Clinical and Ophthalmological Characteristics of Ocular Syphilis in a Retrospective Tertiary Hospital Cohort.

BACKGROUND: Data on ocular syphilis (OS) and its clinical presentation are currently insufficient. This study aimed to investigate the characteristics of a cohort with a high OS incidence at a university hospital in Germany, focusing on the clinical presentation of OS. METHODS: This single-center cohort study retrospectively analyzed data on 90 patients with 109 episodes of syphilis between 2008 and 2018. Cases of OS were identified and additionally reevaluated through a study-specific secondary assessment by an ophthalmologist specializing in uveitis. RESULTS: Twenty-three patients (26%) were diagnosed with OS, 16 (70%) of whom were with binocular involvement. Uveitis, especially that of the posterior segment, showed a high prevalence. Lumbar puncture was performed in 20 OS patients (87%), of whom 17 (85% of those with lumbar puncture/74% in total) met the 2018 Centers for Disease Control and Prevention criteria for likely neurosyphilis. Five (22%) of 23 patients had HIV infection, of whom 2 did not receive antiretroviral therapy. The preferred syphilis treatment regimens were benzylpenicillin and ceftriaxone, which yielded favorable serological, clinical, and ophthalmological outcomes. CONCLUSIONS: A high incidence of OS was identified, and physicians should be aware of uveitis as a manifestation of syphilis. Most patients presented with uveitis and syphilis in an early or late latent stage and showed central nervous system involvement.

Monthly or Weekly Supplementation with Cholecalciferol 20,000 IU in People Living with HIV: Results from a Nested Cohort Study.

BACKGROUND: There is still considerable uncertainty in handling vitamin D deficiency in people living with HIV (PLWH), due to a lack of comparative data and the wide range of recommended daily intake. Nondaily supplementation might be preferred in many PLWH, but recommendation on dosing has not been established. We aimed to compare the efficacy of weekly versus monthly supplementation with cholecalciferol 20,000 IU in a group of PLWH with vitamin D deficiency in Western Europe. STUDY DESIGN: Longitudinal, retrospective nested cohort study of PLWH from two large clinical care centers in Munich, Germany. RESULTS: Of 307 patients with vitamin D deficiency, 124 patients received vitamin D supplementation (weekly supplementation in 84 (67.7%)). 46.4% and 22.5% of patients achieved 25(OH)D levels ≥30 ng/mL after 12 months of weekly and monthly supplementation with cholecalciferol 20,000 IU, respectively (p=0.011). Dosing interval as well as 25(OH)D baseline levels >15 ng/mL were associated with the normalization of 25(OH)D. CONCLUSION: A higher rate of 25(OH)D level normalization can be achieved via weekly supplementation. For several PLWH, even a weekly dose of cholecalciferol 20,000 IU might not be adequate to maintain 25(OH)D levels >30 ng/mL without an initial "loading" dose. The response to supplementation is poorly predictable at an individual level.

Neither boosted elvitegravir nor darunavir with emtricitabine/tenofovir disoproxil fumarate increase insulin resistance in healthy volunteers: results from the STRIBILD-IR study.

