Mind-body therapies adjuvant to chemotherapy improve quality of life and fatigue in top cancers: A systematic review and meta-analysis.

BACKGROUND: Breast, lung and colorectal cancers are 3 of the top 4 most common cancers worldwide. Their treatment with chemotherapy often results in adverse effects on quality of life, fatigue and functional exercise capacity amongst patients. Mind-body therapies, including yoga, Tai chi and Qigong, are commonly used as complementary and alternative therapies in cancer. This meta-analysis evaluates the effects of yoga, Tai chi and Qigong in alleviating the adverse effects of chemotherapy. METHODS: Various databases were systematically interrogated using specific search terms, returning 1901 manuscripts. Removal of duplicates, irrelevant studies, those lacking available data and applying inclusion/exclusion criteria reduced this number to 9 manuscripts for inclusion in the final meta-analyses. Mean differences were calculated to determine pooled effect sizes using RStudio. RESULTS: This is the first systematic review and meta-analysis to demonstrate significant improvements in fatigue for colorectal cancer patients undergoing chemotherapy with a reduction of -1.40 (95 % CI: -2.24 to -0.56; p = 0.001) observed in mind-body therapy intervention groups. CONCLUSION: Yoga, Tai chi and Qigong could all be implemented alongside adjuvant therapies to alleviate the adverse effects on colorectal cancer patient fatigue during chemotherapy treatment. REVIEW REGISTRATION: This systematic review and meta-analysis is registered on InPlasy: registration number INPLASY202390035; doi: https://doi.org/10.37766/inplasy2023.9.0035.

Advancing Health Equity Knowledge, Attitudes, and Beliefs Within a National Health Nonprofit Organization.

OBJECTIVE: This study presents survey results assessing the impact of the American Cancer Society (ACS) health equity (HE) training on staff knowledge, attitudes, and beliefs about HE and social determinants of health (SDOH). DESIGN: This study is a quasi-experimental design examining survey responses over time and comparing responses from staff who participated in ACS HE training sessions and education opportunities and those who did not. SETTING: An electronic Web survey was distributed to all ACS and American Cancer Society Cancer Action Network (ACS CAN) staff in each of the 3 years that the training was held (2018-2020). PARTICIPANTS: ACS and ACS CAN staff who chose to take the survey were included in the study. INTERVENTION: Engagement with training hosted by the ACS HE team was examined. Training sessions were intended to introduce staff to HE and SDOH in the context of cancer outcomes and provide staff with the skills to become HE champions in the organization. MAIN OUTCOME MEASURES: This study examines whether participation in training sessions hosted by the HE team had an impact on knowledge of HE terms, attitudes, and beliefs about HE and engagement with HE. RESULTS: Trained respondents had a significantly higher HE knowledge summary score (98%) than those who were not trained (79%, SD = 0.26100, P < .001). Respondents who participated in training were more likely to believe that they could advance HE through their work at ACS and ACS CAN (88% compared with 66% of those who were not trained, SD = 0.47300, P < .001). Respondents who participated in training scored an average of 4.7 out of 6 on HE engagement compared with 3.8 among the untrained (SD = 1.425, P < .001). CONCLUSIONS: These findings demonstrate that participation in HE training is associated with higher levels of knowledge about HE and stronger personal attitudes and beliefs about the importance of addressing SDOH. This is a foundational step in staff taking action to integrate HE concepts into their day-to-day work toward reducing inequities in access to cancer treatment and health outcomes.

Early efficacy of teprotumumab for the treatment of dysthyroid optic neuropathy: A multicenter study.

