On the bounded generation of arithmetic SL2.

Let K be a number field and S be a finite set of primes of K containing the archimedean valuations. Let 𝒪 be the ring of S-integers in K Morgan, Rapinchuck, and Sury [A. V. Morgan et al, Algebra Number Theory 12, 1949-1974 (2018)] have proved that if the group of units [Formula: see text] is infinite, then every matrix in SL2(𝒪) is a product of at most 9 elementary matrices. We prove that under the additional hypothesis that K has at least 1 real embedding or S contains a finite place we can get a product of at most 8 elementary matrices. If we assume a suitable generalized Riemann hypothesis, then every matrix in SL2(𝒪) is the product of at most 5 elementary matrices if K has at least 1 real embedding, the product of at most 6 elementary matrices if S contains a finite place, and the product of at most 7 elementary matrices in general.

Single-Session Percutaneous Endovascular Mesocaval Shunt Creation and Balloon-Occluded Retrograde Transvenous Obliteration for the Treatment of Gastric Varices.

In the setting of portal hypertension, the body responds by creating portosystemic venous shunts, which may lead to the development of varices. Endoscopic treatment of these varices is often warranted to prevent catastrophic bleeding. During the course of variceal treatment, 1 or more portosystemic shunts may be sacrificed, which may acutely exacerbate portal hypertension and reduce systemic venous return. This report describes percutaneous creation of a mesocaval shunt and balloon-occluded retrograde transvenous obliteration (BRTO) in a patient with cavernous transformation of the portal vein. The patient had previously undergone an unsuccessful attempt at transjugular intrahepatic portosystemic shunt (TIPS) creation with postoperative bleeding requiring splenectomy. As TIPS was not feasible, creation of a percutaneous mesocaval shunt provided an alternate pathway for portosystemic decompression, facilitating safe treatment of gastric varices with BRTO via a gastrorenal shunt. These procedures were performed simultaneously to reduce the risk of variceal bleeding from acute changes in portal venous pressures and redirect blood flow through the shunt to maintain patency. This is the first reported case of combined mesocaval shunt placement and BRTO in a single session.

Percutaneous transgastric interventional radiology-operated duodenoscopy for the identification of duodenal perforation and Graham patch dehiscence.

Patients with a Roux-en-Y gastric bypass may be challenging diagnostic and therapeutic dilemmas for gastroenterologists and endoscopists due to anatomic considerations. Pancreaticobiliary limb pathology is particularly difficult to diagnose from standard endoscopic approaches as it often requires double balloon enteroscopy. Percutaneous access and gastrostomy placement into the gastric remnant, however, is a commonly performed procedure by interventional radiology. This report describes the identification of duodenal perforation and Graham patch dehiscence in the pancreaticobiliary limb of a patient with a prior Roux-en-Y gastric bypass who had failed traditional endoscopic measures, using transgastric remnant interventional duodenoscopy and confirmed with methylene blue injection into a periduodenal abscess.

Personalized health care beyond oncology: new indications for immunoassay-based companion diagnostics.

Personalized health care (PHC) is an evolving field of medicine aimed at providing the right therapy to the right patient at the right time. This approach often incorporates the use of companion diagnostics (CDx) assays that provide information essential for the safe and effective use of the corresponding drug. In addition to oncology, many other therapy areas, such as cardiovascular, neurological, and infectious and inflammatory diseases, may benefit from PHC, owing to disease complexity and heterogeneity. Furthermore, although most U.S. Food and Drug Administration-approved CDx are based on molecular-based technologies, immunoassays can provide a significant contribution to the evolution of CDx in patient management. In this review we discuss how the incorporation of biomarker immunoassays into routine diagnostic testing may allow early and definitive detection of Alzheimer's disease and enable population enrichment in clinical trials. In addition, we will describe how biomarker-based CDx immunoassays have potential utility for stratifying patients with asthma based on their potential response to therapy and for selecting treatment according to phenotypic profile. Continued research into the underlying disease pathology and development of accurate and reliable diagnostic assays may ensure that PHC becomes the future standard for many indications.

The Clinical and Health Economic Value of Clinical Laboratory Diagnostics.

The ultimate goal of diagnostic testing is to guide disease management in order to improve patient outcomes and patient well-being. Patient populations are rarely homogenous and accurate diagnostic tests can dissect the patient population and identify those patients with similar symptoms but very different underlying pathophysiology that will respond differently to different treatments. This stratification of patients can direct patients to appropriate treatment and is likely to result in clinical benefits for patients and economic benefits for the healthcare system. In this article we look at the clinical and economic benefits afforded by clinical laboratory diagnostics in three disease areas that represent substantial clinical and healthcare burdens to society; heart failure, Alzheimer's disease and asthma.

Clinicopathologic characteristics of patients with stage III/IV (M(0)) advanced gastric cancer, according to HER2 status assessed by immunohistochemistry and fluorescence in situ hybridization.

Despite recent advances in chemotherapy, the prognosis for patients with advanced gastric cancer (GC) or gastroesophageal junction cancer remains poor. Human epidermal growth factor receptor 2 (HER2) is a novel target for biologic therapy in metastatic GC. We analyzed the association between HER2 overexpression and the clinicopathologic characteristics of advanced GC. Formalin-fixed, paraffin-embedded tumor samples were collected from patients with stage III or to IV (M(0)) GC who subsequently underwent curative surgery followed by adjuvant chemotherapy with 5-fluorouracil and cisplatin. All the samples were analyzed for HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization. Of 142 samples analyzed, 7.1% scored IHC 2+ and 8.6% scored IHC 3+, whereas 9.3% were HER2-amplified. Of HER2-amplified cases, 76.9% (10/13) scored IHC 3+, showing the correlation between HER2 amplification and overexpression (P=0.01). HER2 IHC 3+ cases were more common in the intestinal-type tumors compared with diffuse-type tumors (16.7% vs. 5.1%, respectively; P=0.049), and a nonsignificant trend was observed using fluorescence in situ hybridization (14.3% vs. 9.2%, respectively; P=0.399). HER2 gene amplification was more frequent in stage IV (M(0)) than stage III disease (15.4% vs. 4.0%, respectively; P=0.037). Interestingly, HER2-amplified disease was more common than nonamplified disease in patients with nodal stage 3 tumors (76.9% vs. 38.6%, respectively; P=0.009); a similar pattern was observed using IHC. HER2 overexpression correlated with nodal stage, and a lymph node ratio greater than 0.5 was more common in HER2-amplified tumors than HER2-nonamplified tumors (69.2% vs. 43.3%, respectively; P=0.086). These findings suggest that further investigations of adjuvant therapy with HER2-targeted therapy for advanced GC are warranted.

Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial.

PURPOSE: To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy. PATIENTS AND METHODS: IHC and/or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry. FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival (DFS) after a median 2 years of follow-up. RESULTS: Central FISH results were available for 2,071 (61%) of the 3,401 patients randomized to the 2 arms. Among patients with FISH-positive disease, (1) the hazard ratios for trastuzumab versus no trastuzumab were 0.56 (95% CI, 0.32 to 0.99) for locally IHC2+ cases (n = 340) and 0.80 (95% CI, 0.40 to 1.61) for centrally IHC2+ cases (n = 299). There was no significant prognostic relationship between (2a) HER2 FISH ratio, (2b) HER2 copy number, or (3) polysomy and DFS in the control arm or predictive relationship defining differential benefit from trastuzumab. CONCLUSION: There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases. The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy.