[Advances in the role of infection in the development of benign tracheal stenosis].

Benign tracheal stenosis (BTS) is a refractory disease with a complex pathogenesis and limited therapeutic drug effects. The management of benign tracheal stenosis remains a major challenge for the interventional physiologist. In recent years, the role of infection in the occurrence and development of tracheal stenosis has attracted some attention, but there is still some controversy. A clear understanding of the relationship between infection and tracheal stenosis is essential to elucidate the pathogenic mechanism of BTS, and then to improve early prevention and management of BTS. This article reviewed the research progress on BTS associated with infection to explore new effective interventions that can reduce the BTS.

Management of postinfectious inflammatory arthritis.

PURPOSE OF REVIEW: Postinfectious inflammatory arthritis can result from various pathogens, including bacteria, viruses, fungi, and parasites. Prompt identification and treatment of acute infection is vital, but some cases progress to chronic arthritis despite successful treatment of infection. Postinfectious inflammatory arthritis varies from mild, self-limited arthralgia to severe, refractory arthritis, necessitating ongoing disease-modifying treatment. This review explores the spectrum of postinfectious inflammatory arthritis to provide insights into effective management. RECENT FINDINGS: Research continues regarding the benefit of antimicrobial therapy, beyond treatment of the acute infection, to diminish the severity of postinfectious inflammatory arthritis. Following treatment of acute infection, most cases are self-limited so treatment is symptomatic. However, a difficult-to-predict fraction of cases develop chronic postinfectious inflammatory arthritis that can be challenging to manage. Recently, as more biologic, and targeted synthetic DMARDs have become available, treatment options have expanded. SUMMARY: In this article, we use the term 'postinfectious inflammatory arthritis' rather than 'reactive arthritis' because it describes a broader spectrum of diseases and emphasizes the common pathogenesis of a postinfectious inflammatory process. We summarize the conventional therapies and recent management developments for the most frequently encountered postinfectious inflammatory arthritides.

Methylobacterium infection-induced peritonitis in a patient with renal insufficiency: A case report and literature review.

Clinical pharmacists participated in the drug therapy of peritonitis caused by Methylobacterium infection in a patient with renal insufficiency. Based on the knowledge of clinical pharmacy, the patient's condition and laboratory parameters, the literature, and the pharmacokinetic/pharmacodynamic characteristics of antibiotics, amikacin in combination with ciprofloxacin was suggested for anti-infection therapy. During the treatment, clinical pharmacists timely evaluated the efficacy of antibiotics, monitored the adverse reactions, and provided individualized pharmaceutical care in the patient.

A matched cohort study evaluating the risks of infections in people with type 1 diabetes and their associations with glycated haemoglobin.

AIMS: People with type 1 diabetes (T1D) have raised infection rates compared to those without, but how these risks vary by age, sex and ethnicity, or by glycated haemoglobin (HbA1c), remain uncertain. METHODS: 33,829 patients with T1D in Clinical Practice Research Datalink on 01/01/2015 were age-sex-ethnicity matched to two non-diabetes patients. Infections were collated from primary care and linked hospitalisation records during 2015-2019, and incidence rate ratios (IRRs) were estimated versus non-diabetes. For 26,096 people with T1D, with ≥3 HbA1c measurements in 2012-2014, mean and coefficient of variation were estimated, and compared across percentiles. RESULTS: People with T1D had increased risk for infections presenting in primary care (IRR = 1.81, 95%CI 1.77-1.85) and hospitalisations (IRR = 3.37, 3.21-3.53) compared to non-diabetes, slightly attenuated after further adjustment. Younger ages and non-White ethnicities had greater relative risks, potentially explained by higher HbA1c mean and variability amongst people with T1D within these sub-groups. Both mean HbA1c and greater variability were strongly associated with infection risks, but the greatest associations were at the highest mean levels (hospitalisations IRR = 4.09, 3.64-4.59) for >97 versus ≤53 mmol/mol. CONCLUSIONS: Infections are a significant health burden in T1D. Improved glycaemic control may reduce infection risks, while prompter infection treatments may reduce hospital admissions.

