Spinal Cord Stimulation for Loin Pain Hematuria Syndrome: Clinical Report.

Loin pain hematuria syndrome (LPHS) is a rare condition characterized by cryptogenic debilitating flank pain and microscopic or macroscopic hematuria. The pathophysiology of LPHS remains poorly understood, and diagnosis is made largely by exclusion of alternate pathology. Management strategies can vary widely and include chronic opioid medication and a variety of invasive procedures, including regional nerve blocks, transcutaneous electrical nerve stimulation, local capsaicin infusion, and surgical renal denervation. Neuromodulation may provide a new paradigm of treatment for LPHS, potentially sparing patients from long-term complications of opiate therapy and invasive surgery. This report demonstrates the first case of successful symptomatic management of LPHS using spinal cord stimulation.

An Investigation of Mucosal Leishmaniasis in the Military Health System.

Leishmaniasis is a protozoal infection with an increased risk of transmission to those serving in the U.S. Military due to theaters of operation in endemic regions. There has, in recent decades, been robust experience with old-world leishmaniasis in the Military Health System (MHS); however, new-world leishmaniasis, which may result in mucosal leishmaniasis, has been less studied. A total of 88 patients from 2012 to 2022 with diagnosis codes for "mucocutaneous leishmaniasis" or "leishmaniasis, unspecified" were identified in the Military Data Repository and reviewed. Within this cohort, upon medical records review, there were 2 cases of leishmaniasis that met inclusion criteria. Case 1 was a 28-year-old active duty male with recent travel to Belize who presented with a mucosal lip lesion that was biopsied and had inconclusive species confirmation but was thought to be either L. braziliensis or L. mexicana. The second case involved a 30-year-old active duty male with a history of travel to French Guiana who had a cutaneous lesion on his left hand that was identified as L. guyanensis, a causative species for mucosal leishmaniasis. Neither had evidence of any further mucosal involvement on otolaryngologic evaluation, and both subsequently received systemic therapy with a good clinical response. Although only 2 cases were identified over an 11-year period, this disease remains an important medical consideration when conducting military operations within Central and South America, as both cases had recent military-specific travel to areas endemic for leishmaniasis.

Monitoring Outcomes of Indeterminate Thyroid Nodules and Predictive Capabilities of Molecular Testing.

OBJECTIVE: This study aimed to compare the effectiveness of reflex molecular testing at identifying thyroid malignancy in indeterminate thyroid nodules (ITNs) since its implementation at our institution. METHOD: Identified all ITNs at our institution from January 2010 to October 2020. Calculated the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of ThyroSeq since the initiation of universal reflex testing of all first-time ITNs beginning in March 2016. Analyze effect on frequency of diagnostic surgeries. RESULTS: Study group: March 2016 to October 2020, 378 ITNs underwent ThyroSeq (318 Bethesda III and 60 Bethesda IV). Mean age 52 years, 35.9% male, 61.1% female. 145 surgically excised with overall resection rate of 38.4% (III: 32.7%; IV 68%). Final histology: 49 malignant with overall rate of malignancy (ROM) of ITNs at 33.8% (III: 31.7%; IV: 39%). ThyroSeq sensitivity for ITNs at 84% (III 78.8%, IV 93.8%). ThyroSeq NPV for ITNs at 86% (III 84%, IV 93.3%). ThyroSeq specificity for ITNs at 52% (III 50.7%, IV 56%). ThyroSeq PPV for ITNs at 47% (III 42.6%, IV 57.7%). Control group: From January 2010 to February 2016 there were 242 ITNs (152 Bethesda III, 90 Bethesda IV). Mean age 52.6 years, 25.8% male, 74.2% female. 157 cases were surgically excised, with an overall resection rate of 64.9% (III: 57.2%; IV: 77.8%). Final histology: 32 malignant, with overall ROM of ITNs at 20.4% (III: 27.6%; IV: 11.4%). CONCLUSION: The initiation of universal Thyroseq (sensitivity 84% and NPV 86%) of ITNs at our institution has significantly decreased our percentage of diagnostic lobectomies, with a decreased resection rate of 26.5%.

