Longitudinal monitoring of laboratory markers characterizes hospitalized and ambulatory COVID-19 patients.

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.

A call to caution when hydroxychloroquine is given to elderly patients with COVID-19.

INTRODUCTION: Use of hydroxychloroquine in patients with coronavirus disease 2019 (COVID-19) was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk of hydroxychloroquine interactions with co-morbidities and co-medications contributing to detrimental, including fatal, adverse treatment effects. METHODS: A retrospective survey was undertaken of health conditions and co-medications of patients with COVID-19 who were pre-screened for enrolment in a randomized, double-blind, placebo-controlled hydroxychloroquine multi-centre trial. RESULTS: The survey involved 305 patients [median age 71 (interquartile range 59-81) years]. The majority of patients (n = 279, 92%) considered for inclusion in the clinical trial were not eligible, mainly due to safety concerns caused by health conditions or co-medications. The most common were QT-prolonging drugs (n = 188, 62%) and haematologic/haemato-oncologic diseases (n = 39, 13%) which prohibited the administration of hydroxychloroquine. In addition, 165 (54%) patients had health conditions and 167 (55%) patients were on co-medications that did not prohibit the use of hydroxychloroquine but had a risk of adverse interactions with hydroxychloroquine. The most common were diabetes (n = 86, 28%), renal insufficiency (n = 69, 23%) and heart failure (n = 58, 19%). CONCLUSION: The majority of hospitalized patients with COVID-19 had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, hydroxychloroquine should be administered with extreme caution in elderly patients with COVID-19, and only in clinical trials.

Q Fever Pneumonia in Southwest Germany: Radiographic and Clinical Findings.

Purpose Q fever is a worldwide zoonosis that causes clinical symptoms ranging from mild flu-like symptoms to severe pneumonia and/or hepatitis. This retrospective study was conducted to describe the radiographic and clinical signs in patients with acute Q fever pneumonia in Southwest Germany. Patients and Methods 40 patients with IgM-positive Q fever-related pneumonia who were treated in the years 2006 to 2016 in our hospital were retrospectively identified. Clinical and laboratory data were analyzed. Chest radiographs were reviewed by two radiologists and interpreted using a standardized protocol. Results Females and males were equally affected. The mean age was 44.9 ±â€Š15.7 years. About half of the patients (45 %) acquired their infection in the second quarter of the year. The main complaints were fever, cough and dyspnea. While the white cell blood count was in the normal range in most of the patients, the CRP value was markedly elevated. Q fever-related hepatitis was found in 63 % of the patients. Air space opacification was the predominant radiographic sign and was found in 27 of the patients (82 %). The typical chest radiographic pattern was a single segmental opacity. However, multiple segmental opacities and patchy opacities were also found. Lobar opacities were found in only 2 (6 %) of the patients. Conclusion Unilobar, unilateral, segmental opacities are the key feature of Q fever pneumonia chest radiographs. Definitive radiographic differentiation from other community-acquired pneumonias is not possible, but Q fever pneumonia should be considered in middle-aged patients with segmental opacities living in an endemic area. Key points · Unilobar, unilateral, segmental opacities are the key feature of Q fever pneumonia.. · Lobar and patchy as well as multisegmental opacities are also found.. · Chest radiography does not allow the differentiation of Q fever from other pneumonias.. Citation Format · Biecker A, Bitzer M, Biecker E. Q Fever Pneumonia in Southwest Germany: Radiographic and Clinical Findings. Fortschr Röntgenstr 2017; 189: 146 - 151.

Diagnosis and therapy of non-variceal upper gastrointestinal bleeding.

