Recombinant Activated Factor VII (rFVIIa) for Bleeding After Thoracic Aortic Surgery: A Scoping Review of Current Literature.

BACKGROUND: Bleeding after surgery on the thoracic aorta is a frequent complication, and can be associated with a significant increase in morbidity and mortality. Recombinant activated factor VII (rFVIIa) was developed initially for treating patients with hemophilia; however, it has been used increasingly "off-label" to achieve hemostasis after thoracic aortic procedures. OBJECTIVE: This scoping review aimed to present the available literature on the role of rFVIIa in the management of refractory postoperative bleeding after thoracic aortic surgery. METHODS/RESULTS: An electronic database search was conducted using Medline, Embase, Cochrane Library, and Google Scholar in June 2023. The authors included studies that reported the use of rFVIIa in patients undergoing surgical repair of ascending or descending aortic aneurysm or dissection. Single-case reports were excluded. Ten publications with a pooled number of 649 patients (319 patients received rFVIIa and 330 in the control groups) were identified: 3 case series, 6 retrospective studies, and 1 nonrandomized clinical trial. All studies reported the potential role of rFVIIa in correcting coagulopathy and reducing postoperative blood loss in this group of patients. Overall, there was not enough evidence to suggest that rFVIIa was associated with higher rates of thromboembolic complications or mortality. CONCLUSION: Limited evidence suggests that rFVIIa may be useful in managing postoperative refractory bleeding in patients undergoing thoracic aortic surgery. However, the impact of rFVIIa on thromboembolic complications and mortality rates remains unclear.

The role of digital mammographic surveillance for detection of asymptomatic recurrence in autologous flap reconstructions.

OBJECTIVE: To evaluate the utility of digital mammography in detecting asymptomatic malignancy in autologous flap reconstructions after mastectomy. METHODS: A retrospective database review identified all mammograms performed on asymptomatic patients with flap reconstructions over a 9-year period (1/1/2009 to 12/31/2017). A negative examination was defined as BI-RADS 1 or 2 and a positive examination was defined as BI-RADS 0, 4, or 5 assigned to the mastectomy side. Malignant outcomes were determined by pathology results. Interval cancers, or false negatives, were defined as locoregional malignant diagnosis within one year of a negative mammogram. Sensitivity, specificity, predictive values, abnormal interpretation rate, and cancer detection rate were calculated. RESULTS: 626 mammograms of asymptomatic flap reconstructions were performed in 183 patients. The most common flap type was TRAM (83.5 %, 523/626) and DIEP (13.4 %, 84/626). Most exams (98.2 %, 615/626) were negative, assessed as BI-RADS 1 or 2, with no interval cancers at follow-up. Eleven exams (1.8 %, 11/626) were positive, assessed as BI-RADS 0, 4, or 5. After diagnostic work-up of all BI-RADS 0 exams, 9 cases had a final recommendation for biopsy of which 3 were malignant. Mammography yielded a cancer detection rate of 0.5 % (3/626), abnormal interpretation rate of 1.8 % (11/626), NPV of 100 % (615/615), overall PPV of 27.3 % (3/11), PPV2 (positive predictive value of a biopsy recommendation) of 33.3 % (3/9), sensitivity of 100 % (3/3), and specificity of 98.7 % (615/623). CONCLUSION: Digital mammography of asymptomatic autologous flap reconstructions after mastectomy demonstrated high sensitivity and low abnormal interpretation rate. Cancer detection rate was comparable to current national benchmarks for mammographic screening in the general U.S. population without mastectomy.

Integrated proteomic and metabolomic analyses of the mitochondrial neurodegenerative disease MELAS.

MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m.14453G>A, specifically affecting the mitochondrial respiratory complex I. Global proteomics was achieved by data-dependent acquisition (DDA) and verified by data-independent acquisition (DIA) using both Spectronaut and the recently launched MaxDIA platforms. Comprehensive metabolite coverage was achieved for both polar and nonpolar metabolites in both reverse phase and HILIC LC-MS/MS analyses. Our proof-of-principle MELAS study with multi-omics integration revealed OXPHOS dysregulation with a predominant deficiency of complex I subunits, as well as alterations in key bioenergetic pathways, glycolysis, tricarboxylic acid cycle, and fatty acid ß-oxidation. The most clinically relevant discovery is the downregulation of the arginine biosynthesis pathway, likely due to blocked argininosuccinate synthase, which is congruent with the MELAS cardinal symptom of stroke-like episodes and its current treatment by arginine infusion. In conclusion, we demonstrated an integrated proteomic and metabolomic strategy for patient-derived fibroblasts, which has great clinical potential to discover therapeutic targets and design personalized interventions after validation with a larger patient cohort in the future.

Endometriosis in pregnancy.

