Squamous papilloma of the proximal oesophagus associated with an inlet patch: a potential aetiological relationship.

Squamous papillomas are rare benign lesions that can be found in the oesophagus. It has been theorised that irritation of the esophageal mucosa leads to squamous papilloma formation. There is evidence to suggest that squamous papillomas of the distal oesophagus are related to irritation due to reflux of gastric acid. In this case report, we describe for the first time a squamous papilloma of the upper oesophagus located just distal to an inlet patch. Inlet patches consist of gastric mucosa located in the proximal oesophagus. They are capable of producing acid. This case raises the possibility that just as squamous papillomas of the distal oesophagus may be related to acid exposure from the reflux of gastric acid, squamous papillomas of the proximal oesophagus may be related to acid exposure from the locally-produced acid of inlet patches.

Real world management of esophageal ulcers: analysis of their presentation, etiology, and outcomes.

BACKGROUND AND STUDY AIMS: Esophageal ulcers are a rare cause of upper gastrointestinal morbidity and may be due to different etiologies. We sought to systematically evaluate patients with esophageal ulcers and describe their presentations, endoscopic findings, etiologies, treatments, and outcomes. PATIENTS AND METHODS: Patients diagnosed with esophageal ulcers over an 11-year period were retrospectively identified from our institution's electronic medical records. RESULTS: We identified 100 patients with esophageal ulcers (0.49% of patients undergoing upper endoscopy). Half of them presented due to gastrointestinal bleeding and three-quarters were admitted to the hospital. The majority were in the lower esophagus. Twenty-two unique etiologies, including multiple iatrogenic causes, were diagnosed in 91 of the cases. The most common etiology was gastroesophageal reflux disease (57%), followed by non-steroidal anti-inflammatory drug use (7%), malignancies (3%), vomiting (3%), caustic ingestion (2%), pill esophagitis (2%) and radiation (2%). Many etiologies showed a predilection for specific segments of the esophagus. Nine ulcers required endoscopic intervention and all were treated successfully. Repeat endoscopies were performed 5 times for diagnostic or "second look" reasons, none of which changed the patients' diagnosis or treatment. No patients required surgery or stricture dilation. One patient's ulcer was complicated by perforation and he subsequently died. Four other patients died from non-ulcer related causes. CONCLUSIONS: While the majority of ulcers were due to gastroesophageal reflux disease, 22 different etiologies were identified. Many were due to medication or iatrogenic causes. Repeat endoscopy did not appear to be helpful. While the incidence was low, they were frequently associated with significant morbidity.

Clinical characteristics and outcomes of immunosuppressed patients hospitalized with COVID-19: experience from London.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health emergency. Despite the widely hypothesized role of a cytokine storm in disease severity, no study thus far has explored the association between immunosuppression and disease severity in patients hospitalized with COVID-19. OBJECTIVE: This study aimed to examine the association between the use of immunosuppressant medication and outcomes of patients hospitalized with COVID-19. METHODS: Nine hundred and eighty-one consecutive patients hospitalized between 12 March 2020 and 15 April 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were enrolled in this cohort study and subdivided by immunosuppression status. The patients were followed up for a minimum of 28 days (median 37 days) for the primary end-point of mortality. Secondary end-points included the composite of intubation or death, and the composite of mortality, intubation or continuous positive airway pressure (CPAP) requirement. RESULTS: During the follow-up period, 354 (36.1%) of study patients died. The immunosuppressed cohort (n = 31) had significantly higher mortality rates (aHR: 2.067, 95% CI: 1.20-3.57, P = 0.009). There was no association between immunosuppression and the composite end-point of mortality or intubation (aHR: 1.49 95% CI: 0.88-2.51, P = 0.14) and of the composite end-point of mortality, intubation or CPAP (aHR: 1.36 95% CI: 0.81-2.30 P = 0.245). CONCLUSION: In this cohort study of 981 confirmed COVID-19 patients consecutively hospitalized at a large North West London hospital, immunosuppressant use was associated with significantly higher mortality rates. These results support the current UK government's early isolation ('shielding') policy for these individuals and should be used to guide future research.

Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study.

COVID-19 has caused a major global pandemic and necessitated unprecedented public health restrictions in almost every country. Understanding risk factors for severe disease in hospitalised patients is critical as the pandemic progresses. This observational cohort study aimed to characterise the independent associations between the clinical outcomes of hospitalised patients and their demographics, comorbidities, blood tests and bedside observations. All patients admitted to Northwick Park Hospital, London, UK between 12 March and 15 April 2020 with COVID-19 were retrospectively identified. The primary outcome was death. Associations were explored using Cox proportional hazards modelling. The study included 981 patients. The mortality rate was 36.0%. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Scale <15 (aHR 1.92), urea (aHR 2.67), alkaline phosphatase (aHR 2.53), C-reactive protein (aHR 1.15), lactate (aHR 2.67), platelet count (aHR 0.77) and infiltrates on chest radiograph (aHR 1.89) were all associated with mortality. These important data will aid clinical risk stratification and provide direction for further research.

Lateralization index but not contralateral suppression at adrenal vein sampling predicts improvement in blood pressure after adrenalectomy for primary aldosteronism.

Adrenal vein sampling (AVS) is essential in differentiating unilateral from bilateral sources of aldosterone excess in primary aldosteronism (PA). However, its ability to predict blood pressure (BP) improvement after adrenalectomy has not been well studied. This is a retrospective observational study of 119 patients who underwent AVS by sequential technique followed by adrenalectomy for PA at the Hospital of the University of Pennsylvania from 1997 to 2015. Median age was 52 years (interquartile range 44-59), 67% were male and median duration of hypertension was 10 (interquartile range 6-20) years. A total of 76% and 90% of patients experienced BP improvement at 0-6 months or at any time point after surgery, respectively. Lateralization index (LI) >8, but not the presence of contralateral suppression, was significantly associated with BP improvement after surgery by multivariate logistic regression analysis adjusted for potential confounders (odds ratio (95% confidence interval): 17.1 (1.7-171.6) and 6.39 (0.06-641.8), respectively). A prediction score was created by covariates that was significantly associated with BP improvement in logistic regression analysis (duration of hypertension, body mass index, preoperative systolic BP and number of antihypertensive medications). Receiver-operating characteristic curve analyses showed that the addition of LI >8 to the score increased its ability to predict BP improvement (area under the curve 0.73-0.80). In conclusion, LI is useful in predicting improvement in BP after adrenalectomy for PA. The results of this study suggest that patients with long-standing severe hypertension may still benefit from surgery if LI >8.

External beam radiation therapy (EBRT) for patients with malignant pheochromocytoma and non-head and -neck paraganglioma: combination with 131I-MIBG.

In patients with malignant pheochromocytoma and paraganglioma, 131I-MIBG radiotherapy can achieve an objective response rate of 30-50% with the dose limiting toxicity being hematologic. Patients with disseminated disease, who also have a few index bulky or symptomatic lesions, may benefit from the addition of targeted external beam radiotherapy alone or in combination with systemic 131I-MIBG. The records of patients with malignant paraganglioma who were treated with external beam radiotherapy at the University of Pennsylvania from February 1973 to February 2011 were reviewed in an institutional review board approved retrospective study. Of the 17 patients with tumors in the thorax, abdomen, or pelvis, 76% had local control or clinically significant symptomatic relief for at least 1 year or until death. As expected, the predominant toxicity was due to irradiation of tumor-adjacent normal tissues without clinically significant hematologic toxicity. Due to widespread systemic metastases with areas of bulky, symptomatic tumor, 5 of the 17 patients were treated with sequential 131I-MIBG (2 mCi/kg per treatment) and external beam radiotherapy to 9 sites. In these patients, all areas that were irradiated with external beam radiotherapy showed durable objective response despite all patients eventually experiencing out-of-field systemic progression requiring other treatment. Four of these patients remain alive with excellent performance status 16, 18, 23, and 24 months after external beam radiotherapy. External beam radiotherapy can be highly effective in local management of malignant paraganglioma and can be used in conjunction with 131I-MIBG due to nonoverlapping toxicities with excellent control of locally bulky tumors.