Non-variceal upper gastrointestinal bleeding (UGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of oesophageal, gastric or duodenal varices. The clinical presentation varies according to the intensity of bleeding from occult bleeding to melena or haematemesis and haemorrhagic shock. Causes of UGIB are peptic ulcers, Mallory-Weiss lesions, erosive gastritis, reflux oesophagitis, Dieulafoy lesions or angiodysplasia. After admission to the hospital a structured approach to the patient with acute UGIB that includes haemodynamic resuscitation and stabilization as well as pre-endoscopic risk stratification has to be done. Endoscopy offers not only the localisation of the bleeding site but also a variety of therapeutic measures like injection therapy, thermocoagulation or endoclips. Endoscopic therapy is facilitated by acid suppression with proton pump inhibitor (PPI) therapy. These drugs are highly effective but the best route of application (oral vs intravenous) and the adequate dosage are still subjects of discussion. Patients with ulcer disease are tested for Helicobacter pylori and eradication therapy should be given if it is present. Non-steroidal anti-inflammatory drugs have to be discontinued if possible. If discontinuation is not possible, cyclooxygenase-2 inhibitors in combination with PPI have the lowest bleeding risk but the incidence of cardiovascular events is increased.

Novel endocuff-assisted colonoscopy significantly increases the polyp detection rate: a randomized controlled trial.

GOALS AND BACKGROUND: Screening colonoscopy for colorectal cancer has proven to reduce mortality rates. Recently the Endocuff (EC), an attachment to the distal tip of the colonoscope, was introduced. The aim of our study was to compare EC-assisted colonoscopies with standard colonoscopies for the detection of colonic polyps. STUDY: This study is a randomized prospective 2-center trial. The study was conducted at 2 tertiary care centers. PARTICIPANTS: A total of 498 patients [249 males; median age 67 y; interquartile range (IQR), 56-75 y] for colon adenoma screening purposes were included. All patients underwent standard colonoscopy with or without the use of EC. Overall polyp detection rate, the number of colonic polyps, and the polyp distribution in the colon were measured. Difference in recognition of polyps with or without the use of EC was assessed. Statistical analysis was applied. RESULTS: In the EC group, the number of polyps detected per patient was 63% higher [2.00 (IQR, 1.00-4.00) vs. 1.00 (IQR, 1.00-2.25), P<0.0001]. The polyp detection rate in patients increased by 14% with the use of EC (56% vs. 42%, P=0.001). For polyp detection, superiority by use of EC could be observed in the sigmoid (P=0.001) and cecum (P=0.002) for polyps <1 cm in diameter. In the EC group, the number of adenomas detected per patient significantly increased by 86% (P=0.002). No major complications occurred in both groups. CONCLUSIONS: The use of the EC is feasible and safe with significantly higher polyp detection rates, especially for those located in the sigmoid region. The cuff system has the potential to improve the accuracy of screening colonoscopies.

Higher adenoma detection rates with endocuff-assisted colonoscopy - a randomized controlled multicenter trial.

OBJECTIVES: The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC). METHODS: This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. PARTICIPANTS: 500 patients (235 males, median age 64[IQR 54-73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR). RESULTS: The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29-41%] vs. 20.7%[95%CI 15-26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01-1.05), male sex (OR 1.74; 95%CI 1.10-2.73), withdrawal time (OR 1.16; 95%CI 1.05-1.30), procedure time (OR 1.07; 95%CI 1.04-1.10), colon cleanliness (OR 0.60; 95%CI 0.39-0.94) and use of Endocuff (OR 2.09; 95%CI 1.34-3.27) were independent predictors of adenoma detection rates. CONCLUSIONS: EC increases the adenoma detection rate by 14.7%(95%CI 6.9-22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas. TRIAL REGISTRATION: ClinicalTrials.gov NCT02034929.

Fulminant sepsis after liver biopsy: A long forgotten complication?

We report on a 74-year-old patient with recurrent cholangitis and a large juxtapapillary duodenal diverticulum. Despite drainage of the common bile duct by an endoscopically placed stent, the elevated liver enzymes normalized only partially. To rule out other possible causes of liver injury, a percutaneous liver biopsy was done. After the liver biopsy the patient developed fulminant septic shock and died within 24 h. We discuss the possible causes of the septic shock following percutaneous liver biopsy in our patient and give a concise overview of the literature.

Portal hypertension and gastrointestinal bleeding: diagnosis, prevention and management.

