Trastuzumab administration during pregnancy: a systematic review and meta-analysis

Landmark studies have established trastuzumab in the treatment of HER2-positive breast cancer. The present systematic review and meta-analysis aims to synthesize all available data, so as to evaluate the safety of trastuzumab during pregnancy. This study was performed in accordance with the PRISMA guidelines. All studies that examined the safety of trastuzumab administered during pregnancy, regardless of sample size, were considered eligible. Overall, 17 studies (18 pregnancies; 19 newborns) were included. In 55.6 % of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration was 14.8 weeks. Occurrence of oligohydramnios/anhydramnios (O/A) was the most common (61.1 %) adverse event. 73.3 % of pregnancies exposed to trastuzumab during the second/third trimester were complicated with O/A; the respective rate of pregnancies exposed to trastuzumab exclusively during the first trimester was 0 % (P = 0.043). The mean GA at delivery was 33.8 weeks, and the mean weight of babies at delivery was 2,261 gr. In 52.6 % of cases, a healthy neonate was born. At the long-term evaluation, all children without problems at birth were healthy with a median follow-up of 9 months, while four out of nine children facing troubles at birth were dead within an interval ranging between birth and 5.25 months. All children exposed to trastuzumab in utero exclusively in the first trimester were completely healthy at birth. Trastuzumab should not be administered during pregnancy. However, for women who become accidentally pregnant during trastuzumab administration and wish to continue pregnancy, trastuzumab should be stopped and pregnancy could be allowed to continue.     

Periodontitis and atherogenesis: causal association or simple coincidence?

OBJECTIVES: The aim of this study was to assess the systemic effects of treating severe widespread periodontitis in a population of otherwise healthy individuals by examining treatment associated changes in markers of inflammation that are also implicated in cardiovascular atherosclerotic diseases. The potential impact of specific polymorphisms in cytokine genes known to influence both periodontitis and cardiovascular diseases was also examined. MATERIALS AND METHODS: A convenience sample of patients affected with severe generalised periodontitis was enrolled into a prospective single blind longitudinal intervention trial with a 6 months follow-up. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assessed by high-sensitivity assays. Serological and clinical periodontal parameters were evaluated at baseline, 2 and 6 months after completion of non-surgical periodontal therapy. Results: In the 94 subjects that completed this pilot trial improvements in all clinical periodontal parameters were achieved. These were accompanied with significant reductions in serum IL-6 and CRP concentrations. In a multivariate model, serum CRP levels were significantly associated with the outcome of periodontal treatment after correcting for potential covariates (age, body mass index, gender, smoking) and polymorphisms in the IL-6 (-174 C/G) and IL-1A (-889) genes. A median decrease in serum CRP of 0.5 mg/l (95% CI 0.4-0.7 mg/l) was observed 6 months after completion of periodontal therapy in this population. Subjects with above average response to periodontal therapy (<30 residual pockets and <30% of sites bleeding on probing) accounted for the observed improvement in serum CRP. CONCLUSIONS: Control of periodontitis, achieved with non-surgical periodontal therapy, significantly decreased serum mediators and markers of acute phase response. The significance of the serum response was associated with the half of the population that responded better to non-surgical periodontal therapy. The results of this pilot study indicate that severe generalised periodontitis causes systemic inflammation. This is consistent with a causative role of periodontitis in atherogenesis.     

The Rotaglide mobile-bearing total knee arthroplasty: no difference between cemented and hybrid implantation

Purpose

The optimal fixation of the Rotaglide total knee arthroplasty’s (TKA) components is controversial. It is hypothesized that the hybrid fixation (cementless femoral component) in a mobile-bearing TKA system might cause increased rate of loosening—especially in the femoral part—and finally failure of the arthroplasty. Consequently, the aim of this study was to compare the survival and revision rates and also the clinical and radiological outcomes of the cemented and hybrid fixation of the Rotaglide TKA.

Methods

One hundred patients, who underwent TKA with the Rotaglide prosthesis, were randomly placed in two groups. In the first group, the prosthesis was cemented, and in the second group, the hybrid technique was used. Revision and mortality rates were compared after 8–12 years of follow-up. Knee and Osteoarthritis Outcome Score (KOOS) questionnaire and the Knee Society Roentgenographic Evaluation and Scoring System were used to demonstrate clinical and radiographic differences.

