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Biomedical subjects

S Kloss

Publications and source records attributed to S Kloss.

7 recordsLinked to original sources

Outcomes of elacestrant in patients with ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer who received prior endocrine therapy and cyclin-dependent kinase inhibitor in a real-world setting.

BACKGROUND: Real-world data analyses show durable benefits with elacestrant, with or without prior treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). This cohort focused on patients with ER-positive/HER2-negative estrogen receptor 1 (ESR1)-mutated metastatic breast cancer (mBC) treated with elacestrant after at least one line of endocrine therapy (ET) combined with CDK4/6i (N = 281). PATIENTS AND METHODS: Claims data from the Komodo Research Dataset linked with Foundation Medicine clinical-genomics data were used. Primary outcome was median time-to-next-treatment (mTTNT). RESULTS: In patients with ER-positive/HER2-negative ESR1-mutated mBC who received one to two prior lines of ET + CDK4/6i (n = 108), mTTNT with elacestrant was 8.2 months [95% confidence interval (CI) 6.0-12.2]. In patients who received one to two prior lines of ET + CDK4/6i for ≥12 months (n = 85), mTTNT was 9.0 months (95% CI 7.7-13.7), including an mTTNT of 12.2 months (95% CI 9.0-not reached) in those who received one prior line of ET (n = 31). In patients with liver and/or lung metastasis (n = 169), mTTNT was 6.9 months (95% CI 5.8-8.3), whereas it was 7.4 months (95% CI 5.6-12.9) in patients with brain metastasis (n = 68). In patients with coexisting ESR1- and phosphoinositide 3-kinase-pathway-mutated tumors (n = 115), mTTNT was 6.1 months (95% CI 5.0-8.1). CONCLUSIONS: Elacestrant showed durable benefits in patients with ER-positive/HER2-negative ESR1-mutated mBC previously exposed to at least one line of ET + CDK4/6i, reinforcing the role of elacestrant as a potential first-choice option for patients with endocrine-sensitive tumors.

ESR1 mutation↗

[Results of surgery for congenital Brown's syndrome].

BACKGROUND: There are various surgical procedures for the treatment of congenital ("true") Brown's syndrome. We have evaluated the effects of a superior oblique tendon recession. PATIENTS AND METHODS: In a retrospective study, we evaluated the files of 22 patients who received surgery for congenital Brown's syndrome in our department. A recession of the superior oblique tendon was performed, when there was a hypotropia in primary position with an abnormal head posture and a significant elevation deficit in adduction, and when these findings did not improve spontaneously. The squint angles (alternate prism and cover test), the monocular motility and the abnormal head posture at distance fixation were assessed. The measurements were performed 1 day before and 3 months after surgery. Thirteen patients were examined 2 - 10 years after surgery. RESULTS: At the time of surgery, the patients were 4 - 17 years old (median 7 years), 13 were male, in 15 patients, the right eye was concerned. Eight patients had an additional esotropia, one patient was exotropic. The vertical deviation in straight gaze was 0 - 12 deg (median 7 deg). The elevation of the eye was restricted to - 10 deg (below horizontal) to 15 deg (median 0 deg) in adduction and to 10 - 35 deg (median 25 deg) in abduction. Sixteen patients had an abnormal head posture. The superior oblique tendon was recessed by 10 mm, in some patients with an additional loop (6x0 polyester). Nine patients received simultaneous surgery for their eso/exotropia. At the end of the operation, the elevation of the eye in adduction (forced duction test) was free. Three months postoperatively, the vertical deviation was 0 - 6 deg (median 1 deg). Twelve patients did not show any abnormal head posture. Inspite of free passive motility, the monocular elevation in adduction was only slightly improved to - 5 to 15 deg (median 5 deg). At the late control, the hypotropia (0 - 4 deg, median 0 deg) and the elevation in adduction (5 - 35 deg, median 15 deg) were significantly improved. CONCLUSION: The recession of the superior oblique tendon is an effective and safe surgical procedure for congenital Brown's syndrome. The efficiency of the procedure is individually variable. Presumably, this variability was caused by the heterogenous etiology of Brown's syndrome rather than by surgical technique. The hypotropia and the abnormal head posture were reduced immediately after surgery, while the delayed improvement of active elevation in adduction often remained incomplete. Postoperative forced upgaze training may be beneficial.

Adolescent↗

[Studies on the recovery of pharmaceutical drug substances from surfaces made of defined stainless-steel alloys].

