A rare presentation of Rosai-Dorfman-Destombes disease with central nervous system involvement and cutaneous wounds.

OBJECTIVE: The aim of this case report is to investigate an uncommon presentation of Rosai-Dorfman-Destombes (RDD) disease, and discuss possible differential diagnoses and treatment options for this pathology. RDD is a rare disorder of histiocytes that typically presents in patients as painless cervical lymphadenopathy. However, this case involves a patient with the central nervous system (CNS) type of RDD who later developed cutaneous lesions. METHOD: Several differential diagnoses were examined, including hidradenitis suppurativa, pilonidal cyst and pressure ulcers. It is important to be able to exclude these diagnoses based on the presentation, patient demographic and wound location. RESULTS: Biopsies verified the presence of RDD in the patient's suprasellar hypothalamic mass and skin lesions, confirming the patient had both CNS-RDD and cutaneous-RDD in the absence of lymphadenopathy. CONCLUSION: Recognising the unique manifestations of rare diseases such as RDD prevents delay of proper intervention and treatment.

Thoracic Outlet Syndrome in the Pediatric and Young Adult Population.

PURPOSE: This study aimed to assess both nonsurgical and operative treatment outcomes of pediatric and young adult patients with thoracic outlet syndrome (TOS) at a tertiary care pediatric hospital. METHODS: A retrospective chart review of patients diagnosed with TOS, who were seen between January 2010 and August 2022 at a tertiary care pediatric hospital, was conducted. Collected pre- and postoperative data included symptoms, provocative testing (ie, Roo's, Wright's, and Adson's tests), participation in sports or upper-extremity activities, additional operations, and surgical complications. Assessment of operative treatment efficacy was based on pre- and post-provocative testing, pain, venogram results, alleviation of symptoms, and return to previous activity level 6 months after surgery. RESULTS: Ninety-six patients, (70 females and 26 males) with an average age at onset of 15 ± 4 (4-25) years, met the inclusion criteria for TOS. Among them, 27 had neurogenic TOS, 29 had neurogenic and vasculogenic TOS, 20 had vasculogenic TOS, 19 had Paget-Schroetter Syndrome, and one was asymptomatic. Twenty-six patients were excluded because of less than 6 months of follow-up. Of the remaining 70, 6 (8.6%) patients (4 bilateral and 2 unilateral) underwent nonoperative management with activity modification and physical therapy only, and one was fully discharged because of complete relief of symptoms. Sixty-four (90.1%) patients (45 bilateral and 19 unilateral) underwent surgery. A total of 102 operations were performed. Substantial improvements were observed in provocative maneuvers after surgery. Before surgery, 79.7% were involved in sports or playing musical instruments with repetitive overhead activity, and after surgery, 86.2% of these patients returned to their previous activity level. CONCLUSIONS: Few patients were successfully managed with nonoperative activity modification and physical therapy. In those requiring surgical intervention, first or cervical rib resection with scalenectomy using a supraclavicular approach provided resolution of symptoms with 86.2% of patients being able to return to presymptom sport or activity level. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Early Post-Natal Immune Activation Leads to Object Memory Deficits in Female Tsc2+/- Mice: The Importance of Including Both Sexes in Neuroscience Research.

There is evidence that viral infections during pre-natal development constitute a risk factor for neuropsychiatric disorders and lead to learning and memory deficits. However, little is known about why viral infections during early post-natal development have a different impact on learning and memory depending on the sex of the subject. We previously showed that early post-natal immune activation induces hippocampal-dependent social memory deficits in a male, but not in a female, mouse model of tuberous sclerosis complex (TSC; Tsc2+/- mice). Here, we explored the impact of a viral-like immune challenge in object memory. We demonstrate that early post-natal immune activation (during the first 2 weeks of life) leads to object memory deficits in female, but not male, mice that are heterozygous for a gene responsible for tuberous sclerosis complex (Tsc2+/- mice), while no effect was observed in wild type (WT) mice. Moreover, we found that the same immune activation in Tsc2+/- adult mice was not able to cause object memory deficits in females, which suggests that the early post-natal development stage constitutes a critical window for the effects of immune challenge on adult memory. Also, our results suggest that mTOR plays a critical role in the observed deficit in object memory in female Tsc2+/- mice. These results, together with previous results published by our laboratory, showing sex-specific memory deficits due to early post-natal immune activation, reinforce the necessity of using both males and females for research studies. This is especially true for studies related to immune activation, since the higher levels of estrogens in females are known to affect inflammation and to provide neuroprotection.

Management of Radiation-induced Tissue Injuries: A Review of Current Treatment Strategies.

