Sarcopenic Obesity Versus Nonobese Sarcopenia in Hemodialysis Patients: Differences in Nutritional Status, Quality of Life, and Clinical Outcomes.

OBJECTIVE: Sarcopenia and sarcopenic obesity (SO) are linked to unfavorable prognosis in maintenance hemodialysis (MHD) populations. We tested whether nonobese sarcopenia and SO, as different stages of extreme protein-energy wasting, have different prognoses. METHODS: In this prospective observational study, 261 MHD patients were recruited from October 2010 to April 2012 and followed until October 2020. Two definitions were used to diagnose sarcopenia: the European Working Group on Sarcopenia in Older People consensus and the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium criteria. Obesity was determined as the percentage of total body fat, ≥27% for men and ≥38% for women. Data for all-cause and cardiovascular morbidity and mortality, baseline nutrition markers, inflammation and oxidative stress, adipokines, body composition parameters, handgrip strength, and quality of life (QoL) scores were measured. RESULTS: According to European Working Group on Sarcopenia in Older People, 115 (44.1%) patients were sarcopenic and 120 (46.0%) according to FNIH definitions. Of them, 28.4% and 34.5% were SO, respectively. Higher levels of albumin, creatinine, uric acid, leptin, phase angle, better nutritional scores, and lower adiponectin levels characterized SO patients compared with nonobese sarcopenic patients regardless of indexing method. Better QoL scores were noted in SO compared with nonobese sarcopenic patients using the FNIH sarcopenia criteria. The hazard of all-cause death, cardiovascular death, and first cardiovascular event for patients with SO was lower compared with the nonobese patients after multivariate adjustments. Statistical significance of these associations disappeared after including fat mass in multivariate models. CONCLUSIONS: MHD patients with SO have better nutritional status and prognosis for cardiovascular events, all-cause and cardiovascular disease mortality, and possibly better QoL compared with nonobese sarcopenic MHD patients. The better prognosis appears to be entirely due to the excess fat, which is protective in sarcopenic MHD patients similar to that described in the entire MHD population.

Memory surfacing among veterans with PTSD receiving hyperbaric oxygen therapy.

Introduction: Growing evidence demonstrates that hyperbaric oxygen therapy (HBO2) induces neuroplasticity and can benefit individuals with post-traumatic stress disorder (PTSD). The aim of the current study was to evaluate the rate and pattern of memory surfacing during the course of HBO2 among veterans with combat-related PTSD. Methods: In a post-hoc analysis of a prospective study of the effect of HBO2 on PTSD symptoms in veterans, we evaluated the rate and character of memory surfacing during the course of HBO2 treatment. The treatment consisted of 60 daily 90-minute sessions, at 2 atmospheres absolute (ATA) pressure and 100% oxygen. Results: For 10 (35.7%) of the 28 participants, surfacing of new memories was reported during the HBO2 treatment course. Memories surfaced mainly during the second month of the treatment, at the mean session of 30.5±13.2. For 9 of these 10 participants, prodromal symptoms such as distress, anxiety, or worsening depression were documented; and in four, somatic pain was reported prior to memory surfacing. The pain and distress of memory surfacing resolved over the course of one to 10 days. Discussion: Among individuals with PTSD, the surfacing of new memories, accompanied by emotional distress and somatic pain, is common during HBO2. The surfacing of memories sheds light on the biological effect of HBO2 on the brain sequela of PTSD. It is highly important that in treating patients for any indication, HBO2 medical teams be aware and capable of addressing memory surfacing, particularly in those with a history of trauma.

COVID-19 and Renal Failure - Adding Insult to Injury? Israel's Experience Based on Nationwide Retrospective Cohort Study.

INTRODUCTION: Renal failure (RF) is a risk factor for mortality among hospitalized patients. However, its role in COVID-19-related morbidity and mortality is inconclusive. The aim of the study was to determine whether RF is a significant predictor of clinical outcomes in COVID-19 hospitalized patients based on a retrospective, nationwide, cohort study. METHODS: The study sample consisted of patients hospitalized in Israel for COVID-19 in two periods. A random sample of these admissions was selected, and experienced nurses extracted the data from the electronic files. The group with RF on admission was compared to the group of patients without RF. The association of RF with 30-day mortality was investigated using a logistic regression model. RESULTS: During the two periods, 19,308 and 2994 patients were admitted, from which a random sample of 4688 patients was extracted. The 30-day mortality rate for patients with RF was 30% (95% confidence interval (CI): 27-33%) compared to 8% (95% CI: 7-9%) among patients without RF. The estimated OR for 30-day mortality among RF versus other patients was 4.3 (95% CI: 3.7-5.1) and after adjustment for confounders was 2.2 (95% CI: 1.8-2.6). Furthermore, RF patients received treatment by vasopressors and invasive mechanical ventilation (IMV) more frequently than those without RF (vasopressors: 17% versus 6%, OR = 2.8, p<0.0001; IMV: 17% versus 7%, OR = 2.6, p<0.0001). DISCUSSION: RF is an independent risk factor for mortality, IMV, and the need for vasopressors among patients hospitalized for COVID-19 infection. Therefore, this condition requires special attention when considering preventive tools, monitoring, and treatment.

[HYPERTENSION AMONG HEMODIALYSIS PATIENTS, NOT NECESSARILY HYPERVOLEMIA].

BACKGROUND: Hypertension in dialysis patients is common. In daily practice, it is not always clear whether adjustment of dry weight or vasodilatory medication should be administered and treatment strategy is often based on clinical impression. We used a whole-body bio-impedance based, non-invasive, hemodynamics monitoring technology to acquire hemodynamic data in order to evaluate the incidence and causes of hypertension in dialysis patients. METHODS: Novel noninvasive impedance based technique was used to collect hemodynamic data from patients undergoing chronic hemodialysis in four different dialysis units. Patients were defined as having hypertension if their predialysis systolic or diastolic BP results were >140mmHg or >90 respectively and as hypervolemic if their total body water (TBW) was greater than normal according to the Kushner formula+1SD. Vasoconstriction was defined as total peripheral resistance index (TPRI) greater than 3000 dyn*sec/cm5*m2. RESULTS: Of 144 hemodialysis patients, 81 (56%) were male; mean age was 67.3±12.1 years and 67 (47%) had hypertension. Among the hypertensive patients, only 18(27%) met hypervolemia criteria and thirty (45%) met vasoconstriction criteria (mean TPRI of 4474±1592dyn*sec/cm5*m2). Patients with hypertension due to vasoconstriction had higher vintage (50±45 vs 20±8 months 0=0.018), lower heart rate (71±11 vs 79±11 BPM p=0.002), lower stroke index (28±7 vs 44±8ml/m2 p<0.001) and cardiac index (2.1±0.5 vs 3.5±0.6 p=0<0.001) compared to patients without vasoconstriction. CONCLUSIONS: Vasoconstriction was the main etiology for pre-dialysis hypertension in chronic hemodialysis patients. This calls for individualized, hemodynamic-based therapeutic intervention.

Non-invasive hemodynamic profiling of patients undergoing hemodialysis - a multicenter observational cohort study.

BACKGROUND: Intradialytic blood pressure (BP) measurement is currently the main parameter used for monitoring hemodynamics during hemodialysis (HD). Since BP is dependent on cardiac output and total peripheral resistance, knowledge of these parameters throughout the HD treatment would potentially be valuable. METHODS: The use of a novel non-invasive monitoring system for profiling hemodynamic response patterns during HD was explored: a whole-body bio-impedance system was used to assess cardiac index (CI), total peripheral resistance index (TPRI), cardiac power index (CPI) among other parameters in chronic HD patients from 4 medical centers. Measurements were made pre, during and post dialysis. Patients were grouped into 5 hemodynamic profiles based on their main hemodynamic response during dialysis i.e. high TPRI; high CPI; low CPI; low TPRI and those with normal hemodynamics. Comparisons were made between the groups for baseline characteristics and 1-year mortality. RESULTS: In 144 patients with mean age of 67.3 ± 12.1 years pre-dialysis hemodynamic measurements were within normal limits in 35.4% but only 6.9% overall remained hemodynamically stable during dialysis. Intradialytic BP decreased in 65 (45.1%) in whom, low CPI (47 (72.3%)) and low TPRI (18 (27.7%) were recorded. At 1-year follow-up, mortality rates were highest in patients with low CPI (23.4%) and low TPRI (22.2%). CONCLUSIONS: Non-invasive assessment of patients' response to HD provides relevant hemodynamic information that exceeds that provided by currently used BP measurements. Use of these online analyses could potentially improve the safety and performance standards of dialysis by guiding appropriate interventions, particularly in responding to hypertension and hypotension.

