Targeted therapies in retinoblastoma: GD2-directed immunotherapy following autologous stem cell transplantation and evaluation of alternative target B7-H3.

BACKGROUND: GD2-directed immunotherapy is highly effective in the treatment of high-risk neuroblastoma (NB), and might be an interesting target also in other high-risk tumors. METHODS: The German-Austrian Retinoblastoma Registry, Essen, was searched for patients, who were treated with anti-GD2 monoclonal antibody (mAb) dinutuximab beta (Db) in order to evaluate toxicity, response and outcome in these patients. Additionally, we evaluated anti-GD2 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in retinoblastoma cell lines in vitro. Furthermore, in vitro cytotoxicity assays directed against B7-H3 (CD276), a new identified potential target in RB, were performed. RESULTS: We identified four patients with relapsed stage IV retinoblastoma, who were treated with Db following autologous stem cell transplantation (ASCT). Two out of two evaluable patients with detectable tumors responded to immunotherapy. One of these and another patient who received immunotherapy without residual disease relapsed 10 and 12 months after start of Db. The other patients remained in remission until last follow-up 26 and 45 months, respectively. In vitro, significant lysis of RB cell lines by ADCC and CDC with samples from patients and healthy donors and anti-GD2 and anti-CD276-mAbs were demonstrated. CONCLUSION: Anti-GD2-directed immunotherapy represents an additional therapeutic option in high-risk metastasized RB. Moreover, CD276 is another target of interest.

Nutrition support in the pediatric total pancreatectomy with islet autotransplantation recipient.

For children with diminished quality of life and chronic pain caused by acute recurrent or chronic pancreatitis who are undergoing total pancreatectomy with islet autotransplantation, postoperative nutrition support has several unique characteristics. Surgical complications may lead to delays in nutrition support initiation or require modifications to the regimen. Early postoperative dysmotility requires the use of temporary enteral nutrition until this improves. The resultant complete exocrine pancreatic insufficiency necessitates lifelong pancreatic enzyme replacement therapy and fat-soluble vitamin supplementation. A low-oxalate diet is recommended to prevent kidney stones. Carbohydrate counting is needed for the provision of short-term insulin dosing and possibly long-term as well, depending on the transplanted islet yield. Children should have careful nutrition assessment and monitoring at several follow-up visits during the first year, then annually, and at any time with concerns.

Induced membrane technique versus one-stage autografting in management of atrophic nonunion of long bone in the lower limb: clinical and health burden outcomes.

OBJECTIVE: In this study, we aimed to compare the outcomes of the two-stage induced membrane technique (IMT) and one-stage autografting in the treatment of aseptic atrophic nonunion in lower limb long bones. METHODS: From January 2014 to January 2022, we reviewed all surgically treated long bone nonunion patients, including patients aged 18 years or older with atrophic nonunion, who were either treated with the two-stage induced membrane technique (IMT) or one-stage autografting. Outcome parameters interns of clinical, quality of life and healthcare burden were recorded and retrospectively analysed between the two treatment populations. The follow-up time was at least 1 year. RESULTS: In total, 103 patients who met the criteria for aseptic atrophic nonunion were enrolled. Among them, 41 (39.8%) patients were treated with two-stage IMT, and 62 (60.2%) patients were treated with one-stage autologous bone grafting. The follow-up time was 12 to 68 months, with an average of 28.4 months. The bone healing rate was comparable in both groups (IMT: 92.7% vs. one-stage grafting: 91.9%, P = 0.089) at 12 months post-operation, and the bone healing Lane-Sandhu score was superior in the IMT group (mean: 8.68 vs. 7.81, P = 0.002). Meanwhile, the SF-12 scores of subjective physical component score (PCS) (mean: 21.36 vs. 49.64, P < 0.01) and mental health component score (MCS) (mean: 24.85 vs. 46.14, P < 0.01) significantly increased in the IMT group, as well as in the one-stage grafting group, and no statistically significant difference was found within groups. However, the total hospital stays (median: 8 days vs. 14 days, P < 0.01) and direct medical healthcare costs (median: ¥30,432 vs. ¥56,327, P < 0.05) were greater in the IMT group, while the complications (nonunion 8, infection 3, material failure 2, and donor site pain 6) were not significantly different between the two groups (17.1% vs. 19.4, P = 0.770). CONCLUSION: The data indicate that two-stage method of IMT serves as an alternative method in treating atrophic nonunion; however, it may not be a preferred option, in comprehensive considering patient clinical outcomes and healthcare burden. More evidence-based research is needed to further guide clinical decision-making.

