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Abstract Diabetes affects multiple systems in complex manners. Diabetic foot ulcers (DFUs) are a result of diabetes‐induced microarterial vessel disease and peripheral neuropathy. The presence of arteriosclerosis‐induced macroarterial disease can further complicate DFU pathophysiology. Recent studies suggest that mesenchymal stromal cell therapies can enhance tissue regeneration. This phase I study was designed to determine the safety and explore the efficacy of local injections of autologous adipose‐derived stromal vascular fraction (SVF) cells to treat nonhealing DFUs greater than 3 cm in diameter. Sixty‐three patients with type 2 diabetes with chronic DFU—all amputation candidates—were treated with 30 × 106 SVF cells injected in the ulcer bed and periphery and along the pedal arteries. Patients were seen at 6 and 12 months to evaluate ulcer closure. Doppler ultrasounds were performed in a subset of subjects to determine vascular structural parameters. No intervention‐related serious adverse events were reported. At 6 months, 51 subjects had 100% DFU closure, and 8 subjects had ≥75% closure. Three subjects had early amputations, and one subject died. At 12 months, 50 subjects had 100% DFU healing and 4 subjects had ≥85% healing. Five subjects died between the 6‐ and 12‐month follow‐up visits. No deaths were intervention related. Doppler studies in 11 subjects revealed increases in peak systolic velocity and pulsatility index in 33 of 33 arteries, consistent with enhanced distal arterial runoff. These results indicate that SVF can be safely used to treat chronic DFU, with evidence of efficacy (wound healing) and mechanisms of action that include vascular repair and/or angiogenesis.

The osteopoikilosis is a rare illness characterized by an alteration of the bone remodeling. The case of two patients, members of the same family (mother and son), who suffered from this illness, is presented here.

Abstract Background Immersion Pulmonary Edema (IPE) is a common and potentially serious diving accident that can have significant respiratory and cardiac consequences and, in some cases, be fatal. Our objective was to characterize cases of IPE among military trainees and recreational divers and to associate their occurrence with exposure and individual background factors such as age and comorbidity. We conducted a retrospective analysis on the medical records and diving parameters of all patients who were treated for IPE at the Hyperbaric Medicine Department of Sainte-Anne Military Hospital in Toulon, France, between January 2017 and August 2019. In total, 57 subjects were included in this study, with ages ranging from 20 to 62 years. These subjects were divided into two distinct groups based on exposure categories: (1) underwater/surface military training and (2) recreational scuba diving. The first group consisted of 14 individuals (25%) with a mean age of 26.5 ± 2.6 years; while, the second group comprised 43 individuals (75%) with a mean age of 51.2 ± 7.5 years. All divers under the age of 40 were military divers. Results In 40% of cases, IPE occurred following intense physical exercise. However, this association was observed in only 26% of recreational divers, compared to 86% of military divers. Among civilian recreational divers, no cases of IPE were observed in subjects under the age of 40. The intensity of symptoms was similar between the two groups, but the duration of hospitalization was significantly longer for the recreational subjects. Conclusion It seems that the occurrence of IPE in young and healthy individuals requires their engagement in vigorous physical activity. Additionally, exposure to significant ventilatory constraints is a contributing factor, with the intensity of these conditions seemingly exclusive to military diving environments. In contrast, among civilian recreational divers, IPE tends to occur in subjects with an average age twice that of military divers. Moreover, these individuals exhibit more prominent comorbidity factors, and the average level of environmental stressors is comparatively lower.

Abstract Background Rectal cancer, one of most common neoplasms, is characterized by an overall survival rate exceeding 60%. Nonetheless, local recurrence (LR) following surgery for rectal cancer remains a formidable clinical problem. The aim of this study was to assess the value of postoperative endoscopic surveillance (PES) for the early detection of LR in rectal cancer after radical anterior resection with sigmoid-rectal anastomosis. Methods We performed an anterior resection in 228 patients with stages I‑III rectal cancer who had undergone surgery from 2001 to 2008 in the Oncology Center in Bydgoszcz, Poland. Of these patients, 169 had perioperative radiotherapy or radiochemotherapy. All patients underwent PES with abdominal and pelvic imaging (abdominal ultrasound, computed tomography, magnetic resonance) and clinical examination. Sensitivities, specificities, positive likelihood ratios, negative likelihood ratios, and receiver operating characteristic curves were calculated to compare the value of colonoscopy versus imaging techniques for the diagnosis of LR. Results During the 5-year follow-up, recurrences occurred in 49 (21%) patients; of these, 15 (6%) had LR, which was most often located outside the intestinal lumen (n = 10, 4%). Anastomotic LR occurred in 5 (2%) patients. The mean time to anastomotic LR was 30 months after initial surgery, similar to that of other locations (29 months). Both imaging and endoscopy were shown to be efficient techniques for the diagnosis of LR in anastomotic sites. In the study group, endoscopy did not provide any additional benefit in patients who were receiving radiation therapy. Conclusions The benefit of PES for the detection of LR after curative treatment of rectal cancer is limited and not superior to imaging techniques. It remains a useful method, however, for the histopathological confirmation of suspected or confirmed recurrence.