Although radiation therapy remains an integral component in cancer treatment, the sequela of tissue damage can result in long-term morbidity and mortality for patients. This article aimed to perform a comprehensive review of the current literature for both nonsurgical and surgical management strategies for radiation-induced injuries. Methods: A literature search was performed on PubMed to review the current described management and treatment options for radiation-induced injuries. Patient demographics, medical diagnoses, complications, strategies of management care, and outcomes were reviewed. Results: The most commonly described management options and reconstructive techniques of radiation wounds were analyzed and reported. Conclusions: Consideration of current techniques and outcomes in the management of radiation-induced wounds demonstrates that impaired wound healing remains a major problem. This literature review provides a detailed overview of the most frequently used therapies with recommendations for surgeons.

Role of Type I Interferon Signaling and Microglia in the Abnormal Long-term Potentiation and Object Place Recognition Deficits of Male Mice With a Mutation of the Tuberous Sclerosis 2 Gene.

Background: Tuberous sclerosis complex is a genetic disorder associated with high rates of intellectual disability and autism. Mice with a heterozygous null mutation of the Tsc2 gene (Tsc2+/-) show deficits in hippocampal-dependent tasks and abnormal long-term potentiation (LTP) in the hippocampal CA1 region. Although previous studies focused on the role of neuronal deficits in the memory phenotypes of rodent models of tuberous sclerosis complex, the results presented here demonstrate a role for microglia in these deficits. Methods: To test the possible role of microglia and type I interferon in abnormal hippocampal-dependent memory and LTP of Tsc2+/- mice, we used field recordings in CA1 and the object place recognition (OPR) task. We used the colony stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia in Tsc2+/- mice and interferon alpha/beta receptor alpha chain null mutation (Ifnar1-/-) to manipulate a signaling pathway known to modulate microglia function. Results: Unexpectedly, we demonstrate that male, but not female, Tsc2+/- mice show OPR deficits. These deficits can be rescued by depletion of microglia and by the Ifnar1-/- mutation. In addition to rescuing OPR deficits, depletion of microglia also reversed abnormal LTP of the Tsc2+/- mice. Altogether, our results suggest that altered IFNAR1 signaling in microglia causes the abnormal LTP and OPR deficits of male Tsc2+/- mice. Conclusions: Microglia and IFNAR1 signaling have a key role in the hippocampal-dependent memory deficits and abnormal hippocampal LTP of Tsc2+/- male mice.

Role of Hyperbaric Oxygen Therapy in Cosmetic and Reconstructive Surgery in Ischemic Soft Tissue Wounds: A Case Series.

Background: Hyperbaric oxygen therapy (HBOT) is an effective primary and adjunctive treatment for a wide spectrum of conditions, ranging from carbon monoxide poisoning to nonhealing wounds. Although HBOT has been shown to improve morbidity and mortality rates when used as adjunctive therapy for compromised skin wounds, the strategy is still underutilized in practice, especially in the field of cosmetic and plastic reconstructive surgery. Methods: Here we present 4 cases in which adjunctive HBOT was used to treat ischemic soft tissue wounds following facial fillers injectables, abdominoplasty, and compromise cutaneous flap after Mohs surgery reconstruction. Results: In this report, we highlight the utility and implications of HBOT in the management of adverse outcomes following medical interventions. Conclusions: The purpose of this case series is to add to the current existing literature examining the expanding role of HBOT as an adjunctive treatment for compromised skin and subcutaneous tissue wounds.

Purse-String Suture Technique in Reducing Surgical Defect Size.

What is the purse-string suture (PSS) technique?When should this technique be used?What are the benefits and risks of the PSS technique?What are other clinical applications of the PSS technique in plastic reconstructive surgery?

Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?

For over a century, a complex relationship between schizophrenia diagnosis and development of many cancers has been observed. Findings from epidemiological studies are mixed, with reports of increased, reduced, or no difference in cancer incidence in schizophrenia patients. However, as risk factors for cancer, including elevated smoking rates and substance abuse, are commonly associated with this patient population, it is surprising that cancer incidence is not higher. Various factors may account for the proposed reduction in cancer incidence rates including pathophysiological changes associated with disease. Perturbations of the adenosine system are hypothesized to contribute to the neurobiology of schizophrenia. Conversely, hyperfunction of the adenosine system is found in the tumor microenvironment in cancer and targeting the adenosine system therapeutically is a promising area of research in this disease. We outline the current biochemical and pharmacological evidence for hypofunction of the adenosine system in schizophrenia, and the role of increased adenosine metabolism in the tumor microenvironment. In the context of the relatively limited literature on this patient population, we discuss whether hypofunction of this system in schizophrenia, may counteract the immunosuppressive role of adenosine in the tumor microenvironment. We also highlight the importance of studies examining the adenosine system in this subset of patients for the potential insight they may offer into these complex disorders.

The Multispecialty Toxin: A Literature Review of Botulinum Toxin.