Colon Cancer Screening Methods: 2023 Update.

Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. National screening guidelines have been implemented to identify and remove precancerous polyps before they become cancer. Routine CRC screening is advised for people with average risk starting at age 45 because it is a common and preventable malignancy. Various screening modalities are currently in use, ranging from stool-based tests (fecal occult blood test (FOBT), fecal immunochemical test (FIT), and FIT-DNA test), radiologic tests (computed tomographic colonography (CTC), double contrast barium enema), and visual endoscopic examinations (flexible sigmoidoscopy (FS), colonoscopy, and colon capsule endoscopy (CCE)) with their varying sensitivity and specificity. Biomarkers also play a vital role in assessing the recurrence of CRC. This review offers a summary of the current screening options, including biomarkers available to detect CRC, highlighting the benefits and challenges encompassing each screening modality.

Toxoplasma infection in male mice alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease.

During chronic infection, the single celled parasite, Toxoplasma gondii, can migrate to the brain where it has been associated with altered dopamine function and the capacity to modulate host behavior, increasing risk of neurocognitive disorders. Here we explore alterations in dopamine-related behavior in a new mouse model based on stimulant (cocaine)-induced hyperactivity. In combination with cocaine, infection resulted in heightened sensorimotor deficits and impairment in prepulse inhibition response, which are commonly disrupted in neuropsychiatric conditions. To identify molecular pathways in the brain affected by chronic T. gondii infection, we investigated patterns of gene expression. As expected, infection was associated with an enrichment of genes associated with general immune response pathways, that otherwise limits statistical power to identify more informative pathways. To overcome this limitation and focus on pathways of neurological relevance, we developed a novel context enrichment approach that relies on a customized ontology. Applying this approach, we identified genes that exhibited unexpected patterns of expression arising from the combination of cocaine exposure and infection. These include sets of genes which exhibited dampened response to cocaine in infected mice, suggesting a possible mechanism for some observed behaviors and a neuroprotective effect that may be advantageous to parasite persistence. This model offers a powerful new approach to dissect the molecular pathways by which T. gondii infection contributes to neurocognitive disorders.

Systematic profiling of the chicken gut microbiome reveals dietary supplementation with antibiotics alters expression of multiple microbial pathways with minimal impact on community structure.

BACKGROUND: The emergence of antimicrobial resistance is a major threat to global health and has placed pressure on the livestock industry to eliminate the use of antibiotic growth promotants (AGPs) as feed additives. To mitigate their removal, efficacious alternatives are required. AGPs are thought to operate through modulating the gut microbiome to limit opportunities for colonization by pathogens, increase nutrient utilization, and reduce inflammation. However, little is known concerning the underlying mechanisms. Previous studies investigating the effects of AGPs on the poultry gut microbiome have largely focused on 16S rDNA surveys based on a single gastrointestinal (GI) site, diet, and/or timepoint, resulting in an inconsistent view of their impact on community composition. METHODS: In this study, we perform a systematic investigation of both the composition and function of the chicken gut microbiome, in response to AGPs. Birds were raised under two different diets and AGP treatments, and 16S rDNA surveys applied to six GI sites sampled at three key timepoints of the poultry life cycle. Functional investigations were performed through metatranscriptomics analyses and metabolomics. RESULTS: Our study reveals a more nuanced view of the impact of AGPs, dependent on age of bird, diet, and intestinal site sampled. Although AGPs have a limited impact on taxonomic abundances, they do appear to redefine influential taxa that may promote the exclusion of other taxa. Microbiome expression profiles further reveal a complex landscape in both the expression and taxonomic representation of multiple pathways including cell wall biogenesis, antimicrobial resistance, and several involved in energy, amino acid, and nucleotide metabolism. Many AGP-induced changes in metabolic enzyme expression likely serve to redirect metabolic flux with the potential to regulate bacterial growth or produce metabolites that impact the host. CONCLUSIONS: As alternative feed additives are developed to mimic the action of AGPs, our study highlights the need to ensure such alternatives result in functional changes that are consistent with site-, age-, and diet-associated taxa. The genes and pathways identified in this study are therefore expected to drive future studies, applying tools such as community-based metabolic modeling, focusing on the mechanistic impact of different dietary regimes on the microbiome. Consequently, the data generated in this study will be crucial for the development of next-generation feed additives targeting gut health and poultry production. Video Abstract.

