PURPOSE OF REVIEWHuman alveolar echinococcosis is caused by the larval stage of Echinococcus multilocularis, occurring in at least 42 countries of the northern hemisphere. Recent studies in Europe ...and Asia have shown that the endemic area of E. multilocularis is larger than previously known and the parasite has regionally expanded from rural to urban areas. Diagnosis of alveolar echinococcosis is supported by results from imaging studies, histopathology and/or nucleic acid detection, and serology. The present review summarizes current understanding of clinical features, knowledge on appropriate treatment, and discusses ways to improve standards of care.
RECENT FINDINGSHigh prevalences of this deadly disease have been discovered in surveys in parts of China. Clinical manifestations, diagnostic tools and the burden of disease were described, and are based on high case numbers. In Europe, excellent tools have been introduced, which improve disease management. Long-term observations in Switzerland provide an optimistic view, as the infection can be well controlled, if patients are cared for in specialized centres. An expert consensus summarizes the current recommendation for diagnosis and treatment of alveolar echinococcosis by the Informal Working Group on Echinococcosis of the WHO.
SUMMARYDiagnosis and treatment of alveolar echinococcosis remains a challenge for clinicians. The updated WHO-recommendations aim to support decisions on diagnosis and treatment of alveolar echinococcosis. Anti-infective therapy is the backbone of treatment; surgery should be restricted to patients at an early stage of the disease. For the majority of cases continuous chemoprophylaxis with benzimidazoles is cost-effective and leads to a good quality of life for patients with this chronic disease.
The earlier recommendations of the WHO-Informal Working Group on Echinococcosis (WHO-IWGE) for the treatment of human echinococcosis have had considerable impact in different settings worldwide, but ...the last major revision was published more than 10 years ago. Advances in classification and treatment of echinococcosis prompted experts from different continents to review the current literature, discuss recent achievements and provide a consensus on diagnosis, treatment and follow-up. Among the recognized species, two are of medical importance –
Echinococcus granulosus and
Echinococcus multilocularis – causing cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively.
For CE, consensus has been obtained on an image-based, stage-specific approach, which is helpful for choosing one of the following options: (1) percutaneous treatment, (2) surgery, (3) anti-infective drug treatment or (4) watch and wait. Clinical decision-making depends also on setting-specific aspects. The usage of an imaging-based classification system is highly recommended.
For AE, early diagnosis and radical (tumour-like) surgery followed by anti-infective prophylaxis with albendazole remains one of the key elements. However, most patients with AE are diagnosed at a later stage, when radical surgery (distance of larval to liver tissue of >2
cm) cannot be achieved. The backbone of AE treatment remains the continuous medical treatment with albendazole, and if necessary, individualized interventional measures. With this approach, the prognosis can be improved for the majority of patients with AE.
The consensus of experts under the aegis of the WHO-IWGE will help promote studies that provide missing evidence to be included in the next update.
Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on ...controlled trials.
We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC.
Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports.
NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During the current pandemic, antibody testing based on venous serum helps to determine whether the tested person has been previously infected with SARS-CoV-2. Alternatively, capillary blood can be ...taken via a finger prick (dried blood spots, DBS). In this study, paired DBS and venipuncture samples were tested using two serological assays to evaluate the usability of DBS for the detection of anti-SARS-CoV-2 antibodies.
Paired samples of DBS and venous serum were collected from 389 volunteers, of whom 75 had a recent PCR-confirmed SARS-CoV-2 infection, and tested for anti-SARS-CoV-2 IgG antibodies against both viral S1 and nucleocapsid protein (NCP) antigens using two ELISAs. Degree of agreement and correlation coefficients between ELISA results based on the two sampling methods were calculated.
Results of DBS showed almost perfect agreement and high correlations with results from corresponding serum samples in both the S1-based ELISA and the NCP-based ELISA.
ELISA results derived from DBS showed very high agreement to those obtained with serum, supposing adequate usability and robustness of DBS as sample material for detection of anti-SARS-CoV-2 antibodies. In the near future, large-scale epidemiological screening for antibodies against SARS-CoV-2 will be carried out. Since DBS reduce the strain on healthcare institutions regarding sample collection, they have a potential to facilitate efficient community- and population-based screening in the current SARS-CoV-2 pandemic.
Optimal glucose control and fluid resuscitation in patients with septic shock remain a challenge. In this study involving more than 500 patients, the potential benefit of maintaining euglycemia ...through intensive insulin therapy and optimal fluid resuscitation with either pentastarch or Ringer's lactate was assessed. There was no benefit in the intensive-therapy group with respect to either 28-day survival or organ function; there was more severe hypoglycemia in the intensive-therapy group and more acute renal failure in the pentastarch group.
The potential benefit of maintaining euglycemia through intensive insulin therapy and optimal fluid resuscitation was assessed. There was no benefit in the intensive-therapy group with respect to either 28-day survival or organ function.
In a study by Van den Berghe et al. involving critically ill surgical patients, intensive insulin therapy to maintain euglycemia (glucose level, 80 to 110 mg per deciliter 4.4 to 6.1 mmol per liter) lowered in-hospital mortality from 10.9% to 7.2%, mostly by reducing deaths from multiple organ failure with a proven septic focus.
1
This beneficial effect occurred predominantly in cardiac surgical patients who received high glucose challenges immediately after surgery (8 to 12 g of glucose intravenously per hour) and was associated with an unusually high rate of death (5.1%) among controls.
Furthermore, in a follow-up study by Van . . .
Cystic and alveolar echinococcosis are diseases of animals and humans caused by the larval stage of tapeworms in the genus Echinococcus. Cystic echinococcosis (CE), caused by E. granulosus sensu lato ...and alveolar echinococcosis (AE), caused by E. multilocularis, have a substantial public health impact globally. Both conditions are considered neglected tropical diseases (NTDs) and neglected zoonotic diseases (NZDs), and prioritized by the World Health Organization (WHO) (http://www.who.int/neglected_diseases/diseases/en/). Within the last 10 years, advancements have taken place in Echinococcus biology and genetics, including the delineation of new species within E. granulosus sensu lato 1 and full sequencing of E. granulosus sensu stricto and E. multilocularis 2. Consequently, researchers are now provided with new tools to better understand parasite biology and host-parasite interactions, with the goal of opening new avenues for therapy 2.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cystic echinococcosis (CE) is endemic in humans and domestic animals in eastern Africa. All the species of the Echinococcus granulosus sensu lato complex have been reported in this region except for ...E. equinus, possibly due to the small number of studies involving equids. This study reports the frequency of different Echinococcus species in donkeys from eastern Africa. A total of 5961 donkeys were examined during meat inspection in 3 slaughterhouses in Kenya. Identification of Echinococcus spp. was achieved through polymerase chain reaction-restriction fragment-length polymorphism and sequencing of the mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 gene. The prevalence of CE was 5.7% (337/5961). The 263 genotyped cysts belonged to E. equinus (n = 163), E. granulosus sensu stricto (n = 70), E. canadensis (G6/7) (n = 26) and E. ortleppi (n = 4). One donkey harboured a metacestode of Spirometra theileri. All E. equinus cases, except 2, originated from southern Ethiopia, whereas the other species were more evenly distributed across the study area. Most of the cysts belonging to E. equinus were fertile (111/163), while those of the other species were non-fertile. This is the first report of Echinococcus spp. in donkeys from sub-Saharan Africa and the first confirmation of E. equinus in East Africa. The frequent fertility of E. equinus cysts in donkeys affirms their suitability as intermediate hosts of this species, while low frequency and cyst fertility suggest a marginal role of donkeys in the transmission of E. granulosus s. s., E. canadensis (G6/7) and E. ortleppi.
Signal transducer and activator of transcription 1 (STAT1) is known to be an important player in inflammatory responses. STAT1 as a transcription factor regulates the expression of multiple ...proinflammatory genes. Inflammatory response is one of the common effects of ototoxicity. Our group reported that hair cells of STAT1 knockout (STAT1-KO) mice are less sensitive to ototoxic agents in-vitro. The effect of inflammatory responses in STAT1-KO mice has primarily been studied challenging them with several pathogens and analyzing different organs of those mice. However, the effect of STAT1 ablation in the mouse inner ear has not been reported. Therefore, we evaluated the cochlear function of wild type and STAT1-KO mice via auditory brain stem response (ABR) and performed histopathologic analysis of their temporal bones. We found ABR responses were affected in STAT1-KO mice with cases of bilateral and unilateral hearing impairment. Histopathologic examination of the middle and inner ears showed bilateral and unilateral otitis media. Otitis media was characterized by effusion of middle and inner ear that varied between the mice in volume and inflammatory cell content. In addition, the thickness of the middle ear mucosae in STAT1-KO mice were more pronounced than those in wild type mice. The degree of middle and inner ear inflammation correlated with ABR threshold elevation in STAT1-KO mice. It appears that a number of mice with inflammation underwent spontaneous resolution. The ABR thresholds were variable and showed a tendency to increase in homozygous and heterozygous STAT1-KO mice. These findings suggest that STAT1 ablation confers an increased susceptibility to otitis media leading to hearing impairment. Thus, the study supports the new role of STAT1 as otitis media predisposition gene.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also ...stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). Materials and Methods: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and/or incidence of EC among women using MHT. Results: 31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10/19 studies with odds ratios (ORs)/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (≥10 years), not confirmed in three other sub-group analyses of women with ≥6, ≥5, and >10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6/12 studies with ORs/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. Conclusion: ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.
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