PURPOSE: To study post-interventional findings in patients with dysthyroid optic neuropathy (DON) treated with teprotumumab. OBSERVATIONS: In this multicenter observational Case series, patients with DON were treated with teprotumumab, an insulin-like growth factor I receptor inhibitor (10 mg/kg for the first infusion then 20 mg/kg for subsequent infusions, every three weeks for a total 8 infusions). This study included patients with acute and chronic thyroid eye disease (TED) with DON who had failed conventional therapies and were not candidates for surgical decompression. Data collected included best corrected visual acuity (BCVA), color vision, RAPD when present, and orbital CT or MRI. Proptosis, clinical activity score (CAS), Gorman diplopia score (GDS), and Humphrey visual fields (HVF) were also evaluated.Ten patients (6 women, 4 men) with an average age 64 years old were included in this study. Mean follow up after completion of infusions was 15 weeks. Baseline visual acuity (VA) impairment ranged from hand motion (HM) to 20/25 in affected eyes. All patients had pre-treatment orbital CT or MRI that confirmed orbital apex compression. Seventy percent of patients had objective improvement in DON after 2 infusions of teprotumumab measured as significant improvement in visual acuity, resolution of RAPD, or both. After completion of treatment, affected eyes had a mean BCVA improvement of 0.87 logMAR (p=0.0207), proptosis reduction of 4.7 mm (p<0.00001), CAS improvement of 5.25 points (p<0.00001), and GDS improvement of 0.75 points (p=0.160). All 6 patients who presented with an RAPD had resolution or improvement of RAPD. All 7 patients who presented with color vision deficits had normalization or improvement of color vision. CONCLUSIONS AND IMPORTANCE: Teprotumumab infusions resulted in medical decompression and objective resolution or improvement of dysthyroid optic neuropathy. Most patients had rapid improvement of visual acuity and reversal of RAPD. Post-infusion imaging demonstrated reduction in extraocular muscle size that correlated with improvement in visual dysfunction. However, patients who presented with longstanding severe visual loss had limited improvement. There was no recurrence of DON after completion of teprotumumab in our cohort.

The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor.

BACKGROUND: Multiple myeloma is a plasma cell tumour with approximately 5500 new cases in the UK each year. Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib. The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors. The most apparent combination for ixazomib is therefore with CD. METHODS: MUK eight is a randomised, controlled, open, parallel group, multi-centre phase II trial that will recruit patients with RRMM who have relapsed after treatment with thalidomide, lenalidomide, and a proteasome inhibitor. The primary objective of the trial is to evaluate whether ixazomib in combination with cyclophosphamide and dexamethasone (ICD) has improved clinical activity compared to CD in terms of progression-free survival (PFS). Secondary objectives include comparing toxicity profiles and the activity and cost-effectiveness of both treatments. Since opening, the trial has been amended to allow all participants who experience disease progression (as per the IMWG criteria) on the CD arm to subsequently switch to receive ICD treatment, once progression has been confirmed with two clinical members of the Trial Management Group (TMG). This 'switch' phase of the study is exploratory and will assess second progression-free survival measured from randomisation to second disease progression (PFS2) and progression-free survival from the point of switching to second disease progression (PFS Switch) in participants who switch from CD to ICD treatment. DISCUSSION: Development of ixazomib offers the opportunity to further investigate the value of proteasome inhibition through oral administration in the treatment of RRMM. Previous studies investigating the safety and efficacy of ICD in patients with RRMM demonstrate a toxicity profile consistent with ixazomib in combination with lenalidomide and dexamethasone, whilst the combination showed possible activity in RRMM patients. Further investigation of the anti-tumour effect of this drug in RRMM patients is therefore warranted, especially since no trials comparing CD with ICD have been completed at present. TRIAL REGISTRATION: ISRCTN number: ISRCTN58227268 . Registered on 26 August 2015.

Visual Outcomes of Patients With Retrobulbar Hemorrhage Undergoing Lateral Canthotomy and Cantholysis.