Serum Electrolyte and Metabolic Changes During Conditioning of Autologous Hematopoietic Stem Cell Transplantation in Patients with Autoimmune Diseases: A Prospective Study in a Single Institution.

BACKGROUND AND OBJECTIVES: A hematopoietic stem cell transplant (HSCT) includes a conditioning regimen which may cause unwanted metabolic changes. We analyzed the changes in electrolytes, glucose, urea, and glomerular filtration rate in patients with multiple sclerosis (MS) who underwent an autologous HSCT employing the "Mexican method." PATIENTS AND METHODS: Serum and urinary electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were prospectively assessed on days -11, -9, and 0 in a group of 75 patients with MS receiving an autologous HSCT employing the "Mexican method," which includes high doses of both cyclophosphamide (Cy, 200 mg/kg) and rituximab (1000 mg). RESULTS: The median age of the patients was 46 years, with a range of 20-65. Baseline data were defined at day -11 of the HSCT. There were significant changes in serum and urinary electrolytes, which diminished substantially after the delivery of high-dose Cy; 12 patients (16%) developed hyponatremia and 2 had hyponatremia-induced seizures, which resulted in hospital admissions. A comparison of baseline blood metabolites with those obtained after the full Cy dosage (day 0) revealed a significant increase in blood glucose and uric acid levels with an associated decrease in serum calcium, sodium, and potassium levels. The salient findings were drug-induced hyponatremia and hyperglycemia. CONCLUSION: Significant changes in serum electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were observed in patients given autologous HSCT for MS employing high-dose Cy. Some of these changes may have clinical consequences, mainly those derived from iatrogenic hyponatremia. No evidence of damage to renal function was observed at day 0.

Nutritional Risks in Patients Undergoing Total Pancreatectomy Islet AutoTransplantation in the POST Consortium.

BACKGROUND AND AIMS: Total pancreatectomy with islet autotransplantation (TPIAT) can relieve pain for individuals with acute recurrent or chronic pancreatitis. However, TPIAT may increase the risk of poor nutritional status with complete exocrine pancreatic insufficiency, partial duodenectomy, and intestinal reconstruction. Our study's objective was to evaluate nutritional status, anthropometrics, and vitamin levels before and after TPIAT. METHODS: The multicenter Prospective Observational Study of TPIAT (POST) collects measures including vitamins A, D, and E levels, pancreatic enzyme dose, and multivitamin (MVI) administration before and 1-year after TPIAT. Using these data, we studied nutritional and vitamin status before and after TPIAT. RESULTS: 348 TPIAT recipients were included (68% adult, 37% male, 93% Caucasian). In paired analyses at 1-year follow-up, vitamin A was low in 23% (vs 9% pre-TPIAT, p < 0.001); vitamin E was low in 11% (vs 5% pre-TPIAT, p = 0.066), and 19% had vitamin D deficiency (vs 12% pre-TPIAT, p = 0.035). Taking a fat-soluble multivitamin (pancreatic MVI) was associated with lower risk for vitamin D deficiency (p = 0.002). Adults were less likely to be on a pancreatic MVI at follow-up (34% vs 66% respectively, p < 0.001). Enzyme dosing was adequate. More adults versus children were overweight or underweight pre- and post-TPIAT. Underweight status was associated with vitamin A (p = 0.014) and E (p = 0.02) deficiency at follow-up. CONCLUSIONS: Prevalence of fat-soluble vitamin deficiencies increased after TPIAT, especially if underweight. We strongly advocate that all TPIAT recipients have close post-operative nutritional monitoring, including vitamin levels. Pancreatic MVIs should be given to minimize risk of developing deficiencies.

Association Between Graft Type and Risk of Repeat Revision Anterior Cruciate Ligament Reconstruction: A Cohort Study of 1747 Patients.

BACKGROUND: With an increasing number of primary anterior cruciate ligament reconstructions (ACLRs), the burden of revision ACLR (rACLR) has also increased. Graft choice for rACLR is complicated by patient factors and the remaining available graft options. PURPOSE: To examine the association between graft type at the time of rACLR and the risk of repeat rACLR (rrACLR) in a large US integrated health care system registry while accounting for patient and surgical factors at the time of revision surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data from the Kaiser Permanente ACLR registry were used to identify patients who underwent a primary isolated ACLR between 2005 and 2020 and then went on to have rACLR. Graft type used at rACLR, classified as autograft versus allograft, was the exposure of interest. Multivariable Cox proportional hazard regression was used to evaluate the risk of rrACLR, with ipsilateral and contralateral reoperation as secondary outcomes. Models included factors at the time of the rACLR (age, sex, body mass index, smoking status, staged revision, femoral fixation, tibial fixation, femoral tunnel method, lateral meniscal injury, medial meniscal injury, and cartilage injury) and a factor from the primary ACLR (activity at injury) as covariates. RESULTS: A total of 1747 rACLR procedures were included. The crude cumulative rrACLR incidence at 8-year follow-up was 13.9% for allograft and 6.0% for autograft. Cumulative ipsilateral reoperation incidence at 8-year follow-up was 18.3% for allograft and 18.9% for autograft; contralateral reoperation cumulative incidence was 4.3% for allograft and 6.8% for autograft. With adjustment for covariates, a 70% lower risk for rrACLR was observed for autograft compared with allograft (hazard ratio [HR], 0.30; 95% CI, 0.18-0.50; P < .0001). No differences were observed for ipsilateral reoperation (HR, 1.05; 95% CI, 0.73-1.51; P = .78) or contralateral reoperation (HR, 1.33; 95% CI, 0.60-2.97; P = .48). CONCLUSION: The use of autograft at rACLR was associated with a 70% lower risk of rrACLR compared with allograft in this cohort from the Kaiser Permanente ACLR registry. When accounting for all reoperations outside of rrACLR after rACLR, the authors found no significant difference in risk between autograft and allograft. To minimize the risk of rrACLR, surgeons should consider using autograft for rACLR when possible.

Effect of total parathyroidectomy in patients with secondary hyperparathyroidism: a retrospective study.

PURPOSE: To investigate the therapeutic efficacy, feasibility, and safety of total parathyroidectomy (tPTX) in the treatment of secondary hyperparathyroidism (SHPT). METHODS: The clinical data of 34 SHPT patients admitted to the Department of Nephrology, Yuxi People's Hospital, from January 2018 to January 2021 who had received tPTX, were retrospectively analyzed. The indications for tPTX were severe SHPT that did not respond to medical treatment and was ineligible for kidney transplantation. tPTX without autotransplantation was adopted to compare the level of symptom relief and changes in serum intact parathyroid hormone (iPTH), blood calcium, and blood phosphorus pre- and postoperatively. RESULTS: In 34 patients, 142 parathyroid glands were removed, including 21 ectopic parathyroid glands (14.78%). Six patients (17.64%, 6/34) had supernumerary parathyroid glands. At 6 h postoperatively, arthralgia and bone pain were significantly reduced to almost zero in 94.12% (32/34) of patients. At 24 h postoperatively, relief of bone pain and improvement of limb movement were observed in 100% (34/34) of patients, and pruritus almost disappeared in 86.36% (19/22) of patients. There were significant differences in iPTH (χ2 = 134.93, P < 0.05), calcium (χ2 = 23.02, P < 0.05), and phosphorus (χ2 = 102.11, P < 0.05) levels preoperatively and 40 min, 24 h, 1 week, half a year, and last available (> 1 year) postoperatively. The patients were followed up for 15-47 months (median 33 months). Hypoparathyroidism was observed in three patients, who underwent neck dissection or partial thymotomy concurrently for different reasons. No intractable hypocalcemia or adynamic bone disease occurred during the follow-up period. CONCLUSION: In SHPT patients who were ineligible for renal transplantation, tPTX was effective, safe, and reliable, with a low recurrence rate. However, when tPTX was performed alone without autologous transplantation, bilateral neck exploration was sufficient, and central neck dissection and thymic resection were inadvisable.

Clinicopathologic characteristics, outcomes, and prognostic factors of angioimmunoblastic T-cell lymphoma in China.

BACKGROUND: This study aimed to better characterize the clinicopathologic characteristics, outcomes, and prognostic factors of AITL in China. METHODS: We retrospectively analyzed 312 patients with AITL enrolled between January 2011 and December 2020 from five institutions in China. RESULTS: The median age was 65 years, with 92.6% advanced stage, 59.7% elevated LDH, 46.1% anemia, and 44.0% hypergammaglobulinemia. The majority of patients (84.9%) received anthracycline-based regimens with or without etoposide, and only 6.1% underwent autologous stem cell transplantation following first remission. The 5-year OS and PFS estimates were 43.4% and 25.0% with no significant improvement of survival between patients treated during 2011-2015 and 2016-2020, respectively. Both the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT), were predictive for OS. In multivariate analysis, age >70 years, elevated LDH, and albumin level <35 g/L were independent prognostic factors for OS. Combining these three factors, a novel prognostic model (the Chinese AITL score) was constructed, which stratified patients into low-, intermediate-, and high-risk groups, with 5-year OS rates of 69.0%, 41.5%, and 23.7%, respectively. This new model was successfully validated in an independent cohort. CONCLUSIONS: Patients with AITL were mainly treated with anthracycline-based regimens, and the outcomes were still unsatisfactory in China. Our novel prognostic model may improve our ability to identify patients at different risks for alternative therapies.

Secondary Hyperparathyroidism: Clinical Exploration of Endoscopic Total Parathyroidectomy Using the Oral Vestibular Approach with Forearm Autotransplantation.

Context: For secondary hyperparathyroidism (SHPT), physicians prefer conservative treatments, and surgical intervention has proven to be the best solution for some patients. Among the surgical interventions, total parathyroidectomy plus autotransplantation (TPTX+AT), using the forearm, is the major effective treatment. TPTX+AT, in conjunction with transoral endoscopic thyroidectomy vestibular approach (TOETVA), includes many advantages. Objective: The study intended to evaluate the clinical value of performing an endoscopic total parathyroidectomy TPTX+AT in conjunction with TOETVA in treating SHPT and to summarize and share the clinical experience. Design: The research team performed a prospective controlled study. Setting: The study took place at the Zhongshan Boai Hospital affiliated with Southern Medical University in Zhong Shan, Guangdong, China. Participants: Participants were 97 SHPT patients who were admitted to the hospital between March 2020 and March 2022. Intervention: The intervention group included 47 SHPT patients who received endoscopic TPTX+AT combined with the TOETVA, and the control group included 50 SHPT patients who received routine TPTX+AT. Outcome Measures: The research team performed comparisons between the groups regarding: (1) operating conditions, including intraoperative blood loss, operating time, and number of parathyroid glands detected intraoperatively; (2) clinical efficacy, (3) postoperative complications, (4) parathyroid hormone (PTH) and calcium (Ca) levels, (5) psychological status using the Hamilton Anxiety (HAMA) and the Hamilton Depression Scale (HAMD), and (9) life quality using the 36-Item Short Form Health Survey (SF-36). Results: The intervention group had significantly longer operation times and significantly greater intraoperative blood loss than the control group did, but the intervention group had fewer complications, lower PTH and Ca levels, and a higher efficacy (P < .05). The intervention group also had a significantly better psychological state and prognostic quality of life than the control group did (P < .05). Conclusions: Endoscopic treatment of SHPT using TPTX+AT in combination with TOETVA can significantly relieve clinical symptoms and lower serum PTH and Ca levels. The results suggest that the operation is safe and effective.

Effect of Hyperbaric Oxygen Therapy on the Survival Rate of Autologous Fat Transplantation.