Does Anterior Plating of Pelvic Ring Fractures Increase Infection Risk in Patients With Bladder or Urethral Injuries?

OBJECTIVES: Evaluate the effect of anterior fixation on infection in patients with operative pelvic fractures and bladder or urethral injuries. DESIGN: Retrospective. SETTING: Eight centers. PATIENT SELECTION CRITERIA: Adult patients with closed pelvic fractures with associated bladder or urethral injuries treated with anterior plating (AP), intramedullary screw (IS), or no anterior internal fixation (NAIF, including external fixation or no fixation). OUTCOME MEASURES AND COMPARISONS: Deep infection. RESULTS: There were 81 extraperitoneal injuries and 57 urethral injuries. There was no difference in infection between fixation groups across all urologic injuries (AP: 10.8%, IS: 0%, NAIF: 4.9%, P = 0.41). There was a higher rate of infection in the urethral injury group compared with extraperitoneal injuries (14.0% vs. 2.5%, P = 0.016). Among extraperitoneal injuries, specifically, there was no difference in deep infection related to fixation (AP: 2.6%, IS 0%, NAIF: 2.9%, P = 0.99). Among urethral injuries, there was no statistical difference in deep infection related to fixation (AP: 23.1%, IS: 0%, NAIF: 7.4%, P = 0.21). There was a higher rate of suprapubic catheter (SPC) use in urethral injuries compared with extraperitoneal injuries (57.9% vs. 4.9%, P < 0.0001). In the urethral injury group, SPC use did not have a statistically significant difference in infection rate (SPC: 18.2% vs. No SPC: 8.3%, P = 0.45). Early removal of the SPC before or during the definitive orthopaedic intervention did not significantly affect infection rate (early: 0% vs. delayed: 25.0%, P = 0.16). CONCLUSIONS: Surgeons should approach operative pelvic fractures with associated urologic injuries with caution given the high risk of infection. Further work must be done to elucidate the effect of anterior implants and SPC use and duration. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

[Discussion on classification and diagnostic nomenclature of burn infection].

Infection is the most common complication after burn injury and one of the leading causes of death in burn patients. Thus, how to effectively prevent the occurrence and development of infection is an important task in treating burns. Till now, there are still many controversies in the clinical definition, diagnosis, and treatment of infection, especially burn infection. The authors of this article put forward their opinions and views on this subject, hoping to deepen the readers' understanding of burn infection.

Protothecosis in four dogs in New Zealand.

CASE HISTORIES: Medical records of four dogs diagnosed with protothecosis in New Zealand were reviewed. The dogs were aged between 4 and 9 years and three of the four dogs were female. Breeds were one Labrador, one Miniature Schnauzer and two crossbreeds. The reasons for initial veterinary evaluation were a cough and opaque appearance of the right eye (Case 1), diarrhoea (Cases 2 and 3), and cutaneous disease (Case 4). CLINICAL FINDINGS: The ocular signs were characterised by panuveitis, retinal detachment and secondary glaucoma. Gastrointestinal signs included chronic haemorrhagic diarrhoea due to colitis. Three cases had disseminated infection and developed both bilateral, blinding, ocular disease and chronic gastrointestinal disease. Cutaneous signs consisted of draining fistulae over the olecranon, multifocal cutaneous nodules, and ulceration and tracts of the foot pads. Disseminated protothecosis was confirmed by histopathology of biopsied ocular tissues in Cases 1 and 2 and by gastrointestinal biopsies in Case 3. Prototheca spp. were also identified in cytological specimens from Cases 1 and 4 and recovered by culture in Cases 2 and 4. Cutaneous protothecosis was diagnosed in Case 4 initially by cytology and histopathology of skin lesions, and Prototheca zopfii was confirmed by PCR of cultured organisms. TREATMENT AND OUTCOME: Prior to diagnosis of protothecosis, a variety of treatments were prescribed to treat the gastrointestinal and ocular signs. After diagnosis, only Cases 2 and 4 received medication aimed at treating the protothecal infection, which was itraconazole in both cases. Following the progression of clinical signs and concerns about quality of life, all four dogs were euthanised. DIAGNOSIS: Disseminated protothecosis in three dogs, cutaneous protothecosis in one dog. CLINICAL RELEVANCE: Canine protothecosis is rarely reported, despite the ubiquity of the causal algae, and the disease usually carries an extremely grave prognosis when infection is generalised. In New Zealand, protothecosis should be considered as a differential diagnosis in dogs with panuveitis, chorioretinitis or retinal detachment, colitis, or nodular, ulcerative or fistulating cutaneous lesions.

