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1.
Cureus ; 16(3): e56653, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38646223

ABSTRACT

Post-mastectomy pain syndrome (PMPS) is a syndrome broadly applied to the development of chronic pain after surgical breast intervention (i.e., lumpectomy and mastectomy). The incidence of PMPS is likely underreported, and this has contributed to a paucity of high-level evidence related to the treatment of the aforementioned condition. A drive to reduce the burden of opioid use has led to pain management physicians trialing a variety of strategies to help patients manage PMPS. This review discusses the latest evidence behind treatment options for PMPS, exploring medications as well as interventional techniques (e.g., nerve blocks, radiofrequency ablation, neuromodulation, and intrathecal drug delivery systems). Recent advances in neuromodulation technology are of particular interest here due to the well-localized nature of PMPS-related pain and the specificity with which modern neuromodulation techniques can generate an effect. Finally, the review proposes a framework with which to approach the care of patients with PMPS, with a specific emphasis on the early consideration of neuromodulation techniques along with functional and physical therapy to reduce patient medication burden and improve overall quality of life.

2.
Cureus ; 15(10): e47827, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38021503

ABSTRACT

Postmastectomy pain syndrome (PMPS) affects nearly half of patients who undergo mastectomy to treat breast cancer. As the survival rate of breast cancer increases with advancements in treatment, the incidence of PMPS is also increasing. Patients with PMPS can experience unrelenting, chronic pain refractory to traditional management with oral pharmacotherapy in conjunction with nonpharmacologic treatment (physical therapy, transcutaneous electrical nerve stimulation (TENS)). Neuromodulation is an emerging treatment modality for numerous chronic pain conditions. This case report highlights the tremendous success of spinal cord stimulator placement for a patient with PMPS.

3.
J Crohns Colitis ; 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37941424

ABSTRACT

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with high rates of post-colonoscopy colorectal cancer (PCCRC), but further in-depth qualitative analyses are required to determine whether they result from inadequate surveillance or aggressive IBD cancer evolution. METHODS: All IBD patients who had a colorectal cancer (CRC) diagnosed between January 2015 to July 2019 and a recent (<4 years) surveillance colonoscopy at one of four English hospital trusts underwent root cause analyses as recommended by the World Endoscopy Organisation to identify plausible PCCRC causative factors. RESULTS: 61% (n=22/36) of the included IBD CRCs were PCCRCs. They developed in patients with high cancer risk factors (77.8%; n=28/36) requiring annual surveillance, yet 57.1% (n=20/35) had inappropriately delayed surveillance. Most PCCRCs developed in situations where (i) an endoscopically unresectable lesion was detected (40.9%; n=9/22), (ii) there was a deviation from the planned management pathway (40.9%; n=9/22) e.g. service, clinician or patient-related delays in acting on a detected lesion, or (iii) lesions were potentially missed as they were typically located within areas of active inflammation or post-inflammatory change (36.4%; n=8/22). CONCLUSIONS: IBD PCCRC prevention will require more proactive strategies to reduce endoscopic inflammatory burden, improve lesion optical characterisation, adherence to recommended surveillance intervals and patient acceptance of prophylactic colectomy. However, the significant proportion appearing to originate from non-adenomatous-looking mucosa which fail to yield neoplasia on biopsy yet display aggressive cancer evolution highlight the limitations of current surveillance. Emerging molecular biomarkers may play a role in enhancing cancer risk stratification in future clinical practice.

4.
J Cardiothorac Vasc Anesth ; 37(10): 1946-1950, 2023 10.
Article in English | MEDLINE | ID: mdl-37455220

ABSTRACT

OBJECTIVES: A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries. DESIGN: This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019. SETTING: The data involved a single community hospital. PARTICIPANTS: A total of 417 patients were included in the study. INTERVENTIONS: The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation. MEASUREMENTS AND MAIN RESULTS: Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663). CONCLUSIONS: The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL.


