Radiofrequency Ablation of Invasive Breast Carcinomas: A Phase II Trial

Background Local ablative therapy of breast cancer represents the next frontier in the minimally invasive breast-conservation treatment. We conducted a phase II trial to evaluate radiofrequency ablation (RFA) of invasive breast carcinomas. Methods Consecutive patients from two Mexican Institutions with invasive breast cancers < 4 cm, with no multicentric tumors and no previous chemotherapy were included in this trial. Under ultrasound guidance, the tumor and a 5 mm margin of surrounding breast tissue were ablated with saline-cooled RFA electrode followed by surgical resection. Routine pathologic analysis and viability evaluation with NADPH-diaphorase stain were performed to assess tumor ablation. Procedure-associated morbidity was recorded. Results Twenty-five patients were included. Mean patient age was 55.3 years (range 42–89 years). Mean tumor size was 2.08 cm (range 0.9–3.8 cm). Fourteen tumors (56%) were <2 cm. The mean ablation time was 11 minutes using a mean power of 35 W. During ablation, the tumors become progressively echogenic that corresponded with the region of severe RFA injury at pathologic examination. Of the 25 patients treated, NADPH stain showed no evidence of viable malignant cells in 19 patients (76%), with significant difference between tumors <2 cm (complete necrosis in 13 of 14 cases, 92.8%) vs. those >2 cm (complete necrosis 6 of 11 cases, 54.5%) (P < .05). No significant morbidity was recorded. Conclusions RFA is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. Further studies are necessary to optimize the technique and evaluate its future role as local therapy for breast cancer.     

Pathophysiology of Takotsubo Cardiomyopathy: Reopened Debate

Takotsubo cardiomyopathy (TTC), a persistently obscure dysfunctional condition of the left ventricle, is uniquely transient but nevertheless dangerous. It features variable ventricular patterns and is predominant in women. For 30 years, pathophysiologic investigations have progressed only slowly and with inadequate focus.It was initially proposed that sudden-onset spastic obliteration of coronary flow induced myocardial ischemia with residual stunning and thus TTC. Later, it was generally accepted without proof that, in the presence of pain or emotional stress, the dominant mechanism for TTC onset was a catecholamine surge that had a direct, toxic myocardial effect.We think that the manifestations of TTC are more dynamic and complex than can be assumed from catecholamine effects alone. In addition, after reviewing the recent medical literature and considering our own clinical observations, especially on spasm, we theorize that atherosclerotic coronary artery disease modulates and physically opposes obstruction during spasm. This phenomenon may explain the midventricular variant of TTC and the lower incidence of TTC in men. We continue to recommend and perform acetylcholine testing to reproduce TTC and to confirm our theory that coronary spasm is its initial pathophysiologic factor. An improved understanding of TTC is especially important because of the condition''s markedly increased incidence during the ongoing COVID-19 pandemic.     

DCTN1 mutations are implicated in multiple neurodegenerative disorders

Exome sequencing identifies the cause of a mendelian disorder Ng et al. (2009) Nature Genetics. Advanced online publication.     

Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes

Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes—cleft lip alone (CL) and CL plus cleft palate (CLP)—are typically grouped into a single phenotype for genetic analysis (i.e., CL with or without cleft palate, CL/P). However, mounting evidence suggests there may be unique underlying pathophysiology and/or genetic modifiers influencing expression of these two phenotypes. To this end, we performed a genome‐wide scan for genetic modifiers by directly comparing 450 CL cases with 1,692 CLP cases from 18 recruitment sites across 13 countries from North America, Central or South America, Asia, Europe, and Africa. We identified a region on 16q21 that is strongly associated with different cleft type (P  = 5.611 × 10^?8). We also identified significant evidence of gene–gene interactions between this modifier locus and two recognized CL/P risk loci: 8q21 and 9q22 (FOXE1 ) (P  = 0.012 and 0.023, respectively). Single nucleotide polymorphism (SNPs) in the 16q21 modifier locus demonstrated significant association with CL over CLP. The marker alleles on 16q21 that increased risk for CL were found at highest frequencies among individuals with a family history of CL (P  = 0.003). Our results demonstrate the existence of modifiers for which type of OFC develops and suggest plausible elements responsible for phenotypic heterogeneity, further elucidating the complex genetic architecture of OFCs.     