Response of Renal Podocytes to Excessive Hydrostatic Pressure: a Pathophysiologic Cascade in a Malignant Hypertension Model.

BACKGROUND/AIMS: Renal injuries induced by increased intra-glomerular pressure coincide with podocyte detachment from the glomerular basement membrane (GBM). In previous studies, it was demonstrated that mesangial cells have a crucial role in the pathogenesis of malignant hypertension. However, the exact pathophysiological cascade responsible for podocyte detachment and its relationship with mesangial cells has not been fully elucidated yet and this was the aim of the current study. METHODS: Rat renal mesangial or podocytes were exposed to high hydrostatic pressure in an in-vitro model of malignant hypertension. The resulted effects on podocyte detachment, apoptosis and expression of podocin and integrinß1 in addition to Angiotensin-II and TGF-ß1 generation were evaluated. To simulate the paracrine effect podocytes were placed in mesangial cell media pre-exposed to pressure, or in media enriched with Angiotensin-II, TGF-ß1 or receptor blockers. RESULTS: High pressure resulted in increased Angiotensin-II levels in mesangial and podocyte cells. Angiotensin-II via the AT1 receptors reduced podocin expression and integrinß1, culminating in detachment of both viable and apoptotic podocytes. Mesangial cells exposed to pressure had a greater increase in Angiotensin-II than pressure-exposed podocytes. The massively increased concentration of Angiotensin-II by mesangial cells, together with increased TGF-ß1 production, resulted in increased apoptosis and detachment of non-viable apoptotic podocytes. Unlike the direct effect of pressure on podocytes, the mesangial mediated effects were not related to changes in adhesion proteins expression. CONCLUSIONS: Hypertension induces podocyte detachment by autocrine and paracrine effects. In a direct response to pressure, podocytes increase Angiotensin-II levels. This leads, via AT1 receptors, to structural changes in adhesion proteins, culminating in viable podocyte detachment. Paracrine effects of hypertension, mediated by mesangial cells, lead to higher levels of both Angiotensin-II and TGF-ß1, culminating in apoptosis and detachment of non-viable podocytes.

Interaction between acyl-ghrelin and BMI predicts clinical outcomes in hemodialysis patients.

BACKGROUND: Ghrelin, a gastric orexigenic peptide, and body mass index (BMI) are known as inversely associated to each other and are both linked to cardiovascular (CV) risk and mortality in maintenance hemodialysis (MHD) patients. However, it is unclear whether the interaction between ghrelin and BMI is associated with a risk of all-cause and CV death in this population. METHODS: A prospective observational study was performed on 261 MHD outpatients (39% women, mean age 68.6 ± 13.6 years) recruited from October 2010 through April 2012, and were followed until November 2014 (median follow-up-28 months, interquartile range-19-34 months). We measured acyl-ghrelin (AG) levels, appetite, nutritional and inflammatory markers, prospective all-cause and cardiovascular (CV) mortality. RESULTS: During follow-up, 109 patients died, 51 due to CV causes. A significant interaction effect of high BMI and high AG (defined as levels higher than median) on all-cause mortality was found. Crude Cox HR for the product termed BMI x AG was 0.52, with a 95% confidence interval (CI): 0.29 to 0.95 (P = 0.03). Evaluating the interaction on an additive scale revealed that the combined predictive value of BMI and AG is larger than the sum of their individual predictive values (synergy index was 1.1). Across the four BMI-AG categories, the group with high BMI and high AG exhibited better all-cause and cardiovascular mortality irrespective of appetite and nutritional status (multivariable adjusted hazard ratios were 0.31, 95% CI 0.16 to 0.62, P = 0.001, and 0.35, 95% CI 0.13 to 0.91, P = 0.03, respectively). Data analyses made by dividing patients according to fat mass-AG, but not to lean body mass-AG categories, provided similar results. CONCLUSIONS: Higher AG levels enhance the favourable association between high BMI and survival in MHD patients irrespective of appetite, nutritional status and inflammation.

The Use of Complementary and Alternative Medicine Among Dialysis Patients.

Context • The use of complementary and alternative medicine (CAM) has been on the rise in the last decade. Subpopulations of patients with chronic diseases are at risk for adverse events and potential drug-herb interactions, among them dialysis patients. Objective • The study aimed to evaluate the prevalence of CAM consumption among dialysis patients and to search for potential interactions. Design • The study was cross-sectional, based on questionnaires. Setting • The study occurred in the hemodialysis unit at Assaf Harofeh Medical Center (Zeriffin, Israel). Participants • Participants were patients of the hemodialysis unit. Outcome Measures • The questionnaires obtained demographic data, information about a patient's medical history and use of prescription medication, and all relevant history of CAM use, including the interest of the medical team in the patient's use of supplements. Results • Eighty-four patients participated in the study. Eight patients (9.5%) had used CAM, 5 of whom were women (62.5%). Of the CAM consumers, 4 (50%) had more than 12 y of education vs 14 (8.4%) in the nonconsumer group (P = .061). Six of the consumers were professionals (75%) in comparison with 30 (39.5%) of the nonconsumers, although that difference was not statistically significant (P = .22). The CAM users' monthly incomes were significantly better than that of the nonconsumers (P = .01). No differences were found regarding smoking, alcohol consumption, or physical activity. The study found potential drug-herb interactions in 4 (50%) of the CAM consumers. Moderate potential interactions were found between Aloe vera and diuretics; Aloe vera and insulin; pyridoxine and calcium-channel blockers and diuretics; and niacin and statins. Those interactions had the potential to result in hypoglycemia, hyperglycemia, hypokalemia, and lower blood pressure. Conclusions • The study found a lower prevalence of CAM consumption in dialysis patients than had been found in other studies of the general population. Still, the unawareness of the harm and potential interactions and the lack of data sharing between the patients and caregivers might have had disastrous consequences. Therefore, caregivers need to inquire of their patients specifically about their use of CAM, especially for populations with chronic diseases, let alone patients undergoing dialysis.

Metformin Does Not Induce Hyperlactatemia in Patients Admitted to Internal Medicine Ward.

BACKGROUND: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive. OBJECTIVES: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward. METHODS: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function. RESULTS: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis. CONCLUSIONS: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

Lactic acidosis and severe septic shock in metformin users: a cohort study.

BACKGROUND: High serum lactate is associated with increased mortality in septic shock patients. Metformin alters lactate metabolism, and may affect its prognostic value. We compared, between metformin users and nonusers, the prognosis of extremely elevated plasma lactate levels in patients with septic shock. METHODS: The electronic medical records (EMR) of patients admitted to the emergency room between January 2011 and June 2013 were reviewed. The study cohort comprised patients with an initial diagnosis of septic shock and blood lactate higher than 10 mmol/L. The selected population was divided into two groups: metformin users (exposed) and metformin nonusers (unexposed). The primary outcome measured was inhospital mortality. RESULTS: The study included 44 metformin users and 118 nonusers. Metformin users were similar to nonusers with respect to levels of lactate, HCO3, and blood pH; however, they were older and had higher incidence rates of cardiovascular disease and acute kidney injury at admission, compared to nonusers. Inhospital mortality rates were significantly lower in the metformin-treated group, 56.8 % vs. 88.1 %, p <0.0001. CONCLUSIONS: Though high lactate concentration indicates poor prognosis in septic patients, mortality rate was found to be significantly lower in those who were treated with metformin. This finding may help clinicians in deciding treatment for these patients, who could otherwise be considered too ill for real treatment benefit.