Subject(s)
Hospitals, General , Operating Rooms , Humans , Retrospective Studies , Hemoglobins , Erythrocytes
5.
Cureus ; 15(2): e35174, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36949968

ABSTRACT

Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state is created by increased levels of nerve growth factor (NGF), which causes a cascade of sympathetic sprouting resulting in increased norepinephrine (NE) systemically. Reversal of this cascade by local anesthetic injection into the stellate ganglion thereby reduces NGF and sympathetic sprouting subsequently lowering overall norepinephrine levels. This is the unifying theory by which SGB is able to provide resolution for the varied clinical conditions described in this article.  This review article discusses the physiology of several conditions where stellate ganglion blocks are being investigated as an adjunct treatment modality, including anosmia, PTSD, long-COVID, chronic fatigue syndrome, menopausal hot flashes, and ventricular tachyarrhythmias. Overall, the current literature supporting the use of stellate ganglion blocks for several esoteric conditions is limited; however, case reports to date have shown promising evidence-based results supporting their use as an adjunctive treatment among patients with refractory symptoms to existing treatment algorithms. In conclusion, SGB should be considered among patients with refractory symptoms for medical management in the conditions discussed in this article. Further research is needed to delineate which patients will benefit from the use of SGB, the use of subsequent blocks and timelines in between injections, and unilateral versus bilateral blockade.

6.
Cureus ; 14(8): e27623, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36072193

ABSTRACT

Introduction Worldwide, diabetic retinopathy (DR) is one of the leading causes of vision loss. Early treatment and screening for DR have a major role in reducing the rate of the disease and the coronavirus disease 2019 (COVID-19) pandemic-related restrictions have altered real-world practice patterns in managing DR. Aims and objectives To evaluate the impact of the COVID-19 pandemic on the management of DR amongst patients presenting to a tertiary eye care center in Gujarat, India. Methods This is a cross-sectional study comparison of ophthalmic findings of 72 patients who presented to a tertiary care hospital with the manifestation of DR before and after the COVID-19 outbreak and subsequent lockdown. All the patients underwent detailed ophthalmic examinations, including optical coherence tomography (OCT) and fundus fluorescein angiography (FFA). Results The mean age of participants was 54.5 years, with the mean duration of diabetes being five years since first detected. Diabetes was present in 26 patients out of 72. The number of follow-up visits to an ophthalmologist before COVID-19 was at least every one to three months, which significantly decreased after the lockdown of COVID-19. We found a significant progression of DR and clinically significant macular edema (CSME) in patients with diabetes. Before COVID-19, there were two mild non-proliferative diabetic retinopathy (NPDR), seven moderate NPDR, 15 severe NPDR, and 15 very severe NPDR, which were increased post lockdown to three, nine, 27, and 21, respectively. The proliferative diabetic retinopathy (PDR) vitreous hemorrhage (VH) and tractional retinal detachment (TRD) were also increased to 12 after lockdown as compared to only six before the COVID-19 lockdown. The causes for progression are inability to attend regular check-ups, inability to take proper treatment of diabetes and DR, poor control of diabetes, episode of COVID-19, history of high dose of steroid use, poor kidney function, and not knowing that there is a progression of the disease. A common reason for not visiting an ophthalmologist was fear of the unknown due to COVID-19. Conclusions COVID-19 has severely impacted the routine follow-up of DR and, in the subsequent years, there might be an increased incidence of severe outcomes due to DR. The second wave of COVID-19 and its lockdown have had very significant effects on the visual outcome of untreated DR patients.

7.
Asian J Neurosurg ; 17(2): 386-388, 2022 Jun.
Article in English | MEDLINE | ID: mdl-36120618

ABSTRACT

Craniopharyngiomas are the most commonly presented nonglial tumors in child patients. They cause significant morbidity and mortality, both before and after surgery. The most common immediate postsurgery complications are attributable to pituitary insufficiency. Neurovascular complications account for only 2.7 to 2.9% surgical cases, and usually involve the vessels of the Circle of Willis. Thrombosis or vasospasm of the vessels of posterior circulation is unheard of. Here, we are reporting a unique case of a child with craniopharyngioma who developed acute spontaneous basilar artery thrombosis and posterior circulation stroke 6 days after surgery.

8.
Cureus ; 14(8): e28477, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36176883

ABSTRACT

Unintentional eye injuries are common in small children. If left unobserved by parents or caretakers, it is challenging to assess as the kids are in distress and pain. Penetrating trauma in or near the eye requires urgent treatment as it can lead to infection and other complications. Early diagnosis and management help avoid further complications. An 11-month-old female was presented by her parents at a tertiary care clinic with inconsolable crying and swelling over the right eye's upper lid for one day. There was a history of possible trauma with a pen while the child was playing. During the examination, swelling in the right periorbital region between the eye and nasal bridge with the opening of the foreign body tract was noted. A skull X-ray with orbit showed a radiopaque nib of the pen in the right periorbital soft tissue. Emergency surgery was planned under general anesthesia. Surgery was performed and the pen was extracted from the right periorbital soft tissue lying between the eye and nasal bridge. Parents and health care providers, including pediatricians, should assess a crying child with a trauma history carefully even with no apparent clinical findings. Efforts must be done to correlate clinical findings with proper history and other needed investigations.

