Tracheobronchopathia osteochondroplastica: a rare cause of tracheal tube cuff leak.

We present the case of a patient with the rare disorder tracheobronchopathia osteochondroplastica who underwent laparoscopic cholecystectomy. After induction of general anaesthesia, we faced difficulties passing the tracheal tube beyond the vocal cords despite bronchoscopic assistance. With a smaller tube, and by using rotating movements, we managed to successfully intubate the trachea. Because of the irregular tracheal surface, however, ventilation was challenging due to a massive cuff leak. Repeated repositioning did not improve this leak. Only cuff overinflation led to adequate ventilation, though we were cognisant of the increased risk of tracheal wall injury with this approach. After completion of the surgery, the patient's trachea was extubated without complication. This case showed that even with good preparation, intra-operative problems can occur with abnormal subglottic airway anatomy. In some circumstances, these problems can only be solved by compromise. There are no professional consensus or guidelines that can be followed as guiding references for such a case, which can lead to indecisiveness.

The social, psychological, and physical impact of COVID-19 restrictions for institutionalized adults with intellectual and developmental disabilities.

During the COVID-19 pandemic, drastic measures to interrupt SARS-CoV-2 infection chains were implemented. In our study we investigated the consequences of pandemic related restrictions on the social, psychological, and physical well-being of institutionalized adults with intellectual and developmental disabilities. Methods: Online survey among professional caregivers in 71 residential groups, caring for 848 residents. Findings: (i.) A lack of participation concerning infection protection measures of the residents, their relatives, and their caregivers; (ii.) A 20% increase in doctor contacts during the pandemic; (iii.) A considerable deterioration in at least one item of the subdomains mood (49%), everyday skills (51%), social interaction (29%), exercise and coordination skills (12%), behavior (11%) and cognition and communication (7%); (iv.) A deterioration of the overall condition in 41%; Summery: Intensive attempts should be made to find individual and less categorical contra-infectious measures without questioning the basic everyday needs of people with intellectual and developmental disabilities.

Beyond Streamflow: Call for a National Data Repository of Streamflow Presence for Streams and Rivers in the United States.

Observations of the presence or absence of surface water in streams are useful for characterizing streamflow permanence, which includes the frequency, duration, and spatial extent of surface flow in streams and rivers. Such data are particularly valuable for headwater streams, which comprise the vast majority of channel length in stream networks, are often non-perennial, and are frequently the most data deficient. Datasets of surface water presence exist across multiple data collection groups in the United States but are not well aligned for easy integration. Given the value of these data, a unified approach for organizing information on surface water presence and absence collected by diverse surveys would facilitate more effective and broad application of these data and address the gap in streamflow data in headwaters. In this paper, we highlight the numerous existing datasets on surface water presence in headwater streams, including recently developed crowdsourcing approaches. We identify the challenges of integrating multiple surface water presence/absence datasets that include differences in the definitions and categories of streamflow status, data collection method, spatial and temporal resolution, and accuracy of geographic location. Finally, we provide a list of critical and useful components that could be used to integrate different streamflow permanence datasets.

[Analysis of a first responder system for emergency medical care in rural areas: first results and experiences]. / Analyse eines First-responder-Systems zur notfallmedizinischen Versorgung im ländlichen Raum: erste Ergebnisse und Erfahrungen.

