Consensus recommendations for the classification and long-term follow up of infants who screen positive for Krabbe Disease.

OBJECTIVE: To provide updated evidence and consensus-based recommendations for the classification of individuals who screen positive for Krabbe Disease (KD) and recommendations for long-term follow-up for those who are at risk for late onset Krabbe Disease (LOKD). METHODS: KD experts (KD NBS Council) met between July 2017 and June 2020 to develop consensus-based classification and follow-up recommendations. The resulting newly proposed recommendations were assessed in a historical cohort of 47 newborns from New York State who were originally classified at moderate or high risk for LOKD. RESULTS: Infants identified by newborn screening with possible KD should enter one of three clinical follow-up pathways (Early infantile KD, at-risk for LOKD, or unaffected), based on galactocerebrosidase (GALC) activity, psychosine concentration, and GALC genotype. Patients considered at-risk for LOKD based on low GALC activity and an intermediate psychosine concentration are further split into a high-risk or low-risk follow-up pathway based on genotype. Review of the historical New York State cohort found that the updated follow-up recommendations would reduce follow up testing by 88%. CONCLUSION: The KD NBS Council has presented updated consensus recommendations for efficient and effective classification and follow-up of NBS positive patients with a focus on long-term follow-up of those at-risk for LOKD.

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study.

BACKGROUND: Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC. METHODS: In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter-related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry. RESULTS: In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter-related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11). CONCLUSIONS: Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.

Interventions to improve adherence to surveillance guidelines in survivors of childhood cancer: a systematic review.

PURPOSE: Many survivors of childhood cancer are at high risk of late effects of their cancer therapy, including cardiac toxicity and subsequent malignant neoplasms (SMN). Current North American guidelines recommend periodic surveillance for these late effects. We conducted a systematic review of the literature to estimate rates of adherence to recommended surveillance and summarize studies evaluating interventions intended to increase adherence. METHODS: We searched MEDLINE, Embase, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) for articles published between January 2000 and September 2018 that reported adherence to surveillance for cardiac toxicity and SMN (breast and colorectal cancer) and interventions implemented to improve completion of recommended testing. Risk of bias was assessed using relevant Cochrane checklists. Due to heterogeneity and overlapping study populations, we used narrative synthesis to summarize the findings. This review was registered in PROSPERO: CRD42018098878. RESULTS: Thirteen studies met our inclusion criteria for assessing adherence to surveillance, while five assessed interventions to improve rates of surveillance. No studies met criteria for low risk of bias. Completion of recommended surveillance was lowest for colorectal cancer screening (11.5-30.0%) followed by cardiomyopathy (22.3-48.1%) and breast cancer (37.0-56.5%). Factors such as patient-provider communication, engagement with the health care system, and receipt of information were consistently reported to be associated with higher rates of surveillance. Of five randomized controlled trials aimed at improving surveillance, only two significantly increase completion of recommended testing-one for echocardiography and one for mammography. Both involved telephone outreach to encourage and facilitate these tests. CONCLUSION: The majority of childhood cancer survivors at high risk of cardiac toxicity or SMN do not receive evidence-based surveillance. There is paucity of rigorous studies evaluating interventions to increase surveillance in this population. IMPLICATIONS FOR CANCER SURVIVORS: Robust trials are needed to assess whether tailored interventions, designed based on unique characteristics and needs of each survivor population, could improve adherence.

A case of late-onset capsular block syndrome and its surgical treatment / Um caso de síndrome de bloqueio capsular tardio e uma abordagem cirúrgica

ABSTRACT - Capsular block syndrome is a rare complication of phacoemulsification surgery with continuous curvilinear capsulorhexis and intraocular lens implantation. Here, we report a case of very late-onset capsular block syndrome that developed 13 years after cataract extraction and present the surgical approach used for its successful treatment.

RESUMO - Síndrome do bloqueio capsular é uma complicação incomum da cirurgia de facoemulsificação com capsulorrexis curvilínea contínua e implante de lente intraocular. Nós relatamos um caso de síndrome de bloqueio capsular de início tardio que se desenvolveu após 13 anos da extração da catarata e apresenta a abordagem cirúrgica utilizada para o sucesso do tratamento.

A case of late-onset capsular block syndrome and its surgical treatment.

Capsular block syndrome is a rare complication of phacoemulsification surgery with continuous curvilinear capsulorhexis and intraocular lens implantation. Here, we report a case of very late-onset capsular block syndrome that developed 13 years after cataract extraction and present the surgical approach used for its successful treatment.

Inflammation in older subjects with early- and late-onset depression in the NESDO study: a cross-sectional and longitudinal case-only design.