Endometriosis constitutes the presence of ectopic endometrial glands and stroma outside the uterine endometrium, which is hormonally responsive and responds to pregnancy hormones as well. Decidualization is a physiologic process, where the normal endometrium readies itself for optimal accommodation of a pregnancy. A similar hormonal response can be seen with ectopic endometrium as well. As such, ovarian endometriomas and deep endometriosis implants can undergo decidualization. Overall, the progestational state of pregnancy favors an improvement in endometriosis, however, decidualization can lead to findings that can lead to increased size of endometriomas and deep infiltrative endometriosis implants, changes in imaging appearance and even complications, such as spontaneous hemoperitoneum in pregnancy. Awareness of this process can help prevent misdiagnosis of decidualized endometriomas as ovarian malignancy and recognize common imaging manifestations of hormonal effects of pregnancy on endometriosis.

Characterization of Metastatic Sternal Lesions on Dynamic Contrast-Enhanced Breast MRI in Women with Invasive Breast Cancer.

RATIONALE AND OBJECTIVES: Detecting sternal lesions is not the purpose of breast MRI, but diagnosing metastasis has major clinical implications. Our purpose was to determine the breast MRI features of sternal metastases detected on PET-CT and bone-scan. MATERIALS AND METHODS: Between 01/2010-09/2018, 379 patients with breast cancer had sternal findings on PET-CT or bone-scan, 21 of which underwent breast MRI within 100 days. Sternal lesions were considered metastatic if (1) biopsy demonstrated metastasis, (2) the lesion had similar appearance to synchronous sites of biopsy-proven osseous metastases, or (3) there were numerous suspicious lesions in which widespread osseous metastasis was presumed. Four radiologists reviewed the MR images to determine if metastases were retrospectively detectable. MRI reports were reviewed to determine if lesions were prospectively described. MRI features of metastatic sternal lesions were compared to benign controls. RESULTS: Fourteen sternal metastases met inclusion criteria. Lesions were retrospectively detectable on breast MRI by all radiologists in 86% (12/14) of cases, but prospectively reported in 57%. Of the 12 MRI-detectable metastases, mean maximum dimension was 33 mm, 7 had >1 lesion, all were T1-hypointense, 11 were T2-hyperintense, 11 were noncircumscribed, 6 extended beyond cortex, 11 enhanced heterogeneously, and 11 demonstrated washout. Heterogeneous enhancement (p = 0.002), noncircumscribed margins (p < 0.001), multiplicity (p = 0.005), and size >1 cm (p < 0.001) were more frequent with metastatic compared to benign sternal lesions. CONCLUSION: Most sternal metastases (86%) were retrospectively detectable on breast MRI, but only 57% were prospectively reported, emphasizing the importance evaluating the sternum on breast MRI. Certain MRI features may raise suspicion for metastasis.

High detection rates of Torque teno sus virus in co-infection with important viral pathogens in porcine kidneys on St. Kitts Island, Lesser Antilles.

We report here high rates of detection (50.8%, 31/61 pigs) of Torque teno sus virus (TTSuV) in kidneys of slaughter-age, apparently healthy pigs on St. Kitts island, Lesser Antilles. TTSuV1 and TTSuVk2a were detected in 23 (37.7%) and 13 (21.3%) pigs, respectively, including mixed infection in five animals. By nucleotide sequence identities and phylogenetic analysis, significant genetic diversity was observed among both TTSuV1 and TTSuVk2a on St. Kitts, with TTSuVk2a showing higher genetic diversity than TTSuV1. Fourteen (45.2%) and 10 (32.2%) of the TTSuV infected pigs tested positive for porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV), respectively, revealing high rates of co-infection of TTSuV with PCV2 and PPV. This is the first report on detection and genetic diversity of TTSuV from the Lesser Antilles. Also, PCV2 and PPV were detected for the first time in the Lesser Antilles. Considering the impact of pig farming on the regional livestock economy, the increasing demand for local pork and lack of information on emerging and re-emerging porcine viruses in the Lesser Antilles, the present findings have important implications on swine health.

Molecular characterization of canine parvovirus and canine enteric coronavirus in diarrheic dogs on the island of St. Kitts: First report from the Caribbean region.

Although canine parvovirus (CPV) and canine enteric coronavirus (CCoV) are important enteric pathogens of dogs and have been studied extensively in different parts of the world, there are no reports on these viruses from the Caribbean region. During 2015-2016, a total of 104 diarrheic fecal samples were collected from puppies and adult dogs, with or without hemorrhagic gastroenteritis, on the Caribbean island of St. Kitts (KNA). By PCR, 25 (24%, n=104) samples tested positive for CPV. Based on analysis of the complete deduced VP2 amino acid sequences, 20 of the KNA CPV strains were assigned to new CPV-2a (also designated as CPV-2a-297A). On the other hand, the VP2 genes of the remaining 5 strains were partially characterized, or could not be sequenced. New CPV-2a was the predominant CPV variant in St. Kitts, contrasting the molecular epidemiology of CPV variants reported in most studies from nearby North and South American countries. By RT-PCR, CCoVs were detected in 5 samples (4.8%, n=104). Based on analysis of partial M-protein gene, the KNA CCoV strains were assigned to CCoV-I genotype, and were closely related to CCoV-I strains from Brazil. To our knowledge, this is the first report on detection and genetic diversity of CPV and CCoV in dogs from the Caribbean region, and underscores the importance of similar studies in the other Caribbean islands.