Autologous bone-marrow stem cells stimulation reverses post-ischemic-reperfusion kidney injury in rats.

BACKGROUND/AIMS: Low-level laser therapy (LLLT) has been found to modulate biological activity. The aim of the present study was to investigate the possible beneficial effects of LLLT application to stem cells in the bone marrow (BM), on the kidneys of rats that had undergone acute ischemia-reperfusion injury (IRI). METHODS: Injury to the kidneys was induced by the excision of the left kidney and 60 min of IRI to the right kidney in each rat. Rats were then divided randomly into 2 groups: non-laser-treated and laser-treated. LLLT was applied to the BM 10 min and 24 h post-IRI and rats were sacrificed 4 days post-IRI. Blood was collected before the sacrifice and the kidney processed for histology. RESULTS: Histological evaluation of kidney sections revealed the restored structural integrity of the renal tubules, and a significant reduction of 66% of pathological score in the laser-treated rats as compared to the non-laser-treated ones. C-kit positive cell density in kidneys post-IRI and laser-treatment was (p = 0.05) 2.4-fold higher compared to that of the non-laser treated group. Creatinine, blood urea nitrogen, and cystatin-C levels were significantly 55, 48, and 25% lower respectively in the laser-treated rats as compared to non-treated ones. CONCLUSION: LLLT application to the BM causes induction of stem cells, which subsequently migrate and home in on the injured kidney. Consequently, a significant reduction in pathological features and improved kidney function post-IRI are evident. The results demonstrate a novel approach in cell-based therapy for acute ischemic injured kidneys.

Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.

The use of hyperbaric oxygen for veterans with PTSD: basic physiology and current available clinical data.

Post-traumatic stress disorder (PTSD) affects up to 30% of veterans returning from the combat zone. Unfortunately, a substantial proportion of them do not remit with the current available treatments and thus continue to experience long-term social, behavioral, and occupational dysfunction. Accumulating data implies that the long-standing unremitting symptoms are related to changes in brain activity and structure, mainly disruption in the frontolimbic circuit. Hence, repair of brain structure and restoration of function could be a potential aim of effective treatment. Hyperbaric oxygen therapy (HBOT) has been effective in treating disruptions of brain structure and functions such as stroke, traumatic brain injury, and fibromyalgia even years after the acute insult. These favorable HBOT brain effects may be related to recent protocols that emphasize frequent fluctuations in oxygen concentrations, which in turn contribute to gene expression alterations and metabolic changes that induce neuronal stem cell proliferation, mitochondrial multiplication, angiogenesis, and regulation of the inflammatory cascade. Recently, clinical findings have also demonstrated the beneficial effect of HBOT on veterans with treatment-resistant PTSD. Moderation of intrusive symptoms, avoidance, mood and cognitive symptoms, and hyperarousal were correlated with improved brain function and with diffusion tensor imaging-defined structural changes. This article reviews the current data on the regenerative biological effects of HBOT, and the ongoing research of its use for veterans with PTSD.

Hyperbaric oxygen therapy compared to pharmacological intervention in fibromyalgia patients following traumatic brain injury: A randomized, controlled trial.

