Enforcing surveillance of antimicrobial resistance and antibiotic use to drive stewardship: experience in a paediatric setting.

BACKGROUND: Antibiotic stewardship (AS) interventions in paediatrics are still not standardized regarding methodology, metrics, and outcomes. We report the results of an AS intervention in the paediatric area based on education and guideline provision via an electronic App. MATERIALS AND METHODS: The AS intervention was conducted in 2021 through observation, education, audit and feedback and provision of an electronic App (Firstline.org) to support antibiotic prescription based on local susceptibility data. The primary outcome was the antibiotic consumption in the 12 months following the intervention (year 2022) compared with a historical 12-month control (year 2019) via an interrupted time series analysis. Secondary outcomes were appropriateness of therapy, length of stay, 30-day readmission, transfers to the paediatric intensive care unit, in-hospital mortality, and prevalence of antimicrobial resistance (AMR). RESULTS: During the post-intervention phase, 29 cross-sectional audits and feedback were conducted including 467 patients. Prescriptions were appropriate according to the guidelines in 85.7% of cases, with a stable trend over time. A significant decrease in antibiotic consumption was measured in terms of defined daily doses per 1000 patient days (-222.13; P<0.001) and days of therapy per 1000 patient days (-452.49; P<0.001) in the post-intervention period with a clear inversion of the Access to Watch ratio (from 0.7 to 1.7). Length of stay, in-hospital mortality, intensive care unit transfers, and incidence of AMR infections remained stable, while 30-day readmission decreased from 4.9 per 100 admissions to 2.8 per 100 admissions (P<0.001). CONCLUSIONS: The intervention was associated with a significant reduction in antimicrobial consumption and an increase in the appropriateness of prescriptions. Electronic tools can be of value in promoting adherence to guidelines and ensuring the sustainability of results.

High-fat meal, systemic inflammation and glucose homeostasis in obese children and adolescents.

We aimed to assess in obese youths the relationships between interleukin-6 (IL-6), fat meal-induced endotoxemia and glucose homeostasis. Twenty obese children/adolescents (9-17 years old, 11 boys) underwent a standard oral glucose tolerance test and, 7-14 days later, a 5-h fat meal test (fat=69% of energy, saturated/monounsaturated/polyunsaturated fatty acids=31.5%/35%/33.5%), with serial measures of IL-6 and two markers of lipopolysaccharide (LPS) exposure and translocation, LPS-binding protein (LBP) and soluble CD14 (sCD14). IL-6 correlated not only with basal (homeostatic model assessment-insulin resistance) but also with post-prandial (Matsuda index) insulin sensitivity (r=0.61 (0.24-0.82), P=0.005, r=-0.53 (0.12-0.78), P=0.03, respectively). IL-6 did not change after the meal whereas LBP and sCD14 decreased significantly, indicating LPS translocation. Neither basal sCD14 and LBP nor their incremental concentrations correlated with IL-6 or glucose homeostasis. In our sample, IL-6 was associated with insulin sensitivity but not with LPS exposure, suggesting that meals with a balanced content of saturated/monounsaturated/polyunsaturated fatty acids may not be associated with LPS-induced inflammation and metabolic impairment.

Phase I/II trial of multicycle high-dose chemotherapy with peripheral blood stem cell support for treatment of advanced ovarian cancer.

Ovarian cancer is chemosensitive, but most patients with advanced disease die from tumor progression. As 25% of the patients can be cured by chemotherapy, it is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients with untreated ovarian cancer were entered in a multicenter phase I/II trial of multicycle HDCT. Median age was 46 (19-59 years); International Federation of Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual disease >1 cm after surgery. Two courses of induction/mobilization therapy with cyclophosphamide (250 mg/m2) and paclitaxel (250 mg/m2) were used to collect peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area under curve (AUC) 18-22) and paclitaxel followed by one course of carboplatin and melphalan (140 mg/m2) with or without etoposide (1600 mg/m2). Main toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating etoposide resulted in manageable toxicity (69% without grade 3/4 toxicity). One patient died from treatment-related pneumonitis. At 8 years median follow-up, median progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0 months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a multicenter setting. A European phase III trial based on this regimen is evaluating the efficacy of HDCT.

Therapy of metastatic breast cancer with humanized antibodies against the HER2 receptor protein.

