitis (50%), infective endocarditis (four patients), sepsis (two patients) and acute bacterial meningitis (two patients). The presumed non-infectious diagnoses were acute rheumatic fever (three patients), seronegative rheumatoid arthritis (two patients) and polymyositis (two patients). Sixteen patients were followed for a mean duration of 30 months (range 2-59). A remission was obtained with indomethacin in three cases (19%), and with prednisolone in the remainder. Relapse was detected in three cases (19%). AOSD is one of the most frequent aetiologies of FUO. During the diagnostic course of a patient with FUO, a maculopapular rash and/or arthralgia and/or sore throat should raise the suspicion of AOSD. Because the disease has heterogeneous clinical findings, certain bacterial infections (e.g. streptococcal pharyngitis and sepsis) are generally considered and the prescribing of antibiotics is common.

Spontaneous pneumothorax: a rare complication of miliary tuberculosis.

Pneumothorax is a rare complication of miliary tuberculosis. In this report, a 25-year old patient developing pneumothorax while on the treatment for miliary tuberculosis treatment is presented and the related literature has been reviewed. Pneumothorax, although rare, should be considered when a patient with miliary tuberculosis develops a sudden, severe pain on either side of the chest with breathlessness. The treatment should be tailored according to the size of pneumothorax either pleural drainage through chest tube or needle aspiration. Meanwhile, antituberculous treatment should be continued without interruption.

Diaphragmatic Morgagni hernia in adulthood: correct preoperative diagnosis is possible with newer imaging techniques.

Morgagni hernia is a rare type of diaphragmatic hernia. It is frequently associated with elusive clinical and radiological findings in the adult and consequently, diagnosis and appropriate therapy are usually delayed. We describe a case in which a Morgagni hernia presented as a right sided cardiophrenic mass on a routine chest X-ray. The diaphragmatic defect was further confirmed by computed tomography (CT), by a magnetic resonance imaging (MRI) of the chest. The defect was closed by a prolene mesh.

Tuberculous lymphadenopathy in adults: a review of 35 cases.

We retrospectively reviewed clinical, diagnostic, therapeutic and prognostic features of 35 patients (25 female, 10 male, mean age: 33 years, range: 16-70) with tuberculous lymphadenopathy (TB LAP) which had been followed since 1980. The diagnosis was established by tissue sampling in 32 cases (caseating granulomatous adenitis in 89%) or presence of acid-fast bacilli (AFB) in the aspirate in 2 cases and in the drainage in 1 case. Paraffin-embedded granulomatous tissues were stained by Ehrlich-Ziehl-Neelsen (EZN) and also Mycobacterium tuberculosis DNA was studied by polymerase chain reaction (PCR) (n = 21). The patients were admitted with enlarging LAP (34%), draining LAP (9%), and both systemic complaints and enlarging LAP (57%). Cervical lymph nodes were the most frequently involved site (77%). Pathologic findings on chest X-ray were seen in 23%. Erythrocyte sedimentation rate (ESR) was higher than 100 mm/hour in 25% and associated with systemic complaints. Tuberculin skin test was positive in 91%. AFB could not be seen in any granulomatous tissue (n: 21), but PCR study was positive in 33% (7/21). All patients were given anti-TB treatment (INH,RMP,EMB and/or PZA). Surgical excision of draining LAP with surrounding inflammatory tissues in addition to the medical treatment was needed in 2 cases. Clinical improvement was obtained within 3 months of the treatment and ESR returned to normal within 5 months. After completion of the treatment, 22 patients were followed-up; mean duration was 3 years, and none relapsed. In conclusion, a patient with TB LAP generally presents with a few small, painless, cervical lymph nodes, which are slowly enlarging. For exact diagnosis, excisional biopsy for histologic and microbiologic studies is essential. Use of anti-TB drugs is the main therapeutic option.

Spontaneous hematoma of the rectus abdominis muscle: a rare cause of acute abdominal pain in the elderly.

A rectus abdominis sheath hematoma (RSH) is uncommon. It may mimic other acute abdominal disorders. The underlying conditions are trauma, coagulation disorders, or anticoagulant therapy, complications related to operations, subcutaneous injections to the abdominal wall, although it can also develop spontaneously. Acute abdominal pain and a palpable mass after muscular strain such as coughing, sneezing, and twisting were features highly suggestive of RSH. The diagnostic means of choice is computerized tomography. The treatment is usually conservative, but surgery may be needed in cases with large or progressing hematomas or with severe symptoms. We herein report an elderly woman presenting with an acute painful abdominal mass, without any underlying conditions, which was diagnosed as spontaneous RSH. She needed an operation. We concluded that RSH should be considered in the differential diagnosis of acute abdominal pain in the elderly, even in the absence of underlying conditions.

A rare complication of miliary tuberculosis: intestinal perforation.

Small bowel perforation is a rare complication of miliary tuberculosis. We report the case of a 21-year old patient who developed a small bowel perforation 70 days after the initiation of adequate tuberculosis treatment. We also present a review of the literature.

Pelvic and retroperitoneal hydatid cysts superinfected with Brucella sp. and review of infected hydatid cysts.

Hydatid disease is a zoonotic infection resulting from the tissue infestation of the larval stage of the parasite Echinococcus granulosus. Hydatid cysts superinfected with pyogenic organisms have been reported previously. Brucellosis is more prevalent in people with close contact to animals and those consuming fresh milk or fresh milk products. Although these two disorders have some similar epidemiological features, we did not encounter any hydatid cyst cases superinfected with Brucella species (sp.) in a search of medical literature (Pubmed). Here, we present a case of hydatid cyst disease superinfected with Brucella and review the literature on other hydatid cyst cases superinfected with pyogenic organisms. We conclude that in regions where brucellosis and hydatid cysts are endemic, cysts may be infected with Brucella sp.