Clinical and immunological outcomes of SARS-CoV-2-infected vaccine responders, vaccine non-responders, and unvaccinated patients evaluated for neutralizing monoclonal antibody treatment at a single German tertiary care center: a retrospective cohort study with prospective follow-up.

PURPOSE: This study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status. METHODS: In this retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients' initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs. RESULTS: In total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs. CONCLUSION: VNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable.

The influence of the morphometric parameters of the intercondylar notch on occurrence of meniscofemoral ligaments.

BACKGROUND: The purpose of this study was to examine the existence of correlation between the morphometric parameters of the intercondylar notch of the femur and the occurrence of meniscofemoral ligaments (MFLs) and if there is any relationship in the running angle (RA) value between narrowed and normal sized intercondylar notch. MATERIALS AND METHODS: Coronal, sagittal and horizontal magnetic resonance (MR) images of 90 patients with specified exclusion criteria were included in this study. The c2 test was used for statistical analysis. In our research either one or both MFLs were identified in 70 (77.8%) of the 90 coronal MR images. In normal sized intercondylar notch, MFLs was seen in 39 (43.3%) cases and on 31 (34.4%) MR images with narrowed intercondylar notch. RESULTS: A significant correlation was established between the occurrence of the MFL and morphometric parameters of the intercondylar notch (p < 0.05). In normal sized intercondylar notch, 12 posterior meniscofemoral ligaments (pMFLs) of type I were detected (RA value 42°), 8 of type II (RA value 33°), 5 of type III (RA value 23°) and two were of indeterminate type, whilst 10 anterior meniscofemoral ligaments (aMFLs) were of type I (RA value 39°), 7 of type II (RA value 31°), 2 of type III (RA value 25°) and the remaining 6 were indeterminate. In narrowed intercondylar notch, 10 ligaments of pMFLs were of type I (RA value 30°), 8 of type II (RA value 25°), 5 of type III (RA value 20°), 10 ligaments of aMFLs were of type I (RA value 35°) and 9 were indeterminate. Statistically significant differences in the value of the running angle of pMFL type I and of type II were evaluated between two groups with different shaped intercondylar notch (p < 0.05). CONCLUSIONS: The results shown in our study may be useful in medical clinical practice, reconstructive surgery, interpretation of knee MR images as well as genetic research.

Concomitant multiple anomalies of renal vessels and collecting system.

Although anomalies of renal vessels and collecting system are relatively frequent, their concomitant occurrence is a rare event. During dissection of a 75-year-old male formalin-embalmed cadaver, we found multiple variations in the renal vessels and renal collecting system. Both kidneys were normal in size and anteriorly malrotated, with duplex collecting system and duplex ureter. One ureter drained the upper part of the kidney and the second ureter drained the lower part of the kidney. Superior and inferior collecting systems were separated by renal parenchyma. The right kidney had two renal arteries, the first renal artery (main renal artery) originating from the abdominal aorta, passing behind the inferior vena cava (IVC) and entering the kidney through the superior and inferior renal hilum. The second artery was the inferior polar artery. In addition, the right kidney had two renal veins as well. Three renal tributaries emerged from the upper and lower portion of the right renal hilum, and they joined to form the main renal vein which drained into the IVC. The lower renal vein was the inferior polar vein. The left kidney had four renal arteries (two hilar arteries and two polar arteries). The main left renal vein emerged from both superior and inferior left renal hilum, passed in front of the abdominal aorta and drained into the IVC. The left kidney also had the inferior polar vein which was divided behind the aorta (retro aortic vein) into two venous trunks. These venous trunks drained separately into posteromedial aspect of the IVC. Finally, the right testicular vein was formed by two tributaries and drained into the IVC, whereas the two left testicular veins drained separately into the left main renal vein.

An activating mutation of AKT2 and human hypoglycemia.

Pathological fasting hypoglycemia in humans is usually explained by excessive circulating insulin or insulin-like molecules or by inborn errors of metabolism impairing liver glucose production. We studied three unrelated children with unexplained, recurrent, and severe fasting hypoglycemia and asymmetrical growth. All were found to carry the same de novo mutation, p.Glu17Lys, in the serine/threonine kinase AKT2, in two cases as heterozygotes and in one case in mosaic form. In heterologous cells, the mutant AKT2 was constitutively recruited to the plasma membrane, leading to insulin-independent activation of downstream signaling. Thus, systemic metabolic disease can result from constitutive, cell-autonomous activation of signaling pathways normally controlled by insulin.