OBJECTIVE: To investigate whether hyperbaric oxygen therapy can improve the survival rate of fat transplantation and analyze the possible mechanisms. METHODS: Ninety SD rats were randomly divided into 3 groups. All the rats were cut into pieces with about 5 mL of fat from the abdominal cavity, rinsed with normal saline for 3 times, and cleaned with cotton pad adsorption method. Then, 3 ml was removed, divided into 3 parts, and injected into three adjacent but not touching parts of the back. Group A received 1h/d hyperbaric oxygen therapy, group B received 2 h/d hyperbaric oxygen therapy, and group C received no hyperbaric oxygen therapy. The hyperbaric oxygen therapy lasted for 10 consecutive days. Fat grafts from one site were randomly removed at 2, 4, and 6 weeks after surgery, respectively. ① the survival rate of fat transplantation in three groups was compared. ② observe the pathological section; ③ immunohistochemistry was used to detect and compare the expression of vascular endothelial growth factor. RESULTS: The survival rate of fat transplantation in group A was the highest. After subcutaneous transplantation of 1 ml of fat and 1 hour/day of continuous hyperbaric oxygen treatment for 10 days, the fat survival rates were 0.796 ± 0.071 ml, 0.644 ± 0.151 ml, and 0.473 ± 0.127 ml at the second, fourth, and sixth weeks, respectively. The survival rate of fat transplantation in group B was the second. After subcutaneous transplantation of 1 ml of fat and 2 hour/day of continuous hyperbaric oxygen treatment for 10 days, the survival rate of fat was 0.624 ± 0.220 ml, 0.494 ± 0.125 ml, and 0.329 ± 0.153 ml at the second, fourth, and sixth weeks, respectively. The survival rate of fat transplantation in group C was the lowest. After subcutaneous transplantation of 1 ml of fat and no hyperbaric oxygen treatment for 10 days, the fat survival rates were 0.461 ± 0.132 ml, 0.290 ± 0.112 ml and 0.169 ± 0.091 ml at the second, fourth, and sixth weeks, respectively. We have made changes in the abstract of the article and marked in red color. CONCLUSION: Hyperbaric oxygen therapy is conducive to the survival of transplanted fat. Importantly, a short period of hyperbaric oxygen therapy (1 h/d) can promote the survival of transplanted fat. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reduced Elastin Fibers and Melanocyte Loss in Vitiliginous Skin Are Restored after Repigmentation by Phototherapy and/or Autologous Minigraft Transplantation.

Vitiligo is a hypopigmentation disease characterized by melanocyte death in the human epidermis. However, the mechanism of vitiligo development and repigmentation is largely unknown. Dermal fiber components might play an important role in vitiligo development and repigmentation. Indeed, our preliminary study demonstrated that elastin fibers were decreased in vitiliginous skin, suggesting that the elastin fiber is one of the factors involved in vitiligo development and repigmentation. To confirm our hypothesis, we investigated whether elastin fibers can be restored after treatment using phototherapy and/or autologous skin transplantation. Punch biopsies from 14 patients of stable nonsegmental vitiligo vulgaris were collected from nonlesional, lesional, and repigmented skin, and processed to dopa and combined dopa-premelanin reactions. Melanocytes positive to the dopa reaction and melanoblasts/melanocytes positive to the combined dopa-premelanin reaction were surveyed. Moreover, elastin fibers were detected by Victoria blue staining. Numerous melanocytes and melanoblasts were observed in the epidermis of repigmented skin after the treatment. Moreover, in the dermis of repigmented skin, elastin fibers were completely recovered or even upregulated. These results suggest that melanocyte loss in the vitiliginous skin, as well as melanocyte differentiation in repigmented skin, may be at least in part regulated by elastin fibers in the dermis.

No Effect of Vitamin C Administration on Neutrophil Recovery in Autologous Stem Cell Transplantation for Myeloma or Lymphoma: A Blinded, Randomized Placebo-Controlled Trial.

Vitamin C is an important micronutrient for various immune cells. It increases phagocytic cell function and is necessary for T and natural killer (NK) cell development. Patients in need of an autologous hematopoietic stem cell transplantation (HSCT) are often vitamin C-depleted. We therefore hypothesized that vitamin C supplementation could improve immune recovery in autologous HSCT patients. This blinded, placebo-controlled trial included 44 patients randomized to receive vitamin C or a placebo. The following outcome measures used were clinical and immunological parameters, among others: time to neutrophil recovery, serum, and intracellular vitamin C values. Twenty-one patients received vitamin C, and 23 received a placebo. The time to neutrophil recovery did not differ between the two groups at 11.2 days (p = 0.96). There were no differences in hospitalization time (19.7 vs. 19.1 days, p = 0.80), the incidence of neutropenic fever (57% vs. 78%, p = 0.20), or 3-month overall survival (90.5% vs. 100%, p = 0.13). Bacteremia seemed to occur less in the vitamin C group (10% vs. 35%, p = 0.07). Our study shows no benefit from vitamin C supplementation on neutrophil recovery and hospitalization, despite possible lower rates of bacteremia in the vitamin C group. Therefore, we do not advise vitamin C supplementation in this treatment group.

Hyperbaric Oxygen Improves the Survival and Angiogenesis of Fat Grafts after Autologous Fat Transplantation.

