Clinical Treatment Course Research Articles

Factors influencing the fascial closure rate after open abdomen treatment: Results from the European Hernia Society (EuraHS) Registry

PurposeDefinitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure.MethodsA multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719).ResultsData were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p < 0.001) and dynamic closure techniques (odds ratio: 2.687, p < 0.001) with fascial closure and a negative correlation of intra-abdominal contamination (odds ratio: 0.630, p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC.ConclusionThe clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.

Oral Alitretinoin for Patients with Refractory Prurigo.

Background: prurigo is a chronic skin disorder associated with a history of chronic pruritus. The pathogenesis of prurigo is largely unknown and the treatment of prurigo is unsatisfactory and challenging. Conventional systemic treatments may be beneficial; however, their possible side effects and possible transient efficacy is still a problem. We aimed to present the clinical course and effect of treatment with alitretinoin on patients with prurigo nodularis initially treated with conventional treatments like oral antihistamine, cyclosporine, and phototherapy. Methods: all the patients had prurigo nodularis refractory to conventional treatment. Their medical records included demographic features, past medical history, duration of disease, and treatment modalities; and the clinical courses of the patients were reviewed for this retrospective study. We evaluated patient pruritus and skin lesions for the duration. Results: we present reports involving 10 patients with refractory prurigo. All the patients in our cases were treated with oral alitretinoin after previous treatments and reported the improvement of skin lesions and pruritus within 2 weeks to 3 months. Conclusions: we suggest that oral alitretinoin may be an effective and well tolerated treatment option for patients with intractable prurigo. Further clinical studies are warranted to confirm the long-lasting efficacy and safety of alitretinoin for treating patients with prurigo.

Multicenter retrospective cohort study of the clinical significance of Staphylococcus lugdunensis isolated from a single blood culture set

BackgroundStaphylococcus lugdunensis is a coagulase negative Staphylococcus species and frequent human skin commensal with the potential for aggressive infection. Guidance surrounding S. lugdunensis bacteremia (SLB) from a single set of blood cultures is lacking. MethodsA multicenter, retrospective cohort of patients with SLB from at least one blood culture set within the University of Maryland Medical System from 2015 to 2019 is presented. Objectives are to describe baseline characteristics, compare the clinical status and treatment course, and to evaluate the clinical outcomes among patients with SLB in single versus multiple sets. ResultsThirty-six patients were included, 24 with one set of blood cultures positive for S lugdunensis and 12 with multiple sets. Baseline characteristics were similar between the groups, though patients with SLB in multiple sets were more commonly on hemodialysis (P = 0.029). Central lines were the most common source (17%). Most (97%) fulfilled systemic inflammatory response syndrome or Souvenir criteria, had an infectious focus on imaging, or had a second positive culture site. Most (78%) were treated as clinically significant. Patients with multiple positive sets were more commonly treated with antibiotics for >2 weeks (P = 0.02). ConclusionsSLB was rare and occurred more frequently as a single set of positive cultures. Patient characteristics and clinical courses were similar between single and multiple set groups. Given the potential severity of S. lugdunensis bacteremia it seems prudent to treat S. lugdunensis in a single blood culture as true bacteremia, pending larger studies and guidelines.

Aroma Acupoint Therapy for Symptom Management with Adolescent Patients: Early Experiences from School-Based Health Centers.

Objectives: The American Academy of Pediatrics has long recognized a need for more resources for integrative medicine for health care providers and for patients. The aim of this study was to introduce Aroma Acupoint Therapy (AAT)-a relatively new integrative medicine modality using essential oils to activate acupoints-and to describe the early experiences of providers using AAT for adolescents at school-based health centers (SBHCs). Materials and Methods: This was a case series of 15 adolescents treated with 1 of 2 AAT specific protocols plus standard medical therapy between April 2018 and February 2019 at SBHCs. Of these 15 patients, ages 12-19, 14 were female. Clinical characteristics and treatment courses were abstracted by retrospective review of the patients' electronic medical records. The main outcomes and measures for this research were clinical characteristics, treatment courses and pre- and post-treatment pain scores for adolescents treated with AAT. Results: All 15 patients had nonspecific symptoms, including headaches, menstrual cramps, nausea, shortness of breath, chest pain, back pain, or dizziness. Pain scores were recorded in 8 of 15 encounters, and suggested improvements in most patients. Subjective documentation by the providers also suggested that most of these patients had reduced symptoms. Conclusions: With the call for nonopiate and integrative approaches to pain management, there is an urgent need to study the effectiveness of such modalities, such as AAT. It is safe, inexpensive, easy to learn, and is well-received by both health care providers and patients.