Fibromyalgia is a chronic pain syndrome with unsatisfactory response to current treatments. Physical trauma, including traumatic brain Injury (TBI) is among the etiological triggers. Hyperbaric Oxygen therapy (HBOT) is an intervention that combines 100% oxygen with elevated atmospheric pressure. HBOT has been applied as a neuro-modulatory treatment in central nervous system-related conditions. The current study investigated the utility of HBOT for TBI-related fibromyalgia. Fibromyalgia patients with a history of TBI were randomized to either HBOT or pharmacological intervention. HBOT protocol comprised 60 daily sessions, breathing 100% oxygen by mask at 2 absolute atmospheres (ATA) for 90 minutes. Pharmacological treatment included Pregabalin or Duloxetine. The primary outcome was subjective pain intensity on visual analogue scale (VAS); Secondary endpoints included questionnaires assessing fibromyalgia symptoms as well as Tc-99m-ECD SPECT brain imaging. Pain threshold and conditioned pain modulation (CPM) were also assessed. Results demonstrated a significant group-by-time interaction in pain intensity post-HBOT compared to the medication group (p = 0.001), with a large net effect size (d = -0.95) in pain intensity reduction following HBOT compared to medications. Fibromyalgia related symptoms and pain questionnaires demonstrated significant improvements induced by HBOT as well as improvements in quality of life and increase in pain thresholds and CPM. SPECT demonstrated significant group-by-time interactions between HBOT and medication groups in the left frontal and the right temporal cortex. In conclusion, HBOT can improve pain symptoms, quality of life, emotional and social function of patients suffering from FMS triggered by TBI. The beneficial clinical effect is correlated with increased brain activity in frontal and parietal regions, associated with executive function and emotional processing.

N-3 fatty acid supplementation to routine statin treatment inhibits platelet function, decreases patients' daytime blood pressure, and improves inflammatory status.

OBJECTIVES: N-3 fatty acids reduce the risks of cardiovascular morbidity and mortality. Administration of N-3 fatty acids to patients treated with statins may potentiate the treatment effects. We examined the operating mechanisms underlying such a combination. METHODS: Thirty-two hypercholesterolemic patients aged 30-70 years with hypercholesterolemia controlled by statins, received sequential treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks. Scheduled clinical visits included physical examination, 24-h blood pressure measurement, endothelial function evaluated by pulse wave analysis, analyses for platelet function, inflammation markers [interleukin (IL)-6, plasminogen activator inhibitor-1 (PAI-1)] and oxidative stress parameters (STAT-8-Isoprostane) were undertaken at baseline, after placebo treatment, and after 6 and 20 weeks of N-3 fatty acid intake. RESULTS: Platelets functions were significantly inhibited, whereas endothelial function parameters were unaltered. IL-6 significantly decreased whereas PAI-1and STAT-8-Isoprostane levels remained unaffected. Daytime blood pressure significantly decreased; however, nighttime pressure and heart rate remained unchanged. No evidence of lipid-profile improvement was observed following combined treatment with statins and N-3 fatty acids. CONCLUSIONS: In hypercholesterolemic patients, combination of statins and N-3 fatty acid inhibits platelet aggregation, alters inflammatory status, and positively affects daytime blood pressure. Close long-term follow-up might reveal additional beneficial effects of N-3 fatty acids in this patient population.

Photobiomodulation Therapy to Autologous Bone Marrow in Humans Significantly Increases the Concentration of Circulating Stem Cells and Macrophages: A Pilot Study.

Objective: The aim of this study was to examine the effect of photobiomodulation therapy (PBMT) of the bone marrow (BM) on the concentration of stem cells and other cells in the circulating blood (CB) in humans. Background: Circulating stem cells have received increasing attention in recent years due to their potential role in regenerative medicine. Various biological processes have been shown to be affected by PBMT. Methods: The study was conducted on 15 volunteers. Ga-Al-As diode laser 808 nm wavelength was applied to both tibias of each volunteer for PBMT to the BM. The kinetics of concentration of various cells in the CB was followed by comparing blood samples relative to their baseline levels prior to application of PBMT to the BM. CD-34+ cells and macrophages were identified in CB samples using flow cytometry technology. Results: PBMT to the BM caused a significant (p < 0.01) increase in the concentration of CD-34+ cells in the CB from 7.8 ± 3.0% (mean ± SD) of total mononucleated cell to 29.5 ± 10.1% of total commencing at about 2 h post-PBMT. The levels of CD-34+ cells peaked at 2-4 days post-PBMT and then gradually returned to baseline levels. Macrophages in the CB were also significantly (p < 0.01) elevated following PBMT to the BM from 7.8 ± 6.0% (mean ± SD) of the total mononucleated cells to 52.1 ± 7.9% of total. Conclusions: Application of PBMT to the BM in humans can significantly increase the concentration of CD-34+ cells and macrophages in the CB. These cells may consequently home in on the impaired target organs and improve their function, as has been previously shown in experimental animal models. Furthermore, the results may also have clinical relevance in respect to enrichment of CB in cells that may be consequently isolated for cell therapy. Clinical Trial Registration No. is 7/14.