Pharmacokinetics of ibuprofen sodium dihydrate and gastrointestinal tolerability of short-term treatment with a novel, rapidly absorbed formulation.

OBJECTIVE: This paper describes four studies investigating the dissolution, plasma pharmacokinetics and safety of a novel, fast-acting ibuprofen formulation, ibuprofen sodium dihydrate. MATERIAL AND METHOD: Four separate studies investigated: the in vitro dissolution rates of ibuprofen sodium dihydrate (at pH 1.2, 3.5 and 7.2); the bioavailability of ibuprofen sodium dihydrate (in two pharmacokinetic studies; combined n = 38) compared with conventional ibuprofen, ibuprofen lysinate, ibuprofen arginate and ibuprofen liquagels (all 2 x 200 mg ibuprofen); and the gastroduodenal tolerance of ibuprofen sodium dihydrate and ibuprofen arginate (both 2 x 200 mg ibuprofen t.i.d.) in an endoscopy safety study, where endoscopy was performed at baseline and at the end of each treatment period using a five-point scale to assess the integrity of the gastric and duodenal mucosa. RESULTS: Ibuprofen sodium dihydrate dissolved significantly more rapidly at pH 1.2, 3.5 and 7.2 than conventional ibuprofen, ibuprofen lysinate and ibuprofen liquagels. Ibuprofen sodium dihydrate had similar C(max) to ibuprofen lysinate and ibuprofen liquagels and significantly higher Cmax than conventional ibuprofen (p = 0.002). The mean plasma concentration for ibuprofen sodium dihydrate was significantly higher than for conventional ibuprofen (p = 0.028) 10 minutes post-dose and the t(max) for ibuprofen sodium dihydrate was reached significantly earlier than for conventional ibuprofen (p = 0.018). All three formulations were bioequivalent according to the acceptable boundaries (90% confidence intervals). No statistically significant difference was observed between the ibuprofen formulations in terms of adverse events and specifically with respect to hemorrhagic scores; 41 (46.0%) adverse events (AEs) occurred after administration of ibuprofen sodium dihydrate, and 46 (52.9%) after ibuprofen arginate. One occurrence of an invasive ulcer was observed after administration of ibuprofen arginate. CONCLUSIONS: The new formulation of ibuprofen sodium dihydrate dissolves quickly in vitro, has the same extent of absorption as other fast-acting ibuprofen formulations, and is absorbed into plasma more rapidly than conventional ibuprofen. In addition, the present studies suggest that the tolerability and safety profile of ibuprofen sodium dihydrate is comparable to existing ibuprofen formulations.

Comparison of efficacy and safety of two doses of two different polyethylene glycol-based laxatives in the treatment of constipation.

AIM: To compare standard and maximum daily doses of polyethylene glycol 3350 plus electrolytes (Transipeg) and polyethylene glycol 4000 (Forlax) in a multicentre, double-blind, randomized, parallel-group study. METHODS: Ambulatory patients with idiopathic chronic constipation were randomized to receive Forlax (10 or 20 g) or Transipeg (5.9 or 11.8 g) for 1 month. The primary efficacy end-point was stool frequency. Secondary efficacy parameters included stool consistency, date of occurrence of first motion, straining on defecation, rectal evacuation, abdominal pain and distension. Adverse events were recorded. RESULTS: Stool frequency was significantly increased compared with baseline in all treatment groups (P = 0.0001). Most patients (> or = 67.3%) had their first stool within 1 day of starting treatment. Stool consistency significantly improved compared with baseline in all treatment groups (P = 0.0001). The percentage of patients with normal stool consistency was significantly higher for standard-dose Transipeg vs. both maximum-dose treatments (P < 0.01). Other secondary parameters were also significantly improved compared with baseline in all treatment groups (P = 0.0001). All medications were well tolerated. CONCLUSIONS: Standard-dose Transipeg (5.9 g) normalized stool consistency with less semi-liquid or liquid stools than maximum-dose Transipeg and Forlax, with a non-significant trend towards less semi-liquid or liquid stools than standard-dose Forlax.

Human red cell adenylate kinase polymorphism in Srbija, Yugoslavia.

Red cell adenylate kinase (AK) phenotypes were determined in 283 unrelated adults in Srbija (Yugoslavia). The gene frequencies observed were: AK1 0.961 and AK2 0.039. The adenylate kinase activity was estimated in all haemolysates; no significant differences were found between individuals of different phenotypes.