Deficient anterior pituitary with common variable immune deficiency (DAVID syndrome): a new case and literature reports.

Deficient anterior pituitary with common variable immune deficiency (DAVID) syndrome is a rare condition characterized by adrenocorticotropic hormone (ACTH) deficiency and primary hypogammaglobulinemia. It is due to heterozygous mutations of the nuclear factor kappa-B subunit 2 (NFKB2) gene. Only a few isolated cases have been reported since its first description by our team. Through the international multicenter GENHYPOPIT network, we identified a new case of DAVID syndrome. We then conducted an extensive review of the DAVID syndrome cases published from 2012 to 2022. A 7-year-old boy was diagnosed with symptomatic hypoglycemia revealing ACTH deficiency. Laboratory tests showed asymptomatic hypogammaglobulinemia. He harbored a heterozygous point mutation in NFKB2 gene (c.2600C > T, p.Ala867Val). His management included hydrocortisone replacement treatment, and he also received subcutaneous immunoglobulins during the Covid-19 pandemic. We analyzed 28 cases of DAVID syndrome with ACTH deficiency. ACTH deficiency was the only hormone deficiency in 79% of patients, but some patients harbored growth hormone (GH) and thyroid stimulating hormone (TSH) deficiencies. The first presenting symptoms were sinus/pulmonary infections (82%, mean age of 3 years) and alopecia (mean age of 4.7 years). ACTH deficiency was the third presenting condition (mean age at diagnosis of 8.6 years). All patients had hypogammaglobulinemia (decreased IgA and IgM levels), and 57% of patients had at least one autoimmune manifestation. Heterozygous mutations at the 3'end of the NFKB2 gene, coding for the C-terminal domain of the protein, were identified in all cases. Better knowledge of DAVID syndrome will help clinicians make an early diagnosis to avoid life-threatening complications.

Observed Improvement in Cognition During a Personalized Lifestyle Intervention in People with Cognitive Decline.

BACKGROUND: Alzheimer's disease (AD) is a chronic condition marked by progressive objective cognitive impairment (OCI). No monotherapy has substantially altered disease progression, suggesting the disease is multifactorial and may require a multimodal therapeutic approach. OBJECTIVE: We sought to determine if cognitive function in a sample with OCI would change in response to a multimodal, individualized care plan based on potential contributors to cognitive decline (e.g., nutritional status, infection, etc.). METHODS: Participants (n = 34) were recruited from the San Diego, CA area. The multimodal intervention included lifestyle changes (i.e., movement, diet, and stress management), nutraceutical support, and medications. It was delivered pragmatically over four clinical visits, and outcome measures were gathered at four study visits, occurring at baseline, one, three, and six months (primary endpoint). Study participants received weekly phone calls for nutrition support throughout study participation. Outcome measures included the Cambridge Brain Sciences (CBS) battery, and the Montreal Cognitive Assessment (MoCA). RESULTS: At 6 months, mean MoCA scores improved from 19.6±3.1 to 21.7±6.2 (p = 0.013). Significant improvement was observed in mean scores of the CBS memory domain [25.2 (SD 23.3) to 35.8 (SD 26.9); p < 0.01] and CBS overall composite cognition score [24.5 (SD 16.1) to 29.7 (SD 20.5); p = 0.02]. All CBS domains improved. CONCLUSION: Multiple measures of cognitive function improved after six months of intervention. Our results support the feasibility and impact of a multimodal, individualized treatment approach to OCI, warranting further research.