Objective: Currently, autologous fat transplantation (AFT) still has a low graft survival rate. Elevation of the AFT graft survival rate is a challenge. This study investigated the effect of hyperbaric oxygen (HBO) on AFT. Methods: Twelve adult male SD rats were randomly divided into two groups after AFT: the control group (n = 6) and the HBO group (n = 6). The rats were killed at 7, 14, and 28 days after transplantation to take the transplanted adipose tissues. The volume and weight of the tissues were detected. The pathological changes in the adipose tissues were observed after H&E staining. Microvessel density and levels of transforming growth factor- (TGF-) ß, tumor necrosis factor- (TNF-) α, and malondialdehyde (MDA) in the transplanted adipose tissues were measured with CD31 immunohistochemical stain, ELISA, and biochemical reagents, respectively. Additionally, the protein expression levels of vascular endothelial growth factor- (VEGF-) A and platelet-derived growth factor- (PDGF) A in the adipose tissues were detected by Western blot. Results: HBO significantly preserved the volume and weight of the transplanted adipose tissue (p < 0.01) and maintained the pathological structure of the transplanted adipose tissue. HBO therapy was effective in reducing inflammatory factor (TGF-ß and TNF-α) levels and oxidative stress (MDA) in the transplanted adipose tissue (p < 0.01) and significantly increased the level of CD31 and angiogenesis-related factors including VEGF-A and PDGF-A (p < 0.01) to promote angiogenesis. Conclusion: HBO therapy regulated the immune response of fat grafts, stimulated their angiogenesis, and ultimately promoted their survival after AFT.

Effect of vitamin C on immune reconstitution after bone marrow transplantation.

BACKGROUND: Vitamin C is an essential nutrient for the adequate function and maturation of the immune system. In vitro studies show that the development, proliferation, and functioning of T cells requires vitamin C, especially for natural killer (NK) cells. Their deficiency during the acute phase post-transplantation could cause greater morbidity and mortality in these patients. A prospective clinical trial using high-dose vitamin C was performed to determine if vitamin C supplementation improves reconstitution of NK lymphocytes after hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: We enrolled 24 patients who underwent autologous HSCT for multiple myeloma and lymphoma. Patients were randomized to receive standard treatment or standard treatment plus 20 g vitamin C once daily (1 - 10 days) and 500 mg twice daily (11 - 100 days) after transplantation. RESULTS: NK and CD3+ lymphocytes showed an increase from days +30 to +100 only in the vitamin C-treated group. Patients in the vitamin C group had a lower frequency of infections. No severe adverse events were reported. CONCLUSION: Our results suggest that high-dose vitamin C supplementation is an effective and safe therapeutic option to decrease the frequency of infections and enhance immune reconstitution after HSCT.

Response-An Extreme Ordeal: Writing Emotion in Qualitative Research.

Responding to the stimulus afforded by Little et al.'s "Pragmatic pluralism: Mutual tolerance of contested understandings between orthodox and alternative practitioners in autologous stem cell transplantation," this paper explores how the norms of qualitative inquiry affect the representation of emotion in research reports. It describes a conflict between the construction of emotion in qualitative research accounts and its application to analysis and theorization, whose origins may lie in researchers' reticence when it comes to conveying or using the emotional features of data. The technical aspects of report writing that are associated with this conflict are explored via a deconstruction of Little et al.'s paper and a survey of the qualitative research methods literature. Writing to convey emotion and analysing to include author-constructed emotional context are neglected topics. Using data in Little et al.'s text, the paper demonstrates the importance of author-constructed emotional context to theory generation. The paper recommends the inclusion of emotional context as data in analysis and points to lessons Little et al.'s paper offers in the areas of narrative technique and reflexive practice.

Vitamin B6 deficiency as a cause of polyneuropathy in POEMS syndrome: rapid recovery with supplementation in two cases.

