Evidence for abnormal cholinergic neuromuscular transmission in diabetic rat small intestine

Proximal and distal rat small intestine from control, diabetic, and insulin-treated diabetic rats was cut into strips measuring 6.0 X 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, while those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (0.1-1.0-ms pulse duration, 30-270 mA, 1-26 Hz) in the presence of Krebs' solution and Krebs' solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in all strips. Significant differences among the three groups were found in the amplitudes of atropine-sensitive contractions in strips from distal longitudinal muscle. Controls showed the highest amplitude contractions and diabetics the lowest, whereas the insulin-treated diabetics showed contractions intermediate in amplitude. No significant differences were noted among the atropine-resistant contractions. Field stimulation delivered at pulse durations of 5.0 and 50.0 ms in the presence of neural blockade with tetrodotoxin (5 X 10(-6) M) produced similar contraction amplitudes among the three groups. These results suggest that streptozotocin-induced diabetes mellitus is associated with defective cholinergic neuromuscular transmission in the myenteric plexus of the distal small intestine. Insulin therapy seems to improve the abnormality.     

Passive smoking--current position of science

Among all indoor pollutants, environmental tobacco smoke (ETS) might be the most important. In population-based studies 30 to 60 % of the participants reported regular exposure to ETS. ETS has been classified as carcinogenic by several national and international agencies. In 2002, a paragraph on restriction of smoking at the workplace has been added to the German Workplaces Ordinance. International meta-analyses have been published on the potential health effects of ETS exposure. In these studies, the pooled relative risk (RR) for lung cancer has been estimated between 1.1 and 1.3. The pooled risk estimate for coronary heart disease (CHD) was slightly higher (1.25 - 1.35). The RR in the group with the highest exposure might be as high as 2. An increased risk has also be shown consistently for respiratory symptoms, asthma, and COPD. Because of the high incidence of CHD the public health impact of ETS exposure on CHD might be higher than the impact due to additional lung cancer cases.     

Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection

BackgroundThe clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes.ObjectiveTo determine 30-day post-hospitalization outcomes following COVID-19 infection.DesignRetrospective cohort studySettingQuaternary referral hospital and community hospital in New York City.ParticipantsCOVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020.MeasurementOutcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge.ResultsThirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00–1.02]), diabetes (1.54 [1.06–2.23]), and the need for inpatient dialysis (3.78 [2.23–6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05–1.11]) and Asian race (2.89 [1.27–6.61]) were significantly associated with mortality.ConclusionsAmong patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06924-0.KEY WORDS: COVID-19, mortality, re-admission, discharge     

Patent foramen ovale closure in patients with transient ischemia attack/stroke

Paradoxical embolism through a patent foramen ovale (PFO) has been recognized as a potential cause of transient ischemia attack (TIA) and stroke especially in younger patients. The therapeutic options are medical treatment (antiaggregation or anticoagulation) with an annual recurrence rate of 3% to 4% for stroke or TIA, surgical PFO closure, or catheter closure. Randomized studies are ongoing; however, the results will not be available soon. Since August 1994, we have attempted catheter closure of a PFO in 281 patients (age 17 to 79 years, mean 46.8 +/- 13.2) with paradoxical embolism. Of these, 184 patients had at least one embolic stroke, 112 patients at least one TIA, and 15 patients at least one peripheral embolism. The diameter of the PFO, measured with a balloon catheter, ranged from 3 mm to 24 mm with a mean of 10 +/- 3.5 mm. Implantation of the occluder was technically successful in all patients (two attempts in four patients). Seven different devices were used: 26 Sideris buttoned, 11 ASDOS, 19 Angel Wings, 98 PFO-Star, 37 Cardioseal-Starflex, 57 Amplatzer and, 33 Helex devices. One patient suffered from septicemia and subsequently died. In 2 patients, device embolization occurred during or after the procedure (1 Sideris, 1 PFO-Star; catheter retrieval successful). Thirty-seven patients had other minor complications without long-term sequelae: atrial fibrillation within the first weeks after implantation in five patients, asymptomatic thrombus on the device at routine transesophageal echocardiogram (TEE) in 7 patients (1 Angel Wings, 1 ASDOS, 1 CardioSeal, 4 PFO-Star), and device frame fracture in 25 patients (2 Sideris, 4 ASDOS, 1 Angel Wings, 1 CardioSeal, 17 PFO-Star). No complications occurred with the newer devices (Amplatzer and Helex). A residual shunt after 6 months was found in 5.5% of the patients who had completed their 6-month TEE follow-up. In two patients, a second occluder was implanted because of a residual shunt. During a follow-up period of 1 month to 71 months (mean 12 +/- 16 months, 268 patient years), a recurrence of an embolic event (seven TIA, two stroke) occurred in eight patients. None of these occurred with the newer devices (Amplatzer, Helex). Freedom from recurrence of the combined end point of TIA, ischemic stroke, and peripheral embolism was 95.7% (95% CI: 89.0%-98.4%) at 1 year and 94.1% (95% CI: 80.1-98.4%) at 3 years. Catheter PFO closure is a technically simple procedure. With the newer devices and increasing experience, the success rate has improved and the complication rate has decreased. The advantage of the procedure is that closing the defect means a causal treatment. However, catheter closure of PFO despite a very low morbidity has inherent potential risks like any other interventional procedure. Furthermore, selection of patients who definitely have PFO as the cause of their cerebral event has not been defined. For these reasons, further studies are warranted.     