9.
Cureus ; 14(12): e32295, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36628048

ABSTRACT

Stellate ganglion block (SGB) is gaining increasing acceptance as a treatment modality for various medical conditions. It works by blocking neuronal transmissions which in turn alleviates sympathetically-driven disease processes. Many of the prolonged sequelae of long COVID are thought to be mediated by dysregulation of the autonomic nervous system, and SGB is being investigated as a potential option for symptomatic management of long COVID. This case report demonstrates the efficacy of SGB in a previously healthy patient for the management of long COVID symptoms including fatigue, post-exertional malaise, shortness of breath, and gastrointestinal symptoms. .

10.
Front Behav Neurosci ; 15: 725856, 2021.
Article in English | MEDLINE | ID: mdl-34744651

ABSTRACT

While a bidirectional positive link between palatable food intake and alcohol drinking has been suggested, several rodents studies report reduced alcohol drinking following palatable diets exposure. These studies utilized purified rodents' diets high in sugar/fat; however, the effects of hyper-palatable food (HPF) rich in fat and sugar on alcohol drinking remain unclear. Furthermore, neural substrates involved in HPF-mediated changes in alcohol consumption are poorly understood. Therefore, the present study evaluated the effects of patterned feeding of a hyper-palatable food (Oreo cookies) on alcohol drinking as well as dopamine (DA) and serotonin (5-HT) content in rat's mesocorticolimbic (medial-prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens) circuitry. Male Long Evans rats received 8-weeks of intermittent (Mon, Tue, Wed) Oreo cookies access, which induced a patterned feeding, in which rats in the Oreo group overconsumed calories on HPF days whereas underconsumption was observed on chow only (Thu, Fri) days. Following HPF exposure, alcohol consumption was evaluated while patterned feeding continued. Alcohol intake in the Oreo group was significantly lower as compared to the chow controls. However, alcohol intake in the Oreo group increased to the levels seen in the group receiving chow following the suspension of patterned HPF feeding. Finally, DA levels in the nucleus accumbens were significantly greater, whereas its metabolite (DOPAC) levels were lower in the Oreo group compared to the chow controls. Surprisingly, 5-HT levels remained unaltered in all tested brain areas. Together, these data suggest that HPF-associated increased DA availability and reduced DA turnover within mesocorticolimbic circuitry may regulate alcohol drinking following patterned HPF feeding.

11.
J Pain Res ; 14: 2139-2164, 2021.
Article in English | MEDLINE | ID: mdl-34295184

ABSTRACT

Moderate to severe pain occurs in many cancer patients during their clinical course and may stem from the primary pathology, metastasis, or as treatment side effects. Uncontrolled pain using conservative medical therapy can often lead to patient distress, loss of productivity, shorter life expectancy, longer hospital stays, and increase in healthcare utilization. Various publications shed light on strategies for conservative medical management for cancer pain and a few international publications have reviewed limited interventional data. Our multi-institutional working group was assembled to review and highlight the body of evidence that exists for opioid utilization for cancer pain, adjunct medication such as ketamine and methadone and interventional therapies. We discuss neurolysis via injections, neuromodulation including targeted drug delivery and spinal cord stimulation, vertebral tumor ablation and augmentation, radiotherapy and surgical techniques. In the United States, there is a significant variance in the interventional treatment of cancer pain based on fellowship training. As a first of its kind, this best practices and interventional guideline will offer evidenced-based recommendations for reducing pain and suffering associated with malignancy.