Outcome of Surgical Treatment of Spontaneous Spinal Epidural Abscesses for a 10-year Period.

Spinal epidural abscess is uncommon but potentially debilitating infection. Delay in early diagnosis may be associated with increased morbidity and mortality despite recent advances in medicine. To present the clinical course and outcome of treatment of spontaneous spinal epidural abscesses. Thirty-four patients (20 men and 14 women) with clinical, neuroimaging and/or histological data for spinal epidural abscess were treated at the Clinic of Neurosurgery at St George University Hospital, Plovdiv, Bulgaria, for the period 2009-2018. The average age of patients was 62 years (21-76 years) and the ratio of men to women was 1.4:1. All patients (100%) presented with vertebralgia, 13 patients (38.2%) had additional radiculalgia, and 10 patients (29.4%) presented with sensory or motor deficit. The duration of complaints varied from 4 to 180 days. At hospital admission, only 9 patients (26.4%) had intact neurological status. The most common localization of the spinal epidural abscess was in the lumbar and lumbosacral area (52.9%), concomitant spondylodiscitis was present in 31 patients (91.2%). Twenty-four patients (70.6%) underwent emergency surgery within 24 hours, and the rest had planned surgery. Decompressive interlaminotomy or hemilaminectomy was performed in 9 patients (26.5%). The remaining 25 patients (73.5%) underwent laminectomy, in 15 patients (44.1%) it was combined with posterior pedicle screw fixation. After the treatment, 23 patients (67.6%) had a good outcome, the remaining 11 (32.4%) had a poor outcome, and 3 patients died (8.8%). In patients with spinal epidural abscess, emergency surgery is the treatment method of choice. It allows decompression of neural structures, correction of the spinal deformity, segmental stabilization and rapid mobilization of patients.

Інфантильна гемангіома

Infantile hemangioma is one of the most common benign vascular malformations in children. Besides that, some questions about classification, diagnostic, and choice of method of treatment remains the questionable. The modern data about classification, clinical course, diagnostic, and main principles of treatment of infantile hemangioma are presented in this work. In most cases, the uncomplicated clinical course of infantile hemangioma was observed. However, in some patients the complications may arise. Ulceration, obstruction, functional impairment, and disfigurement are the most often complications of infantile hemangioma. Although, most infantile hemangiomas tend to regress spontaneously, some of them required the treatment. Applying of the β-blockers (systemic or topical), laser therapy, and surgery are the main methods that used for the treatment of infantile hemangiomas. Patients with infantile hemangiomas, despite the simplicity of diagnostic, should be treated on specialized centers. Early detection of at-risk infantile haemangioma is a major point, requiring an increased awareness by paediatricians, with the aim to prevent the complications development. However, it was proven the efficacy of propranolol treatment for the all types of infantile hemangiomas, the long-term follow-up studies are needed to assess its safety with regard to neurodevelopment. No conflict of interest was declared by the authors. Key words: infantile hemangioma, diagnostic, treatment.

Non-saccular aneurysms: pathogenesis, clinic and methods of treatment (review)

In clinical practice, we use the term “fusiform aneurysm” for local expansion of artery. Under this generic term specialists understand heterogeneous arterial pathology, which is very important for diagnosis and choosing the treatment. We conducted an analysis of scientific literature published in 1987–2019, including 63 foreign and 4 Russian sources devoted to pathogenesis and types of non-saccular aneurysms. Among non-saccular aneurysms, dolichoectatic aneurysms are distinguished, rather of genetically or non-atherosclerotic origin and fusiform aneurysm acquired due to dissection processes. Features of mechanisms of their formation, variants of clinical course and methods of treatment are presented.

Clinical characteristics of coronavirus disease 2019 patients with diarrhea in Daegu.

