Human Papillomavirus Infection and Oropharyngeal and Gastrointestinal Cancers: A Causal Relationship?

The human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The risk of being infected at least once in a lifetime among both men and women is estimated to be 50%. Although the majority of HPV infections are asymptomatic and improve within 2 years, approximately 10% of individuals develop a persistent infection and have an increased risk of developing carcinomas. The association of HPV and genital cancer is well established. However, there is evidence that HPV may also be associated with other cancers, including those of the gastrointestinal system. The aim of this review is to organize the current evidence of associations between HPV infections and oropharyngeal and gastrointestinal cancers, including the following: oropharyngeal, esophageal, gastric, colorectal, and anal cancers. A comprehensive review of the most up-to-date medical literature concluded that an HPV infection might have a role in the oncogenesis of gastrointestinal tract cancers. HPV may have a causal relationship with oropharyngeal and esophageal squamous cell cancers. However, the association between HPV and gastric and colorectal cancers is weaker. The development of cancer in the oropharyngeal and gastrointestinal tract is usually multifactorial, with HPV having a role in at least a subset of these cancers. HPV infections pose a big challenge due to their burden of infection and their oncogenic potential.

COVID 19 and febrile neutropenia: Case report and systematic review.

OBJECTIVES: In pandemic conditions, patients with febrile neutropenia are also at risk of COVID-19. Aim of this systematic review is to evaluate COVID-19 cases presented with febrile neutropenia and provide information regarding incidence, clinical course and prognosis. METHODS: We systematically searched on COVID-19 and febrile neutropenia cases in PubMed, SCOPUS and Web of Science. RESULTS: A total of 19 febrile neutropenic patients were analyzed. A male predominance was noted. Eleven cases had hematological malignancies. Fourteen of the cases were previously received chemotherapy. Five patients had severe neutropenia: 3 had hematologic cancer and none died. 17 (89.5%) cases have pulmonary involvement and seven of them had severe disease with acute respiratory distress syndrome (ARDS). Three cases with ARDS were died. 12 of them received G-CSF for treatment. Five cases were developed respiratory failure after G-CSF use. Overall mortality was 15.8%, while death was not observed in patients without malignancy and solid organ tumors, the mortality rate was 27% in cases with hematological malignancies. CONCLUSION: In ongoing pandemic, febrile neutropenic patients should be precisely evaluated for COVID-19 disease. It should be remembered that there may not be typical signs and symptoms and laboratory findings of COVID-19 disease because of the immunosuppression.

Systematic review of COVID-19 and autoimmune thyroiditis.

COVID-19 is a severe acute respiratory syndrome. Recent reports showed that autoimmune thyroiditis might occur following COVID-19 infection. We aimed to review the literature to assess the prevalence, clinical features and outcome of autoimmune thyroid disorders triggered by COVID-19. We reviewed case reports, case series, and observational studies of autoimmune thyroiditis including Graves' disease, Hashimoto thyroiditis, and silent thyroiditis developed in COVID-19 patients by searching PubMed, SCOPUS and Web of Science and included in the systematic review. Our search yielded no prevalence study. We noted 20 reported cases: Fourteen cases of Graves' disease, 5 cases of hypothyroidism due to Hashimoto's thyroiditis and one case of postpartum thyroiditis. The majority (16/20, 80%) were middle-aged (mean age: 40 years) female patients. Autoimmune thyroiditis was diagnosed either concomitantly or 7-90 days after the COVID-19 infection. Eight out of 14 cases with Graves' disease had a known thyroid disorder and they were stable in remission. One out of 5 cases with Hashimoto's thyroiditis had known prior hypothyroidism. The majority of the patients achieved remission within 3 months. One patient with thyroid storm due to Graves' disease and one patient with myxedema coma have died. Current data suggest that COVID-19 may cause autoimmune thyroid disease or exacerbate the underlying thyroid disease in remission. It is reasonable to routinely assess the thyroid functions both in the acute phase and during the convalescence so as not to overlook a thyroid disorder and not to delay treatment especially in patients with preexisting autoimmune thyroid diseases.

Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries.