BACKGROUND: The etiology of POEMS syndrome and its associated polyneuropathy have not been fully elucidated. The clinical picture of POEMS-associated polyneuropathy and nutritional polyneuropathy due to vitamin B6 (VB6) deficiency are strikingly similar, both being typically sensorimotor, symmetrical, stocking and glove distribution, and more severe in the lower extremities. CASE PRESENTATION: We report two consecutive POEMS patients with VB6 deficiency who showed unusual rapid and drastic recovery of polyneuropathies within 6-8 weeks after oral VB6 supplementation. Case 1 was supplemented with VB6 from time of autologous stem cell transplantation. Polyneuropathy began to improve within one week, and he became walker-free and could walk unaided with a cane within 6 weeks. Case 2 was supplemented with VB6 from time of stem cell harvest, and he became cane-free and his gait almost normalized within two months. Nerve conduction studies were also confirmatory of neurologic recovery in both cases. CONCLUSIONS: Objective physical improvement of POEMS-associated polyneuropathy has been reported to typically require approximately a year after autologous stem cell transplantation, and together with our observations of VB6 deficiency and supplementations leading to accelerated recoveries of polyneuropathy, VB6 deficiency most probably contributes to POEMS-associated polyneuropathy. VB6 acts as a coenzyme in approximately 150 biochemical reactions. VB6 has been reported to inhibit the hypoxia-inducible factor/vascular endothelial growth factor (VEGF) pathway, and VEGF levels are known to corollate with disease activity of POEMS syndrome. Therefore, VB6 deficiency may contribute not only to POEMS-associated polyneuropathy, but also to the etiology of POEMS syndrome itself.

Why and how to use the body's own stem cells for regeneration in musculoskeletal disorders: a primer.

BACKGROUND: Recently, the management of musculoskeletal disorders with the patients' own stem cells, isolated from the walls of small blood vessels, which can be found in great numbers in the adipose tissue, has received considerable attention. On the other hand, there are still misconceptions about these adipose-derived regenerative cells (ADRCs) that contain vascular-associated pluripotent stem cells (vaPS cells) in regenerative medicine. METHODS: Based on our previous publications on this topic, we have developed a concept to describe the significance of the ADRCs/vaPS cells in the field of orthobiologics as briefly as possible and at the same time as precisely as possible. RESULTS: The ADRCs/vaPS cells belong to the group of orthobiologics that are based on autologous cells. Because the latter can both stimulate a patient's body's localized self-healing power and provide new cells that can integrate into the host tissue during the healing response when the localized self-healing power is exhausted, this group of orthobiologics appears more advantageous than cell-free orthobiologics and orthobiologics that are based on allogeneic cells. Within the group of orthobiologics that are based on autologous cells, enzymatically isolated, uncultured ADRCs/vaPS cells have several advantages over non-enzymatically isolated cells/microfragmented fat as well as over uncultured bone marrow aspirate concentrate and cultured cells (adipose-derived stem cells, bone marrow-derived mesenchymal stem cells). CONCLUSIONS: The use of ADRCs/vaPS cells can be seamlessly integrated into modern orthopedic treatment concepts, which can be understood as the optimization of a process which-albeit less efficiently-also takes place physiologically. Accordingly, this new safe and effective type of treatment is attractive in terms of holistic thinking and personalized medicine.

Efficacy of complementary treatment with autologous platelet concentrates and/or mesenchymal stem cells in chemical osteonecrosis of the jaw. Systematic review of the literature.

The aim of this systematic review was to establish the current status of the subject and find out what scientific evidence we have on the use of autologous plasma concentrates (APCs) and mesenchymal stem cells (MSCs) as complementary therapies at the management of Medication-related Osteonecrosis of the jaw (MRONJ). We performed a literature search of articles published between December 2019 to January 2020 in electronic databases, in accordance to PRISMA system. The variables analyzed were: the number of patients, age, sex, medical history, origin of MRONJ, imaging studies, treatment performed, and evolution of MRONJ. The articles included in the review were grouped into two groups (Group A "Therapy with APCs" and Group B "Therapy with APCs and MSCs"). Newcastle-Ottawa scale (NOS) was used to assess the quality of the articles. Fisher's exact test was used to evaluate eventual differences between groups. Of the 306 patients who were included, 297 belonged to Group A and 9 to Group B. In our sample, women predominated against men and no significant differences in age were observed. Osteoporosis was the most frequent underlying disease in both groups. The most common origin of MRONJ was oral surgery in group A. Conservative surgery was performed in all patients, but complementary treatment was applied in different ways in each group. The resolution of the pathology was achieved in 90% of cases in both groups without significant differences between them. The mean score of the reviewed studies at NOS was 4. There are currently no published scientific data that can sufficiently support the use of APCs and MSCs for the treatment of established MRONJs.