BACKGROUND: In emergency situations it is essential to get access to medical treatment as early as possible. In Germany, the time interval from alarm to arrival should be less than 10-15 min. The emergency medical service (EMS) cannot comply with this recommendation in approximately 10% of the emergencies in Baden-Württemberg. In addition to the traditional EMS system, a voluntary system of first responders has been developed over the last years to reduce this interval. They are incorporated into the alarm system of the traditional EMS and are alarmed as soon as an emergency call arrives. Data on process times (from alarm to begin of treatment or duration of treatment until arrival of EMS) and quality are rare. In Baden-Württemberg, the emergency aid "Deutsche Lebens-Rettungs-Gesellschaft e.V. (DLRG)" Nordhardt can only estimate times and quality of primary care. The objective of this analysis was to describe and evaluate such a first responder system. METHODS: The presented study investigated the emergency responses of a first responder system in Nordhardt, close to Karlsruhe, Germany. A total of 367 emergency data sets from 2017 containing information on operating time, medical history, suspected diagnosis and medical treatment, were evaluated. Of these, 363 anonymized emergency records including the complete information (concerning process time and medical treatment) were analyzed. The focus was on different time intervals from alarm to treatment and until arrival of the EMS. Additionally, the quality of medical treatment and the measured vital data were examined. RESULTS: The median response time and time to access to the patient was 2 min in both. The patient was reached within approximately 4 min and treated for another 5 min until the EMS arrived. In two thirds of the patients, the vital parameters were measured, 5 patients were resuscitated, 23 received supplementary oxygen, 4 patients were ventilated and 11 patients suffering from hypoglycemia showed a clinical benefit from the early treatment. A total of 50 trauma patients were treated, 5 with cervical spine stabilization and 38 received a body check. CONCLUSION: The first responders from Nordhardt received an emergency call nearly every day. In two thirds of the calls they were faster than the EMS as they usually have local sites with a shorter distance to the emergency scene where they are able to deal with critical medical cases until the EMS arrives. Despite the small case numbers, it could be concluded that the early medical treatment with respect to resuscitation based on earlier arrival on site may help to increase the survival rate of patients. The first responders were also able to manage airway problems with additional oxygen or other airway devices. Other medical treatment performed by the first responders, such as administration of glucose in hypoglycemic patients positively affected the patient's condition. There is a tactical advantage to include first responders in traditional EMS services. Further studies are needed to examine these questions in larger samples also over a longer time period. Standardization and digitalization of the records could help to gain more data in this field.

Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection.

Type I interferon (IFNα/ß) pathways are fine-tuned to elicit antiviral protection while minimizing immunopathology; however, the initiating stimuli, target tissues, and underlying mechanisms are unclear. Using models of physiological and dysregulated IFNα/ß receptor (IFNAR1) surface expression, we show here that IFNAR1-dependent signals set the steady-state IFN signature in both hematopoietic and stromal cells. Increased IFNAR1 levels promote a lung environment refractory to early influenza virus replication by elevating the baseline interferon signature. Commensal microbiota drive the IFN signature specifically in lung stroma, as shown by antibiotic treatment and fecal transplantation. Bone marrow chimera experiments identify lung stromal cells as crucially important for early antiviral immunity and stroma-immune cell interaction for late antiviral resistance. We propose that the microbiota-driven interferon signature in lung epithelia impedes early virus replication and that IFNAR1 surface levels fine-tune this signature. Our findings highlight the interplay between bacterial and viral exposure, with important implications for antibiotic use.

[Accidental central venous administation of 0.1 % chlorhexidine mouthwash]. / Akzidentelle zentralvenöse Verabreichung von 0,1 %iger Chlorhexidinmundspüllösung.

Medication errors are frequent and a serious safety concern. Chlorhexidine (CHX) is used daily in healthcare as a disinfectant. Its accidental intravascular injection is scarcely described. Serious complications, such as acute respiratory distress syndrome (ARDS) could be a consequence. We describe a case of central venous administration of 0.1% CHX mouthwash, its potential complications and possibilities of treatment. In contrast to another case report our patient had no detectable adverse side effects. The immediate hemofiltration and cleansing of the i. v. line may have contributed to this favorable outcome.

Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice.

The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load. This phenotype did not map to the NS gene segment, and NS1 protein of H5N1 virus functioned as a type I IFN antagonist as efficient as NS1 of H1N1 or H3N2 viruses. Instead we discovered that the internal genes of H5N1 virus supported a much higher level of replication of viral RNAs in myeloid cells in vitro, but not in epithelial cells and that this was associated with high induction of type I IFN in myeloid cells. We also found that in vivo during H5N1 recombinant virus infection cells of haematopoetic origin were infected and produced type I IFN and proinflammatory cytokines. Taken together our data infer that human and avian influenza viruses are differently controlled by host factors in alternative cell types; internal gene segments of avian H5N1 virus uniquely drove high viral replication in myeloid cells, which triggered an excessive cytokine production, resulting in severe immunopathology.

Low left amygdala volume is associated with a longer duration of unipolar depression.