BACKGROUND: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries. METHODS: A survey including 20-item questionnaire was sent to experts in viral hepatitis. Countries were evaluated according to their income categories by the World Bank stratification. RESULTS: Experts from 26 countries responded to the survey. As of May 2016, HCV prevalence was reported as low (≤1%) in Croatia, Czech Republic, Denmark, France, Germany, Hungary, the Netherlands, Portugal, Slovenia, Spain, Sweden, UK; intermediate (1-4%) in Azerbaijan, Bosnia and Herzegovina, Italy, Kosovo, Greece, Kazakhstan, Romania, Russia, Serbia and high in Georgia (6.7%). All countries had national guidelines except Albania, Kosovo, Serbia, Tunisia, and UK. Transient elastography was available in all countries, but reimbursed in 61%. HCV-RNA was reimbursed in 81%. PegIFN/RBV was reimbursed in 54% of the countries. No DAAs were available in four countries: Kazakhstan, Kosovo, Serbia, and Tunisia. In others, at least one DAA combination with either PegIFN/RBV or another DAA was available. In Germany and the Netherlands all DAAs were reimbursed without restrictions: Sofosbuvir and sofosbuvir/ledipasvir were free of charge in Georgia. CONCLUSION: Prevalence of HCV is relatively higher in lower-middle and upper-middle income countries. DAAs are not available or reimbursed in many Eurasia and European countries. Effective screening and access to care are essential for reducing liver-related morbidity and mortality.

Telbivudine attenuates gentamicin-induced kidney injury in rats.

Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P <0.007) and between the LdT and PC groups (P <0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment.

Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

A case of central nervous system infection due to Cladophialophora bantiana.

BACKGROUND: Cladophialophora bantiana is a melanised mold with a pronounced tropism for the central nervous system, almost exclusively causing human brain abscesses. CASE REPORT: We describe a case of cerebral infection by this fungus in an otherwise healthy 28-year-old coal-miner. Environmental occurrence, route of entry, and incubation period of this fungus are unknown, but our case is informative in that the first symptoms occurred about eight weeks after known traumatic inoculation. Lesions were compatible with tuberculous granulomas, and the patient initially received antitubercular treatment. Melanised fungal cells were seen in a brain biopsy and abscess materials. Therapy was switched from empirical antitubercular treatment to amphotericin B (0.5mg/kg/d), but was changed to voriconazole 200mg/d, i.v. on the basis of antifungal susceptibility test results. The patient responded clinically, and gradually improved. The isolate was identified by sequencing of the Internal Transcribed Spacer domain of rDNA. CONCLUSIONS: Given the non-specific clinical manifestations of C. bantiana cerebral abscesses, clinicians and laboratory workers should suspect infections caused by C. bantiana, particularly in immunocompromised patients with a trauma history.

Simultaneous cryptococcal and tuberculous meningitis in a patient with systemic lupus erythematosus.

Simultaneous central nervous system (CNS) infection with Cryptococcus and tuberculosis (TB) is very rare. Despite improved therapeutic options, treatment of CNS cryptococcosis is still difficult and needs invasive treatment modalities, such as intrathecal or intraventricular amphotericin B, in refractory cases. We describe a patient with systemic lupus erythematosus diagnosed with simultaneous cryptococcal and TB meningitis who had a poor response to intravenous liposomal amphotericin B and fluconazole, but was successfully treated with intraventricular amphotericin B, in addition to anti-TB therapy.

Bilateral idiopathic granulomatous mastitis.

OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is a benign rare inflammatory pseudotumor. Bilateral involvement of IGM has been reported in a few cases. To our knowledge, this study is the largest series of bilateral cases to date. The goals of this study were to present clinical features of bilateral IGM and to evaluate the results of treatments. MATERIALS AND METHODS: We performed a retrospective review of the idiopathic granulomatous mastitis database from 2010 to 2013. Ten female patients who met required histologic and clinical criteria of IGM in both breasts were included in study. Demographic data, clinical findings, medication history, and radiologic findings are presented. RESULTS: The mean age at onset of the disease was 38.4 ± 8.3 years (range: 29-52 years). Nine patients had no recurrence during a mean follow-up period of 21 months (range: 11-26 months). Additionally, the median time to second breast involvement was 15.6 months. CONCLUSION: Bilateral IGMs have a higher rate of more relapse and greater resistance to medical therapies than do unilateral IGMs. Surgical management should be avoided unless all medical treatment options have been exhausted. Nevertheless, expectant management seems a rational option for the treatment of bilateral IGM.

The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients.