PURPOSE: Evaluate visual outcomes in relation to time from injury to intervention in patients who undergo lateral canthotomy with cantholysis (LCC) for retrobulbar hemorrhage (RBH). METHODS: Retrospective study of patients with orbital compartment syndrome (OCS) secondary to RBH who underwent LCC. OCS due to RBH was defined by a combination of decreased vision, proptosis, resistance to retropulsion, increased intraocular pressure, and relative afferent pupillary defect. Time from injury to intervention and change in visual acuity were calculated, with regression analysis identifying predictors of vision recovery. RESULTS: Fifteen participants were included. Three (20%) participants presented with no light perception, 7 (47%) with count fingers (CF) to light perception, and 5 (33%) with better than count fingers vision. All 5 participants who had LCC within 3 hours (twice the standard 90 minutes) gained some vision, and 6 of 10 participants who had LCC after 3 hours recovered some vision. The latest intervention with visual acuity improvement was performed 9 hours postinjury. Of 3 participants who presented with no light perception vision, 1 regained vision to 20/40 (intervention 1.7 hours postinjury), and 2 did not regain any vision (interventions at 5 and 8.7 hours postinjury). Duration from injury to intervention was associated with decreased amount of vision recovery (P = 0.03). CONCLUSIONS: Increased time to intervention with LCC was associated with less vision recovery after OCS from RBH. However, over half of participants with intervention more than 90 minutes after injury still showed visual acuity improvement. The authors recommend LCC in all patients who present with OCS regardless of the time since injury.Patients with orbital compartment syndrome may see visual recovery after lateral canthotomy and cantholysis, even if performed outside of the previously accepted 3-hour window.

Orbitocerebral Mucormycosis in a Patient With Central Nervous System Lymphoma.

A 61-year-old man with well-controlled diabetes mellitus type 2, cirrhosis from hepatitis C, alcohol abuse, and portal hypertension presented with painful vision loss and left orbital swelling. Imaging showed diffuse orbital, perineural, and pachymeningeal inflammation. He was initially diagnosed with neurosarcoidosis. However, cerebrospinal fluid analysis revealed central nervous system lymphoma, and lacrimal gland biopsy showed fungal organisms consistent with mucormycosis. The authors describe a case of Mucorales infection lacking sinonasal involvement and discuss the differential diagnosis and management of patients presenting with orbital and central nervous system inflammation from this uncommon fungal infection.

Orbital apex syndrome from bacterial sinusitis without orbital cellulitis.

PURPOSE: To describe a case of orbital apex syndrome as a result of isolated bacterial sinusitis. OBSERVATIONS: A 63-year-old woman presented with an orbital apex syndrome from isolated bacterial sinusitis with rapidly declining visual acuity to no light perception. We compared our case with 6 similar cases of severe vision loss from isolated bacterial sinusitis. In contrast to previously published cases, our patient presented with good vision yet deteriorated to no light perception despite appropriate treatment. CONCLUSIONS AND IMPORTANCE: Orbital apex syndrome can present as a constellation of cranial neuropathies including optic neuropathy from conditions affecting the orbital apex. Although vision loss remained permanent, prompt initiation of broad-spectrum antibiotics and antifungals and surgical intervention prevented further extension of infection into intracranial structures.

Ophthalmic and Glaucoma Treatment Characteristics Associated With Changes in Health-related Quality of Life Before and After Newly Diagnosed Primary Open-angle Glaucoma in Nurses' Health Study Participants.

PURPOSE: To identify attributes related to glaucoma diagnosis or early glaucoma treatment patterns that are associated with changes in health-related quality of life among those with newly diagnosed primary open-angle glaucoma. METHODS: Among Nurses' Health Study participants with incident medical record-confirmed primary open-angle glaucoma diagnosed in 1992 to 2000, we included 317 women who completed the Short Form-36 Health Survey prediagnosis and postdiagnosis. The 2 primary outcomes were 4-year changes (1992 to 1996 or 1996 to 2000) in the physical and mental component summary scores. Multiple regression models were used to estimate differences in score changes by early treatment pattern history and characteristics as of diagnosis (ie, number of eyes affected, history of cataract, macular degeneration, cup-to-disc ratio, intraocular pressure, visual field loss type). RESULTS: In multivariable models, no ophthalmologic characteristics were associated with physical component score change. However, compared with treatment with eye drops or pills only, laser trabeculoplasty treatment (concomitant with history of treatment with eye drops or pills in 84%) was associated with a worse mental component score change over 4 years (-2.5 units; 95% confidence interval: -4.6, -0.3); this association was stronger with a family history of glaucoma (P-interaction=0.04) or with bilateral disease (P-interaction=0.001). CONCLUSIONS: Among patients with incident glaucoma, no major factors were associated with change in physical well being. However, compared with medical treatment only, a history of laser trabeculoplasty, which was commonly accompanied with a history of medical treatment and likely represented the need for a second line of treatment, was associated with a worse decline in mental well being.