The amygdala plays a crucial role in the pathogenesis of major depressive disorder (MDD). While robust findings support a negative impact of illness duration on hippocampal volume in MDD, morphometric studies of the amygdala have yielded inhomogeneous results. Considering the methodical problems of automatic segmentation methods, a standardized segmentation protocol with proven inter- and intra-rater reliability was employed using high-resolution magnetic resonance imaging. To identify the effect of MDD on amygdala morphometry, 23 unipolar depressed patients who responded to antidepressant medication and 30 age-matched healthy controls (HC) were enrolled. First, gray matter volumes (GMV) of the bilateral amygdala were delineated manually in 3D by three blinded experts using the MultiTracer. The whole brain GMV was determined by using voxel-based morphometry. Second, the differences of the whole brain and the bilateral amygdala GMV values between MDD and HC were calculated with t-statistics. The GMV of the whole brain and the amygdala did not differ between HC and MDD patients. Third, MDD characteristics were correlated with amygdala GMV. Within the normal range, the left amygdala GMV was larger in patients with later onset and smaller in cases of prolonged depression. In line with prior reports of depressed patients responding to antidepressant treatment, amygdala GMV was negatively related to illness duration, suggesting volume loss with disease progression. It remains unclear as to whether the association between illness duration and GMV reduced left amygdala volume indicates a neurotoxic effect of prolonged MDD or is rather a negative predictor of chronic depression.

Quality Improvement Intervention for Reduction of Redundant Testing.

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (-) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P < .001) in services not receiving peer leader intervention and to >80% (P < .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care.

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10-3) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

[Ventilator-associated pneumonia (VAP) : A risk already at the time of anesthetic induction]. / Ventilatorassoziierte Pneumonie (VAP) : Bereits ein Thema bei der Narkoseeinleitung.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common and preventable infections in mechanically ventilated patients. It is associated with a high mortality rate. To prevent VAP, various strategies address this issue using "VAP-bundles", which are implemented in many intensive care units. The risk of acquiring VAP starts with the induction of anesthesia, strictly speaking at the time of intubation. This article considers measures to prevent VAP during general anesthesia in adult patients (>18 years). Procedures beyond standard hygienic precautions for VAP prevention are reviewed. METHODS: A literature search in different databases (PubMed, Cochrane, Ovid und CINAHL) over the last five years. RESULTS: Beyond standard hygienic precautions, microaspiration should be avoided to prevent VAP. During mechanical ventilation at least 5 cm H2O PEEP is advised. Continuous monitoring and adjustment of cuff pressure is necessary. All patients mechanically ventilated after general anesthesia for more than 24 h should be intubated with an ETT with a port for subglottic suctioning.

Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.

Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

[Sudden cardiac death during a city marathon run]. / Plötzlicher Herztod beim Stadtmarathon.

Sudden cardiac death (SCD) in young athletes during physical stress is a rare event with an incidence of 1-3 deaths per 100,000 athletes per year. A coronary anomaly is the second most common cause of death following hypertrophic cardiomyopathy. Symptomatic prodromes occur in 20% of cases prior to the SCD event. This case report describes a 35-year-old male who collapsed near the finishing line of a half marathon run. Despite immediate resuscitation attempts and initial return of spontaneous circulation (ROSC), a pulseless electrical activity (PEA) followed and the patient died 1 h after arrival in the resuscitation unit. The autopsy revealed an anomalous left coronary artery (ALCA), which can lead to ischemia of the respective heart muscles under severe stress.

Hematologic Disorders: Anemia.

Anemia occurs in up to 25% of the US population. Normal hemoglobin levels vary by race, sex, and age. Classification of anemia by mean corpuscular volume guides the differential diagnosis and evaluation. Iron studies, reticulocyte count, the red blood cell distribution width index, and blood test results are used to make the diagnosis. Iron deficiency anemia is the most common microcytic anemia and is managed with iron therapy. Parenteral iron is available when the oral route cannot be used. Patients who do not benefit from therapy should be evaluated for adherence, malabsorption, occult bleeding, systemic disease, or less common inherited disorders. A source of gastrointestinal bleeding is found in 60% to 70% of patients with iron deficiency anemia who are referred for endoscopy. Normocytic anemia has a broad differential, including nutritional deficiencies, blood loss, renal disease, malignancy (solid tumors or hematologic cancer), rheumatologic disorders, endocrine disorders, and other systemic diseases. Macrocytic anemias are seen with vitamin B12 and folate deficiency, alcohol use, thyroid disease, hydroxyurea, antiretroviral drugs, myelodysplastic syndromes, and myeloma. Oral vitamin B12 is underused, and can be as effective as intramuscular vitamin B12 in managing anemia due to vitamin B12 deficiency.