OBJECTIVE: Patients receiving hematopoietic stem cell transplantation (HSCT) are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs) are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively. MATERIALS AND METHODS: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated. RESULTS: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62%) and allogeneic (38%) HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28%) and Hodgkin lymphoma (21.5%). A total of 142 (45%) patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011), and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2%) and Acinetobacter baumannii (8.8%) were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively. CONCLUSION: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.

Recommendations for intra-abdominal infections consensus report.

Guidelines include the recommendations of experts from various specialties within a topic in consideration of data specific to each country. However, to date there has not been a guideline standardizing the nomenclature and offering recommendations for intra-abdominal infections (IAIs) in Turkey. This is mainly due to the paucity of laboratory studies regarding the clinical diagnosis and treatment of IAIs or the sensitivity of microorganisms isolated from patients with IAIs. However, due to the diversification of host characteristics and advancements in technological treatment methods, it has become imperative to 'speak a common language'. For this purpose May 2015, a group of 15 experts in intra-abdominal infections, under the leadership of the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey (EKMUD) and with representatives from the Turkish Surgical Association, Turkish Society of Colon and Rectal Surgery, Hernia Society, Turkish Society of Hepato-pancreato-biliary Surgery, and the Turkish Society of Hospital Infections and Control, was formed to analyze relevant studies in the literature. Ultimately, the suggestions for adults found in this consensus report were developed using available data from Turkey, referring predominantly to the 2010 guidelines for diagnosing and managing complicated IAIs in adults and children by the Infectious Diseases Society of America (IDSA) and the Surgical Infection Society. The recommendations are presented in two sections, from the initial diagnostic evaluation of patients to the treatment approach for IAI. This Consensus Report was presented at the EKMUD 2016 Congress in Antalya and was subsequently opened for suggestions on the official websites of the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey and Turkish Surgical Association for one month. The manuscript was revised according to the feedback received.

Early Changes of Mannose-Binding Lectin, H-Ficolin, and Procalcitonin in Patients with Febrile Neutropenia: A Prospective Observational Study.

OBJECTIVE: The significance of mannose-binding lectin (MBL) and H-ficolin deficiency in febrile neutropenic (FN) patients and the correlation of these markers along with consecutive C-reactive protein (CRP) and procalcitonin (PCT) levels during the infectious process are investigated. MATERIALS AND METHODS: Patients with any hematological malignancies who were defined to have "microbiologically confirmed infection", "clinically documented infection", or "fever of unknown origin" were included in this single-center prospective observational study. Serum levels of CRP, PCT, MBL, and H-ficolin were determined on 3 separate occasions: at baseline (between hospital admission and chemotherapy), at the onset of fever, and at the 72nd hour of fever. RESULTS: Forty-six patients (54% male, mean age 41.7 years) with 61 separate episodes of FN were evaluated. Eleven patients (23.9%) had "microbiologically confirmed infection", 17 (37%) had "clinically documented infection", and 18 (39.1%) had "fever of unknown origin". Fourteen (30.4%) patients had low (<500 ng/mL) initial MBL levels and 7 (15.21%) had low (<12,000 ng/mL) H-ficolin levels. Baseline MBL and H-ficolin levels did not significantly change on the first and third days of fever (p=0.076). Gram-negative bacteremia more frequently occurred in those with low initial MBL levels (p=0.006). PCT levels were significantly higher in those with microbiologically documented infections. Mean and median PCT levels were significantly higher in cases with bacteremia. There was no significant difference between hemoculture-positive and-negative patients in terms of CRP levels. CONCLUSION: Monitoring serum H-ficolin levels was shown to be of no benefit in terms of predicting severe infection. Low baseline MBL levels were correlated with high risk of gram-negative bacteremia; however, no significant correlation was shown in the follow-up. Close monitoring of PCT levels is warranted to provide more accurate and specific data while monitoring cases of bacteremia.

More on hepatic granulomas.

We have read the case report of Nihon-Yanagi et al. The patient they described developed hepatic granuloma two times and the granulomatous lesion was surrounding metal staples/clips suggesting that the granuloma was due to surgical staples/clips. Hepatic granulomas (HGs) are reported in around 5% of patient who undergo a liver biopsy and caused by several diseases including sarcoidosis, tuberculosis, hydatid cyst, brucellosis, typhoid fever, chronic hepatitis B and C and primary biliary cirrhosis (PBC). Chronic hepatitis B and C infections are the most common and serious causes of liver damage in patient with renal failure. Their prevalence is a higher than people without renal failure. We have previously reported that the prevalences of HGs in patients with chronic hepatitis B and C are 1.5 and 1.3% respectively. The described patient was on hemodialysis for 12 years. The other causes of HG seem excluded; however hepatitis B and C infections and PBC should have been tested and excluded before ascribing the HGs to surgical staples/clipping material.