Molecular characterization of complete genomic segment-2 of picobirnavirus strains detected in a cat and a dog.

We report here molecular characterization of complete genomic segment-2 of picobirnavirus (PBV) strains PBV/Cat/KNA/K40/2014 and PBV/Dog/KNA/RVC7/2015 detected in a cat (Felis catus) and a dog (Canis lupus familiaris), respectively, on the Caribbean island of St. Kitts. To obtain the full-length nucleotide (nt) sequence of gene segment-2 of the canine and feline PBV strains, the 5'- and 3'- portions of gene segment-2 containing an overlapping region were amplified using a non-specific primer-based amplification method with modifications. The complete gene segment-2 of feline PBV strain K40 and canine PBV strain RVC7 was 1784nt and 1689nt long, respectively, and encoded a putative RNA-dependent RNA polymerase (RdRp) of 534 amino acid (aa) and 531 aa, respectively. The complete gene segment-2 of strains K40 and RVC7 exhibited a high degree of genetic diversity between themselves, and with those of PBVs from other host species. On the other hand, both the canine and feline PBV strains retained the 5'- and 3'- end nucleotide sequences and the three domains of putative RdRp that are conserved in PBVs. To our knowledge, this is the first report on molecular characterization of complete gene segment-2 of PBV strains detected in cats and dogs, allowing us to study the features of putative RdRps of PBVs in these host species, and providing important insights into the genetic makeup and evolution of feline and canine PBV strains. PBVs were detected for the first time in cats and dogs from the Caribbean region.

Detection of picobirnaviruses in vervet monkeys (Chlorocebus sabaeus): Molecular characterization of complete genomic segment-2.

During 2014-2015, 270 fecal samples were collected from non-diarrheic, captive and wild African green monkeys (AGMs) on the island of St. Kitts, Caribbean region. By RNA-PAGE, picobirnaviruses (PBVs) were detected in sixteen captive AGMs. By RT-PCR and sequencing of partial gene segment-2, PBVs in 15 of these 16 samples were assigned to genogroup-I. The full-length nucleotide (nt) sequence of gene segment-2 of one of the genogroup-I PBV strains, strain PBV/African green monkey/KNA/016593/2015, was obtained using a non-specific primer-based amplification method with modifications. Gene segment-2 of strain 016593 was 1707bp long, and encoded a putative RNA-dependent RNA polymerase (RdRp) of 538aa. Furthermore, the nearly complete gene segment-2 sequences of three other AGM PBV strains were determined using primers designed from gene segment-2 sequence of 016593. The gene segment-2 of the 4 AGM PBV strains were almost identical to each other, and exhibited a high degree of genetic diversity (maximum nt and deduced aa sequence identities of 66.4% and 65.3%, respectively) with those of PBVs from other host species. The 5'- and 3'- (except for one mismatch) end nt sequences and the three domains of RdRps were retained in the AGM PBV strains. To our knowledge, this is the first report on detection, and molecular characterization of complete gene segment-2 of PBVs in vervet monkeys. PBVs were detected for the first time from the Caribbean region.

Whole genome analysis provides evidence for porcine-to-simian interspecies transmission of rotavirus-A.

We report here whole genome analysis of a porcine rotavirus-A (RVA) strain RVA/Pig-wt/KNA/ET8B/2015/G5P[13] detected in a diarrheic piglet, and nearly whole genome (except for VP4 gene) analysis of a simian RVA strain RVA/Simian-wt/KNA/08979/2015/G5P[X] detected in a non-diarrheic African green monkey (AGM) on the island of St. Kitts, Caribbean region. Strain ET8B exhibited a G5-P[13]-I5-R1-C1-M1-A8-N1-T7-E1-H1 genotype constellation that was identical to those of Brazilian porcine RVA G5P[13] strains RVA/Pig-wt/BRA/ROTA01/2013/G5P[13] and RVA/Pig-wt/BRA/ROTA07/2013/G5P[13], the only porcine G5P[13] RVAs that have been analyzed for the whole genome so far. Phylogenetically, all the 11 gene segments of ET8B were closely related to those of porcine and porcine-like human RVAs within the respective genotypes. Although the porcine G5P[13] RVAs exhibited identical genotype constellations, ET8B did not appear to share common evolutionary pathways with the Brazilian porcine G5P[13] RVAs. Interestingly, the VP2, VP3, VP6, VP7, and NSP1-NSP5 genes of simian RVA strain 08979 were closely related to those of porcine and porcine-like human RVA strains, exhibiting 99%-100% nucleotide sequence identities to cognate genes of co-circulating porcine RVA strain ET8B. On the other hand, the VP1 of 08979 appeared to be genetically divergent from porcine and human RVAs within the R1 genotype, and its exact origin could not be ascertained. Taken together, these observations suggested that simian strain 08979 might have been derived from interspecies transmission events involving transmission of ET8B-like RVAs from pigs to AGMs. In St. Kitts, AGMs often stray from the wild into livestock farms. Therefore, it may be possible that the AGM acquired the infection from a pig farm on the island. To our knowledge, this is the first report on detection of porcine-like RVAs in monkeys. Also, the present study is the first to report whole genomic analysis of a porcine RVA strain from the Caribbean region.

