Intrarenal Surgery vs Percutaneous Nephrolithotomy in the Management of Lower Pole Stones Greater than 2 cm

Purpose

To compare the efficacy of RIRS and PNL in lower pole stones ≥2 cm. Materials and and Methods: A total of 109 patients who underwent PNL or RIRS for solitary lower pole stone between April 2009 and December 2012, were retrospectively analyzed. Lower pole stone was diagnosed with CT scan. Stone size was assessed as the longest axis of the stone. All patients were informed about the advantages, disadvantages and probable complications of both PNL and RIRS before the selection of the procedure. Patients decided the surgery type by themselves without being under any influences and written informed consent was obtained from all patients prior to the surgery. Patients were divided into two groups according to the patients’ preference of surgery type. Group 1 consisted of 77 patients who underwent PNL and Group 2 consisted of 32 patients treated with RIRS. Stone free statuses, postoperative complications, operative time and hospitalization time were compared in both groups.

Results

There was no statistical significance between the two groups in mean age, stone size, stone laterality, mean follow-up periods and mean operative times. In PNL group, stone-free rate was 96.1% at first session and 100% after the additional procedure. In Group 2, stone-free rate was 90.6% at the first procedure and 100% after the additional procedure. The final stone-free rates and operative times were similar in both groups.

Conclusions

RIRS should be an effective treatment alternative to PNL in lower pole stones larger than 2 cm, especially in selected patients.     

New global viral threats

Infectious diseases have caused great catastrophes in human history, as in the example of the plague, which wiped out half of the population in Europe in the 14th century. Ebola virus and H7N9 avian influenza virus are 2 lethal pathogens that we have encountered in the second decade of the 21st century. Ebola infection is currently being seen in West Africa, and H7N9 avian flu appears to have settled in Southeast Asia. This article focuses on the current situation and the future prospects of these potential infectious threats to mankind.Outbreak is an epidemiological definition to describe an unexpected occurrence of an infection at a certain time and place. It may affect a small and a localized group, or impact on millions of people across continents. Two cases of a linked rare infection can be defined as an outbreak. A revisit through the history discloses that outbreaks were vast, deadly, and basically changed the course of human history.1 As an example, the plague reshaped the landscape of Europe and the world between 1347 and 1351. During this period, the global population was estimated to be 450 million, and 75 million at a minimum are believed to have perished. Consequently, half of Europe died in a period of 4 years.2 In the pre-antibiotic era, bacterial outbreaks caused much more mass destruction compared with other outbreaks with different infectious agents.1 But, this trend changed with the advent of antibiotics and viral outbreaks emerged. We believed that Ebola virus and H7N9 avian influenza virus are the most potential pathogens to cause mass destruction in the world. Thus, in this paper, we will focus on the current outbreaks of these 2 viral infections with the potential to cause mass destruction, and to greatly impact the international travelers.

Ebola hemorrhagic fever

The Filoviridae (Ebola, and Marburg viruses are the commonly known 2 members of Filoviridae) were originally documented in 1967 when the apes from Uganda led to outbreaks of hemorrhagic fevers among vaccine plant workers in Germany and Yugoslavia. These workers had direct contact with the animals by killing the apes, removing their kidneys, or preparing cell cultures for polio vaccine production.3 The Ebola hemorrhagic fever (EHF) is known to be the world’s deadliest infection, and many people lost their lives this year due to this filoviral pathogen.

