Interstitial nephritis and autoimmune pancreatitis: a case report

Autoimmune pancreatitis is a rare form of pancreatitis characterized by responsiveness to steroid therapy and an often relapsing disease course. The mainstay of therapy is oral corticotherapy. Associations of interstitial nephritis with various autoimmune disorders have been described. We hereby report the case of a 69-year-old Caucasian man with a 2-year history of autoimmune pancreatitis, who presented with impairment of kidney function, proteinuria, and hypertension. Renal histopathology showed severe diffuse interstitial nephritis. With oral prednisone and ACE inhibitor therapy, complete recovery of kidney function was not achieved and proteinuria persisted. Therefore, mycophenolate mofetil was initiated. After 8 weeks, serum creatinine decreased, and a nearly complete and sustained resolution of proteinuria was seen, while tapering oral steroid doses. With autoreactive T cells playing a major role in the pathogenesis of both diseases, a common etiology of pancreatitis and interstitial nephritis can be assumed, and the beneficial effects of an inhibitor of lymphocyte proliferation, such as mycophenolate mofetil, can be explained. We infer from our case that mycophenolate mofetil can be effective in the control of simultaneous autoimmune pancreatitis and interstitial nephritis.     

Marine biodiversity,ecosystem functioning,and carbon cycles

Although recent studies suggest that climate change may substantially accelerate the rate of species loss in the biosphere, only a few studies have focused on the potential consequences of a spatial reorganization of biodiversity with global warming. Here, we show a pronounced latitudinal increase in phytoplanktonic and zooplanktonic biodiversity in the extratropical North Atlantic Ocean in recent decades. We also show that this rise in biodiversity paralleled a decrease in the mean size of zooplanktonic copepods and that the reorganization of the planktonic ecosystem toward dominance by smaller organisms may influence the networks in which carbon flows, with negative effects on the downward biological carbon pump and demersal Atlantic cod (Gadus morhua). Our study suggests that, contrary to the usual interpretation of increasing biodiversity being a positive emergent property promoting the stability/resilience of ecosystems, the parallel decrease in sizes of planktonic organisms could be viewed in the North Atlantic as reducing some of the services provided by marine ecosystems to humans.     

Aligning Funding and Need for Family Planning: A Diagnostic Methodology

With limited international resources for family planning, donors must decide how to allocate their funds to different countries. How can a donor for family planning decide whether countries are adequately prioritized for funding? This article proposes an ordinal ranking framework to identify under‐prioritized countries by rank‐ordering countries by their need for family planning and separately rank‐ordering them by their development assistance for family planning. Countries for which the rank of the need for family planning is lower than the rank of its funding are deemed under‐prioritized. We implement this diagnostic methodology to identify under‐prioritized countries that have a higher need but lower development assistance for family planning. This approach indicates whether a country is receiving less compared to other countries with similar levels of need.     

Differentiated thyroid carcinoma: the new UICC 6th edition TNM classification system in a retrospective analysis of 169 patients.

AIM: To compare the new, 6th edition, UICC TNM staging system with the former edition, we updated TNM staging in patients with differentiated thyroid carcinoma. METHODS: The new and old TNM classification systems for differentiated thyroid carcinoma were applied in a retrospective analysis of 169 patients who underwent therapy with radioiodine (131I) from 1975 through 2002 at the Department of Nuclear Medicine, Frankfurt. RESULTS: According to the new staging system, 83 patients (49%) were classified as T1 compared to 54 patients (32%) based on the former edition; 32 patients (19%) as T2 compared to 61 (36%) patients formerly. In 44 patients with minimal extrathyroid extension, formerly classified T4, the new TNM staging changed to T3, and no patient was classified T4. The one year relapse-free survival fraction under the former edition staging was 100% for T1 and 92.2% for T2, compared to 96.8% for new edition T1 and 93.3% for T2. CONCLUSION: The new TNM classification causes a significant change in staging. New T1 classified tumors had a slightly worse relapse-free survival fraction compared with the old T1 carcinomas. For patients treated at our department, the altered criteria for classifying extrathyroid extensions have had only a minor impact on disease management.     

Surgical recurrence in Crohn’s disease: a comparison between different types of bowel resections

Purpose

To compare recurrence frequency and location between different types of bowel resections in Crohn’s disease patients.

Methods

This was a retrospective study of consecutive patients undergoing bowel resection for Crohn’s disease between 2006 and 2016. Type of primary operation was recorded and grouped as ileocolic resection, small bowel resection, segmental colon resection with colocolic anastomosis or colorectal anastomosis, colectomy with ileorectal anastomosis, or end stoma operation. Binary logistic regression was used to compare surgical recurrence frequency between groups. We also investigated how Crohn’s disease location at reoperations was related to the primary bowel resection type.

Results

Altogether, 218 patients with a median follow-up of 4.7 years were included in our study. Reoperation was performed in 42 (19.3%) patients. The risk of reoperation using the ileocolic resection group as reference was the following: small bowel resection (odds ratio (OR) 2.95, 95% confidence interval (CI) 1.01–8.66; P?=?0.049), segmental colon resection with colocolic or colorectal anastomosis (OR 6.20, 95% CI 2.04–18.87; P?=?0.001), colectomy with ileorectal anastomosis (OR 26.57, 95% CI 2.59–273.01; P?=?0.006), and end stoma operation (OR 4.62, 95% CI 1.90–11.26; P?=?0.001). In case of surgical recurrence, the reoperation type and location correlated with the primary bowel resection type.