12.
Nutr Res ; 89: 45-55, 2021 05.
Article in English | MEDLINE | ID: mdl-33894660

ABSTRACT

Visual analogue scales (VAS) have commonly been used to assess appetite in children 8 years and older; however, these tools have been considered unreliable for children 7 years old and under. The objective of this pilot study was to develop a picture-based appetite assessment (PBAA) tool for children aged 4-10 years and pilot test it compared to a VAS-based appetite assessment. The study hypothesis was that the PBAA scores would decrease following the consumption of an ad libitum snack compared to the scores in the fasted state in children 4 to 10 years old; furthermore, there would be a good level of agreement (intraclass correlation coefficients >0.75) between the appetite scores by the PBAA and VAS tools in children aged 8 years or older. At Visit 1, in a fasted state, all children (n = 15) completed the PBAA. Children who were 8-10 years old (n = 8) also completed the VAS-based appetite assessment. Then, an ad libitum snack was provided, and appetite assessments were repeated at 5-, 30- and 60-minutes post-snack. The same assessments were completed at visit 2 pre (fasting)- and post-consumption of a snack containing 25% of the amount consumed at visit 1 (limited snack). PBAA scores were different across time (P < .001) and between types of meal (ad libitum vs limited snack) (P = .015) in all children. A good agreement between the PBAA and VAS scores at 30 and 60 minutes after both types of meal was found (intraclass correlation coefficients >0.75). The PBAA tool was able to detect expected changes in appetite sensations and was in good agreement with the VAS instrument.


Subject(s)
Appetite , Child , Child, Preschool , Fasting , Female , Humans , Hunger , Male , Meals , Pilot Projects , Satiation , Sensation , Snacks , Visual Analog Scale
13.
Article in English | MEDLINE | ID: mdl-33927839

ABSTRACT

Background. Pediatric endodontics is a field with constant evolution, resulting in the shifting of paradigms from the use of conventional hand files to rotary files for biomechanical preparation in primary teeth. Biomechanical preparation plays a crucial role in the success of root canal treatment. Primary teeth need special attention since they differ from permanent teeth in root canal morphology. Cleaning and shaping of the canals damage the root dentin, leading to dentinal cracks. Newer techniques for root canal preparation, including Ni-Ti rotary files and SAF system, have been developed for use in pediatric endodontics to overcome the drawbacks of conventional methods. The present study compared dentinal defects formed by rotary systems in primary teeth. Methods. Eighty primary teeth were included. The teeth were decoronated with a diamond disc. All the roots were inspected for any pre-existing cracks or craze lines under transmitted light under a stereomicroscope. The specimens were then divided into four groups (n=20): group 1: control, group 2: hand files (HF), group 3: ProTaper files, and group IV: SAF files. The samples were instrumented according to the group they were assigned to. Results. The HF and SAF groups exhibited fewer microcracks. Dentinal microcracks were observed in roots prepared with rotary ProTaper files. There were significant differences between HF/SAF and rotary files (P <0.05). Conclusion. Stainless steel hand K-files and SAF instruments resulted in fewer dentinal damage than the ProTaper Universal files. SAF exhibited satisfactory results with minimal or no crack formation.

15.
Int J Clin Pharm ; 42(5): 1319-1325, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32865678

ABSTRACT

Background The Transit Care Hub (TCH) is an inpatient ward traditionally used as a waiting area for patients who require transport to return home. In July 2018, a six-month pilot of a TCH pharmacist was funded to improve the flow of patients through the hospital. Setting Major Australian teaching hospital. Objective(s) To determine the effect that the TCH pharmacist had on patient flow within the hospital and on the time saved for other clinical pharmacists, as well as estimating cost savings. Methods A service delivery framework for the TCH pharmacist was developed and tested. This involved a proactive approach to patient discharge with ward-based staff. Data were collected from July to November 2018, 20 weeks prior to and 20 weeks after the commencement of the pilot. Main outcome measure Measurements included the number of best possible medication histories (BPMHs) completed during admission, improvements in arrival time to TCH from inpatient wards and cost savings. Results During the pilot study period (20 weeks), 791 patients were discharged by the TCH pharmacist, arriving an average of 70 minutes earlier than other patients discharging through TCH. There was a 16% increase in patients discharging through TCH which released ward beds. The TCH pharmacist increased the number of BPMHs on day of admission by 14%. There was an estimated annual saving of AU$252,008 for the hospital. Conclusions The TCH pharmacist service enhanced patient flow by coordinating earlier discharges, increasing the timely completion of BPMHs, and saving ward pharmacist time. Significant cost savings supported a permanently funded position.