Resolution of nephrotic syndrome after successful bariatric surgery in patient with biopsy-proven FSGS.

The incidence of obesity-related nephropathy (ORG) is increasing with the growing incidence of obesity. ORG is associated with morbid obesity, proteinuria and renal biopsy findings of focal global and segmental glomerulosclerosis (FSGS), which can be associated with significant renal impairment. Weight reduction is associated with improvement of ORG, however, conservative measures aiming at long-term weight reduction are difficult to achieve. Bariatric surgery is the most effective way of achieving long-term weight reduction. We present a case of ORG with nephrotic-range proteinuria and FSGS on renal biopsy. Following bariatric surgery, patient achieved successful weight reduction with significant decrease in proteinuria and stabilization of renal function.

Change in the pattern of adrenal venous sampling over time in patients with primary aldosteronism.

We report six patients with primary aldosteronism who had serial adrenal venous sampling. Patients with contralateral suppression of aldosterone to cortisol ratio compared with that in inferior vena cava developed lateralization over time whereas patients without contralateral suppression remained with a bilateral pattern.

U.S. Food Guide Pyramid food group intake by Asian Indian immigrants in the U.S.

This study examined the food group intake and the dietary quality of middle-aged and older Gujarati Asian Indian immigrants (45 years or older) living in two urban metropolitan areas in the U.S. Participants (90 men, 99 females) completed a 24-hour dietary recall, which was used to determine if they met the daily food group intake guidelines of the U.S. Food Guide Pyramid. The overall quality of their reported dietary intake was determined using the Healthy Eating Index based on their nutrient and food group intake. Both men and women met the daily number of servings recommendations for the grains (men: 9.3 servings/day; women: 6.9 servings/day) and vegetables (men: 4.5 servings/day; women: 3.6 servings/day) groups, but did not meet the recommendations for fruits, dairy and meats groups. The total score on the Healthy Eating Index of the diets of these participants was 73, indicative of a dietary intake that does not meet the established U.S. dietary guidelines. These immigrants should be educated about appropriate food choices (ethnic and non-ethnic) within each of the U.S. Food Guide Pyramid food groups to improve the overall quality of their dietary intakes.

Squid p196, a new member of the myosin-V class of motor proteins, is associated with motile axoplasmic organelles.

Axoplasmic organelles obtained from the squid giant axon move on actin filaments at an average velocity of 1 microm/s [Nature 356 (1992) 722]. The unconventional myosins, in particular, the myosin-V class of motor proteins, represent the most likely candidates to have a role in this motility. Experiments were performed to determine whether a member of the myosin-V class of unconventional myosins is present in axoplasm and optic lobes. Western blots of axoplasm probed with an affinity purified antibody to chicken brain myosin-V (CBM-V) showed cross-reactivity with a protein of Mr 196 kD (p196) which was subsequently purified from squid optic lobes using a modification of a protocol for the purification of CBM-V [Methods Enzymol. 298 (1998) 3; Cell 75 (1993) 215]. Western blots of CBM-V probed with an alpha-p196 polyclonal IgG showed cross-reactivity with CBM-V. Purified p196 has been found to be a calmodulin (CaM) binding protein that possesses calcium-stimulated actin-activated ATPase activity. Equilibrium density fractionation of motile axoplasmic organelle preparations has revealed that p196 cosedimented with the peak organelle fraction into Percoll gradients in the presence of cytochalasin B and ATP. Based on this evidence, we conclude that the p196 present in axoplasm and purified from optic lobes is a squid homolog of CBM-V and functions as a motor for fast transport of membranous organelles on actin filaments in neurons.