A simple whole blood bioassay detects cytokine responses to anti-CD28SA and anti-CD52 antibodies.

INTRODUCTION: In 2006 the anti-CD28 superagonistic IgG4 TGN1412, having passed pre-clinical safety screens, caused a severe 'cytokine storm' in 6 healthy volunteers. Others have shown that for TGN1412 to induce an inflammatory signal in human peripheral blood mononuclear cells (PBMCs) or in human diluted blood, endothelial cells or bound monoclonal antibody (mAb) is required as part of a bioassay complex. These types of protocols rely on different donor cells and therefore have limitations as bioassays for pre-clinical testing. METHODS: We performed studies using human PBMC/endothelial cell co-cultures, whole blood/endothelial cell co-cultures and human whole blood alone. We bracketed responses of a CD28 superagonist antibody with mAbs against CD52 (alemtuzumab, MabCampath-1H) or epidermal growth factor receptor (cetuximab, Erbitux) and with the immunostimulant lipopolysaccharide. We detected cytokine responses at the level of protein release (using ELISAs and Luminex assays) and gene induction (using real-time PCR arrays). RESULTS: Here we confirm that IL-8 release was induced in a mixed endothelial cell-PBMC system by the anti-CD28 mAb. We go on to show that an alemtuzumab and an anti-CD28 mAb, but not cetuximab induced the release of a range of cytokines including IL-8, IL-6, IFNγ, IL-2 and IL10 after 24h and induced cytokine gene induction after 1h. Co-cultures of whole blood and HUVECS showed larger variability but no superiority over whole blood alone at a range of time points (0.5-48h). DISCUSSION: We suggest that, whilst limitations exist, human blood-based in vitro assays may prove useful in assessing the potential of mAbs and other biotherapeutics to cause release of cytokines in humans.

Open and laparoscopically assisted oesophagectomy: a prospective comparative study.

OBJECTIVES: Although a number of studies have examined minimally invasive approaches for oesophagectomy, these procedures have typically been offered only to selected patients with the limited long-term follow-up data. The purpose of this prospective study was to assess the feasibility of performing laparoscopically assisted oesophagectomy (LAO) for all-comers and to compare the short- and long-term clinical outcomes of this surgical strategy with a matched cohort of patients who had undergone open surgery. METHODS: From November 2009, all patients referred for trans-thoracic resection of an oesophageal cancer underwent a two-stage laparoscopically assisted Ivor-Lewis oesophagectomy. This consisted of laparoscopic mobilization of the stomach and distal oesophagus, followed by open thoracotomy, thoracic lymphadectomy and intrathoracic anastomosis. The clinical and oncological outcomes of the first 39 consecutive LAO patients were compared with those of the preceding 31 consecutive patients who had undergone open surgery. RESULTS: Of the 39 LAO cases, 37 cases were completed laparoscopically and 2 were converted to an open surgery. LAO was associated with a decreased incidence of postoperative complications (specifically cardiac and infectious complications) when compared with open surgery (54 vs 77%, P = 0.04). In addition, the initial intensive care unit stay (2 vs 4 days; P = 0.04) and overall length of hospital stay (14 vs 18 days; P = 0.02) were shorter in the LAO group. In terms of pathological outcomes, the lymph node yield and R0 resection rate of the LAO and open groups were comparable, as were the 1-year survival rates (62 vs 61%, P = 0.97). CONCLUSIONS: LAO can be offered to an unselected cohort of all-comers with a reduced postoperative complication rate and comparable oncological and long-term survival outcomes when compared with open surgery.