Subject(s)
Patient Discharge , Patient Transfer/organization & administration , Pharmacists/organization & administration , Pharmacy Service, Hospital/organization & administration , Australia , Cost Savings , Hospitals, Teaching/economics , Humans , Medication Reconciliation , Patient Discharge/economics , Patient Transfer/economics , Pilot Projects , Professional Role , Time Factors
16.
Physiol Behav ; 224: 113020, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32574662

ABSTRACT

Recent studies from our lab have demonstrated that intermittent high-fat diet access reduces alcohol drinking in rats. However, it was unclear if caloric overload, palatability, or diet itself triggered reduced alcohol drinking. It is also unknown if a similar paradigm could reduce relapse-like alcohol drinking. The presented study tested the hypothesis that acute intermittent palatable diet (PD) access would rescue relapse-like drinking and palatability, but not diet itself contributes to reduced drinking. Male Long Evans rats received six-weeks intermittent or chronic chow (controls) or PDs (high-fat diet, high-sugar diet) exposure, and alcohol testing occurred following PDs suspension. Alcohol intake was not significantly different among groups in either condition, suggesting that diet itself did not impact alcohol drinking. A subset of these rats received two-weeks intermittent PDs (Int-PDs) exposure and alcohol testing reinitiated while Int-PDs access continued. Alcohol intake significantly escalated (~137% compared to baseline; alcohol deprivation effect) in the chow controls, whereas it remained unchanged in PD groups. These data demonstrate the critical importance of acute intermittent PDs availability and its protective effect in relapse-like drinking. To assess the contribution of palatability in reduced alcohol drinking, a separate group of rats received two-weeks intermittent high-sugar diet (Int-HSD) or saccharin (Int-SAC) access and tested for alcohol drinking while Int-HSD/SAC continued. Alcohol drinking significantly decreased (~30%) in both HSD and SAC groups compared to the controls. These data identify the critical parameters by which acute intermittent PD access reduces alcohol drinking and could have important therapeutic implications in the management of alcoholism.


Subject(s)
Alcohol Drinking , Diet, High-Fat , Animals , Diet, High-Fat/adverse effects , Ethanol , Male , Rats , Rats, Long-Evans , Saccharin
17.
Nutrients ; 11(11)2019 Nov 11.
Article in English | MEDLINE | ID: mdl-31717954

ABSTRACT

We have previously shown that 6 weeks of intermittent high-fat diet (Int-HFD) pre-exposure significantly reduced alcohol drinking in rats, providing preliminary evidence of the effectiveness of a dietary intervention in reducing alcohol intake. However, the functional framework and underlying neurobiological mechanisms of such dietary intervention are unknown. Here, we examined the impact of Int-HFD pre-exposure duration on alcohol drinking, plasma feeding peptides, and central neurotransmitter receptors gene expression. Male Long Evans rats (n = 6-7/group) received no pre-exposure, 1 or 2 weeks pre-exposure to Int-HFD and alcohol drinking (two-bottle choice) was evaluated. We observed HFD pre-exposure-dependent decrease in alcohol drinking, with a significant decrease observed following 2 weeks of Int-HFD pre-exposure. No significant between-group differences in plasma feeding peptides (i.e., ghrelin, leptin, insulin) were detected. A PCR array revealed that the expression of several neurotransmitter receptors was significantly (p < 0.05 and ≥2-fold) altered in the striatum and ventral tegmental area compared to controls. These data suggest that pre-exposure to a palatable diet is critical to reduce alcohol drinking in rats, possibly through genetic alterations in the brain reward circuitry. Importantly, the present study is a step forward in identifying the critical framework needed to evaluate the therapeutic potential of nutritional contingency in the management of alcoholism.


Subject(s)
Alcohol Drinking/metabolism , Diet, High-Fat , Receptors, Neurotransmitter/metabolism , Animals , Body Weight , Dietary Fats/metabolism , Feeding Behavior , Male , Peptide Hormones/metabolism , Rats , Rats, Long-Evans , Transcriptome
18.
J Anaesthesiol Clin Pharmacol ; 35(4): 548-552, 2019.
Article in English | MEDLINE | ID: mdl-31920244