Bleeding from esophageal varices is a life threatening complication of portal hypertension. Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal. Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol. Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method. Therapy of acute bleeding is based on three strategies: vasopressor drugs like terlipressin, antibiotics and endoscopic therapy. In refractory bleeding, self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt (TIPS). Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate. Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking. Therapy of refractory bleeding relies on shunt-procedures like TIPS. Bleeding from ectopic varices, portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common. Possible medical and endoscopic treatment options are discussed.

Gastrointestinal Bleeding in Cirrhotic Patients with Portal Hypertension.

Gastrointestinal bleeding related to portal hypertension is a serious complication in patients with liver cirrhosis. Most patients bleed from esophageal or gastric varices, but bleeding from ectopic varices or portal hypertensive gastropathy is also possible. The management of acute bleeding has changed over the last years. Patients are managed with a combination of endoscopic and pharmacologic treatment. The endoscopic treatment of choice for esophageal variceal bleeding is variceal band ligation. Bleeding from gastric varices is treated by injection with cyanoacrylate. Treatment with vasoactive drugs as well as antibiotic treatment is started before or at the time point of endoscopy. The first-line treatment for primary prophylaxis of esophageal variceal bleeding is nonselective beta blockers. Pharmacologic therapy is recommended for most patients; band ligation is an alternative in patients with contraindications for or intolerability of beta blockers. Treatment options for secondary prophylaxis include variceal band ligation, beta blockers, a combination of nitrates and beta blockers, and combination of band ligation and pharmacologic treatment. A clear superiority of one treatment over the other has not been shown. Bleeding from portal hypertensive gastropathy or ectopic varices is less common. Treatment options include beta blocker therapy, injection therapy, and interventional radiology.

Diagnosis and therapy of ascites in liver cirrhosis.

Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm(3) and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis.

Critical flicker frequency as a marker of hepatic encephalopathy in patients before and after transjugular intrahepatic portosystemic shunt.

BACKGROUND: Overt hepatic encephalopathy (HE) following insertion of a transjugular intrahepatic portosystemic shunt (TIPS) is a problem in some patients. In contrast to overt HE, minimal HE (MHE) following TIPS is studied to a limited degree only. We therefore evaluated the incidence of MHE in patients following TIPS insertion by determination of the critical flicker frequency (CFF). METHODS: 45 cirrhotic patients (Child A/B/C: 7/24/14; Child-Pugh score 8.5 ± 2.0) underwent TIPS because of recurrent esophageal bleeding (n = 15), refractory ascites (n = 25) or a combination of bleeding and refractory ascites (n = 5). Hemodynamic parameters were recorded during TIPS insertion. CFF was determined using a portable analyzer 2 days before and 3, 28 and 84 days after TIPS. At these time points the number connection test and biochemical markers were recorded as well. RESULTS: TIPS led to a reduction of the portal pressure gradient from 19.1 ± 5.9 to 9.3 ± 6.1 mm Hg together with a slight but significant increase in bilirubin from 1.5 ± 0.9 to 2.2 ± 1.9 mg/dl and in the international normalized ratio from 1.2 ± 0.3 to 1.4 ± 0.5. Creatinine decreased from 1.3 ± 0.6 to 1.1 ± 0.5 mg/dl. Pre-TIPS, 27 patients had normal CFF (>38 Hz, CFF 41.1 ± 2.4 Hz) and 18 patients had altered CFF (≤38 Hz, CFF 34.4 ± 3.0 Hz): 3 had grade I and 15 MHE. Three days post-TIPS, 3 of the 27 patients (11.1%) with normal CFF deteriorated to MHE, 1 of the patients with grade I HE deteriorated to grade II HE, 1 maintained grade I HE and the other improved. No patient with MHE deteriorated to overt HE. CONCLUSIONS: Using the determination of the CFF, we were able to show that elective TIPS insertion in patients with preserved liver function causes a MHE in only the minority of patients. In addition, patients with preexisting MHE did not deteriorate to overt HE.