Single-Incision Fasciotomy Decreases Infection Risk Compared with Dual-Incision Fasciotomy in Treatment of Tibial Plateau Fractures With Acute Compartment Syndrome.

OBJECTIVES: Comparison of surgical site infection (SSI) rates in tibial plateau fractures with acute compartment syndrome treated with single-incision (SI) versus dual-incision (DI) fasciotomies. DESIGN: Retrospective cohort study. SETTING: Two, Level-1, academic, trauma centers. PATIENTS: Between January 2001 and December 2021, one-hundred ninety patients with a diagnosis of tibial plateau fracture and acute compartment syndrome met inclusion criteria (SI: n = 127, DI: n = 63) with a minimum of 3-month follow-up after definitive fixation. INTERVENTION: Emergent 4-compartment fasciotomy, using either SI or DI technique, and eventual plate and screw fixation of the tibial plateau. OUTCOMES: The primary outcome was SSI requiring surgical debridement. Secondary outcomes included nonunion, days to closure, method of skin closure, and time to SSI. RESULTS: Both groups were similar in demographic variables and fracture characteristics (all P > 0.05). The overall infection rate was 25.8% (49 of 190), but the SI fasciotomy patients had significantly fewer SSIs compared with the DI fasciotomy patients [SI 18.1% vs. DI 41.3%; P < 0.001; OR 2.28, (confidence interval, 1.42-3.66)]. Patients with a dual (medial and lateral) surgical approach and DI fasciotomies developed an SSI in 60% (15 of 25) of cases compared with 21.3% (13 of 61) of cases in the SI group ( P < 0.001). The nonunion rate was similar between the 2 groups (SI 8.3% vs. DI 10.3%; P = 0.78). The SI fasciotomy group required fewer debridement's ( P = 0.04) until closure, but there was no difference in days until closure (SI 5.5 vs. DI 6.6; P = 0.09). There were zero cases of incomplete compartment release requiring return to the operating room. CONCLUSIONS: Patients with DI fasciotomies were more than twice as likely to develop an SSI compared with SI patients despite similar fracture and demographic characteristics between the groups. Orthopaedic surgeons should consider prioritizing SI fasciotomies in this setting. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cachexia: A systemic consequence of progressive, unresolved disease.

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches. Here, we review drivers, mechanisms, organismal predispositions, evidence for multi-organ interaction, model systems, clinical research, trials, and care provision from early onset to late cachexia. Evidence is emerging that distinct inflammatory, metabolic, and neuro-modulatory drivers can initiate processes that ultimately converge on advanced cachexia.

Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke.

Though rare, stroke in infants and children is an important cause of mortality and chronic morbidity in the pediatric population. Neuroimaging advances and implementation of pediatric stroke care protocols have led to the ability to rapidly diagnose stroke and in many cases determine the stroke etiology. Though data on efficacy of hyperacute therapies, such as intravenous thrombolysis and mechanical thrombectomy, in pediatric stroke are limited, feasibility and safety data are mounting and support careful consideration of these treatments for childhood stroke. Recent therapeutic advances allow for targeted stroke prevention efforts in high-risk conditions, such as moyamoya, sickle cell disease, cardiac disease, and genetic disorders. Despite these exciting advances, important knowledge gaps persist, including optimal dosing and type of thrombolytic agents, inclusion criteria for mechanical thrombectomy, the role of immunomodulatory therapies for focal cerebral arteriopathy, optimal long-term antithrombotic strategies, the role of patent foramen ovale closure in pediatric stroke, and optimal rehabilitation strategies after stroke of the developing brain.