Background/AimsCoronavirus disease 2019 (COVID-19) can reportedly cause gastrointestinal symptoms. Therefore, we investigated the clinical characteristics of COVID-19 patients with diarrhea.MethodsWe included 118 COVID-19 patients admitted to a single hospital from February 20 to March 31, 2020. Medical records with clinical characteristics, laboratory data, treatment course, and clinical outcomes were compared based on the presence or absence of diarrhea. Prognostic factors for disease severity and mortality in COVID-19 were also assessed.ResultsAmong patients, 54 (45.8%) had diarrhea, whereas seven (5.9%) had only diarrhea. The median age of patients with diarrhea was 59 years (44 to 64), and 22 (40.7%) were male. Systemic steroid use, intensive care unit admission, septic shock, and acute respiratory distress syndrome were less frequent in the diarrhea group than in the non-diarrhea group. No significant differences were observed in total hospital stay and mortality between groups. On multivariate analysis, age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01 to 1.12; p = 0.044), diabetes (OR, 3.00; 95% CI, 1.25 to 20.47; p = 0.042), and dyspnea (OR, 41.19; 95% CI, 6.60 to 823.16; p < 0.001) were independent risk factors for septic shock. On Cox regression analysis, diabetes (hazard ratio [HR], 4.82; 95% CI, 0.89 to 26.03; p = 0.043) and chronic obstructive pulmonary disease (HR, 16.58; 95% CI, 3.10 to 88.70; p = 0.044) were risk factors for mortality.ConclusionsDiarrhea was present in 45.8% of patients and was a common symptom of COVID-19. Although patients with diarrhea showed less severe clinical features, diarrhea was not associated with disease severity or mortality.

Evaluation of an educational concept for risk-oriented prevention in undergraduate dental education

BackgroundAim of this observational study with a three-month follow-up was to evaluate an educational concept for risk-oriented prevention applied by fifth-year undergraduate dental students.MethodsDental students from two clinical treatment courses of the last undergraduate year were included. The subjects were divided into two groups according to their assignment to the two clinical classes. Group A received a sequence of seminars, including the basics of a risk classification system (RCS) with the theoretical background and case studies in the context of preventive dentistry. Thereby, 1) a theoretical seminar (background, RCS, cases) and 2) the transfer of the RCS on a clinical patient case chosen by the student, and its presentation within a discussion round was applied. Group B served as a comparison group with students who did not receive any of teaching events in terms of RCS. The self-perceived knowledge and importance of RCS, as well as objective knowledge (qualitative questions), were assessed with a standardized questionnaire at baseline and after 3 months.ResultsOut of 90 students at baseline, 79 (group A: 39, group B: 40) were re-evaluated after 3 months. At this follow-up, Group A estimated their confidence in handling the medication (p = 0.02), the RCS (p < 0.01), and in identifying the risk of oral diseases (p = 0.02) higher than group B. Furthermore, group A felt it was more important to identify patients at risk (p = 0.02), the risk of complications (p = 0.02) and to apply an RCS (p = 0.03). At follow-up, group A exhibited more correct answers of qualitative questions than group B regarding risk of complications (p < 0.01) and bacteremia (p < 0.01). Group A felt more confident with at-risk patients and more competent concerning RCS than group B (p < 0.01).ConclusionThe concept for educating risk-oriented prevention increased the self-perceived skills and the knowledge of undergraduate dental students after 3 months within a clinical treatment course.

Consumption of spine by tuberculosis in the era of directly observed treatment, short-course and genomic diagnosis

BackgroundExtra Pulmonary Tuberculosis (EPTB) is a significant health problem in both developing and developed countries. Spinal tuberculosis (STB) is one of the significant forms of EPTB lacking epidemiological data. The present study was conducted to study the clinical, radiological, microbiological and histopathological features, treatment and outcome of Spinal tuberculosis. MethodsThis study was conducted for a duration of 19 years, from 2000 to 2018 at the department of Neuromicrobiology, NIMHANS, Bengaluru. It comprised of 252 patients with STB. All patients were diagnosed with the clinical features and confirmed by radiological, microbiological and histopathological findings. ResultsResults were tabulated and statistically studied. The most common age group is 30–40 years with male preponderance. Most patients presented with motor paraplegia/para paresis (99.6%). Thoracic spine was the most common vertebra affected (47.62%). The commonest imaging feature is soft tissue collection (81.74%). Most common histopathological feature was necrotising granulomatous inflammation (65.87%). Microbiology reports showed growth of Mycobacterium tuberculosis (MTB) in 29.76%, Ziehl Neelsen (ZN) smear showed acid fast bacilli (AFB) in 25.79%. Anti tubercular drugs and surgery were advised in 55.55% patients and only anti TB drugs for 39.28%. The entire course of anti tubercular treatment (ATT) was completed in 60.71% and 4.76% were defaulters. ConclusionSpinal tuberculosis is a global disease, timely diagnosis with clinical, imaging, microbiological, histopathological features and complete course of anti-tubercular treatment along with symptomatic treatment appears to be safe and effective.