ABSTRACT

BACKGROUND AND AIMS: Epidural analgesia is believed to be the most difficult technique to learn for a trainee. The reason for this is not only inexperience of the provider and the complexity of the technique but also patient factors like obesity, spinal deformity and others which makes the epidural placement difficult. The aim of this study was to evaluate some of the common risk factors for difficult epidural placement as perceived by the anesthesia providers during training, with varying level of experience. MATERIAL AND METHODS: This prospective observational study includes patients who received epidural placement for labor analgesia. Data recorded on these patients included age, height, weight, body mass index (BMI), ease of palpation of the spinous process, level of epidural placement, number of attempts, time taken for epidural placement and experience of the provider. The association between the variables were assessed using logistic regression for first attempt success and Cox proportional hazard ratio for time to epidural placement. RESULTS: A total of 373 patients received epidural placement for labor analgesia. The mean BMI at the time of placement was 34. The first attempt success rate for the placement of epidural was 67% (n = 273). Women with well palpable spinous process were 3.3 times more likely to have a successful first attempt placement irrespective of the provider experience or BMI [3.39 (1.77-6.51), P < 0.001]. The time to placement was shorter in patients with good anatomical landmarks [1.58 (1.20-2.07), P < 0.001) and when performed by a trainee who had performed a minimum of 20 epidural procedures [1.57 (1.26-1.94), P < 0.001). CONCLUSION: Inability to palpate the spinous process contributes to multiple attempts at epidural placement when performed by a trainee.

19.
J Clin Invest ; 128(11): 5137-5149, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30188869

ABSTRACT

Despite the success of immune checkpoint blockade against melanoma, many "cold" tumors like prostate cancer remain unresponsive. We found that hypoxic zones were prevalent across preclinical prostate cancer and resisted T cell infiltration even in the context of CTLA-4 and PD-1 blockade. We demonstrated that the hypoxia-activated prodrug TH-302 reduces or eliminates hypoxia in these tumors. Combination therapy with this hypoxia-prodrug and checkpoint blockade cooperated to cure more than 80% of tumors in the transgenic adenocarcinoma of the mouse prostate-derived (TRAMP-derived) TRAMP-C2 model. Immunofluorescence imaging showed that TH-302 drives an influx of T cells into hypoxic zones, which were expanded by checkpoint blockade. Further, combination therapy reduced myeloid-derived suppressor cell density by more than 50%, and durably reduced the capacity of the tumor to replenish the granulocytic subset. Spontaneous prostate tumors in TRAMP transgenic mice, which completely resist checkpoint blockade, showed minimal adenocarcinoma tumor burden at 36 weeks of age and no evidence of neuroendocrine tumors with combination therapy. Survival of Pb-Cre4, Ptenpc-/-Smad4pc-/- mice with aggressive prostate adenocarcinoma was also significantly extended by this combination of hypoxia-prodrug and checkpoint blockade. Hypoxia disruption and T cell checkpoint blockade may sensitize some of the most therapeutically resistant cancers to immunotherapy.


Subject(s)
Adenocarcinoma/therapy , Immunotherapy , Neoplasms, Experimental/therapy , Nitroimidazoles/pharmacology , Phosphoramide Mustards/pharmacology , Prostatic Neoplasms/therapy , T-Lymphocytes/immunology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Animals , Cell Hypoxia/genetics , Cell Hypoxia/immunology , Cell Line, Tumor , Male , Mice , Mice, Knockout , Neoplasm Proteins/genetics , Neoplasm Proteins/immunology , Neoplasms, Experimental/genetics , Neoplasms, Experimental/immunology , Neoplasms, Experimental/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/immunology , Prostatic Neoplasms/pathology , T-Lymphocytes/pathology
20.
J Obes ; 2018: 8419120, 2018.
Article in English | MEDLINE | ID: mdl-29666701

ABSTRACT

Purpose: There are limited resources for long-term specialist follow-up after bariatric surgery. In selected centres, patients can access a postoperative support group, but there is no clear evidence to guide their delivery. Materials and Methods: A retrospective study of bariatric surgery patients (n = 152) who had been discharged from specialist follow-up (mean time since surgery 5.5 years), covering weight history, physical and psychosocial comorbidities, and the need for a postoperative bariatric support group. Results: Fifty-eight percent wanted a postbariatric surgery patient support group. This was not associated with operation type or the amount of weight lost or regained. However, those who wanted a support group were significantly more likely to be struggling to keep the weight off, to be unhappy with the way they look, or to be experiencing difficulties returning to work. Conclusions: These data point to an unmet patient requirement for a postoperative support group that is independent of weight loss success. More research is required to ascertain how such a group should be delivered, but our data would suggest that supporting patients with weight loss maintenance, body image, and return to work is an important part of postoperative care, and these needs extend well beyond the immediate period of specialist follow-up.


Subject(s)
Bariatric Surgery , Needs Assessment , Obesity, Morbid/surgery , Self-Help Groups , Weight Loss , Adult , Aged , Female , Humans , Male , Middle Aged , Obesity, Morbid/psychology , Patient Preference , Retrospective Studies , Surveys and Questionnaires
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