The association between hypogammaglobulinemia severity and infection risk in rituximab-treated patients with childhood-onset idiopathic nephrotic syndrome.

BACKGROUND: Hypogammaglobulinemia is a major adverse effect from rituximab. However, the association between rituximab-induced hypogammaglobulinemia and infection frequency is unknown. METHODS: Patients who received rituximab for complicated nephrotic syndrome between February 2006 and October 2020 were enrolled in this retrospective observational study. Infections requiring antibacterial or antiviral agents or hospitalization were identified, and the characteristics of infections were compared according to infection type. RESULTS: One hundred and forty patients were enrolled. Fifty infection events were detected in 36 patients, 45 infection events in 32 patients required hospitalization, and 1 severe infection event required intensive care unit admission. In eight patients who developed severe hypogammaglobulinemia (serum IgG level < 200 mg/dL) for more than 1 year after rituximab treatment, eight infections occurred in six patients; six of these infections did not occur during the period of severe hypogammaglobulinemia. Febrile neutropenia accounted for 54.2% (13/24) of all infections among the patients with hypogammaglobulinemia. The incidence of infections was 0.028 (95% confidence interval = 0.017-0.448), 0.071 (95% [CI] = 0.041-0.114), and 0.096 (95% [CI] = 0.019-0.282) patient-years in patients with normal serum IgG levels and those with mild and severe hypogammaglobulinemia, respectively. Immunoglobulin replacement therapy was not administered to any patients except for the treatment of infection. CONCLUSIONS: Our results showed no statistically significant association between hypogammaglobulinemia severity and infection rate. In addition, the frequency of infection was relatively low even in patients with severe hypogammaglobulinemia, suggesting that immunoglobulin replacement therapy may not be necessary for rituximab-treated patients with severe hypogammaglobulinemia. A higher resolution version of the Graphical abstract is available as Supplementary information.

Insuficiência cardíaca em cão / Congestive heart failure in a dog / Insuficiencia cardíaca congestiva en un perro

A insuficiência cardíaca congestiva é considerada, atualmente, a principal causa de óbitos em cães, sendo resultante da degeneração mixomatosa da válvula mitral, processo que inviabiliza o fechamento total da mesma durante a sístole. Apesar de se tratar de uma doença progressiva, os efeitos patológicos podem ser reduzidos significativamente e concomitantemente prolongar a vida do animal, desde que haja protocolos de tratamentos específicos e descritos por profissionais capacitados na área médica animal. Esse estudo teve como objetivo relatar um caso de insuficiência congestiva em um animal da espécie canina, sem raça definida, sexo masculino resgatado pela prefeitura do município de Botucatu, São Paulo, Brasil. Durante a necropsia foi observado os seguintes achados macroscópicos: neoplasias cutâneas aderidas ao tecido, tártaro dentário, pneumonia intersticial hemorrágica, companhias de fibrose e enfisema pulmonar hemorrágico, metástase calcificada circular em lobo pulmonar direito, necrose pulmonar, cardiomiopatia hipertrófica concêntrica, insuficiência cardíaca congestiva, aderência de pericárdio na cavidade torácica, fígado em aspecto de noz moscada, metástase hepática, hepatite, esplenomegalia, dilatação entérica multifocal, intussuscepção, necrose intestinal, hipertrofia de pelve renal e aderência de cápsula renal. Esses achados demonstram o comprometimento de todos os órgãos do animal, demonstrando que a causa mortis foi em decorrência de uma insuficiência respiratória de origem infecciosa que ocasionou a insuficiência cardíaca congestiva.(AU)