Waking Up to Monkeypox in the Midst of COVID-19.

The first incidence of the monkeypox virus (MPXV) was reported in a Danish research facility. Even though first discovered in monkeys, rodents account for the largest reservoir of the disease. It is an encapsulated, brick-shaped double-stranded DNA virus strongly related to the smallpox virus. The risk of acquiring MPXV has been found to be inversely related to smallpox vaccination. Although the cases were initially restricted to African countries, they were first reported outside Africa in the early 2000s. MPXV is transmitted through close personal contact, most commonly through direct skin-skin contact. The fatality rates associated with the MPXV tend to vary in different regions, with Congo clad basin having the highest mortality rate. The majority of the cases of MPXV have been reported in men who have sex with men. Although optimal infection control and treatment strategies are under investigation, the current management focus is on immunization and the isolation of patients. Effective control strategies are based on implementing a method of contact tracing, quarantining exposed and infected individuals, and using vaccines. There is no proven cure for MPXV, and most infected patients recover without medical intervention. Extensive studies are being conducted to determine the efficacy of antivirals in managing MPXV, with tecovirimat being the first antiviral medication approved by the Food and Drug Administration (FDA) to manage MPXV. The smallpox vaccine has traditionally been thought of as the most effective method of controlling the infection, possibly due to the similarities between the two viruses. However, numerous obstacles prevent the effective control of MPXV, including social isolation and stigma, poor understanding of the disease dynamics, lack of adequate patient education, and public health strategies.

A Comprehensive Review of Bradykinin-Induced Angioedema Versus Histamine-Induced Angioedema in the Emergency Department.

Angioedema (AE) is a condition that is frequently encountered in the emergency department (ED). It is a rare condition with localized, asymmetrical swelling of the skin and/or mucosa that is frequently nonpruritic and primarily affects locations with loose connective tissue. Physicians must have a thorough understanding of this condition since it can cause fatal airway compromise, which might be the presenting symptom. Histamine-mediated AE is the most common type of AE seen in EDs. However, ED physicians must be on the lookout for the less common bradykinin-mediated types of AE as these do not respond to the same therapy as histamine-mediated AE. Hospitals may lack specialized drugs or protocols, and many ED staff may be unable to identify or treat bradykinin-mediated AE. It is crucial to understand the pathophysiology of the various kinds of AE in order to optimize treatment. The goal of this review paper is to provide an overview of the pathophysiology, clinical manifestations, and treatment options for bradykinin and histamine-induced AE in the ED.

Transfusing Platelets During Bypass Rewarming in Neonates Improves Postoperative Outcomes: A Randomized Controlled Trial.

BACKGROUND: In neonates, transfusion of platelets after hemodilution from cardiopulmonary bypass (CPB) has been standard. We hypothesize that platelet administration during the rewarming phase before termination of CPB would reduce coagulopathy, enhance hemostasis, reduce transfusion, and improve postoperative outcomes after neonatal cardiac surgery. METHODS: A prospective, randomized trial was performed in 46 neonates. Controls received platelets only at the end of bypass with other blood products to assist in hemostasis. The treatment group received 10 mL/kg of platelets during the rewarming phase of bypass after cross-clamp release. After protamine, transfusion and perioperative management protocols were identical and constant among groups. RESULTS: Two neonates in each group were excluded secondary to postoperative need for extracorporeal support. Controls (n = 21) and treatment patients (n = 21) were similar in age, weight, case complexity, associated syndromes, single ventricle status, and CPB times. Compared to controls, the treatment group required 40% less postbypass blood products (58 ± 29 vs 103 ± 80 mL/kg, P = .04), and case completion time after protamine administration was 28 minutes faster (P = .016). The treatment group required fewer postoperative mediastinal explorations for bleeding (P = .045) and had a lower fluid balance (P = .04). The treatment group had shorter mechanical ventilation (P = .016) and length of intensive care unit times (P = .033). There were no 30-day mortalities in either group. CONCLUSION: Platelet transfusion during the rewarming phase of neonatal cardiac surgery was associated with reduced bleeding and improved postoperative outcomes, compared to platelets given after coming off bypass. Further studies are necessary to understand mechanisms and benefits of this strategy.