Viral characteristics

Ebola virus is a non-segmented, negative-sense, single-stranded RNA virus from the Filoviridae family. The genus of Ebola virus is classified into 5 different species (Zaire, Sudan, Bundibugyo, Tai Forest, and Reston agents) with differing virulence.4 The Zaire subtype has caused multiple outbreaks with case numbers up to several hundreds since 1976. The mortality reached 90% in these epidemics.5-8 The Sudan virus has been associated with fatality in half of the cases in Sudan and Uganda outbreaks.9,10 Interestingly, the Tai Forest virus has only been identified in one ethologist who performed a necropsy on a chimpanzee found dead in the Tai Forest. At the end, the patient survived.11 The fourth species, Reston virus, differs markedly from the others, was identified only in an animal reservoir in the Philippines.12 Finally, the Bundibugyo virus appeared in Uganda in 2007 causing an outbreak with 30% mortality.13 In 2014, the first outbreaks occurred in remote villages in Central Africa, near tropical rainforests, but the most recent outbreak in west Africa involved the major urban as well as rural areas.14 Molecular analysis indicated that the current virus was closely linked (97% identical) to variants of Ebola virus identified in the Democratic Republic of the Congo and Gabon.7

Modes of transmission

It is likely that Ebola virus is maintained in small animals serving as a source of infection for both humans and wild primates. Bats have long been at the top of the list of potential reservoirs since Marburg virus, filoviral hemorrhagic fever agent, was recovered from the fruit bats captured at a cave in Uganda.13 Ebola virus has been known to be disseminating in nonhuman primates, seemingly as a result of their contact with unidentified reservoirs. This has contributed to a striking drop in chimpanzee and gorilla populations, and facilitated human outbreaks probably owing to the consumption of sick apes as food sources.15-17 According to the Animal Mortality Monitoring Network found in Gabon and Congo, the carcass of duiker was tested positive along with primates in 2005.18 Once introduced into the community, human to human transmission via contact with infected persons or their body fluids or secretions are considered the primary mode of transmission.19

Impact of the current outbreak

In March 2014, the Ministry of Health of Guinea reported a disease outbreak characterized by fever, severe diarrhea, vomiting, and a high case-fatality rate. The first cases occurred in Guéckédou and Macenta districts. In May 2014, the epidemic jumped to neighboring districts of Kenema and Kailahun in Sierra Leone, and in June it expanded to Lofa district in Liberia.19 In September 2014, 5 countries from West Africa (Guinea, Liberia, Nigeria, Senegal, and Sierra Leone) documented EHF patients.20 The disease had a deep impact in Guinea, Liberia, and Sierra Leone.19 Moreover, the disease jumped to the United States of America (USA) and Spain with travel-associated cases and localized transmission.21 There have been 22,495 EHF cases, with 8,891 recorded deaths by February 1, 2015.22 Thus, the average case fatality rate was approximately 40%.According to the World Health Organization (WHO) Ebola Response Roadmap Situation Report, released on 26 October 2014, a total of 521 cases, including 272 deaths, had been reported among health care workers while caring for sick people.23

Clinical presentation

The pathogen is classified as a hemorrhagic fever virus based on its clinical manifestations comprising coagulation defects, a capillary leak syndrome, and shock. The Ebola virus has been known to be the most virulent human pathogen along with Marburg virus causing severe hemorrhagic fever, fulminant septic shock, and finally, death.24 The course of infection, including signs and symptoms, incubation period (~11 days), and serial interval (~15 days), which is defined as the interval between disease onset in an index case patient and disease onset in a person infected by that index case patient were similar to that reported in previous outbreaks of EHF.19 The most common symptoms were fever (87%), fatigue (76%), loss of appetite (65%), vomiting (68%), diarrhea (66%), headache (53%), and abdominal pain (44%).19

Treatment and immunization

Severely ill EHF patients require intensive supportive care, which is the mainstay of therapy.19 In October 1, 2014, 2 candidates for EHF vaccines had clinical-grade vials available for phase-1 clinical trials. One of these formulations was cAd3-ZEBOV (GlaxoSmithKline, Raleigh, SC, USA) and recombinant vesicular stomatitis virus - Zaire ebolavirus (rVSV-ZEBOV) (Public Health Agency in Winnipeg, Canada). A series of coordinated phase-1 trials will be initiated in more than 10 sites in Africa, Europe, and North America.25 Although no approved specific therapy is currently available in the treatment of EHF, several drugs such as brincidofovir, favipiravir, and ZMapp are under investigation for EHF. In the current outbreak, convalescent blood and plasma therapies have been used in a few patients. The numbers are too small to draw any conclusions on their efficacy.26