Does laparoscopic mobilisation of the stomach as part of a trans-thoracic oesophageal resection result in improved peri-operative outcomes as compared with an open approach?

A best evidence topic in surgery was written according to a structured protocol. The question addressed was whether laparoscopic mobilisation of the stomach as part of a trans-thoracic oesophageal resection results in improved peri-operative outcomes as compared with an open approach. 319 papers were found using the reported search; the 5 representing the best evidence to answer the question are discussed. The evidence on this subject is poor, none of the studies were randomised and only one was prospective. We conclude that laparoscopically-assisted gastric mobilisation during trans-thoracic oesophageal resection may have advantages over open surgery in terms of short-term peri-operative outcomes including reduced blood loss, reduced dependence on ventilatory support and shortened intensive care and overall hospital stay. However there was no difference between laparoscopic and open surgery in terms of overall morbidity or mortality rates.

Mortality and morbidity from combat neck injury.

BACKGROUND: Neck injury represents 11% of battle injuries in UK forces in comparison with 2% to 5% in US forces. The aim of this study was to determine the causes of death and long-term morbidity from combat neck injury in an attempt to recommend new methods of protecting the neck. METHOD: Hospital and postmortem records for all UK servicemen sustaining battle injuries to the neck between January 1, 2006 and December 31, 2010 were analyzed. RESULTS: Neck wounds were found in 152 of 1,528 (10%) of battle injured service personnel. Seventy-nine percent of neck wounds were caused by explosions and were associated with a mortality rate of 41% compared with 78% from gunshot wounds (GSWs). Although current UK OSPREY neck collars can potentially protect zone I from explosive fragments, in the 58% in which the wearing of a neck collar was known, all service personnel chose not to wear the collar. The most common cause of death from explosive fragments was vascular injury (85%). Zone II was the most commonly affected area overall by explosive fragments and had the highest mortality but zone I was associated with the highest morbidity in survivors. CONCLUSIONS: Nape protectors, that cover zone III of the neck posteriorly, would only have potentially prevented 3% of injuries and therefore this study does not support their use. Current UK OSPREY neck collars potentially protect against the majority of explosive fragments to zones I and II and had these collars been worn potentially 16 deaths may have been prevented. Reasons for their lack of uptake by UK servicemen is therefore being evaluated. Surface wound mapping of penetrating explosive fragments in our series has been used to validate the area of coverage required for future designs of neck protection.

Toll-like receptor 2 is essential for the sensing of oxidants during inflammation.

RATIONALE: The mechanisms by which oxidants are sensed by cells and cause inflammation are not well understood. OBJECTIVES: This study aimed to determine how cells "sense" soluble oxidants and how this is translated into an inflammatory reaction. METHODS: Monocytes, macrophages, or HEK293 cells (stably transfected with human Toll-like receptor [TLR]2, TLR2/1, TLR2/6, or TLR4/MD2-CD14) were used. CXC ligand-8 (CXCL8) levels were measured using ELISA. Phosphorylated IL-1 receptor-associated kinase 1 levels were measured using Western blot. TLR2(-/-) and TLR4(-/-) mice were challenged with oxidants, and inflammation was measured by monitoring cell infiltration and KC levels. MEASUREMENTS AND MAIN RESULTS: Oxidants evoked the release of CXCL8 from monocytes/macrophages; this was abrogated by pretreatment with N-acetylcysteine or binding antibodies to TLR2 and was associated with the rapid phosphorylation of IL-1 receptor-associated kinase 1. Oxidants added to HEK293 cells transfected with TLR2, TLR1/2, or TLR2/6 but not TLR4/MD2-CD14 or control HEK nulls resulted in the release of CXCL8. Oxidant challenge delivered intraperitoneally (2-24 hours) or by inhalation to the lungs (3 days) resulted in a robust inflammation in wild-type mice. TLR2(-/-) mice did not respond to oxidant challenge in either model. TLR4(-/-) mice responded as wild-type mice to oxidants at 2 hours but as TLR2(-/-) mice at later time points. CONCLUSIONS: Oxidant-TLR2 interactions provide a signal that initiates the inflammatory response.