Intensive therapies have become increasingly popular for children with hemiparesis in the last two decades and are specifically recommended because of high levels of scientific evidence associated with them, including multiple randomized controlled trials and systematic reviews. Common features of most intensive therapies that have documented efficacy include: high dosages of therapy hours; active engagement of the child; individualized goal-directed activities; and the systematic application of operant conditioning techniques to elicit and progress skills with an emphasis on success-oriented play. However, the scientific protocols have not resulted in guiding principles designed to aid clinicians with understanding the complexity of applying these principles to a heterogeneous clinical population, nor have we gathered sufficient clinical data using intensive therapies to justify their widespread clinical use beyond hemiparesis. We define a framework for describing moment-by-moment therapeutic interactions that we have used to train therapists across multiple clinical trials in implementing intensive therapy protocols. We also document outcomes from the use of this framework during intensive therapies provided clinically to children (7 months–20 years) from a wide array of diagnoses that present with motor impairments, including hemiparesis and quadriparesis. Results indicate that children from a wide array of diagnostic categories demonstrated functional improvements.

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.

Introduction: Neoplastic monoclonal gammopathies are frequently associated with production of excess free monoclonal light chains. A sensitive method for detecting free monoclonal light chains in serum could provide a marker for residual/minimal residual disease and as an adjunct to serum protein electrophoresis to serve as a screening method for monoclonal gammopathies. Methods: Conventional serum immunofixation electrophoresis was modified by applying undiluted serum samples, and staining for serum free light chains with antisera specific to free light chains. Washing/blotting of gels was enhanced to remove residual proteins that did not bind to the antibodies including intact monoclonal immunoglobulins. Results from this modified immunofixation electrophoresis were compared with results from commercially available MASS-FIX/MALDI assay. Results: Monoclonal free kappa light chains could be detected to a concentration of about 1.78 mg/L and monoclonal free lambda light chains to a concentration of about 1.15 mg/L without the need for special equipment. Comparison of these thresholds with parallel results from a commercially available MASS-FIX/MALDI assay revealed the modified electrophoretic method to be more sensitive in the context of free monoclonal light chains. Conclusions: Modified serum immunofixation electrophoresis has been shown to detect low levels of monoclonal free light chains at a sensitivity suitable for the method to be used in detecting minimal residual disease, and potentially in a screening assay for monoclonal gammopathies. The disparity in the results with commercially available MASS-FIX/MALDI assay is postulated to be due to limited repertoire of reactivity of nanobodies of camelid origin.

In recent years, the advancement of eXtended Reality (XR) technologies including Virtual and Augmented reality (VR and AR respectively) has created new human-computer interfaces that come increasingly closer to replicating natural human movements, interactions, and experiences. In medicine, there is a need for tools that accelerate learning and enhance the realism of training as medical procedures and responsibilities become increasingly complex and time constraints are placed on trainee work. XR and other novel simulation technologies are now being adapted for medical education and are enabling further interactivity, immersion, and safety in medical training. In this review, we investigate efforts to adopt XR into medical education curriculums and simulation labs to help trainees enhance their understanding of anatomy, practice empathetic communication, rehearse clinical procedures, and refine surgical skills. Furthermore, we discuss the current state of the field of XR technology and highlight the advantages of using virtual immersive teaching tools considering the COVID-19 pandemic. Finally, we lay out a vision for the next generation of medical simulation labs using XR devices summarizing the best practices from our and others’ experiences.

Background and Objectives: Despite advances in treatment, local recurrence remains a great concern in patients with rectal cancer. The aim of this study was to investigate the incidence and risk factors of local recurrence of rectal cancer in our single center over a 7-year-period. Materials and Methods: Patients with stage I-III rectal cancer were treated with curative intent. The necessity for radiotherapy and chemotherapy was determined before surgery and/or postoperative histopathological results. Results: Of 365 rectal cancer patients, 76 (20.8%) developed recurrent disease. In total, 27 (7.4%) patients presented with a local tumor recurrence (isolated in 40.7% of cases). Radiotherapy was performed in 296 (81.1%) patients. The most often used schema was 5 × 5 Gy followed by immediate surgery (n = 214, 58.6%). Local recurrence occurred less frequently in patients treated with 5 × 5 Gy radiotherapy followed by surgery (n = 9, 4%). Surgical procedures of relapses were performed in 12 patients, six of whom were operated with radical intent. Only two (7.4%) patients lived more than 5 years after local recurrence treatment. The incidence of local recurrence was associated with primary tumor distal location and worse prognosis. The median overall survival of patients after local recurrence treatment was 19 months. Conclusions: Individualized rectal cancer patient selection and systematic treatment algorithms should be used clinical practice to minimize likelihood of relapse. 5 × 5 Gy radiotherapy followed by immediate surgery allows good local control in resectable cT2N+/cT3N0 patients. Radical resection of isolated local recurrence offers the best chances of cure.