Nodular regenerative hyperplasia and portal hypertension in a patient with coeliac disease.

Nodular regenerative hyperplasia (NRH) of the liver is often associated with rheumatologic or lymphoproliferative disorders and a cause of portal hypertension in some patients. We report the case of a 71-year-old patient with celiac disease and unexplained portal hypertension. Biopsy of the liver revealed NRH as the underlying cause. The patient did not suffer from an autoimmune, rheumatologic or lymphoproliferative disease. A thrombophilic disorder that might cause NRH was ruled out. Celiac disease is often associated with mild elevation of liver enzymes and steatosis of the liver, but the association with NRH was described in only a few patients. We discuss the possible relationship of celiac disease and NRH.

Coexisting gastric varices should not preclude prophylactic ligation of large esophageal varices in cirrhosis.

BACKGROUND/AIMS: Coexisting gastric varices at baseline or the risk of their formation during treatment could alter the approach for primary bleeding prophylaxis in patients with large esophageal varices. METHODS: Data analysis of 152 patients with cirrhosis and large esophageal varices included in the German multicenter trial on primary prevention of variceal bleeding. RESULTS: 20 patients (13.6%) had coexisting gastric varices at baseline (GOV+). 10 of those each received either band ligation or propranolol, respectively. During follow-up (34.4 +/- 18.9 months) new gastric varices occurred in 2/75 (2.7%, ligation) and 4/77 (5.2%, propranolol) patients, respectively. One patient with newly developed gastric varices bled (propranolol group). GOV+ patients had a better baseline liver function and overall survival. Bleeding incidence did not differ significantly between GOV+ and GOV- patients (3-year actuarial risk: 20.0 +/- 10.6% (GOV+), 38.1 +/- 4.4% (GOV-), p = 0.195). Among GOV+ patients, bleeding occurred in 3/10 patients of the propranolol group and in 0/10 in the ligation group (p = 0.038). CONCLUSION: Prophylactic band ligation of large esophageal varices is safe and effective also in patients with coexisting gastric varices. Band ligation did not increase the risk of secondary gastric varices compared to propranolol.

Does therapy of oesophageal varices influences the progression of varices?

BACKGROUND: Aim of this study was to determine the progression time of oesophageal varices in patients with cirrhosis and to study whether therapy of varices has an impact on the progression time. Parameters associated with the progression of oesophageal varices were analyzed as well. METHODS: One hundred and eighty-one cirrhotic patients (Child A/B/C: 105/69/15; Child score 7.6+/-2.0, initial variceal grade 1.7+/-0.9) undergoing repeated endoscopy for follow-up and/or treatment of oesophageal varices were retrospectively analyzed. A multivariate logistic regression analysis was applied to identify independent determinants of progression of oesophageal varices. RESULTS: Of the 189 patients, 26 patients were on beta-blocker therapy only, 52 patients underwent ligation therapy only, and 37 patients received a combination of ligation and beta-blocker therapy of varices. The mean time of progression of oesophageal varices by one grade was 384+/-364 days. This interval did not vary significantly between patients who underwent no treatment or were on a beta-blocker and/or ligation therapy. The serum bilirubin (hazard ratio 1.030; 95% confidence interval, 1.004, 1.055; P<0.03) was the only parameter independently associated with the progression of varices. Initial eradication of varices was achieved after 2.2+/-1.5 ligation sessions. Rings of 6.1+/-2.5 were used in the first banding session and 11.5+/-8.9 rings were needed to achieve eradication of varices. CONCLUSION: Therapy of oesophageal varices does not influence the progression time of oesophageal varices in patients with cirrhosis of the liver.

Diagnosis of megacystis-microcolon intestinal hypoperistalsis syndrome with aplastic desmosis in adulthood: a case report.