Hyperbaric Oxygen Therapy for Veterans With Treatment-resistant PTSD: A Longitudinal Follow-up Study.

INTRODUCTION: PTSD is common among veteran combatants. PTSD is characterized by brain changes, for which available treatments have shown limited effect. In a short-term study, we showed that hyperbaric oxygen therapy (HBOT) induced neuroplasticity and improved clinical symptoms of veterans with treatment-resistant PTSD. Here, we evaluated the long-term clinical symptoms of the participants of that study. MATERIALS AND METHODS: Veterans from our short-term study were recruited 1 or more years after completing HBOT. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and self-reported questionnaires were administered at a single site visit. Changes in clinical scores between long-term, short-term, and pretreatment evaluations were analyzed. RESULTS: Of the 28 participants who received HBOT during or following the short-term study, 22 agreed to participate in the current study. At a mean of 704 ± 230 days after completing the HBOT course, the mean CAPS-5 score (26.6 ± 14.4) was significantly better (lower) than at the pre-HBOT evaluation (47.5 ± 13.1, P < .001) and not statistically different from the short-term evaluation (28.6 ± 16.7, P = .745). However, for the CAPS-5 subcategory D (cognition and mood symptoms), the mean score was significantly better (lower) at long-term than at short-term evaluation (7.6 ± 5.1 vs. 10.0 ± 6.0, P < .001). At the long-term compared to the pretreatment evaluation, higher proportions of the participants were living with life partners (10 (46%) vs. 17 (77%), P = .011) and were working (9 (41%) vs. 16 (73%), P = .033). Decreases were observed between pretreatment and the long-term follow-up, in the number of benzodiazepine users (from 10 (46%) to 4 (18%), P = .07) and in the median (range) cannabis daily dose (from 40.0 g (0-50) to 22.5 g (0-30), P = .046). CONCLUSIONS: The beneficial clinical effects of HBOT are persistent and were not attenuated at long-term follow-up of about 2 years after completion of HBOT. Additional long-term effects of the treatment were observed in social function and in decreased medication use.

Hyperbaric oxygen therapy improves symptoms, brain's microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: A prospective, randomized, controlled trial.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is characterized by changes in both brain activity and microstructural integrity. Cumulative evidence demonstrates that hyperbaric oxygen therapy (HBOT) induces neuroplasticity and case-series studies indicate its potentially positive effects on PTSD. The aim of the study was to evaluate HBOT's effect in veterans with treatment resistant PTSD. METHODS: Veterans with treatment resistant PTSD were 1:1 randomized to HBOT or control groups. All other brain pathologies served as exclusion criteria. Outcome measures included clinician-administered PTSD scale-V (CAPS-V) questionnaires, brief symptom inventory (BSI), BECK depression inventory (BDI), brain microstructural integrity evaluated by MRI diffuse tensor imaging sequence (DTI), and brain function was evaluated by an n-back task using functional MRI (fMRI). The treatment group underwent sixty daily hyperbaric sessions. No interventions were performed in the control group. RESULTS: Thirty-five veterans were randomized to HBOT (N = 18) or control (n = 17) and 29 completed the protocol. Following HBOT, there was a significant improvement in CAPS-V scores and no change in the control (F = 30.57, P<0.0001, Net effect size = 1.64). Significant improvements were also demonstrated in BSI and BDI scores (F = 5.72, P = 0.024 Net effect size = 0.89, and F = 7.65, P = 0.01, Net effect size = 1.03). Improved brain activity was seen in fMRI in the left dorsolateral prefrontal, middle temporal gyri, both thalami, left hippocampus and left insula. The DTI showed significant increases in fractional anisotropy in the fronto-limbic white-matter, genu of the corpus callosum and fornix. CONCLUSIONS: HBOT improved symptoms, brain microstructure and functionality in veterans with treatment resistant PTSD.