3D post-processing technique highlights lesions: A thought triggered by an elderly, severe, complicated COVID-19 patient

The coronavirus disease 2019 (COVID-19) has swept across all countries in the world within half a year, which is taking the world by surprise. We reported an elderly, severe, complicated COVID-19 case, describing the clinical manifestations, laboratory examinations, CT findings, diagnosis, treatment and dynamic disease course. 3D post-processing technique was used to reconstruct different pulmonary lesions, and it was found to be useful for highlighting and observing them, thereby helping diagnose and distinguish different diseases.

Clinical implications of agoraphobia in patients with panic disorder.

Agoraphobia is frequently accompanied by panic disorder and causes considerable suffering. The aim of this study was to compare clinical features and treatment courses between patients with and without agoraphobia in panic disorder.In this retrospective study, 87 patients with panic disorder were divided into two groups depending on the presence of agoraphobia: patients with agoraphobia (PDA, n = 41) and patients without agoraphobia (PD, n = 46). Agoraphobia subscale score of the Albany Panic and Phobia Questionnaire was used to identify correlations between agoraphobia and panic and affective symptoms.The PDA group showed more severe panic and affective symptoms than the PD group. Patients with PDA were more likely to be younger at the age of onset, take benzodiazepines for longer durations, and be treated with antipsychotics augmentation. Agoraphobia subscale was associated with panic symptoms, depression, anxiety, and the duration of benzodiazepines use.The findings suggest that patients with PDA experienced more severe panic symptoms, more profound psychiatric comorbidity, and worse illness progression than those with PD.

MECHANISMS AND FEATURES OF IMMUNE STATUS AND "OXIDATIVE STRESS - ANTIOXIDANT PROTECTION" SYSTEM IN PATIENTS WITH TUBERCULOSIS

The study of the human immune system state in infection with M. tuberculosis is relevant because the course and outcome of this disease are largely determined by the immune status of the patient. However, 98 % of patients with pulmonary tuberculosis have an immune imbalance. It is known that in the protection against tuberculosis an important role belongs to the body's natural resistance, which is provided by a variety of cellular and humoral factors, physicochemical characteristics of tissues, lymphoid cells, leukocyte and macrophage responses and genetic resistance. When mycobacteria enter the body, polymorphonuclear leukocytes, monocytes and macrophages are the main phagocytic cells. Optimally high level of resistance to the pathogen develops only in the coordinated interaction of T−lymphocytes with macrophages. Studies of cellular immunity and genetic markers have shown that the course of tuberculosis infection is associated with suppression of their functional activity. Immune response deregulation is closely related to oxidative stress, which results from an imbalance between free reactive oxygen species and antioxidant mechanisms, with a higher risk of developing it rather in lungs than other organs. Many studies have presented the results of studying the state of the immune system and the "oxidative stress − antioxidant protection" system in tuberculosis. This is an important component, because the clinical course and outcome of treatment is largely determined by the status of these systems. A number of experts point out that the study of immunological and oxidative parameters in tuberculosis is of a great importance for deciding on the tactics of treatment and the choice of direction of influence on the course of the disease. Key words: M. Tuberculosis, immunity in tuberculosis, oxidative stress, antioxidant protection.

Neural Memory Networks for Seizure Type Classification.

Classification of seizure type is a key step in the clinical process for evaluating an individual who presents with seizures. It determines the course of clinical diagnosis and treatment, and its impact stretches beyond the clinical domain to epilepsy research and the development of novel therapies. Automated identification of seizure type may facilitate understanding of the disease, and seizure detection and prediction have been the focus of recent research that has sought to exploit the benefits of machine learning and deep learning architectures. Nevertheless, there is not yet a definitive solution for automating the classification of seizure type, a task that must currently be performed by an expert epileptologist. Inspired by recent advances in neural memory networks (NMNs), we introduce a novel approach for the classification of seizure type using electrophysiological data. We first explore the performance of traditional deep learning techniques which use convolutional and recurrent neural networks, and enhance these architectures by using external memory modules with trainable neural plasticity. We show that our model achieves a state-of-the-art weighted F1 score of 0.945 for seizure type classification on the TUH EEG Seizure Corpus with the IBM TUSZ preprocessed data. This work highlights the potential of neural memory networks to support the field of epilepsy research, along with biomedical research and signal analysis more broadly.