Congestive heart failure is currently considered the main cause of death in dogs, resulting from myxomatous degeneration of the mitral valve, a process that prevents its total closure during systole. Despite being a progressive disease, the pathological effects can be significantly reduced and, at the same time, prolong the animal's life, as long as there are specific treatment protocols described by trained professionals in the field of animal medicine. This study aimed to report a case of congestive insufficiency in an animal of the canine species, mixed breed, male, rescued by the municipality of Botucatu, Sao Paulo, Brazil. During the necropsy, the following macroscopic findings were observed: skin neoplasms adhered to the tissue, dental tartar, hemorrhagic interstitial pneumonia, fibrosis and hemorrhagic pulmonary emphysema, circular calcified metastasis in the right pulmonary lobe, pulmonary necrosis, concentric hypertrophic cardiomyopathy, congestive heart failure, adherence of pericardium in the thoracic cavity, nutmeg liver, liver metastasis, hepatitis, splenomegaly, multifocal enteric dilation, intussusception, intestinal necrosis, renal pelvis hypertrophy and renal capsule adherence. These findings showed the involvement of all tissues, demonstrating that the cause of death was due to respiratory failure of infectious origin that caused congestive heart failure.(AU)

Actualmente se considera la insuficiencia cardíaca congestiva como la principal causa de muerte en perros, resultante de la degeneración mixomatosa de la válvula mitral, proceso que impide su cierre total durante la sístole. A pesar de ser una enfermedad progresiva, los efectos patológicos pueden reducirse significativamente y, al mismo tiempo, prolongar la vida del animal, siempre y cuando existan protocolos de tratamiento específicos descritos por profesionales capacitados en el campo de la medicina animal. Este estudio tuvo como objetivo reportar un caso de insuficiencia congestiva en un animal canino, mestizo, macho, rescatado por el municipio de Botucatu, São Paulo, Brasil. Durante la necropsia se observaron los siguientes hallazgos macroscópicos: neoplasias cutáneas adheridas al tejido, sarro dental, neumonía intersticial hemorrágica, compañías de fibrosis y enfisema pulmonar hemorrágico, metástasis circular calcificada en lóbulo pulmonar derecho, necrosis pulmonar, miocardiopatía hipertrófica concéntrica, insuficiencia cardíaca, adherencia del pericardio en la cavidad torácica, hígado de nuez moscada, metástasis hepática, hepatitis, esplenomegalia, dilatación entérica multifocal, intususcepción, necrosis intestinal, hipertrofia de la pelvis renal y adherencia de la cápsula renal. Estos hallazgos demuestran la afectación de todos los órganos del animal, demostrando que la causa de la muerte se debió a una insuficiencia respiratoria de origen infeccioso que provocó una insuficiencia cardíaca congestiva.(AU)

Inborn errors of immunity underlying a susceptibility to pyogenic infections: from innate immune system deficiency to complex phenotypes.

BACKGROUND: Pyogenic bacteria are associated with a wide range of clinical manifestations, ranging from common and relatively mild respiratory and cutaneous infections to life-threatening localized or systemic infections, such as sepsis and profound abscesses. Despite vaccination and the widespread use of effective antibiotic treatment, severe infection is still observed in a subset of affected patients. OBJECTIVES: We aim to summarize the available data regarding inborn errors of immunity that result in a high risk of severe pyogenic infections. SOURCES: Case series, as well as review and original articles on human genetic susceptibility to pyogenic infections were examined. CONTENT: We review host-associated factors resulting in inborn errors of immunity and leading to a susceptibility to pyogenic infections, including deficiency in major components of the immune system (e.g., neutrophils, complement, immunoglobulin, and spleen function) and novel monogenic disorders resulting in specific susceptibility to pyogenic infection. Specifically, innate immune system deficiency involving toll-like receptors and associated signaling typically predispose to a narrow spectrum of bacterial diseases in otherwise healthy people, making a diagnosis more difficult to suspect and confirm. More complex syndromes, such as hyper IgE syndrome, are associated with a high risk of pyogenic infections due to an impairment of the interleukin-6 or -17 signaling, demonstrating the pivotal role of these pathways in controlling bacterial infections. IMPLICATIONS: In clinical practice, awareness of such conditions is essential, especially in the pediatric setting, to avoid a potentially fatal diagnostic delay, set the most proper and prompt treatment, and ensure prevention of severe complications.