The aim of this study is to assess the impact of frailty on short-term outcomes after hepatectomy... more The aim of this study is to assess the impact of frailty on short-term outcomes after hepatectomy for colorectal liver metastasis (CRLM). Patients were identified using the National Surgical Quality Improvement Program (NSQIP). Patients were divided into 3 categories using the 5-item Modified Frailty Index (mFI). There were 5230 patients included. 52%, 35%, and 13% had mFI scores of 0, 1, and ≥ 2 respectively. Patients with a ≥ 2 mFI score were more likely to experience minor complication (OR 1.34, 95% CI 1.06–1.69), major complication (OR 1.56, 95% CI 1.15–2.12), readmission (OR 1.55, 95% CI 1.12–2.14), unfavorable discharge (OR 2.48, 95% CI 1.62–3.80), 30-day mortality (OR 3.02, 95% CI 1.02–8.95), prolonged length of stay (OR 1.47, 95% CI 1.18–1.83), and bile leak (OR 1.51, 95% CI 1.02–2.24). Frailty is associated with increased post-operative complications. The 5-item mFI can guide risk stratification, optimization, and counseling.
Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral... more Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral nervous systems. Axonopathy is characterized by axonal degeneration and dysfunctional axonal transport. Peripheral axonopathies are more common than central axonopathies due to their lack of protection from the blood–brain barrier and resultant vulnerability to metabolic challenges. Although the pathogenic mechanisms of peripheral axonal neuropathy are
A punch biopsy of the skin is commonly used to quantify intraepidermal nerve fiber densities (IEN... more A punch biopsy of the skin is commonly used to quantify intraepidermal nerve fiber densities (IENFD) for the diagnosis of peripheral polyneuropathy (1,2). At present, it is common practice to collect 3 mm skin biopsies from the distal leg (DL) and the proximal thigh (PT) for the evaluation of length-dependent polyneuropathies (3). However, due to the multidirectional nature of IENFs, it is challenging to examine overlapping nerve structures through the analysis of two-dimensional (2D) imaging. Alternatively, three-dimensional (3D) imaging could provide a better solution for this dilemma. In the current report, we present methods for applying 3D imaging to study painful neuropathy (PN). In order to identify IENFs, skin samples are processed for immunofluorescent analysis of protein gene product 9.5 (PGP), a pan neuronal marker. At present, it is standard practice to diagnose small fiber neuropathies using IENFD determined by PGP immunohistochemistry using brightfield microscopy (4). ...
Abstract Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and p... more Abstract Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral nervous systems. Axonopathy is characterized by axonal degeneration and dysfunctional axonal transport. Peripheral axonopathies are more common than central axonopathies ...
Journal of Neuropathology and Experimental Neurology, 2009
C57BLKS db/db (db/db) mice develop a neuropathy with features of human type 2 diabetic neuropathy... more C57BLKS db/db (db/db) mice develop a neuropathy with features of human type 2 diabetic neuropathy. Here, we demonstrate that these mice develop transient mechanical allodynia at the early stage of diabetes. We hypothesized that nerve growth factor (NGF), which enhances the expression of key mediators of nociception (i.e. substance P [SP] and calcitonin gene-related peptide), contributes to the development of mechanical allodynia in these mice. We found that NGF, SP, and calcitonin gene-related peptide gene expression is upregulated in the dorsal root ganglion (DRG) of db/db mice before or during the period that they develop mechanical allodynia. There were more small- to medium-sized NGF-immunopositive DRG neurons in db/db mice than in control db+ mice; these neurons also expressed SP, consistent with its role in nociception. Nerve growth factor expression in the hind paw skin was also increased in a variety of dermal cell types and nerve fibers, suggesting the contribution of a peripheral source of NGF to mechanical allodynia. The upregulation of NGF coincided with enhanced tropomyosin-related kinase A receptor phosphorylation in the DRG. Finally, an antibody against NGF inhibited mechanical allodynia and decreased the numbers of SP-positive DRG neurons in db/db mice. These results suggest that inhibition of NGF action is a potential strategy for treating painful diabetic neuropathy.
To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DP... more To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, normalized measures of serum oxidative stress and triglycerides, but had no effect on low density lipoproteins or total cholesterol. Moreover, while pioglitazone treatment normalized renal function, pioglitazone had no effect on measures of large myelinated nerve fibers, specifically sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals identified an unanticipated increase in adipogenesis-, adipokine signaling- a...