Future prospects

When an outbreak comes to an end, it is a matter of great concern. According to the WHO, an EHF outbreak in a country is reported to be over when 42 days have passed, and new cases have not been observed. The maximum incubation period for EHF was 21 days. The 42-day period was set by the WHO (twice the maximum incubation period) to provide a strong margin of security.27 Currently, the USA, Spain, Mali, Senagal, and Nigeria are categorized as affected countries.21 Currently, EHF epidemic appears to be ending after the slowing of transmission.22

Avian influenza A (H7N9) virus

Influenza, usually known as “flu”, was defined by Hippocrates approximately 2,400 years ago.28 The first considerable influenza-like illness pandemic recorded was of an outbreak in 1580, started in Russia and disseminated to Europe via Africa. During the outbreak, more than 8,000 people died in Rome.29,30 The major historical flu pandemics and their deep impacts on mankind are presented in Open in a separate windowThree (H7N9, H6N1, and H10N8) avian influenza viruses broke the animal-human barrier in Asia in 2013.31 One avian influenza case was detected in Taiwan due to H6N1 subtype, whereas 2 of 3 H10N8 human infections observed in China were lethal.31 However, human infections due to H7N9 have been progressively increasing since its first identification in 2013, and approximately one-third of the H7N9-infected patients died.31-33 Avian flu had the potential to spread “silently” among poultry and H7N9 infections did not cause severe disease in poultry, accordingly.34

Viral characteristics

Influenza is an infection of birds and mammals caused by RNA viruses from the family of Orthomyxoviridae. There are 2 main types of influenza virus, type A and type B. Type A viruses are the most virulent human pathogens among the other influenza types and cause the most severe disease. Influenza A viruses are divided into subtypes based on the hemagglutinin (H) and the neuraminidase (N) localized on the virus surface. So far, 18 hemagglutinin and 11 neuraminidase subtypes were documented.35 Influenza B almost exclusively infects humans and is less common than influenza A.36

Modes of transmission

All identified influenza A subtypes other than H17N10 and H18N11 viruses have been found among birds and these 2 particular influenza subtypes were recorded in bats. Wild birds have been the primary reservoir for all influenza A viruses and have been believed to be the source of the diseases in all other animals.37 In human influenza infections large amounts of influenza virus are often present in respiratory secretions of infected persons. Thus, the infection can be transmitted through sneezing and coughing, and is primarily acquired by large droplets (>5 microns).35,38 This mode of transmission facilitated the dissemination of influenza in the history and resulted in major outbreaks. Further, animal flu viruses transmitted to humans are usually dead-end infections, and the virus does not have the capacity to be acquired between humans easily. This limitation is an important barrier to global dissemination. Accordingly, for human H7N9 infections, which are the focus of this review, the available information strongly indicated that they originated from infected poultry with either direct contact or indirect exposures such as visiting wet markets and contact with environments where infected poultry have been stored or slaughtered. Currently, there is no evidence of sustained, ongoing person-to-person spread of H7N9.39 Since the influenza virus can be inactivated by soap, disinfectants, and detergents, frequent hand washing, and other sanitary measures reduce the risk of influenza transmission.40,41