Hematologic Disorders: Blood Transfusion Products.

Until the 1980s, liberal blood transfusion criteria with limited evidence were used regardless of the patient's clinical condition. However, blood transfusion products are associated with several risks, such as infection, acute lung injury, circulatory overload, and hemolytic transfusion reactions. More restrictive transfusion criteria and patient monitoring can decrease the need for transfusions, as well as decrease morbidity and mortality rates and costs. The national supply of blood products continues to decline with more stringent blood donor criteria. Preoperative autologous blood donation has fallen out of favor in patients without antibodies to high-incidence antigens because of increased rates of transfusion, waste of predonated units, and significant costs. Instead, preoperative erythropoietin plus iron therapy in patients who are at high risk of postoperative anemia as well as intraoperative techniques, such as use of antifibrinolytics and cell salvage, can prevent the need for allogeneic blood transfusion. Artificial blood products remain problematic and are not used in the United States.

Hematologic Disorders: Bone Marrow Failure.

Pancytopenia with hypocellular bone marrow most often is caused by idiopathic aplastic anemia, but can be caused by inherited bone marrow failure syndromes, drugs, infections, nutritional deficiencies, and rheumatologic disease. Aplastic anemia (AA) can remain stable for years but can become severe or transform into a myelodysplastic syndrome, acute leukemia, or paroxysmal nocturnal hemoglobinuria. Corticosteroids and erythropoietin are ineffective for management of aplastic anemia; and granulocyte colony-stimulating factor is only indicated in severe infections that do not improve with antibiotics. Supportive care with leukocyte-poor red blood cell transfusions reduces HLA antigen alloimmunization and platelet transfusion refractoriness. Horse or rabbit antithymocyte globulin plus cyclosporine typically is first-line therapy for patients with nonsevere AA who are transfusion-dependent, patients older than 40 years with severe AA, and patients with severe AA who lack an HLA antigen-matched sibling for bone marrow transplantation. The overall 5-year survival rate among patients taking antithymocyte globulin plus cyclosporine therapy is 75% to 85%. Bone marrow transplantation from an HLA antigen-matched sibling is considered the treatment of choice for severe AA in children and adults younger than 40 years. Less than approximately 33% of patients with AA have an HLA antigen-matched sibling donor, so matched unrelated donor hematopoietic stem cells are increasingly used. Umbilical cord stem cell transplantation is in clinical trials.

Hematologic Disorders: Sickle Cell Disease.

Sickle cell disease, the most common inherited hemoglobinopathy in the United States, is a group of autosomal recessive red cell disorders resulting from hemoglobin S. Hemoglobin S forms rigid polymers when deoxygenated that give red blood cells their sickle crescent shape. Increased viscosity and cell adhesion result in vasoocclusion. Universal screening of US newborns enables early detection. Prophylactic penicillin through age 5 years and pneumococcal immunization lower the risk of serious pneumococcal infections. Vasoocclusive crises are a major complication and cause severe pain; there is no objective confirmatory test. Intravenous hydration and rapid pain treatment with parenteral opioids are indicated for severe pain. Acute chest syndrome presents as a new pulmonary infiltrate with acute onset of symptoms of lower respiratory disease with or without fever. Stroke, acute ocular conditions, leg ulcers, priapism, and anemia are common complications of sickle cell disease. Hydroxyurea decreases sickling, improves red cell survival, and reduces the frequency of vasoocclusive crises. Hydroxyurea should be considered if three or more vasoocclusive crises occur per year. Multiple therapeutic transfusions are required, and the risks of iron overload and blood antibody development are high. Increased maternal-fetal risk occurs in pregnancy with sickle cell disease.

New colleges of osteopathic medicine, branch campuses, and additional locations--what is the difference?

The American Osteopathic Association Commission on Osteopathic College Accreditation (AOA COCA) is recognized by the US Secretary of Education as the only accrediting agency for predoctoral osteopathic medical education. To maintain its recognition with the US Secretary of Education, the AOA COCA is required to adhere to all federal laws and regulations associated with recognition of accrediting agencies. In this article, the authors discuss the development of new colleges of osteopathic medicine (COMs). They also discuss the development of additional locations and branch campuses of existing COMs and compare the 2 processes. Also included is a review of the AOA COCA- approved class sizes of the accredited COMs.