Case report: secondary hypertension in a 6-year old child with bilateral renal artery stenosis

Background. Renovascular hypertension (RVH) is an elevated blood pressure caused by partial or complete occlusion of one or both renal arteries or their branches. According to different studies, renal artery stenosis accounts for 5–10% of all cases of hypertension in children. The most common causes of renal artery stenosis are deemed to be atherosclerosis and fibromuscular dysplasia.Case description. The article describes clinical case of a newly diagnosed renovascular hypertension amid background of fibromuscular dysplasia of renal arteries in a 6-year old child, particulars of the clinical course, laboratory and instrumental methods of investigation and treatment including aortography and balloon angioplasty of renal arteries.Conclusion. This case report illustrates that in the absence of complaints and pronounced clinical symptoms the diagnosis of renovascular hypertension in a 6-year old child could not be established for a long time. Timely detection of elevated BP in children, including the young ones, not only during visiting specialist physicians but also during prophylactic examination by pediatrician, is required for early diagnosis of the disease and development of the examination and treatment strategy.

Case report: secondary hypertension in a 6-year old child with bilateral renal artery stenosis

Background. Renovascular hypertension (RVH) is an elevated blood pressure caused by partial or complete occlusion of one or both renal arteries or their branches. According to different studies, renal artery stenosis accounts for 5–10% of all cases of hypertension in children. The most common causes of renal artery stenosis are deemed to be atherosclerosis and fibromuscular dysplasia.Case description. The article describes clinical case of a newly diagnosed renovascular hypertension amid background of fibromuscular dysplasia of renal arteries in a 6-year old child, particulars of the clinical course, laboratory and instrumental methods of investigation and treatment including aortography and balloon angioplasty of renal arteries.Conclusion. This case report illustrates that in the absence of complaints and pronounced clinical symptoms the diagnosis of renovascular hypertension in a 6-year old child could not be established for a long time. Timely detection of elevated BP in children, including the young ones, not only during visiting specialist physicians but also during prophylactic examination by pediatrician, is required for early diagnosis of the disease and development of the examination and treatment strategy.

Case report: secondary hypertension in a 6-year old child with bilateral renal artery stenosis

Background. Renovascular hypertension (RVH) is an elevated blood pressure caused by partial or complete occlusion of one or both renal arteries or their branches. According to different studies, renal artery stenosis accounts for 5–10% of all cases of hypertension in children. The most common causes of renal artery stenosis are deemed to be atherosclerosis and fibromuscular dysplasia.Case description. The article describes clinical case of a newly diagnosed renovascular hypertension amid background of fibromuscular dysplasia of renal arteries in a 6-year old child, particulars of the clinical course, laboratory and instrumental methods of investigation and treatment including aortography and balloon angioplasty of renal arteries.Conclusion. This case report illustrates that in the absence of complaints and pronounced clinical symptoms the diagnosis of renovascular hypertension in a 6-year old child could not be established for a long time. Timely detection of elevated BP in children, including the young ones, not only during visiting specialist physicians but also during prophylactic examination by pediatrician, is required for early diagnosis of the disease and development of the examination and treatment strategy.

Clinical Features, Treatment Courses, and Distribution of Cytomegalovirus Genotypes among Thrombocytopenia Patients Aged Younger than 12 Months.