Results

There were no statistically significant differences in revision (n.s.) or mortality (n.s.) rates between the two treatment arms. The clinical outcome at the time of last follow-up (mean 9.5 years, SD ±1.4) ranged from very good to excellent (77.8 ± 17.5 for the cemented group and 77.2 ± 20.4 for the hybrid group). No statistically significant differences in all KOOS subscales. Radiographs showed no significant difference in prosthesis alignment and no evidence of loosening between groups.

Conclusion

The hypothesis that the hybrid fixation in a mobile-bearing TKA system might cause increased rate of loosening and finally failure of the arthroplasty was not confirmed. The fixation technique (cemented or hybrid) had no influence on the prosthesis’s survivorship, and also on mortality rates, clinical and radiographic outcomes in a mean follow-up time of 9.5 ± 1.4 years. The Rotaglide TKA is a safe and reliable prosthesis regardless the fixation technique.

Level of evidence

Prospective comparative study, II.     

Quantification of Tumor Microvascularity with Respiratory Gated Contrast Enhanced Ultrasound for Monitoring Therapy

The aim of this feasibility study was to evaluate the response to cytotoxic and antiangiogenic treatment of colorectal liver metastasis using respiratory gated contrast enhanced ultrasonography. Seven patients were monitored with contrast enhanced ultrasound. Sulfur hexafluoride filled microbubbles (SonoVue; Bracco S.P.A., Milan, Italy) were used as contrast agent and the scans were performed with a nonlinear imaging technique (power modulation) at low transmit power (MI=0.06). The mean image intensity in the metastatic lesion and in the normal liver parenchyma were measured as a function of time and time-intensity curves from linearized image data were formed. A novel respiratory gating technique was utilized to minimize the effects of respiratory motion on the images. A reference position of the diaphragm (or other echogenic interface) was selected and all frames where the diaphragm deviated from that position were rejected. The wash-in time (start of enhancement to peak) of metastasis and adjacent normal liver parenchyma was measured from time-intensity curves. The ratio of wash-in time of the lesion to that of the normal parenchyma (WITR) was used to compare the perfusion rate. In a reproducibility study (five patients), the average deviation of WITR was found to be 9%. There was an increase in the WITR for patients responding to treatment (mean WITR increase of 17% after first dose of treatment and 75% at the end of the therapy). In four out of five patients (80%) responding to therapy WITR predicted their response from the first treatment. All six patients that responded to therapy by the end of the therapy cycle (6–9 doses) were correctly predicted by using WITR. The WITR may be a new surrogate marker indicative of early tumor response for colorectal cancer patients undergoing cytotoxic and antiangiogenic therapy. (E-mail: maverk@ucy.ac.cy)     

Assessing the knowledge of bronchial asthma among primary health care physicians in Crete: A pre- and post-test following an educational course

Aim  

To assess the level of knowledge for bronchial asthma of the primary healthcare physicians serving a rural population on the island of Crete, both before and immediately after a one-day educational course.     

Endoscopic Fibrin Sealing of High-output Non- healing Gastrocutaneous Fistulas after Vertical Gastroplasty in Morbidly Obese Patients

Background: Fibrin glue was used in a various fields of surgery during the last 15 years, but its use has not been reported in bariatric surgery yet. Methods: In 2 out of 215 morbidly obese patients who underwent vertical banded gastroplasty, a nonhealing gastrocutaneus fistula (GCF) developed. In both patients sepsis occurred, caused by a leak of the posterior gastric wall, which was managed by means of an unsuccessful reoperation. After that, sepsis recurred, and a non-healing GCF developed. These GCF were managed endoscopically by the use of a fibrin sealant (Beriplast P 2 ml set, Behring?) as a tissue adhesive. Results: One injection was needed for the first case and six for the second in achieving full healing of the fistulas. No evidence of fistula was observed at gastroscopy 3 and 24 months after the end of therapy. Conclusions: Endoscopic use of human fibrin sealant is simple, safe, effective and in some cases life-saving. This is a therapeutic option in high output GCF in morbidly obese patients.