The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c-erbB-2. Its overexpression, occurring in approximately one-third of all breast carcinomas, is associated with a poor prognosis. A humanized mouse antibody against HER2 has been developed by genetic engineering. Here an unspecific human IgG was connected to the recognizing mouse IgG fragment. The allergization typical for allogeneic antibodies does not take place in this context. The effectiveness of this antibody has been confirmed by two international prospective phase III trials that tested it alone and combined with chemotherapy. Both modes of application increased the response rates and the time to progression. Side-effects were rare except for a high rate of cardiac dysfunction when the antibody was combined with anthracyclines. The effectiveness and negligible side-effects of the chimeric antibody against HER2 (Herceptin) render it a valuable tool in the treatment of breast cancer.

Congenital cystic adenomatoid malformation of the lung and fetal hydrops--a case with favourable outcome.

We present a case of congenital cystic adenomatoid malformation of the lung (CCAM) diagnosed at 23 weeks of gestation with concomitant fetal hydrops. The sonographical picture of CCAM disappeared in the third trimester of pregnancy and fetal hydrops resolved under medication with digitalis to the mother. The neonate showed mild dyspnea; the prenatal diagnosis of CCAM was confirmed by chest X-ray and computed tomography. The affected lung segments were dissected at 5 days of age. The diagnosis of CCAM type III was confirmed histologically.

[Rectal resection within the scope of multi-visceral interdisciplinary resection in the pelvis]. / Die Rektumresektion im Rahmen der multivisceralen interdisziplinären Resektion im kleinen Becken.

Multivisceral resectioning is the only curative treatment for progressive carcinomas extending beyond the organ. The results of 25 consecutively operated patients are presented in this prospective observational study. Twelve patients underwent surgery for a primary tumor and 13 for a recurrence. Radical resectioning was achieved in 5 of 12 and in 3 of 13 patients. Restoration of continuity obtained in 11 of 12 and in 7 of 13 patients. Morbidity was 33% and 62%. None of the patients died from complications. An aggressive surgical approach is justifiable on account of the acceptable morbidity and mortality as well as the high rate of preserved continence through modern reconstruction procedures.

Differentiation of breast lesions by measurements under craniocaudal and lateromedial compression using a new sonographic method.

RATIONALE AND OBJECTIVES: The authors differentiate breast lesions on sonography by measurements in two compression states that are perpendicular to each other. METHODS: Diameters of 100 breast lesions were measured preoperatively under lateromedial and craniocaudal compression with a new sonographic method. This method uses mammography-identical positioning of the breast and a reference structure for detection of changes of sound amplitude and velocity by through transmission of lesions. Sizes parallel to sound propagation were corrected for abridgement by increased velocity within some lesions. For each lesion, an average length and breadth was calculated by adding sizes parallel and perpendicular to sound propagation in the two compression states and dividing it by 2. An average ratio was calculated for each lesion by dividing the average size perpendicular to sound propagation by the corrected average size along sound propagation. After obtaining histopathologic results, a threshold of ratios and other features that might help differentiate benign from malignant lesions were studied. RESULTS: Ninety-six percent of the malignant lesions appeared with ratios < or = 1.2, whereas 92% of the benign lesions had a ratio > 1.2. Further differentiation is possible by observation of velocity in lesions with ratios > 1.2. CONCLUSIONS: Examination of lesions in two compression states that are perpendicular to each other allows discrimination of benign and malignant masses by measurements in most patients.

[Insulin-like-growth-factor-binding-protein 1 (IGFBP-1) and fetal fibronectin in diagnosis of premature rupture of fetal membranes]. / Insulin like growth factor binding protein 1 (IGFBP-1) und fetales Fibronectin in der Diagnostik eines vorzeitigen Blasensprunges.

The diagnosis of a premature rupture of membranes presents no problem in the vast majority of cases. However, a reliable diagnosis is clinically not possible in about 10%. Most methods available lack the necessary sensitivity and specificity. Since the clinical consequences of a false diagnosis are considerable (overtreatment for false-positive and risk of infection for false-negative results), it is essential to clinically establish new, minimally invasive methods with higher predictive powers. In the present study we compared: the AMNI Check for detection of insulin-like growth-factor binding protein 1 (IGFBP-1); a membrane immunoassay for detection of fetal fibronectin (fFn); pH indicator paper; and, to verify a rupture of membranes in unclear cases, amniocentesis with installation of indigo carmine. The examination was performed in a group of 75 patients, 35 with and 40 without rupture of the membranes. The best results were obtained for the AMNI Check (sensitivity and negative correctness 100%, specificity and positive correctness 83%). With the same sensitivity and negative correctness, the membrane immunoassay for fFn achieved a specificity of 70% and a positive correctness of 74%. The pH indicator paper had the lowest predictive value (sensitivity 94%, negative correctness 93%, specificity 63%, positive correctness 69%). Both the AMNI Check and the test for detection of fetal fibronectin can be recommended for reliable exclusion of premature rupture of membranes. Amniocentesis should however be performed in uncertain cases with a positive test result. Nevertheless, considerable reduction of this invasive method is possible.