Pilot Study: Occurrence of Ear Mites and the Otic Flora in Domestic Ruminants on St. Kitts.

Psoroptes, a globally occurring mite, and Raillietia, a primarily tropical mite, have been attributed to otitis in ruminants. Within the Caribbean, little is known about the prevalence of these mites and their relation to the microbial flora of the ears. From May 2015 to May 2016, ears of cattle, sheep and goats brought to the St. Kitts abattoir were examined post-slaughter for mite infestations. No Raillietia spp. were seen and none of the sheep had ear mites. Psoroptes spp. were found in 2.6% of the cattle and 22.6% of the goats. Tick control programs, focused on cattle and sheep, might influence the occurrence seen in this study.

Whole genomic analysis of a porcine G6P[13] rotavirus strain.

We report here the whole genomic analysis of an unusual porcine G6P[13] rotavirus-A (RVA) strain, RVA/Pig-wt/IND/HP113/2002/G6P[13], detected from a diarrheic piglet in eastern India in 2002. Strain HP113 exhibited a G6-P[13]-I2-R1-C1-M1-A1-N1-T7-E1-H1 genotype constellation, not reported previously. The VP1, VP3, VP4, NSP1 and NSP3-NSP5 genes of RVA strain HP113 were found to be closely related to those of porcine and/or porcine-like human RVAs. On the other hand, the NSP2 gene of HP113 was found to share a more common origin with those of several recent and archival human Wa-like RVA strains than those of other RVAs, whilst its VP6 and VP7 genes appeared to be derived from co-circulating bovine RVAs from India. Within the VP7-G6 genotype, strain HP113 and the Indian bovine RVAs appeared to constitute a new G6 lineage, tentatively designated as G6 lineage-VI. Based on the available data, it was difficult to pinpoint the porcine or human origin of VP2 gene of HP113. Taken together, whole genomic analysis of strain HP113 revealed important insights into the complex evolutionary patterns of atypical porcine RVAs, providing evidence for reassortment events involving strains from different host species and evolutionary relationships between porcine and human RVAs. To our knowledge, this is the first report on whole genomic analysis of a G6P[13] RVA strain.

Medical student debt and major life choices other than specialty.

BACKGROUND: Median indebtedness at graduation is now more than $170,000 for graduates of US Medical Schools. Debate still exists as to whether higher debt levels influence students to choose high paying non-primary care specialties. Notably, no previous research on the topic has taken into account cost of attendance when constructing a debt model, nor has any research examined the non-career major life decisions that medical students face. METHODS: Medical students were surveyed using an anonymous electronic instrument developed for this study. The survey was delivered through a link included in a study email and students were recruited from school wide listservs and through snowball sampling (students were encouraged to share a link to the survey with other medical students). No incentives were offered for survey completion. RESULTS: Responses were recorded from 102 US Allopathic medical schools (n=3,032), with 22 institutions (11 public, 11 private) meeting inclusion criteria of 10% student body response proportion (n=1,846). Students with higher debt relative to their peers at their home institution reported higher frequencies of feeling callous towards others, were more likely to choose a specialty with a higher average annual income, were less likely to plan to practice in underserved locations, and were less likely to choose primary care specialties. Students with higher aggregate amounts of medical student loan debt were more likely to report high levels of stress from their educational debt, to delay getting married and to report disagreement that they would choose to become a physician again, if given the opportunity to revisit that choice. Increases in both aggregate and relative debt were associated with delaying having children, delaying buying a house, concerns about managing and paying back educational debt, and worrying that educational debt will influence one's specialty choice. CONCLUSIONS: Medical student debt and particularly debt relative to peers at the same institution appears to influence the way that students approach major life choices like when to start a family, when to buy a home, and what specialty to choose. Future research should take into account cost of attendance when looking for the impact of medical student debt on major life choices.