Impact of the current outbreak

In late March 2013, novel human infections due to avian influenza A H7N9 virus were reported from China.32 This particular influenza A virus had not previously been seen in either animals or people. The preliminary 133 cases were seen between February and May 2013. In this first wave, 44 patients died constituting a mortality of 33%, which was exceedingly high compared with other major historical pandemics.42 Most of these patients were considered to upsurge from exposure to infected poultry or contaminated environments. The number of new cases was highest in April 2013 and subsequently the patient flow dropped.43 The probable reasons for this reduction were the implementation of control strategies, such as closing live bird markets, summer weather conditions, and increased public awareness. Studies indicated that avian flu viruses, like seasonal influenza, have a seasonal pattern and they circulate better in cold weather and less in warm weather.44 Thus, a rise in the number of cases occurred in late 2013 and early 2014, coinciding with influenza season. More than 200 new cases have been confirmed during the second wave.45 Until May 2013, H7N9 cases were reported from 9 Chinese provinces at the Pacific region. After this, H7N9 infections were reported from 12 provinces, indicating the rapid dissemination of the outbreak.46In February 2014, the Malaysian Ministry of Health reported a human infection with avian influenza A (H7N9) in a traveler from China. This was the first imported case of H7N9 detected outside of China.47 There have been other H7N9 cases detected until April 2014. In April 2014, Taipei Centers for Disease Control in Taiwan informed 2 laboratory reported patients, as the last reported cases as per the 27 June 2014 WHO report.48

Clinical presentation

The most common signs of influenza are fever, chills, sore throat, runny nose, severe headache, muscle pains, coughing, and fatigue.28 Although it is often confused with other influenza-like illnesses, the common cold in particular, influenza is a more severe disease.49 Complications of H7N9 virus infection include respiratory failure, acute respiratory distress syndrome, refractory hypoxemia, septic shock, acute renal dysfunction, multiple organ dysfunction, rhabdomyolysis, encephalopathy, bacterial and fungal infections like ventilator associated pneumonia, and blood stream infection with multidrug resistant bacteria.50 Approximately, two-thirds of hospitalized patients are admitted to the intensive care units, indicating the severity of the illness.51

Treatment and immunization

The WHO Vaccine Composition Meeting for the 2014-2015 season held in February 2014 in Geneva approved that A/California/7/2009 (H1N1)pdm09-like virus, A/Texas/50/2012 (H3N2)-like virus, and B/Massachusetts/2/2012-like virus should be included in the trivalent vaccine formulation in the Northern Hemisphere.52 Consequently, the aforementioned novel avian strains are out of scope of the current vaccine formulation indicating the severity of the situation if the H7N9 influenza has global dissemination.Laboratory testing in preliminary cases showed that neuraminidase inhibitors (oseltamivir, zanamivir) were effective against H7N9 infections, but the adamantanes were not. In addition, early treatment with neuraminidase inhibitors have been reported to restrict the severity of illness.34,53

Future prospects

Although it is likely that sporadic cases of H7N9 associated with poultry exposure will continue to occur in China, the virus has a pandemic potential, and it is possible that the virus can gain the ability to spread easily.49 The future prospects of H7N9 infections are still unclear. However, there is no scientific evidence implying it will trigger a current global outbreak. Thus, international surveillance for H7N9 and other influenza viruses with pandemic potential is of paramount importance.     

Small-volume gallbladders and decreased motility in patients with achalasia

AIM/BACKGROUND: Achalasia may be associated with extraesophageal dysmotility. However, this relation is still poorly understood. In the present study, we used noninvasive real-time ultrasonography to examine the motility function of the gallbladder in the patients with achalasia. MATERIALS AND METHODS: Thirty-three achalasic patients and 33 healthy volunteers were included in the study. All subjects were investigated after 12 hours of fasting and 30 minutes after a standard test meal. Premeal and postmeal gallbladder volumes were used for calculation of the ejection fraction of the gallbladder and fasting gallbladder volume. RESULTS: The mean fasting volume (18.52+/-1.45 vs. 24.63+/-1.84 cm; P<0.05) and ejection fractions of gallbladder (35.84+/-4.12 vs. 54.47+/-2.47; P<0.05) in the patients with achalasia were lower than the control group. CONCLUSIONS: Such a finding may confirm the possible extraesophageal extension of primary achalasia. Achalasic patients have smaller gallbladders than do others. It could be speculated that it is congenital and/or achalasic patients' gallbladder has incomplete relaxation (as in the lower esophageal sphincter of the achalasia).     

The comparison of high and standard definition computed tomography techniques regarding coronary artery imaging

ObjectiveThe aim was to compare coronary high-definition CT (HDCT) with standard-definition CT (SDCT) angiography as to radiation dose, image quality and accuracy.ResultsThe intraclass correlation coefficient (ICC) of measured vessel attenuation values in SDCT between the two radiologists was exceedingly good. The ICC was higher in HDCT. The radiation dose of HDCT was higher than that of SDCT. The mean tube current was 180 (mA) in HDCT and 147(mA) in SDCT with the same tube voltage (kVp). There was no significant difference between image quality.ConclusionHDCT has a higher radiation dose but has much more atenuation and the spatial resolution which improve measurement accuracy for imaging coronary arteries.     

Functional Anatomy of the Syrinx of the Chukar Partridge (Galliformes: Alectoris chukar) as a Model for Phonation Research

The phonation process of vertebrates is influenced by the material characteristics of the participating structures, ranging from molecular to macroscopic dimensions. Good animal models for phonation research are still lacking. Due to easy availability and relatively simple structure, the syrinx of birds might serve as a good animal model for this purpose. Our aim was therefore to determine structural features of the syrinx and obtain insights into its mucus layer characteristics. Epithelium and glands were analyzed using histological, histochemical, and immunohistochemical methods and conclusions were drawn on the use of the syrinx as a model for phonation research by comparing the epithelium and its mucus characteristics to human laryngeal secretions. Ten adult partridges were analyzed. The tympanum of the syrinx developed from the last two tracheal cartilages, whereas the caudal part of the syrinx was formed from eight pieces of bronchial cartilages. The tracheal and bronchial epithelia and the pessulus of the syrinx were lined by pseudo‐stratified columnar epithelium in which goblet cells and intraepithelial glands were localized. Collagen fibers were distributed in the lamina propria of all parts of the syringeal mucosa. Elastic fibers in the membranes of the syrinx showed evident distribution. All glandular epithelial cells and goblet cells were positive for neutral, acidic and carboxylated mucins were dominant in particular. Epithelium and glands revealed positive reactivity with antibodies to the mucins MUC1, MUC2, and MUC5AC. Of these, MUC2 and MUC5AC were dominant. The syrinx of partridge can serve as a good ex vivo model for phonation research. Anat Rec, 298:602–617, 2015. © 2014 Wiley Periodicals, Inc.     

Bis-Benzimidazole Hits against Naegleria fowleri Discovered with New High-Throughput Screens

Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC₅₀) of 177 nM. Similarly, we identified 10 additional analogues with IC₅₀s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri.     

The Effects of Passive Smoking on the Six-Minute Walk Test in Obese Pediatric Cases

Objective: The aim of this study was to evaluate whether exposure to second-hand smoke affected the six-minute walk test (6MWT) of obese non-asthmatic pediatric cases.Methods: Obese pediatric patients (body mass index >95th p) with no existing co-morbidities were included in the study. Smoke exposure was assessed with a self-reported questionnaire completed by the parents. The subjects were divided into two groups: Group 1 consisting of obese children exposed to passive smoking and Group 2 of obese children not exposed to passive smoking. In addition to 6MWT, spirometric flow and volume, including forced expiratory volume in 1 s and peak expiratory flow rate, were also measured in all subjects. The results of the 6MWT were assessed to determine any association with passive smoking.Results: The study included 75 obese pediatric cases (40 male, 35 female) with a mean age of 9.06±0.97 years. The 6MWT results in Group 1 was 501.88±62.12 meters and in Group 2 559.63±72.93 meters. The difference was statistically significant (p=0.001).Conclusions: Passive smoking may negatively affect the respiratory and cardiovascular capacity in obese children, who are already at risk of lower cardiopulmonary function. The evaluation of 6MWT in these pediatric patients may be useful for monitoring and families should be warned about potential problems due to smoking.