Pattern of microbial translocation in patients living with HIV-1 from Vietnam,Ethiopia and Sweden

Introduction

The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.

Methods

Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.

Results

All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.

Conclusions

Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.     

Social Network Effects of Nonlifesaving Early-Stage Breast Cancer Detection on Mammography Rates

Objectives. We estimated the effect of anecdotes of early-stage, screen-detected cancer for which screening was not lifesaving on the demand for mammography.Methods. We constructed an agent-based model of mammography decisions, in which 10 000 agents that represent women aged 40 to 100 years were linked together on a social network, which was parameterized with a survey of 716 women conducted through the RAND American Life Panel. Our model represents a population in equilibrium, with demographics reflecting the current US population based on the most recent available census data.Results. The aggregate effect of women learning about 1 category of cancers—those that would be detected but would not be lethal in the absence of screening—was a 13.8 percentage point increase in annual screening rates.Conclusions. Anecdotes of detection of early-stage cancers relayed through social networks may substantially increase demand for a screening test even when the detection through screening was nonlifesaving.Women often overestimate the mortality reduction from mammograms,1–3 and anecdotes of women with early-stage breast cancer being diagnosed through mammography can serve as particularly powerful motivators in encouraging other women to have screening mammograms.4–6 Such diagnoses, which are often shared through discussions between friends, family, coworkers, and other acquaintances, are also often viewed by patients as lifesaving.7 These discussions can be viewed as the transmission of information through a social network. Typically, social networks are defined as sets of individuals with links between pairs of individuals. In this article, we define 2 individuals as linked if they discuss their health history and outcomes (such as breast cancer diagnosis and treatment) with each other.Although women often view the detection of early-stage breast cancer through mammography as lifesaving, a recent study estimated that more than three quarters of women with screen-detected cancer have not actually had their lives saved by early detection.8 Rather, these women have cancers that (1) would never have been detected clinically if not detected through screening (thus, they were overdiagnosed), (2) eventually would have been detected clinically but would not be lethal, or (3) eventually would be lethal despite being detected by screening. Physicians and epidemiologists have long understood that high rates of early-stage diagnosis through screening do not necessarily indicate that the screening reduces mortality. Furthermore, when issuing cancer screening recommendations, professional organizations generally use mortality reduction as a primary measure of the screening’s efficacy.9–12Understanding how nonlifesaving early detection of breast cancer through screening drives patient demand for screening has several important implications. First, professional organizations currently disagree about when and how frequently women should be screened for breast cancer.9,10 Those who believe that some women are screened too early and too often may find demand for mammograms driven by such nonlifesaving diagnoses problematic. Our analysis estimated how much demand for mammograms may be driven by women’s incorrect assumptions about whether breast cancer screening was lifesaving for individuals in their social networks. More generally, the fact that patients often use frequency of early detection as a proxy for the screening efficacy7 means that patients with limited time and resources might prioritize a screening test that is relatively ineffective at reducing mortality over a test that more successfully reduces mortality if the former has higher early detection rates than the latter. We examined the potential patient-driven demand for screening that is motivated by nonlifesaving screen-detected cancers discussed in a social network.It is challenging to quantify this demand through observation or experiment because it is often not possible to determine at the individual level whether early detection through screening affected mortality. If a woman with early-stage, screen-detected breast cancer does not die of breast cancer, it is usually not possible to know with certainty if she would have died from breast cancer had she not been screened. If a woman with early-stage, screen-detected breast cancer ultimately dies of breast cancer, we know that screening was not lifesaving, but there may be many years between her initial diagnosis and death from breast cancer. Therefore, we used an agent-based simulation model to estimate how nonlifesaving early-stage breast cancer detection relayed through a social network might influence mammography rates. A major advantage of using a simulation model to study this problem is that, within the model, we can distinguish between agents (individual women) whose early detection of breast cancer through screening was lifesaving and those whose early detection was not lifesaving.In our analysis, we explored how population-level mammography rates might change if individuals were able to account for the fact that not all early-stage, screen-detected cancers are lifesaving. We used the results of a customized survey conducted through RAND’s American Life Panel to inform and parameterize our behavioral model. Many individuals assume that detection of early-stage breast cancer through mammography is lifesaving,7 and we assumed that if those diagnoses were known to be nonlifesaving, they would not serve as such powerful motivators in encouraging others to screen. Mammography is lifesaving only when a cancer that would have been lethal when detected clinically is not lethal when detected by mammography. We focused our analysis on categories of cancers whose detection by screening was not lifesaving. First, we simulated changing the incidence of cancers that would not have been detected in the absence of mammography (i.e., were overdiagnosed). Second, we simulated hypothetical interventions that allowed individuals in our model to know that mammography was nonlifesaving for (1) cancers that would be detected but would not have been lethal in the absence of mammography (never-lethal cancers) and (2) cancers that were ultimately lethal despite being screen detected (always-lethal cancers).     