[137 local recurrences after breast carcinoma--a retrospective study]. / 137 Lokalrezidive nach Mammakarzinom--Eine retrospektive Untersuchung.

A retrospective study was performed to follow up the course of the disease in 137 female premenopausal and postmenopausal patients in whom local recurrence of carcinoma of the breast had occurred. Particular attention was given to the dependence of the recurrence-free interval on the tumorobiological parameters of the primary tumour. In 23% of the cases the local recurrence was an expression of generalisation of the tumour with simultaneous occurrence of distant metastases. The average recurrence-free interval was four years, but more than half of the recurrences were seen during the first two postoperative years. For the following parameters we found a statistically significant correlation with the recurrence-free interval: size of the primary tumour (p = 0.0003), the nodal status (p = 0.0006) and in this connection also the number of the metastatically involved lymphatic node level (p = 0.00001). There was also a significant correlation between the duration of the recurrence-free interval and the immunohistochemical oestrogen and progesterone receptor status (p = 0.0005) and the growth fraction (p = 0.0106) determined with the monoclonal antibody Ki67. However, although there was no correlation between recurrence-free survival and the kind of surgical primary therapy that had been employed, adjuvant therapy did exercise a decisive influence: there was significant later incidence of local recurrences (p = 0.00001) subsequent to adjuvant radiotherapy.

Successful emergency splenectomy during pregnancy in a patient with life-threatening idiopathic thrombocytopenia. Case report.

Thrombocytopenia can be a pathophysiological feature of pregnancy. In the case reported, the thrombocyte count was reduced to 1% of normal (1 x 10(9) thrombocytes/l) at 28 weeks of gestation. In chronological order, the patient showed epistaxis, macrohematuria and gingival, conjunctival, intracerebral and pulmonary bleeding. The latter was life-threatening. An emergency splenectomy was undertaken, without complications. The operation was followed by a massive increase in the thrombocyte count, reaching 200 x 10(9)/l four days later. Unfortunately, a premature rupture of the membranes, with signs of amnion infection, occurred on the seventh day. A Cesarean section was undertaken (30 weeks of gestation), without complications. Both mother and baby are in good health 10 months later. The newborn had a normal thrombocyte count at delivery and thereafter. The life-threatening hemorrhage of the mother, the delivery of an unaffected baby and the relatively quick remission after splenectomy suggest an upregulated destruction of thrombocytes by the maternal spleen. The increased level of Macrophage-Colony Stimulating Factor (M-CSF), a normal feature of pregnancy, has the potential to augment thrombocyte destruction by activating macrophages. The production of anti-thrombocyte antibodies, especially if localized in the spleen, could result in increased thrombocyte sequestration by macrophages with severe effects focused on the mother.

[Colpohysterectomy. A contribution to gynecologic geriatric surgery]. / Kolpohysterektomie. Ein Beitrag zur gynäkologischen Alterschirurgie.

From 1983 to 1992 we performed 70 interventions because of a total genital prolapse: 51 vaginal hysterectomies and four removals of the cervical stump, both combined with vaginectomy and fifteen vaginectomies of the prolapsed vaginal vault. Two patients underwent another procedure during the same anesthesia: mastectomy and treatment of an inguinal hernia respectively. The youngest patient was 59 years old and the oldest 89. Fifty-four patients were aged between 71 and 82. Thirteen women had worn a pessary before the operation. Fifty-one interventions took less than 75 minutes. Serious postoperative complications included myocardial infarction on postoperative day eight in one patient and bronchopneumonia and cardiovascular decompensation in a second patient. No case of relapsing prolapse has come to our knowledge so far. We hold hysterectomy combined with vaginectomy to be the treatment method of choice in women with total genital prolapse and no further desire of cohabitation. When performed by an experienced surgeon it is the method with the lowest potential of recurrence and therefore to be preferred to other procedures.

[Reconstruction of the breast with the m. latissimus dorsi flap after previous mastectomy]. / Wiederaufbau der Brustdrüse mit dem M. latissimus dorsi-Lappen nach erfolgter Mastektomie.

The application of this method over 11 years has shown that careful preoperative planning is crucial for the achievement of good results. There is, however, no restitutio ad integrum. The reconstructed breast will always have a rather firm structure and tend to be scarred. However, the risk of necrosis is reduced by the good vascular and nervous supply which also provides optimal conditions for mamilla reconstruction. Intra- and postoperative antibiotic treatment lowers the risk of infection.