Monotherapy for hepatitis B infection: a review of treatment options.

Chronic hepatitis B (CHB) is a global health problem, causing liver failure, cirrhosis and hepatocellular carcinoma. CHB treatment aims to prevent liver-related complication. The treatment of CHB infection includes monotherapy with either interferons (IFNs) or nucleos(t)ide (NUC) analogs. IFNs have moderate antiviral effects, and their use is limited by side effects. With the availability of NUCs, IFN-intolerant and decompensated cirrhotic patients began to be treated. Lamivudine and telbivudine, nucleoside analogs, have low genetic barrier to resistance. Adefovir, a nucleotide analog, has moderate potency and potential nephrotoxicity. Entecavir and tenofovir, with their high potency, high genetic barrier to resistance and favorable safety profile are the standard of care in CHB treatment. Long-term use of NUCs with maintained viral suppression results in a decrease in liver-related complications.

Secondary Infections in Febrile Neutropenia in Hematological Malignancies: More Than Another Febrile Neutropenic Episode.

INTRODUCTION: Febrile neutropenic episodes (FNEs) are among major causes of mortality in patients with hematological malignancies. Secondary infections develop either during the empirical antibiotic therapy or one week after cessation of therapy for a FNE. The aim of the study was to investigate the risk factors associated with secondary infections in febrile neutropenic patients. METHODS: We retrospectively analyzed 750 FNEs in 473 patients between January 2000 and December 2006. RESULTS: Secondary infections were diagnosed in 152 (20%) of 750 FNEs. The median time to develop secondary infection was 10 days (range 2-34 days). The duration of neutropenia over 10 days significantly increased the risk of secondary infections (p<0.001). The proportion of patients with microbiologically documented infections was found to be higher in primary infections (271/750, 36%) compared to secondary infections (43/152, 28%) (p=0.038). Age, sex, underlying disease, antibacterial, antifungal or antiviral prophylaxis, blood transfusion or bone marrow transplantation, central venous catheter or severity of neutropenia did not differ significantly between primary and secondary infections (p>0.05) While fever of unknown origin (FUO) (p=0.005) and catheter-related bacteremia (p<0.001) were less frequently observed in secondary infections, the frequency of microbiologically (p=0.003) and clinically (p<0.001) documented infections, fungal pneumonias (p<0.001), infections related with gram positive bacteria (p=0.04) and fungi (p<0.001) and 30-day mortality rate (p<0.001) were significantly higher in secondary infections (p<0.001). DISCUSSION AND CONCLUSION: Secondary infections should be regarded as life-threatening complications of febrile neutropenia. Secondary infections represent a more severe and mortal complication and cannot be regarded just as another febrile neutropenic episode.

Corticosteroid treatment in the management of idiopathic granulomatous mastitis to avoid unnecessary surgery.

PURPOSE: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of the breast. It can mimic breast carcinoma clinically and radiologically, and usually affects females of childbearing age. There is no commonly accepted optimal treatment for IGM. In this study, we present the clinical and histopathological features and outcomes of the therapeutic management of IGM, as well as the clinical course of the disease when patients were treated with oral corticosteroids. METHODS: This retrospective study included 49 of 87 patients who met the required histological criteria for IGM who were followed up between January 2009 and December 2011. All patients had a disease-free follow-up period of at least 6 months. The data regarding the clinical features at presentation, laboratory values and the treatment modalities were obtained from the medical records of the patients. RESULTS: The mean age of the patients was 34.3 ± 4.37 years. Forty patients were treated with prednisolone, five were started on antituberculosis treatment, two received non-steroidal anti-inflammatory drugs, one received antibiotics and one underwent wide excision. All patients who received steroids responded well to the therapy. CONCLUSION: Systemic therapy with corticosteroids is an effective and appropriate treatment option for IGM. It can provide complete disease resolution and prevent recurrence in the long term. A multidisciplinary approach including specialists in the fields of both general surgery and infectious diseases is essential for the diagnosis, treatment and follow-up of IGM.