An endolymphatic sac tumor with imaging features of aneurysmal bone cysts: differential diagnostic considerations

Background

Endolymphatic sac tumors (ELSTs) are rare, slow-growing tumors of the petrous bone. Despite the typical localisation, their radiological diagnosis can be challenging due to the variety of other tumors potentially showing similar features.

Case report

We present a 16-year-old child with progressive hearing loss, vertigo, and tinnitus who had a large petrous bone lesion showing imaging features of both ELSTs and aneurysmal bone cysts (ABCs). The patient underwent preoperative embolization of the tumor-supplying vessels and subsequently a subtotal resection. Histological examination revealed an ELST.

Conclusion

Despite the rarity of petrous bone ABCs, they should be considered as a differential diagnostic alternative of ELSTs due to their similar imaging appearance.     

Immunity to Amoeba

Amoebic infections in fish are most likely underestimated and sometimes overlooked due to the challenges associated with their diagnosis. Amoebic diseases reported in fish affect either gills or internal organs or may be systemic. Host response ranges from hyperplastic response in gill infections to inflammation (including granuloma formation) in internal organs. This review focuses on the immune response of Atlantic salmon to Neoparamoeba perurans, the causative agent of Amoebic Gill Disease (AGD).     

A single nucleotide polymorphism −35 kb T > C (rs9264942) is strongly associated with psoriasis vulgaris depending on HLA-Cw06

HLA class I molecules play a role both in viral infection control and in autoimmune diseases development. rs9264942T > C polymorphism in HLA-C gene was found to impact on HLA-C surface expression level and to be associated with HIV-1 control. It was found that these HLA alleles which protect against AIDS are associated with autoimmune disease e.g. psoriasis vulgaris (PsV). Whether rs9264942 SNP is associated with PsV was investigated here. rs9264942T > C was genotyped in 292 PsV patients, and 254 controls using TaqMan Genotyping Assay.