Dramatic recovery of renal function after 6 months of dialysis dependence following surgical correction of total renal artery occlusion in a solitary functioning kidney.

Revascularization of renal artery stenosis for the treatment of hypertension is an established procedure. In selected clinical scenarios, successful revascularization procedures may preserve or restore renal function. We present a 31-year-old man who underwent successful renal revascularization of a solitary functioning kidney after being dialysis dependent for approximately 190 days. He had dramatic improvement of renal function and has remained off dialysis since his surgery 18 months ago. He continues to have severe but controllable hypertension.

Safety of intravenous gadolinium (Gd-BOPTA) infusion in patients with renal insufficiency.

The safety of gadolinium (Gd-benzyloxypropionictetra-acetate [BOPTA] dimeglumine) infusion was evaluated in 32 patients with severe or moderate chronic renal failure in a prospective, randomized, double-blind, placebo-controlled study. Renal failure was defined as severe if creatinine clearance was between 10 and 29 mL/min, and as moderate if creatinine clearance was between 30 and 60 mL/min. Serum creatinine level and 24-hour urine samples for creatinine clearance were followed up serially for 7 days after the administration of either gadolinium (Gd-BOPTA dimeglumine), 0.2 mmol/kg, or a saline infusion. No patient experienced a significant change in renal function, defined as an increase in serum creatinine level greater than 0.5 mg/dL more than baseline, and no patient required hospitalization or dialysis during the study period. Gadolinium (Gd-BOPTA dimeglumine) appears to be well tolerated in patients with moderate to severe renal failure.

Chronic salicylism resulting in noncardiogenic pulmonary edema requiring hemodialysis.

Salicylate intoxication is frequently overlooked as a cause of noncardiogenic pulmonary edema and altered mental status in adult patients. We describe a 42-year-old woman who presented with two episodes of recurrent noncardiogenic pulmonary edema requiring intubation. The first admission to hospital triggered an extensive initial workup that did not indicate a cause for the pulmonary edema. At the second presentation, recognition of the clinical syndrome in the emergency department led to the correct diagnosis of salicylate intoxication. The patient was successfully treated with hemodialysis and urinary alkalinization, leading to rapid resolution of pulmonary edema and extubation. Several aspects of the clinical presentation suggest that the patient suffers from chronic salicylism, probably complicated by episodic superimposed acute intoxication, a condition often misdiagnosed or diagnosed late in the course of disease, contributing to substantial morbidity and mortality in these patients. Maintenance of a high index of suspicion and rapid institution of appropriate therapy including hemodialysis once the diagnosis is established is an important determinant of outcome in this serious but underdiagnosed disorder.

Purification of plasmid DNA by tangential flow filtration.

A simple, scalable method for purification of plasmid DNA is described. The method includes modification of the classical alkaline-lysis-based plasmid extraction method by extending the solubilization step from less than 30 min to 24 h. The extraction is followed by the novel use of tangential flow filtration (TFF) for purification of the remaining contaminants. The method does not include the use of any organic solvents, RNase, high-speed centrifugation, or column chromatography steps. The method typically yields 15 to 20 mg of plasmid DNA per liter of bacterial culture and results in removal of >99% of RNA and >95% of the protein that remains after the modified alkaline lysis procedure. The procedure has been demonstrated to be effective in the isolation of seven different plasmids. Plasmids isolated using this method had comparable transfection capability relative to plasmid isolated using a classical, cesium chloride gradient-based method.

Performance degradation of a Michelson interferometer due to random sampling errors.

The performance of a standard Michelson interferometer is degraded by disturbances that cause the interferogram signal to be sampled at nonconstant time intervals. A formula that shows how the power spectrum of the random disturbances interacts with the signal to contaminate different regions of the measured spectrum is derived for the spectral noise. The sampling noise does not look conventionally noiselike because it is correlated over large regions of the measured spectrum, and adjustment of the unbalanced background interferogram to match the size of the balanced background interferogram minimizes the sampling-noise amplitude.