The aims of this study were to evaluate the clinical characteristics, laboratory data, and treatment of the cytomegalovirus (CMV)-associated thrombocytopenia in infants aged younger than 12 months and to investigate the possible relationship between genotypes of glycoprotein B (gB) and glycoprotein H (gH) and CMV-associated thrombocytopenia. Infants with positive identification of cytomegalovirus (CMV) and thrombocytopenia, being treated at Hubei Maternal and Child Health Hospital from January 2015 to June 2019 were included. Genotype of gB and gH analysis were done by nested polymerase chain reaction (nPCR) and restrictions length polymorphism. The prevalence of CMV congenital, perinatal, and postnatal infection were 1.4% (76/5428), 29.1% (378/1301), and 41.8% (243/581), respectively. A total of 29 immunocompetent patients with CMV-associated thrombocytopenia were analyzed, including 7 (9.2%, 7/76) congenital infections, 14 (3.7%, 14/378) perinatal infections, and 8 (3.3%, 8/243) postnatal infections. Platelet count at diagnosis <20 × 109/L was the common hematologic finding of CMV-associated thrombocytopenia in perinatal infection (1/7 congenital infection vs. 10/14 perinatal infection vs. 3/8 postnatal infection, Chi-square (χ2) = 6.616, p = 0.037). Notably, significantly higher frequency of hepatobiliary symptoms was found in congenital and perinatal infections groups (4/7 congenital infection vs. 10/14 perinatal infection vs. 1/8 postnatal infection, χ2 = 7.188, p = 0.027). Intravenous immunoglobulin was prescribed for 24 (82.8%, 24/29) patients, and antiviral agents were prescribed for 9 (31.0%, 9/29) patients. The most prevalent genotypes of CMV in the study were gB1 (60.7%, 17/28) and gH2 (57.1%, 16/28). There was a substantial percentage of symptomatic CMV infection in patients aged younger than 12 months. Thrombocytopenia is one of the common clinical manifestations in congenital CMV infection. The gB1 genotype had more virulence in infants with acquired CMV infection. There might be an association between gH2 genotype of CMV and CMV-associated thrombocytopenia.

Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale

BackgroundPopulations of closely related microbial strains can be simultaneously present in bacterial communities such as the human gut microbiome. We recently developed a de novo genome assembly approach that uses read cloud sequencing to provide more complete microbial genome drafts, enabling precise differentiation and tracking of strain-level dynamics across metagenomic samples. In this case study, we present a proof-of-concept using read cloud sequencing to describe bacterial strain diversity in the gut microbiome of one hematopoietic cell transplantation patient over a 2-month time course and highlight temporal strain variation of gut microbes during therapy. The treatment was accompanied by diet changes and administration of multiple immunosuppressants and antimicrobials.MethodsWe conducted short-read and read cloud metagenomic sequencing of DNA extracted from four longitudinal stool samples collected during the course of treatment of one hematopoietic cell transplantation (HCT) patient. After applying read cloud metagenomic assembly to discover strain-level sequence variants in these complex microbiome samples, we performed metatranscriptomic analysis to investigate differential expression of antibiotic resistance genes. Finally, we validated predictions from the genomic and metatranscriptomic findings through in vitro antibiotic susceptibility testing and whole genome sequencing of isolates derived from the patient stool samples.ResultsDuring the 56-day longitudinal time course that was studied, the patient’s microbiome was profoundly disrupted and eventually dominated by Bacteroides caccae. Comparative analysis of B. caccae genomes obtained using read cloud sequencing together with metagenomic RNA sequencing allowed us to identify differences in substrain populations over time. Based on this, we predicted that particular mobile element integrations likely resulted in increased antibiotic resistance, which we further supported using in vitro antibiotic susceptibility testing.ConclusionsWe find read cloud assembly to be useful in identifying key structural genomic strain variants within a metagenomic sample. These strains have fluctuating relative abundance over relatively short time periods in human microbiomes. We also find specific structural genomic variations that are associated with increased antibiotic resistance over the course of clinical treatment.

Deep Functional and Molecular Characterization of a High-Risk Undifferentiated Pleomorphic Sarcoma.

Nonrhabdomyosarcoma soft-tissue sarcomas (STSs) are a class of 50+ cancers arising in muscle and soft tissues of children, adolescents, and adults. Rarity of each subtype often precludes subtype-specific preclinical research, leaving many STS patients with limited treatment options should frontline therapy be insufficient. When clinical options are exhausted, personalized therapy assignment approaches may help direct patient care. Here, we report the results of an adult female STS patient with relapsed undifferentiated pleomorphic sarcoma (UPS) who self-drove exploration of a wide array of personalized Clinical Laboratory Improvement Amendments (CLIAs) level and research-level diagnostics, including state of the art genomic, proteomic, ex vivo live cell chemosensitivity testing, a patient-derived xenograft model, and immunoscoring. Her therapeutic choices were also diverse, including neoadjuvant chemotherapy, radiation therapy, and surgeries. Adjuvant and recurrence strategies included off-label and natural medicines, several immunotherapies, and N-of-1 approaches. Identified treatment options, especially those validated during the in vivo study, were not introduced into the course of clinical treatment but did provide plausible treatment regimens based on FDA-approved clinical agents.