The aim of this study is to assess the impact of frailty on short-term outcomes after hepatectomy... more The aim of this study is to assess the impact of frailty on short-term outcomes after hepatectomy for colorectal liver metastasis (CRLM). Patients were identified using the National Surgical Quality Improvement Program (NSQIP). Patients were divided into 3 categories using the 5-item Modified Frailty Index (mFI). There were 5230 patients included. 52%, 35%, and 13% had mFI scores of 0, 1, and ≥ 2 respectively. Patients with a ≥ 2 mFI score were more likely to experience minor complication (OR 1.34, 95% CI 1.06–1.69), major complication (OR 1.56, 95% CI 1.15–2.12), readmission (OR 1.55, 95% CI 1.12–2.14), unfavorable discharge (OR 2.48, 95% CI 1.62–3.80), 30-day mortality (OR 3.02, 95% CI 1.02–8.95), prolonged length of stay (OR 1.47, 95% CI 1.18–1.83), and bile leak (OR 1.51, 95% CI 1.02–2.24). Frailty is associated with increased post-operative complications. The 5-item mFI can guide risk stratification, optimization, and counseling.
Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral... more Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral nervous systems. Axonopathy is characterized by axonal degeneration and dysfunctional axonal transport. Peripheral axonopathies are more common than central axonopathies due to their lack of protection from the blood–brain barrier and resultant vulnerability to metabolic challenges. Although the pathogenic mechanisms of peripheral axonal neuropathy are
A punch biopsy of the skin is commonly used to quantify intraepidermal nerve fiber densities (IEN... more A punch biopsy of the skin is commonly used to quantify intraepidermal nerve fiber densities (IENFD) for the diagnosis of peripheral polyneuropathy (1,2). At present, it is common practice to collect 3 mm skin biopsies from the distal leg (DL) and the proximal thigh (PT) for the evaluation of length-dependent polyneuropathies (3). However, due to the multidirectional nature of IENFs, it is challenging to examine overlapping nerve structures through the analysis of two-dimensional (2D) imaging. Alternatively, three-dimensional (3D) imaging could provide a better solution for this dilemma. In the current report, we present methods for applying 3D imaging to study painful neuropathy (PN). In order to identify IENFs, skin samples are processed for immunofluorescent analysis of protein gene product 9.5 (PGP), a pan neuronal marker. At present, it is standard practice to diagnose small fiber neuropathies using IENFD determined by PGP immunohistochemistry using brightfield microscopy (4). ...
Abstract Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and p... more Abstract Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral nervous systems. Axonopathy is characterized by axonal degeneration and dysfunctional axonal transport. Peripheral axonopathies are more common than central axonopathies ...
Journal of Neuropathology and Experimental Neurology, 2009
C57BLKS db/db (db/db) mice develop a neuropathy with features of human type 2 diabetic neuropathy... more C57BLKS db/db (db/db) mice develop a neuropathy with features of human type 2 diabetic neuropathy. Here, we demonstrate that these mice develop transient mechanical allodynia at the early stage of diabetes. We hypothesized that nerve growth factor (NGF), which enhances the expression of key mediators of nociception (i.e. substance P [SP] and calcitonin gene-related peptide), contributes to the development of mechanical allodynia in these mice. We found that NGF, SP, and calcitonin gene-related peptide gene expression is upregulated in the dorsal root ganglion (DRG) of db/db mice before or during the period that they develop mechanical allodynia. There were more small- to medium-sized NGF-immunopositive DRG neurons in db/db mice than in control db+ mice; these neurons also expressed SP, consistent with its role in nociception. Nerve growth factor expression in the hind paw skin was also increased in a variety of dermal cell types and nerve fibers, suggesting the contribution of a peripheral source of NGF to mechanical allodynia. The upregulation of NGF coincided with enhanced tropomyosin-related kinase A receptor phosphorylation in the DRG. Finally, an antibody against NGF inhibited mechanical allodynia and decreased the numbers of SP-positive DRG neurons in db/db mice. These results suggest that inhibition of NGF action is a potential strategy for treating painful diabetic neuropathy.
To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DP... more To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, normalized measures of serum oxidative stress and triglycerides, but had no effect on low density lipoproteins or total cholesterol. Moreover, while pioglitazone treatment normalized renal function, pioglitazone had no effect on measures of large myelinated nerve fibers, specifically sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals identified an unanticipated increase in adipogenesis-, adipokine signaling- a...
Uploads
Papers by Jacqueline Dauch