Conclusions

Reoperation frequency in Crohn’s disease is lower after ileocolic resection than after other types of bowel resections. Surgical recurrence in Crohn’s disease tends to maintain the disease location of the primary operation. One third of Crohn’s patients undergoing an end stoma operation will still need new bowel resections due to recurrence.

     

Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes

BACKGROUND & AIMS: Studies on the early steps in the life cycle of hepatitis B virus have been hampered by the lack of readily available target cells. In this study, we mapped a defined virus attachment site to primary hepatocytes that is essential for infection. METHODS: We used purified virus particles from human carrier plasma as an inoculum and primary cultures of tupaia hepatocytes as susceptible target cells and studied the inhibitory effect of amino-terminally acylated preS1-derived lipopeptides on infection interference. RESULTS: Infectivity of virus could be blocked efficiently in this system by amino-terminally acylated peptides containing amino acids 2-18 from the preS1 domain. The addition of amino acids 28-48 enhanced the inhibitory capacity, whereas amino acids 49-78 did not contribute to inhibition. Myristoylated preS1 peptides 2-48 bound strongly to tupaia hepatocytes but not to nonhepatic cells or rodent hepatocytes and thereby inhibited infection even at concentrations of 1 nmol/L completely. Particles consisting only of the small hepatitis B surface protein-the active component of current hepatitis B vaccines-did not bind at all to tupaia hepatocytes, but the addition of the preS1 domain to the particles allowed binding. CONCLUSIONS: The preS1 sequence 2-48 mediates attachment of the virus to its target cells, whereas the small surface protein seems to be involved in other steps. These findings indicate that the current subunit hepatitis B vaccines may be improved by the addition of distinct preS1 epitopes. Moreover, preS1 lipopeptides are promising candidates for specific antiviral therapy against hepatitis B infections.     

Impact of cardiac resynchronisation therapy on adaptation of circulatory and respiratory systems to exercise assessed by cardiopulmonary exercise test in patients with chronic heart failure

BACKGROUND: Cardiac resynchronisation therapy (CRT) has become a valuable therapeutic tool in patients with advanced chronic heart failure (CHF). The search for optimal methods for the assessment of CRT efficacy is still underway. AIM: To evaluate the impact of implantation of CRT devices in patients with CHF on adaptation of circulatory and respiratory systems to maximal exercise assessed by cardiopulmonary exercise tests (CPX) and 6-minute walking tests (6MWT). METHODS: We investigated 27 patients (22 males, 5 females, 61.2+/-9.1 years) with a CRT device implanted due to advanced CHF, which resulted from ischaemic or dilated cardiomyopathy. All patients before implantation underwent echocardiography, CPX with expired gas analysis and 6MWT. Investigations were repeated at 3-6 months after CRT implantation. In CPX we evaluated peak oxygen uptake (peak VO2), oxygen pulse, maximal minute ventilation-carbon dioxide production (VE/VCO2 (max)), and its slope (VE/VCO2 slope) and VE/VO2 slope, VO2 in anaerobic threshold (AT), and cardiac and respiratory reserve. In 6MWT we evaluated walking distance and heart rate and blood pressure response to exercise. RESULTS: We noted statistically higher mean peak VO2 after CRT implantation in the studied group: 11.34+/-3.38 vs. 14.56+/-3.99 ml/kg/min (p<0.0001) and 1.01 +/-0.44 vs. 1.4+/-0.55 l/min (p=0.003) and higher values of expired CO2: 1.00+/-0.43 vs. 1.43+/-0.67 l/min (p=0.004). The O2 pulse rose from 9.65+/-3.39 to 13.23+/-5.43 ml/beat (p=0.015). We also observed a significant reduction of VE/VCO2 slope from 42.34+/-13.35 before CRT to 34.77+/-6.04 after CRT (p=0.0196) and a significant decrease of VE/VO2 slope from 41.32 +/-15.46 to 34.01+/-6.27 (p=0.037). VE/VCO2 (max) fell from 58.02+/-15.86 to 50.1+/-13.14 (p=0.009). Patients estimated their dyspnoea on the Borg scale at peak exercise at 4.75+/-0.75 points before CRT and at 3.67+/-1.15 points (p=0.002) after CRT. Patients could walk a longer distance during 6MWT than before CRT (367+/-154.9 vs. 231.1+/-170.3 m, p<0.001). CONCLUSIONS: Cardiac resynchronisation therapy improves exercise tolerance measured by means of CPX and 6MWT, improves respiratory system efficiency and restores its adaptive mechanisms during exercise in patients with advanced CHF. Better exercise adaptation after CRT may be objectively measured with CPX parameters, and correlates with improvement of clinical symptoms. CPX seems to be a very helpful tool in assessing the results of CRT.     

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Background

Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism.

Methods

Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated.

Results

The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and S-adenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients.

Conclusion

Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia. The clinical phenotype varies from an exclusively neurological to a multi-organ manifestation. Methionine-restricted diet should be considered as a therapeutic option.