BACKGROUND: Insulin resistance (IR) was one of the first reported complications in HIV-positive patients who were receiving antiretroviral therapy (ART). However, the metabolic effects of newer fixed-dose ART combinations are unclear. METHODS: This Phase I prospective randomized open-label study evaluated the effects on IR in 30 healthy volunteers who were receiving newer fixed-dose combinations of tenofovir disoproxil fumarate, emtricitabine, elvitegravir and cobicistat (E/C/F/TDF, 10 patients) or the established ART regimens, such as tenofovir disoproxil fumarate/emtricitabine with lopinavir/ritonavir (F/TDF+LPV/r, 9 patients) or darunavir/ritonavir (F/TDF+DRV/r, 9 patients). IR was measured before and after the 14-day treatments using the hyperinsulinemic-euglycemic clamp technique, and changes in IR were evaluated using the mean glucose disposal rate that was normalized to body weight (MBW) and lipid metabolism. RESULTS: The groups exhibited similar pretreatment IR, although MBW was significantly lower after the 14-day F/TDF+LPV/r treatment compared with baseline (12.5 ±3.3 versus 9.2 ±1.8 mg glucose/min×kg; P=0.037). No significant IR changes were observed for E/C/F/TDF (11.2 ±3.2 versus 11.3 ±2.5) or F/TDF+DRV/r (11.6 ±2.5 versus 11.3 ±2.4). Compared with baseline, F/TDF+LPV/r and F/TDF+DRV/r treatments significantly increased day 14 triglyceride levels (62 [54-73] versus 119 [77-147] mg/dl, P=0.0109; 75 [56-95] versus 96 [93-128] mg/dl, P=0.009, respectively). CONCLUSIONS: Short-term treatment using fixed-dose combinations of E/C/F/TDF or F/TDF+DRV/r did not affect IR, although IR significantly increased after treatment using F/TDF+LPV/r.

Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data.

BACKGROUND: While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5'-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power. METHODS: We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used. RESULTS: High intra-personal variability in raltegravir serum levels was seen. Comparable Cmax concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While Cmax seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC12 is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels. CONCLUSIONS: We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations.

Fungal "colonisation" is associated with increased mortality in medical intensive care unit patients with liver cirrhosis.

OBJECTIVES: Patients with liver cirrhosis are at increased risk for fungal infections. However, distinction of fungal colonisation (FC) and invasive mycoses is difficult. Aim of this study was to analyse the impact of FC on mortality of cirrhotic ICU-patients. METHODS: Retrospective mortality analysis of a prospectively maintained database on 120 cirrhotic patients with and without FC. Comparison to 120 noncirrhotic controls matched for APACHE-II (24.9 ± 3.7 vs. 25.0 ± 2.6; p = 0.263). RESULTS: About 69/120 (58%) of patients with cirrhosis had FC. These patients had significantly higher APACHE-II score and mortality compared to cirrhotic patients without FC (27 ± 3 vs. 23 ± 4, p < 0.001; 78 vs. 35%, p < 0.001). In multivariate analysis, FC was independently (p = 0.047) associated to mortality. Mortality of noncirrhotic patients with FC (14/31; 45.2%) was not different to noncirrhotic controls without FC [28/89 (31.2%; p = 0.168)]. Similarly, in multivariate analysis of noncirrhotics, APACHE-II (p < 0.001), but not FC, was independently associated to mortality. Multiple regression analysis of all 240 cirrhotic and noncirrhotic patients demonstrated that APACHE-II (p < 0.001), cirrhosis (p = 0.001) and FC (p = 0.049) were independently associated with mortality. CONCLUSION: Fungal "colonisation" is independently associated to mortality in cirrhotic ICU-patients. Early antimycotic therapy should be considered in critically ill cirrhotic patients with FC.

Invasive mycosis in medical intensive care unit patients with severe alcoholic hepatitis.

BACKGROUND: Severe alcoholic hepatitis (AH) has a poor short-term prognosis often caused by infections. However, the incidence of invasive mycosis in patients with AH treated with corticosteroids and its impact still remains unknown. METHODS: Retrospective analyses of twelve medical ICU patients (out of 120 patients with liver cirrhosis) with histological proven AH. RESULTS: Twelve patients were diagnosed with histological proven AH during there stay at the ICU. All patients were treated with corticosteroids; three patients were treated with corticosteroids and pentoxifylline. Five patients had invasive aspergillosis (IA); three patients had candidemia; and two had fungal colonization with candida species. Only two patients had no evidence for fungals. IA was associated with death in all cases. Death occured in most cases shortly after diagnosis despite antifungal medication. Two patients with candidemia died; one patient died in the group with fungal colonization. Overall, the mortality rate was 100% in patients with IA and 70% in the group with candidemia. CONCLUSIONS: Patients with severe AH have an increased susceptibility to invasive mycosis associated with high mortality. A high level of suspicion of invasive mycosis in AH patients and prophylactic strategies are needed in those patients.

