Persistent Radiculopathy Subsequent to Selective Nerve Root Block.

Transforaminal selective nerve root blocks are commonly performed for low back pain but are not without risk. This case report describes a 55-year-old man who underwent transforaminal selective nerve root block at the left lumbar (L) 4, L5, and sacral (S) 1 levels for radiating low back pain in the setting of moderate narrowing of the left L4-L5 foramen with impingement on the exiting left L4 nerve roots seen on magnetic resonance imaging (MRI). He developed left foot drop immediately after the procedure and presented to the acupuncture clinic two weeks later with persistent pain, left foot drop, and paresthesia of the left lateral shin. A repeat MRI of the lumbar spine showed mild enhancement of the left cauda equina, including the L5 and possibly L4 nerve roots. The large volume of injection into an area with neuroforaminal narrowing as well as the cytotoxicity of the contrast and anesthetic agents may have contributed to axon damage and left foot drop.

Hypopituitarism After Mild Traumatic Brain Injury: A Case Report.

Hypopituitarism is characterized by an underactive pituitary gland and may result in growth hormone deficiency, hypothyroidism, testosterone deficiency, and/or adrenal insufficiency. Traumatic brain injury (TBI) exposure is a known risk factor for hypopituitarism. However, patients with hypopituitarism secondary to TBI exposure may go undiagnosed because the signs and symptoms of hypopituitarism can be subtle. This case report describes a 40-year-old male US military veteran who endorsed fatigue, sexual dysfunction, and weight gain several years after experiencing multiple mild TBIs during his military service. He ultimately underwent a full neuroendocrine workup that revealed low testosterone in addition to previously diagnosed hypothyroidism with a resolution of symptoms after starting testosterone therapy.

A Systematic Review of Testosterone Therapy in Men With Spinal Cord Injury or Traumatic Brain Injury.

Spinal cord injuries (SCI) and traumatic brain injuries (TBI) increase the risk of testosterone deficiency and result in adverse changes in body composition and poor functional outcomes. The current systematic review aims to provide insights into the use of testosterone therapy for treating men with SCI and TBI. The PubMed and EMBASE databases were systematically reviewed using appropriate terms, and resulting manuscripts were screened using defined Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The patient population included male patients with SCI or TBI. Further inclusion criteria were: a) human participants 18 years of age or older; b) manuscript published in English; c) study included an intervention with exogenous testosterone; and d) articles published in peer-reviewed journals with full text available. Two reviewers independently extracted data regarding injury type, intervention, and outcomes. Following screening for inclusion/exclusion criteria, a total of 12 primary research studies conducted over the last 30 years were included. Men with SCI were investigated in 11 articles. The combination of testosterone patches and resistance training with functional electrical stimulation (FES) for 16 weeks in men with SCI and an average baseline testosterone level above the cutoff for testosterone deficiency increased muscle mass, strength, bone quality, and basal metabolic rate while testosterone patches without exercise for 16 weeks produced no significant changes in these parameters. Testosterone patches for 12 months in men with SCI and testosterone deficiency also increased lean tissue mass (LTM) and resting energy expenditure (REE). In one study, men with TBI and testosterone deficiency receiving testosterone gel for eight weeks showed a non-statistically significant greater absolute change in functional independence measure (FIM) and grip strength compared to a placebo group. Testosterone therapy with exercise may help improve muscle mass, bone health, strength, energy expenditure, and cardiac health in men with SCI without major side effects. It is difficult to draw conclusions regarding the effects of testosterone therapy in men with TBI based on the limited available evidence. Further investigation is warranted to explore the relationship between testosterone therapy and recovery after SCI and TBI.

Human-interpretable image features derived from densely mapped cancer pathology slides predict diverse molecular phenotypes.

Computational methods have made substantial progress in improving the accuracy and throughput of pathology workflows for diagnostic, prognostic, and genomic prediction. Still, lack of interpretability remains a significant barrier to clinical integration. We present an approach for predicting clinically-relevant molecular phenotypes from whole-slide histopathology images using human-interpretable image features (HIFs). Our method leverages >1.6 million annotations from board-certified pathologists across >5700 samples to train deep learning models for cell and tissue classification that can exhaustively map whole-slide images at two and four micron-resolution. Cell- and tissue-type model outputs are combined into 607 HIFs that quantify specific and biologically-relevant characteristics across five cancer types. We demonstrate that these HIFs correlate with well-known markers of the tumor microenvironment and can predict diverse molecular signatures (AUROC 0.601-0.864), including expression of four immune checkpoint proteins and homologous recombination deficiency, with performance comparable to 'black-box' methods. Our HIF-based approach provides a comprehensive, quantitative, and interpretable window into the composition and spatial architecture of the tumor microenvironment.

Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity.

The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen. MnTBAP treatment significantly decreased body weight and reduced white adipose tissue (WAT) mass in mice fed a HFD and a low fat diet (LFD). The reduction in adiposity was associated with decreased caloric intake without significantly altering energy expenditure, indicating that MnTBAP decreases adiposity in part by modulating energy balance. MnTBAP treatment also improved insulin action in HFD-fed mice, a physiologic response that was associated with increased protein kinase B (PKB) phosphorylation and expression in muscle and WAT. Since MnTBAP is a metalloporphyrin molecule, we hypothesized that its ability to promote weight loss and improve insulin sensitivity was regulated by heme oxygenase-1 (HO-1), in a similar fashion as cobalt protoporphyrins. Despite MnTBAP treatment increasing HO-1 expression, administration of the potent HO-1 inhibitor tin mesoporphyrin (SnMP) did not block the ability of MnTBAP to alter caloric intake, adiposity, or insulin action, suggesting that MnTBAP influences these metabolic processes independent of HO-1. These data demonstrate that MnTBAP can ameliorate pre-existing obesity and improve insulin action by reducing caloric intake and increasing PKB phosphorylation and expression.