How much different genders contribute to citations and whether we see different gender patterns between STEM and non-STEM researchers are questions that have long been studied in academia. Here we analyze the research output in terms of citations collected from the Web of Science of males and females from the largest Croatian university, University of Zagreb. Applying the Mann–Whitney statistical test, for most faculties, we demonstrate no gender difference in research output except for seven faculties, where males are significantly better than females on six faculties. We find that female STEM full professors are significantly more cited than male colleagues, while male non-STEM assistant professors are significantly more cited than their female colleagues. There are ten faculties where females have the larger average citations than their male colleagues and eleven faculties where the most cited researcher is woman. For the most cited researchers, our Zipf plot analyses demonstrate that both genders follow power laws, where the exponent calculated for male researchers is moderately larger than the exponent for females. The exponent for STEM citations is slightly larger than the exponent obtained for non-STEM citations, implying that compared to non-STEM, STEM research output leads to fatter tails and so larger citations inequality than non-STEM.

The objective was to assess clinical efficacy of 3 dosages of intravenous gammaglobulins to prevent infectious episodes in adult common variable immunodeficiency. We designed a randomized, double blind, dose-assessing study. The setting was at University Hospital, Out-patient Clinic. Our patients were twenty-one adult patients with common variable immunodeficiency. The measurements were comparative study of the number and severity of infections using 3 various dosages of intravenous gammaglobulins, each given monthly for M least 6 months. Results indicated four hundred and eighty-four infectious episodes occurred while giving 305 infusions of IVIG 200 mg/kg; 205 infectious episodes while giving 170 infusions of 400 mg/kg and 436 infectious episodes while giving 247 infusions of 600 mg/kg. The morbidity scores (infection/infusion) were 1.59, 1.21 and 1.77 respectively (p - N/S). There was no significant difference in the severity of infections on the above 3 dosages, and no difference in the duration of infection-free intervals. The conclusions resulted in no significant differences in morbidity in adult patients with common variable immunodeficiency treated in cross-over pattern with IVIG 200 mg/kg, 400 mg/kg and 600 mg/kg. Thus, high dosages of IVIG are not conferring better protection against infections in such patients.

Allergic reactions from handling psyllium have been reported since 1970. Health professionals and workers in laxative-manufacturing plants are at greatest risk. Sensitized people are at risk of life-threatening anaphylactic reactions. Two illustrative cases are presented. The first is A 39-year-old female dialysis nurse with a 3-year history of nasal and eye symptoms from exposure to psyllium. She obtained an over-the-counter psyllium bulk laxative, took it for constipation and developed flushing, tachycardia, urticaria, angioedema, laryngeal edema, and lightheadedness. An epicutaneous skin test and radioallergosorbent test for psyllium were both strongly positive. The second is a 42-year-old female nurse with a history of asthma who had allergic nasal and eye symptoms while dispensing psyllium. She received a prescription for crystallized psyllium, took it by mouth, and developed immediate flushing, tachycardia, urticaria, and angioedema. With subsequent ingestion of psyllium she had, in addition, severe wheezing, lightheadedness, and loss of consciousness. A psyllium epicutaneous skin test was strongly positive. These patient reports illustrate the risk of severe allergic reactions in sensitized people. Ingestion by sensitized people, such as from a routine postoperative and postpartum order, is potentially dangerous.

Local application of guanethidine to the eye results in miosis. The sympathicolytic action of guanethidine on the pupil was proved by the consistent appearance of a Horner's syndrome after instillation of a 10% solution into the conjunctival sac. Lack of cocaine mydriasis and unimpaired adrenaline mydriasis after guanethidine application are further evidence of this mode of action. Guanethidine is the first drug that can be consistently relied upon to produce miosis by inhibiting sympathetic impulses to the intraocular pupillary muscles; it also inhibits sympathetic impulses to Horner's muscle of the upper lid. It is a reliable sympathicolytic agent for testing the reaction of abnormal pupils.