Acute hypophysitis and hypopituitarism in early syphilitic meningitis in a HIV-infected patient: a case report.

BACKGROUND: Sexually transmitted diseases and most notably syphilis-infections are rising amongst men who have sex with men. In HIV-co-infected patients, an accelerated clinical course of syphilis neurological involvement is known. CASE PRESENTATION: A 46 year old HIV-positive male patient came in to our emergency department in the late evening with acute fever, rapidly progressive cephalgia and photophobia. Palmar skin efflorescence was evocative of an active syphilis infection. A reactive Treponema pallidum particle agglutination (TPPA) assay with positive Treponema pallidum-specific IgG/IgM immunofluorescence as well as a highly reactive Veneral diseases research laboratory (VDRL) test confirmed the diagnosis. Liquor pleocytosis, liquor protein elevation and a highly positive VDRL test in cerebrospinal fluid (CSF) were interpreted in context of the clinical symptoms as neurosyphilitic manifestations within an early syphilis infection (stage II). Cranial nuclear magnetic resonance scans of the sella turcica, which were performed due to low thyroidea stimulation hormone (TSH) and thyroxin levels, showed signs of hypophysitis such as pituitary gland enlargement and inhomogeneous contrast enhancement. Advanced endocrine laboratory testing revealed hypopituitarism. Fourteen days of intravenous ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to complete disappearance of all clinical symptoms. Two months later, nuclear magnetic resonance scan showed normal pituitary size and that the syphilis serology had normalized. CONCLUSION: We report to the best of our knowledge the first case of a HIV-positive patient with acute hypophysitis and hypopituarism due to early neurosyphilis infection. Ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to the disappearance of all clinical symptoms. We strongly recommend to exclude syphilis infection in every clinical situation unclear in HIV-patients, especially when additional risk factors are known.

Deletion of IκBα activates RelA to reduce acute pancreatitis in mice through up-regulation of Spi2A.

BACKGROUND & AIMS: The transcription factor nuclear factor-κB (NF-κB) (a heterodimer of NF-κB1p50 and RelA) is activated rapidly in acute pancreatitis (AP). However, it is not clear whether NF-κB promotes or protects against AP. We used the NF-κB inhibitor protein, inhibitor of κB (IκB)α, to study the roles of NF-κB in the development of AP in mice. METHODS: IκBα or the combination of IκBα and RelA selectively were deleted from pancreas of mice using the Cre/locus of cross-over P strategy; cerulein or L-arginine were used to induce AP. We performed microarray analyses of the IκBα- and RelA-deficient pancreata. DNA from healthy individuals and patients with acute or chronic pancreatitis were analyzed for variants in coding regions of alpha-1-antichymotrypsin. RESULTS: Mice with pancreas-specific deletion of IκBα had constitutive activation of RelA and a gene expression profile consistent with NF-κB activation; development of AP in these mice was attenuated and trypsin activation was impaired. However, AP was fully induced in mice with pancreas-specific deletion of IκBα and RelA. By using genome-wide expression analysis, we identified a cluster of NF-κB-regulated genes that might protect against the development of AP. The serine protease inhibitor 2A (Spi2a) was highly up-regulated in IκBα-deficient mice. Lentiviral-mediated expression of Spi2A reduced the development of AP in C57BL/6 and RelA-deficient mice. However, we did not correlate any variants of alpha-1-antichymotrypsin, the human homologue of Spi2a, with acute or chronic pancreatitis. CONCLUSIONS: Pancreas-specific deletion of IκBα results in nuclear translocation of RelA and reduces AP induction and trypsin activation in mice after administration of cerulein or L-arginine. Constitutive activation of RelA up-regulates Spi2A, which protects mice against the development of AP.