[Tumor properties of primary tumors and local recurrence of breast cancer]. / Tumoreigenschaften von Primärtumoren und Lokalrezidiven des Mammakarzinoms.

In 137 patients suffering from a local recurrence after primary treatment of breast cancer, the features examined in a retrospective manner included: staging parameters (TNM-criteria), grading according to Bloom and Richardson, growth fraction by Ki67 positive cells as well as immunohistology and biochemical steroidreceptor-expression. In the primary tumours, a good correlation was detected between size of the tumour and lymph-node involvement, between histopathological grading and Ki67 growth fraction and between low histopathological grading and poor immunohistological and biochemical steroidreceptor content. The results of this particular study show that local recurrence is not accompanied by any significant de-differentiation, neither in its histopathological grading nor in its growth fraction nor in its steroidreceptor-status.

Local therapy of malignant pleural effusion with mitoxantrone.

Twelve patients received intrapleural instilments of the cytostatic agent mitoxantrone in a total dosage of 30 mg for locoregional palliative therapy of malignant pleural effusion. Effusion could be stopped for a mean period of 3.2 months in 11 patients.

[Cytologic cancer prevention with smears of the uterine cervix and endocervical canal in pregnancy]. / Zytologische Krebsvorsorge durch Abstriche von Portio uteri und Endozervikalkanal während der Schwangerschaft.

This study was performed to evaluate the importance of obtaining prepartum Papanicolaou smears routinely. 1,417 patients receiving pregnancy care had normal prenatal Pap smears. 88 (5.85%) had abnormal prepartum Pap smears. Thirteen (14.8%) of the abnormal smears showed squamous dysplasia, 2 (2.3%) showed an adenocarcinoma or squamous invasive carcinoma. The results of this study support the practice of performing Pap smears during prenatal care.

Mammary mycoses.

Since 1969 we have had at our hospital a special consulting room for mammary gland diseases in which we have so far seen more than 17,000 patients. Mycoses are a rare disease of the mammary glands. We are reporting below on the incidence of this disease, the mode of infection and the diagnostic possibilities within the framework of our special clinic.

[Studies into carcino-embryonic antigen (CEA) and enzyme activities of alkaline and acid phosphatase in patients with fibrocystic breast disease (author's transl)]. / Untersuchungen über das carcinoembryonale Antigen (CEA) und über die Enzymaktivitäten von alkalischer und saurer Phosphatase bei Mastopathia fibro-cystica.

CEA as well as alkaline and acid phosphatase were measured in patients with fibrocystic breast disease. The values recorded from the punctured fluids were compared to those in peripheral blood. CEA concentrations in cyst fluid were elevated in patients with proliferative breast disease, whereas no correlations could be established between alkaline and acid phosphatase, on the one hand, and various histological forms of breast disease, on the other.

[Socio-psychological factors of "family-oriented obstetrics", including "rooming in" (author's transl)]. / Sozialpsychologisehe Faktoren einer "Familienorientierten Geburtshilfe" unter Einschluss des "Roomin In".

The introduction of the "rooming in" system to maternity wards of many hospitals has been accompanied by additional demands on the hospital made by parents together with their desire tor "natural birth". Therefore, additional factors have to be taken into due consideration in the context of "family-oriented obstetrics". Interviews were made with 1,000 mothers, just after delivery to find out what they thought about certain marginal conditions in maternity advisory centres, delivery rooms, and on maternity wards. Their replies were statistically evaluated.

[Diagnosis of foetal malformations--amniographic representation of encephalomeningocele in 32nd week of pregnancy (author's transl)]. / Diagnostik fetaler Missbildungen. Amniografische Darstellung einer Enzephalo-Meningozele in der 32. Schwangerschaftswoche.

Described in this paper is prepartum diagnosis of an encephalomeningocele in the 32nd week of pregnancy. Reference is made to real case histories to expound the importance of amniography, including indications and counterindications. Complications implied in using the method are mentioned.

[Relevance of CEA in benign breast disease (author's transl)]. / Die Bedeutung des carcinoembryonalen Antigens (CEA) bei den verschiedenen Formen der Mastopathie.

Serum CEA-concentrations were measured in patients with various benign breast tumors; in addition, CEA levels were determined in the fluid of mammary cysts present. Patients with proliferating mastopathia with and without atypia had CEA values exceeding 25 ng/ml in the cystic fluid (= 46). No significant correlation existed between serum and cystic fluid concentrations. CEA determination allows for a differentiation between simple and proliferating mastopathias.