Laparoscopic cholecystectomy: Histopathological analysis of metabolic associated fatty liver disease and fibrosis

IntroductionMetabolic (dysfunction) associated fatty liver disease (MAFLD) and cholelithiasis are highly prevalent and are associated with common risk factors such as obesity, hypertriglyceridemia, and fasting glucose levels; however, it is not clear whether cholelithiasis is associated with MAFLD or fibrosis.ObjectiveTo determine MAFLD severity and associated risk factors in patients diagnosed with cholelithiasis.Materials and methodsObservational, cross-sectional and prolective study (from October 2018 to March 2020) of patients undergoing elective laparoscopic cholecystectomy with liver biopsy, excluding other causes of hepatic disease or significant alcohol consumption. MAFLD detection was based on histology using the Kleiner score and one of the following criteria: overweight/obesity, T2DM, or evidence of metabolic dysregulation. The AST to Platelet Ratio Index, the NAFLD Fibrosis Score, the fibrosis-4 index and the hepatic steatosis index were performed to assess the relationship of non-invasive hepatic scores with histopathology.Results80 patients median age (interquartile range) was 42 (18) years, with a BMI of 27.9 (6.11) Kg/m². Of all patients, 58.8% had MAFLD, 78.7% were women, and 13.8% had the severe form (formerly named NASH). No substantial correlation between biochemical parameters and histopathological analysis of MAFLD and fibrosis was observed.ConclusionBecause cholelithiasis and MAFLD are highly prevalent diseases, it is essential to conduct studies on the relationship between both pathologies. Currently, liver biopsy is the best diagnostic method since the predictive biochemical models did not show a substantial correlation to classify MAFLD. Its early detection is relevant since a considerable percentage of advanced fibrosis (8.7%) was found.     

Pediatric Liver Transplant Outcome Using Severe Hypernatremic Donors

IntroductionPediatric liver transplantation is limited by donation. In the last 5 years, urgent conditions have forced transplant teams to accept donors with minor suboptimal conditions, termed “extended donor criteria.” Among those, the risk of using severe hypernatremic donors (SHD) for liver transplant is not yet well established. The aim of this study is to report the outcome of pediatric patients receiving grafts from SHD.MethodsClinical records of patients transplanted in the last 3 years at Hospital Luis Calvo Mackenna, Santiago, Chile, were reviewed. Outcome was evaluated in terms of patient and graft survival and complications potentially associated to the donor condition.ResultsFive of 33 deceased donor transplants presented with SHD. All recipients were waiting transplant in an acute condition, one of them in acute liver failure (ALF). No living related donor was available. Donors' serum sodium was 169 to 193 mEq/L before medical management and between 157 and 172 mEq/L at procurement. One patient died from sepsis related to biliary complications, and the patient suffering ALF developed primary graft nonfunction, received a second transplant 2 weeks later, and recovered to stable medical condition. No other complication was registered in these patients.DiscussionOur findings allow us to postulate that hypernatremic deceased donors may be used for pediatric liver transplant under special circumstances.     

Forced oscillation measurements do not affect upper airway muscle tone or sleep in clinical studies.

Upper airway obstruction in the sleep apnoea/hypopnoea syndrome (SAHS) can be easily assessed by measuring respiratory impedance with the forced oscillation technique (FOT). This methodology has been proposed as a useful clinical tool both for the diagnosis of sleep breathing disorders and for continuous positive airway pressure (CPAP) titration. However, previous studies suggest that the application of high-frequency pressure oscillation to the upper airway may induce changes in the electroencephalogram (EEG) or upper airway muscle function. The effect of FOT measurements on upper airway muscle tone and EEG in clinical sleep studies was examined. Seven patients with moderate SAHS were included (age: 54+/-11 yrs; apnoea/hypopnoea index: 43+/-21 events x h(-1); body mass index: 30+/-2 kg x m(-2)). Genioglossus surface electromyogram activity (EMGgg) and EEG signal were analysed with and without FOT application (frequency: 5 Hz and 30 Hz; peak-to-peak pressure oscillation: 1 cmH2O) during stable sleep. Measurements were carried out in two different situations. Step 1: applying FOT during episodes of obstructive events or flow limitation; and step 2: during prolonged periods of normal breathing at optimal CPAP. The root mean square of EMGgg activity and fast Fourier analysis (alpha and delta bands) of the EEG signal were performed. The application of FOT did not increase EMGgg activity in any of the situations studied. In addition, no evidence of the effects on EEG was found: alpha/delta relationship: awake:0.70, baseline sleep:0.13, FOT(5 Hz):0.18, FOT(30 Hz):0.11. The presented results suggest that the use of forced oscillation technique over the ranges of frequency and amplitude proposed for clinical sleep studies does not induce changes in upper airway muscle activity and neurological variables in patients with sleep apnoea/hypopnoea syndrome.