Gram-positive and Gram-negative bacteria synergize with oxidants to release CXCL8 from innate immune cells.

We have recently demonstrated that oxidants can activate monocytes via an action on Toll-like receptor (TLR) 2; however, it is unclear what functional consequence this has on immune surveillance for Gram-negative and -positive bacteria. Gram-negative and -positive bacteria and their related pathogen-associated molecular patterns (PAMPs) are sensed by TLR4 and TLR2, respectively. In the current study, we used a human monocyte cell line to show that oxidants prime cells to subsequent challenge with Gram-negative or -positive bacteria as well as PAMPs specific for TLR4 (LPS), TLR2/1 (Pam(3)CSK4), TLR2/6 (FSL-1), Nod1 (FK565), and Nod2 (MDP Lys 18). Similarly, activation of TLR4 with LPS primed for subsequent activation of cells by agonists of the TLR2/6 or TLR2/1 complex. However, no synergy was noted when cells were costimulated with Pam(3)CSK4 and FSL-1. We then tested blood (and isolated monocytes) derived from healthy smokers, which is oxidant primed, making it more sensitive to bacterial or PAMP stimulation when compared with blood of nonsmokers. Thus an oxidant stimulation, possibly via an action on TLR2 or associated transduction pathways, provides a signal that initiates inflammatory responses and sensitizes cells to pathogenic insults.

Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium.

The endothelium lines the luminal surface of every blood vessel, allowing it contact with circulating blood elements, as well as the underlying vascular smooth muscle layer. In healthy vessels, the endothelium expresses constitutive forms of nitric oxide synthase (NOSIII) and cyclo-oxygenase (COX-1), which produce the vasoactive hormones NO and prostacyclin, respectively. Both NO and prostacyclin relax blood vessels and inhibit platelet activation. The actions of prostacyclin are mediated by cell surface prostacyclin (IP) receptors and/or intracellular peroxisome proliferator-activated receptors (PPAR) beta. The actions of NO are mediated predominately by activation of intracellular guanylyl cyclase, leading to the formation of cGMP. In platelets, the actions of NO and prostacyclin are synergistic, but in vessels their actions are additive. In diseased vessels, inducible forms of NOS (NOSII) and cyclo-oxygeanse (COX-2) are expressed in vascular smooth muscle, resulting in the release of large amounts of NO, prostacyclin and prostaglandin E2. The relative contribution of NOSII and COX-2 to vascular inflammation is still debated, but is likely to result in both protective and damaging responses. The relative contribution of constitutive forms of NOS and COX, as well as interactions between IP, PPAR beta and guanylyl cyclase pathways in vessels and platelets, is discussed.

Supportive care needs of people with brain tumours and their carers.

GOALS OF WORK: The diagnosis and treatment of a brain tumour may result in long-term changes in a patient's functional and social abilities and/or in a greatly reduced life span. A qualitative investigation was conducted to examine the supportive care needs of patients with brain tumour and their carers. MATERIALS AND METHODS: Overall, 18 patients and 18 carers participated in focus groups or telephone interviews, following a structured interview guide to elicit supportive care services of importance to these patients and carers. MAIN RESULTS: Six major themes were identified using the framework analysis method, including needs for information and coping with uncertainty, practical support, support to return to pretreatment responsibilities or prepare for long-term care, support to deal with social isolation and organize respite care, support to overcome stigma/discrimination and support to discuss potentially reduced life expectancy. CONCLUSIONS: Five recommendations to improve service delivery include: assignment of a dedicated member of the care team or case manager; proactive dissemination of information, education and psychosocial support; access to objective assessment of neuropsychological functioning; facilitating easier access to welfare payments; and services facilitating communication about difficult illness-related topics. Provision of services along these recommendations could improve supportive care of brain tumour patients and their carers.