Tibial nerve decompression for the prevention of the diabetic foot: a cost-utility analysis using Markov model simulations.

OBJECTIVE: To determine whether tibial neurolysis performed as a surgical intervention for patients with diabetic neuropathy and superimposed tibial nerve compression in the prevention of the diabetic foot is cost-effective when compared with the current prevention programme. DESIGN: A baseline analysis was built on a 5-year model to determine the cumulative incidence of foot ulcers and amputations with each strategy. Subsequently, a cost-effectiveness analysis and cohort-level Markov simulations were conducted with a model composed of 20 6-month cycles. A sensitivity analysis was also performed. SETTING: A Markov model was used to simulate the effects of standard prevention compared with tibial neurolysis on the long-term costs associated with foot ulcers and amputations. This model included eight health states. PARTICIPANTS: Each cohort includes simulated patients with diabetic neuropathy at different levels of risk of developing foot ulcers and amputations. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the long-term trends concerning the development of ulcers and amputations with each strategy. The secondary outcome measures were quality adjusted life years (QALYs), incremental cost-effectiveness and net monetary benefits of the optimal strategy. RESULTS: When compared with standard prevention, for a patient population of 10 000, surgery prevented a simulated total of 1447 ulcers and 409 amputations over a period of 5 years. In a subsequent analysis that consisted of 20 6-month cycles (10 years), the incremental cost of tibial neurolysis compared with current prevention was $12 772.28; the incremental effectiveness was 0.41 QALYs and the incremental cost-effectiveness ratio was $31 330.78. Survival was 73% for those receiving medical prevention compared with 95% for those undergoing surgery. CONCLUSION: These results suggest that among patients with diabetic neuropathy and superimposed nerve compression, surgery is more effective at preventing serious comorbidities and is associated with a higher survival over time. It also generated greater long-term economic benefits.

Microbe and host interaction in gastrointestinal homeostasis.

RATIONALE: Researchers in psychiatry and neuroscience are increasingly recognizing the importance of gut-brain communication in mental health. Both genetics and environmental factors influence gut microbiota composition and function. This study examines host-microbe signaling at the gastrointestinal barrier to identify bottom-up mechanisms of microbiota-brain communication. OBJECTIVES: We examined differences in gut microbiota composition and fecal miRNA profiles in BALB/c and C57BL/6 mice, in relation to gastrointestinal homeostasis and evaluated the response to perturbation of the gut microbiota by broad-spectrum antibiotic treatment. METHODS AND RESULTS: Differences in the gut microbiota composition between BALB/c and C57BL/6 mice, evaluated by fecal 16S rRNA gene sequencing, included significant differences in genera Prevotella, Alistipes, Akkermansia, and Ruminococcus. Significant differences in fecal miRNA profiles were determined using the nCounter NanoString platform. A BLASTn analysis identified conserved fecal miRNA target regions in bacterial metagenomes with 14 significant correlations found between fecal miRNA and predicted taxa relative abundance in our dataset. Treatment with broad-spectrum antibiotics for 2 weeks resulted in a host-specific physiological response at the gastrointestinal barrier including a decrease in barrier permeability in BALB/c mice and alterations in the expression of barrier regulating genes in both strains. Genera Parabacteroides and Bacteroides were associated with changes in barrier function. CONCLUSIONS: The results of this study provide insight into how specific taxa influence gut barrier integrity and function. More generally, these data in the context of recent published studies makes a significant contribution to our understanding of host-microbe interactions providing new knowledge that can be harnessed by us and others in future mechanistic studies.