Botulinum toxin (BoNT) is a potent biological exotoxin produced from Clostridium botulinum. Although it was first used therapeutically to treat strabismus, its clinical role has since expanded rapidly over the years to include treatment of a variety of head and neck, gastrointestinal, urogenital, musculoskeletal, neurological, dermatological, and cosmetic disorders. The main purpose of this review is to provide a brief updated overview of the history, mechanism of action, and clinical applications of BoNT therapy across multiple medical specialties, including the most common adverse effects and recommended Botox dosages. Methods: A literature review was conducted in the PubMed database limited to English language articles. Specific search terms related to botulinum toxin in combination with various subspecialty fields were used, and relevant articles were identified and analyzed. The reference section for each article was also searched to find additional articles. Results: BoNT is a powerful therapeutic tool and has a vast array of clinical uses in many specialties, including ophthalmology, neurology, plastic surgery, dermatology, orthopedic, gastrointestinal, gynecology, urology, and rheumatology. Due to its chemodenervation effects at the presynaptic nerve terminal, it is useful in treatments of disorders characterized by abnormal inappropriate muscle contractions. Conclusions: BoNT has many clinical applications in several medical specialties. Future studies should focus on any additional indications of BoNT therapy as they arise and on any novel product developments.

Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications.

There is growing evidence that prenatal immune activation contributes to neuropsychiatric disorders. Here, we show that early postnatal immune activation resulted in profound impairments in social behavior, including in social memory in adult male mice heterozygous for a gene responsible for tuberous sclerosis complex (Tsc2+/−), a genetic disorder with high prevalence of autism. Early postnatal immune activation did not affect either wild-type or female Tsc2+/− mice. We demonstrate that these memory deficits are caused by abnormal mammalian target of rapamycin­dependent interferon signaling and impairments in microglia function. By mining the medical records of more than 3 million children followed from birth, we show that the prevalence of hospitalizations due to infections in males (but not in females) is associated with future development of autism spectrum disorders (ASD). Together, our results suggest the importance of synergistic interactions between strong early postnatal immune activation and mutations associated with ASD.

Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling.

RATIONALE: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). MEASUREMENTS AND MAIN RESULTS: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. CONCLUSIONS: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).

Rituximab-induced interstitial lung disease: five case reports.

Rituximab (RTX), a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody has been effectively used as a single agent or in combination with chemotherapy regimen to treat lymphoma since 1997. In addition, it has been used to treat idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lung diseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about this serious side effect of RTX treatment, as the indication for its use increases with time, we report five cases of probable RTX-ILD and discuss the current literature on this potentially lethal association.

[Lung cancer screening with low dose CT requires careful consideration].

Results from the American National Lung Screening Trial (NLST) show a significant reduction in lung cancer and all-cause mortality in a high risk population screened with annual low-dose CT. Handling of pulmonary nodules, false positive tests, overdiagnosis, psychosocial consequences and cost-efficiency etc. are all aspects that require careful consideration. This paper gives an overview of the current knowledge on these issues. Before a recommendation can be made, we need an overall evaluation of both the benefits and harms in CT screening for lung cancer.

[Lung cancer screening with low-dose CT - Danish and international results].

Lung cancer is the cancer type that causes the largest number of deaths in Denmark. With advances in medical imaging and widespread use of computed tomography (CT), it is possible to detect even small abnormalities in lung tissue. This has led to a great interest in lung cancer screening with low-dose CT and launching of randomised screening trials worldwide. This paper gives an overview of the current lung cancer screening trials in Denmark and internationally and focuses on main lung cancer findings and mortality results.

CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT.

BACKGROUND: The effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial. METHODS: 4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice. RESULTS: Participation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs. 24, p<0.001), and more were low stage (48 vs 21 stage I-IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA-IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428). CONCLUSION: CT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.

A relationship-based intervention to improve social connectedness in street-involved youth: a pilot study.

PROBLEM: Street-involved youth experience a range of mental health problems with elevated rates of psychiatric disorders compared with non-homeless youth. The overall objective of this pilot study was to evaluate the impact of a relationship-based intervention for homeless youth receiving services from agencies in downtown Toronto. METHODS: The final sample included 15 homeless youth who met the study inclusion criteria. The intervention and comparison groups were compared at baseline and post-treatment on measures of mental health symptoms, hopelessness, self-esteem, resilience, and social connectedness. FINDINGS: Participants receiving the intervention demonstrated a significant improvement in social connectedness, with a trend toward decreased hopelessness. Those participants who did not receive the intervention did not demonstrate any improvements in social connectedness and hopelessness. CONCLUSION: This preliminary pilot study suggests that providing a relationship-based intervention to street-involved youth may offer promise to strengthen social relationships and to mitigate overwhelming hopelessness and despair.

Mental health challenges and strengths of street-involved youth: the need for a multi-determined approach.