Megacystis-microcolon intestinal hypoperistalsis syndrome (MMHIS or Berdon syndrome) is an autosomal-recessive disorder characterized by chronic intestinal obstruction. Although the disease is often diagnosed in female infants we describe a man with late diagnosis in adulthood. Our patient presented soon after birth with intestinal obstruction and developed short bowel syndrome after multiple intestinal resections. Of note, the connective tissue net within the muscle layers of the intestinal wall was absent ('aplastic desmosis'). This case illustrates the variable clinical features of MMHIS and aplastic desmosis, which might delay the correct diagnosis of a severe disorder.

Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats.

UNLABELLED: In cirrhosis, splanchnic vasodilation contributes to portal hypertension, subsequent renal sodium retention, and formation of ascites. Urotensin II(U-II) is a constrictor of large conductive vessels. Conversely, it relaxes mesenteric vessels, decreases glomerular filtration, and increases renal sodium retention. In patients with cirrhosis, U-II plasma levels are increased. Thus, we investigated hemodynamic and renal effects of U-II and its receptor antagonist, palosuran, in cirrhotic bile duct-ligated rats (BDL). In BDL and sham-operated rats, we studied acute effects of U-II (3 nmol/kg; intravenously) and palosuran (10 mg/kg; intravenously) and effects of oral administration of palosuran (30 mg/kg/day; 3 days) on hemodynamics and renal function. We localized U-II and U-II-receptor (UTR) in livers and portal veins by immunostaining. We determined U-II-plasma levels by enzyme-linked immunosorbent assay (ELISA), and mesenteric nitrite/nitrate-levels by Griess-reaction. RhoA/Rho-kinase and endothelial nitric oxide synthase (eNOS) pathways were determined by western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) in mesenteric arteries. U-II plasma levels, as well as U-II and UTR-receptor expression in livers and portal veins of cirrhotic rats were significantly increased. U-II administration further augmented the increased portal pressure (PP) and decreased mean arterial pressure (MAP), whereas palosuran decreased PP without affecting MAP. The decrease in PP was associated with an increase in splanchnic vascular resistance. In mesenteric vessels, palosuran treatment up-regulated expression of RhoA and Rho-kinase, increased Rho-kinase-activity, and diminished nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling. Moreover, palosuran increased renal blood flow, sodium, and water excretion in BDL rats. CONCLUSION: In BDL rats, U-II is a mediator of splanchnic vasodilation, portal hypertension and renal sodium retention. The U-II-receptor antagonist palosuran might represent a new therapeutic option in liver cirrhosis with portal hypertension.

Treatment of bile duct-ligated rats with the nitric oxide synthase transcription enhancer AVE 9488 ameliorates portal hypertension.

AIM: Nitric oxide levels are decreased in the cirrhotic liver and increased in the systemic vasculature. We investigated whether the nitric oxide synthase (NOS) transcription enhancer AVE 9488 ameliorates portal hypertension in cirrhotic rats. METHODS: Rats with secondary biliary cirrhosis [bile duct ligation (BDL)] were treated with AVE 9488. BDL animals without treatment served as controls. Blood flow was determined with the microsphere technique. Intrahepatic resistance was measured by in situ perfusion. NOS-3 mRNA and protein levels in the liver, aorta and superior mesenteric artery (SMA) were measured. RESULTS: Arterial pressure did not differ between treated and non-treated animals. Portal pressure, hepatic portal-vascular resistance and perfusion pressure of the in situ perfused liver were lower in the AVE 9488-treated animals. Arterial splanchnic resistance, portal venous inflow and shunt volume were increased by AVE 9488. N (G)-nitro-l-arginine methyl ester abolished the effect of AVE 9488. AVE 9488-treated rats had higher liver NOS-3 mRNA and protein levels, whereas NOS-3 mRNA and protein in the aorta and the SMA did not vary between groups. Phosphorylation of liver vasodilator-stimulated phosphoprotein (VASP) and NOS-3 as well as hepatic nitrite/nitrate was increased by AVE 9488. CONCLUSIONS: Treatment of BDL rats with the NOS transcription enhancer AVE 9488 induces an increase in NOS-3 mRNA and protein in the liver. This is associated with an amelioration of portal hypertension.