Deep Tracheal Extubation Using Dexmedetomidine in Children With Congenital Heart Disease Undergoing Cardiac Catheterization: Advantages and Complications.

Objective. Deep tracheal extubation using dexmedetomidine is safe and provides smooth recovery in children with congenital heart disease undergoing cardiac catheterization. Design. Single-institution, retrospective study of prospectively collected data. Participants. All patients aged between 1 month and 5 years who underwent general endotracheal anesthesia for diagnostic and interventional cardiac catheterizations in the cardiac catheterization suite from January 2015 (change in standard operating procedure) through October 2016 (approval of institutional review board for study). Measurement and Main Results. One hundred and eighty-nine patients (81%) of the 232 patients who underwent cardiac catheterization during the study period were noted to undergo deep tracheal extubation. Cyanotic heart disease was present in 87 patients (46%), history of prematurity in 51 (27%), and pulmonary hypertension in 26 (14%) patients. A documented smooth recovery in the postoperative care unit (PACU) requiring no additional analgesics or sedatives was observed in 91% of the patients. The majority of patients required no airway support after deep extubation (n = 140, 74%, P = .136). The presence of pulmonary hypertension (odds ratio = 4.45, P = .035) and presence of a cough on the day of the procedure (odds ratio = 7.10, P = .03) were significantly associated with the use of oxygen or use of oral airway for greater than 20 minutes in the PACU. After extubation, there were no reported events of aspiration, the use of noninvasive positive pressure ventilation, reintubation, heart block, or systemic hypotension requiring treatment or cardiac arrest. Conclusions. Deep extubation using dexmedetomidine in infants and toddlers after cardiac catheterization is feasible and enables smooth postoperative recovery with minimal adverse effects.

What Is Swimmer's Ear?

This Patient Page describes the causes, symptoms, and treatment of swimmer's ear.

Injection drug use in North America.

Injection drug use of psychotropic agents for nontherapeutic purposes is associated with some of the most pernicious infectious diseases seen in the United States. There is an inextricable link between infection, injection drug use (IDU) and other risk behaviors, especially those related to sexual activity. A number of national surveys now provide excellent databases to track the breadth, scope and impact of IDU across the United States. The prevalence of heroin use has increased over the past decade with larger numbers of users presenting for treatment of drug use disorders. A host of serious infections can result from IDU. Prevention and early intervention with evidence-based harm-reduction strategies are crucial to reducing and eliminating these odious consequences.

A randomized trial of one-day vs. three-day buprenorphine inpatient detoxification protocols for heroin dependence.

Detoxification from opioids remains an important first step in the treatment of many patients with opioid dependence. Several pharmacologic regimens have been used for opioid detoxification. In the United States, the partial mu-opioid agonist, buprenorphine (BUP) is the most recently approved pharmacotherapy for opioid detoxification and replacement. The literature in recent years has described detoxification protocols using a single high dose of BUP and a three-day BUP regimen. In many settings, such as drug-free programs, a single-dose detoxification protocol would be of significant benefit. There have been no prior studies comparing one-day and three-day BUP-assisted opioid withdrawal. In this pilot study, we conducted an open-label, randomized trial of one-day vs. three-day BUP/naloxone sublingual tablet-assisted opioid withdrawal. Twenty patients from a therapeutic community treatment program were randomly assigned to receive either 32 mg sublingual BUP over one hour (one-day group), or 32 mg sublingual BUP over three days (three-day group). Nine of 10 subjects (90 percent) in each group completed seven days in the detoxification protocol. There was no statistically significant difference between the two groups in all other outcome variables, including retention in the treatment program, intensity of withdrawal signs and symptoms, amounts of adjunct medications used, and ability to produce opiate-free urine. This study further validates the feasibility of the single high dose of BUP as a rapid detoxification method.