The social environments and activities of homeless youth frequently create a downward spiral, leading to drug abuse and survival sex as well as self-harm behaviours and suicidality. This study employed a mixed-methods approach to assess the mental health challenges and strengths of street-involved youth. A convenience sample of 70 homeless young people completed a series of standardized questionnaires evaluating mental health symptoms as well as resilience and self-esteem. Two focus groups were also held to capture the perceived mental health needs of street-involved youth. These young people (aged 16-24) were found to have high levels of mental health symptoms compared to other groups of young adults. However, they also exhibited moderately high levels of resilience and self-esteem. Therefore, multi-component mental health programs and interventions that address both strengths and challenges may well help street-involved youth to work towards social re-integration and, ultimately, improved quality of life.

Clinical impact of endoscopic ultrasound-fine needle aspiration of left adrenal masses in established or suspected lung cancer.

INTRODUCTION: Correct lung cancer staging is pivotal for optimal allocation to surgical and nonsurgical treatment. A left adrenal gland (LAG) mass is found in 5 to 16%, and malignancy preclude surgery. Endoscopic ultrasound (EUS) is superior to other imaging procedures in visualizing LAG, but the impact of EUS-fine needle aspiration (FNA) on tumor, node, metastasis (TNM)-staging, treatment, and survival is unknown. METHODS: The impact of EUS-FNA of the LAG on TNM staging, treatment, and survival was evaluated retrospectively in all patients (n = 40) referred to EUS during 2000-2006 for known or suspected lung cancer and where EUS disclosed an enlarged LAG. Conventional workup had preceded EUS. RESULTS: EUS-FNA of an enlarged LAG altered the TNM staging in 70% (downstaged: 26 of 28 patients) and treatment in 48% (gained surgery 25%, avoided surgery 5%, surgically verified benign disease 5%, no cancer and no further workup 5%, and no cancer, control computed tomography, and then no further workup 8%). A malignant LAG lesion was found in 28% and was significantly associated with shorter survival. CONCLUSION: EUS-FNA of an enlarged LAG in patients with known or suspected lung cancer had a significant impact on TNM staging, treatment, and survival. The impact of routine visualization of the LAG in lung cancer workup needs to be prospectively validated.

Minimally invasive aortic valve replacement reduces atelectasis in cardiac intensive care.

OBJECTIVE: Respiratory failure is a major complication after cardiac surgery. The purpose was to evaluate the impact of minimally invasive aortic valve replacement (mini AVR) on the occurrence of left lower lobe atelectasis (LLLA) in the cardiac intensive care unit (ICU). PATIENTS AND METHODS: 98 patients were scheduled to undergo mini AVR. 14 of these patients were converted to a full sternotomy due to technical problems. These patients were compared to a group of 50 patients having planned AVR through a full sternotomy. The incidence of LLLA was evaluated on the first postoperative chest X-ray in the cardiac ICU. RESULTS: In the group having completed mini AVR 20/84 (24%) had a partial LLLA while in the group having extension to a full sternotomy 9/14 (64%) had LLLA lobe (P<0.005). In the group of 50 patients who had AVR through a full sternotomy, 27 patients (54%) had LLLA in the ICU which is also significantly higher (P<0.008) than the percentage of atelectasis in the mini AVR group. CONCLUSIONS: Patients who had mini AVR had a significantly lower incidence of LLLA in the cardiac ICU than patients who had AVR through a full sternotomy.

The Danish randomized lung cancer CT screening trial--overall design and results of the prevalence round.

INTRODUCTION: Lung cancer screening with low dose computed tomography (CT) has not yet been evaluated in randomized clinical trials, although several are underway. METHODS: In The Danish Lung Cancer Screening Trial, 4104 smokers and previous smokers from 2004 to 2006 were randomized to either screening with annual low dose CT scans for 5 years or no screening. A history of cigarette smoking of at least 20 pack years was required. All participants have annual lung function tests, and questionnaires regarding health status, psychosocial consequences of screening, smoking habits, and smoking cessation. Baseline CT scans were performed in 2052 participants. Pulmonary nodules were classified according to size and morphology: (1) Nodules smaller than 5 mm and calcified (benign) nodules were tabulated, (2) Noncalcified nodules between 5 and 15 mm were rescanned after 3 months. If the nodule increased in size or was larger than 15 mm the participant was referred for diagnostic workup. RESULTS: At baseline 179 persons showed noncalcified nodules larger than 5 mm, and most were rescanned after 3 months: The rate of false-positive diagnoses was 7.9%, and 17 individuals (0.8%) turned out to have lung cancer. Ten of these had stage I disease. Eleven of 17 lung cancers at baseline were treated surgically, eight of these by video assisted thoracic surgery resection. CONCLUSIONS: Screening may facilitate minimal invasive treatment and can be performed with a relatively low rate of false-positive screen results compared with previous studies on lung cancer screening.