Facilities for the manufacturing of pharmaceutical drug substances on the pilot-plant and the industrial scale as well as chemical reactors and vessels used for chemical work-up mainly consist of alloyed stainless steel. The influence of the alloy composition and the surface condition, i.e. of the roughness of the stainless-steel materials, on the adsorption of structurally diverse steroidal substances and, hence, on the quality of the products was studied. In general, stainless-steel alloys with smooth, not so rough surfaces are to be favored as reactor material. However, it was demonstrated in this study that, on account of the weak interaction between active substances and steel materials, mechanically polished materials of a medium roughness up to approx. 0.4 microm can be employed instead of the considerably more cost-intensive electrochemically polished stainless-steel surfaces. The type of surface finishing up to a defined roughness, then, has no influence on the quality of these pharmaceutical products. Substances that, because of their molecular structure, can function as "anions" in the presence of polar solvents, are adsorbed on very smooth surfaces prepared by electrochemical methods, forming an amorphous surface film. For substances with this structural characteristics, the lower-cost mechanically polished reactor materials of a medium roughness up to approx. 0.5 microm should be used exclusively.

Algorithms↗

[Dissociated near reflex and accommodative convergence excess].

We report on an 8-year-old boy whose near reflex could be elicited exclusively when the left eye was fixing (LF) but not when the right eye was fixing (RF). With RE +1.25/-1.25/169 degrees and LE +1.0/-0.75/24 degrees, the visual acuity was 1.0 OU at 5 m and RE 0.5, LE 1.0 at 0.3 m improving to 1.0 OU by a near addition of 3.0 D. Stereopsis was 100 degrees (Titmus test). The prism and cover test revealed an esophoria of 4 degrees at 5 m. At 3 m there was an esophoria of 6 degrees (RF) and an esotropia of 28 degrees (LF), compensating to an esophoria of 3 degrees (RF/LF) with a near addition of 3.0 D. Accommodation and the pupillary near reaction (OU) were hardly elicitable during RF. During LF, retinoscopy revealed an accommodation of 8 D (OU) and the pupils constricted normally. Correction by bifocal glasses yielded orthotropia with random dot stereopsis at near.

Accommodation, Ocular↗

Epilepsy surgery in children with focal cortical dysplasia (FCD): results of long-term seizure outcome.

The purpose of this study was to assess the effect of epilepsy surgery on seizure outcome in children and adolescents under 18 years with intractable epilepsy due to focal cortical dysplasia. We analysed clinical data, such as age at seizure onset, epilepsy course, localisation of focus from presurgical evaluation, MRI, tissue pathology and seizure outcome in 68 patients 6 months to 9 years after epilepsy surgery. Seizure outcome was classified according to the Engel classification. Mean age at seizure onset was 7 months, ranging from the first days of life to 7 years. All patients had medically intractable epilepsy. Localisation of the lesion was predominantly extratemporal: posterior (uni- or multilobar) 43 %, frontal without central region 26 %, multilobar involving central area 19 % and temporal in 12 %. MRI signs typically seen in cortical dysplasia (FCD) such as localised blurring of gray-white matter junction was found in 68 %, dysgyria in 62 %, thickening of the cortical ribbon in 46 % and T2 signal elongation of the subcortical white matter in 40 % of the patients' MRI. Age at surgery ranged from 5 months to 16 years; 14 patients were under 2 years when operated on. In 34 patients (6 patients under 3 years) subdural grid electrode evaluation was performed prior to surgery. Pathology revealed focal cortical dysplasia without balloon cells (type I) in 60 %, FCD of the balloon cell subtype (type II) in 40 % of the specimens. Postoperative complications were subdural hygroma in 5 and an increased motor deficit in 2 patients. Up to two years after epilepsy surgery 50 % of the children were seizure free (Engel class I), 10 % Engel class II, 33 % Engel class III and 7 % unchanged (Engel class IV). Long-term seizure outcome (> 3 years post surgery) in 32 patients showed similar results (class I 50 %, class II 19 %, class III 28 %, class IV 3 %). Complete resection of the dysplastic lesion was significantly correlated with favorable seizure outcome, whereas seizure outcome was not significantly different in patients with mild (type I) or balloon cell (type II) FCD. Children operated after 6 years of age had no better outcome than children operated in infancy or at preschool age. Epilepsy surgery resulted in good (class I and II) seizure control in 60 % of children with intractable epilepsy due to focal cortical dysplasia.

Adolescent↗

Control of proven pulmonary and suspected CNS aspergillus infection with itraconazole in a patient with chronic granulomatous disease.

An 11-year-old boy with chronic granulomatous disease caused by cytochrome b deficiency developed right upper lung lobe aspergillosis. Intracerebral lesions developed on maximum doses of flucytosine and amphotericin B. Treatment with 16 mg/kg oral itraconazole was followed by a dramatic clinical improvement and almost complete disappearance of the intracerebral lesions. Plasma itraconazole levels were between 40 and 3440 ng/ml depending on concomitant medication. Toxicity was restricted to transient elevation of alkaline phosphatase and gamma glutamyl transferase. We conclude that further trials with itraconazole are justified in high risk patients in whom conventional therapy has failed.

Antifungal Agents↗