OBJECTIVE: Different biological mechanisms may underlie depression beginning in early life (early-onset) and depression beginning later in life (late-onset). Although the relation between inflammation and depression has been studied extensively, the distinct role of inflammation in early and late-onset depression in older patients has not been addressed before. In the cross-sectional part of this study, we explored differences in levels of circulating inflammatory markers and cytokine levels in lipopolysaccharide (LPS) stimulated whole blood between older subjects with a late-life onset depression (≥60 years) and older subjects with an early-onset depression (<60 years). Secondly, in a 2-year follow-up study, we examined if circulating and stimulated inflammatory markers influenced the change in Inventory of Depressive Symptomatology (IDS) scores, and if this relation was different for early- and late-onset depression. METHODS: The study was part of the Netherlands Study of Depression in Older Persons (NESDO). We included 350 patients, all aged 60 and older, with a depressive episode in the previous 6 months: 119 with a late-onset depression and 231 with an early-onset depression. Blood samples were collected and CRP, IL-6, NGAL, GDF15, and, LPS plasma levels were determined and whole blood was LPS stimulated and cytokine levels IL-1ß, IL-6, TNFα, IFNγ, IL-10, and IL-1 receptor antagonist (IL-1ra) were determined. RESULTS: After adjustment for demographics, health indicators, and medication use, increased plasma CRP levels were more strongly associated with late-onset depression than early-onset depression (OR [95% CI]: 1.43 [1.05-1.94]). In the longitudinal analyses, higher circulating IL-6 levels were associated with a significantly slower decline in IDS scores in the crude and the adjusted models (p ≤ 0.027). This relation was not different between late- and early-onset depression. Other circulating and stimulated inflammatory markers were not associated with late- and/or early-onset depression. CONCLUSIONS: This study provides preliminary evidence that low-grade inflammation is more strongly associated with late-onset than early-onset depression in older adults, suggesting a distinct inflammatory etiology for late-onset depression. Cytokine production capacity did not distinguish between early- and late-onset depression.

[Twenty years later A story of intra-thoracic textiloma]. / Vingt ans après Histoire d'un textilome intra-thoracique.

INTRODUCTION: Intrathoracic textiloma is a rare complication possibly leading to misdiagnosis. It could present as haemoptysis, lung abscess, pseudo-tumour or a chronic cough. CASE REPORT: A 65-year-old patient with a history of multiple cardiac problems and needing long-term anticoagulation, complained since 2007 of recurrent haemoptysis of increasing abundance, the etiological investigation of which was negative. A thoracic CT-scan revealed a lesion in the lingula in contact with the pericardial plates of an implanted automatic defibrillator dating from 1989. In 2016, after two failures of arterial embolization, a diagnostic and therapeutic surgical exploration was undertaken on this patient who was a high operative risk. A segmental resection revealed an intra-pulmonary textiloma on pathological examination. CONCLUSION: The diagnosis of intrathoracic textiloma remains rare and its late presentation is non specific. Radiological imaging with a CT-scan and/or MRI could lead to the diagnosis. Surgery remains the reference treatment for the diagnosis and cure of intrathoracic textiloma with pathological examination, essential for confirmation. A means of prevention has to be developed because swab count is not totally reliable.

Late onset adrenal insufficiency after adrenalectomy due to latent nonclassical 21-hydroxylase deficiency: A case report.

RATIONALE: Adrenal incidentaloma is sometimes complicated with 21-hydroxylase deficiency (21-OHD). Latent nonclassical 21-OHD in incidentaloma is difficult to diagnose. Although adrenalectomy in 21-OHD has been conducted when malignancy could not be excluded, adrenal insufficiency sometimes occurs, and it might not be observed immediately after operation. Here, we report a case of a 71-year-old man who experienced adrenal insufficiency over 2 decades postadrenalectomy, leading to a diagnosis of latent nonclassical 21-OHD. PATIENT CONCERNS: A 71-year-old man was admitted to the hospital due to difficulty in movements and a sodium level of 119 mEq/L. His medical history revealed precocious puberty and left adrenalectomy because of an incidentaloma at 49 years of age, diagnosed pathologically as an adenoma. He did not attend follow-up visits because he did not have any symptoms. In 2017, 3 months before hospitalization, he experienced general fatigue. A few days before admittance, he complained of difficulty in moving and visual hallucination of small animals. DIAGNOSES: Laboratory evaluations revealed a high level of adrenocorticotropic hormone (ACTH) and low cortisol level. ACTH-stimulating test revealed a low basal level and low response for cortisol, and a high basal level and low response for 17-hydroxyprogesterone. We analyzed large gene deletion or conversion and the 9 most common micro mutations in the CYP21A2 gene by polymerase chain reaction; micro mutation of I172N and heterozygous large gene deletion or conversion were detected leading to the diagnosis of nonclassical 21-OHD. INTERVENTIONS: Immediately, 100 mg hydrocortisone was administered, followed by daily hydrocortisone and saline. The symptoms and hyponatremia improved in a few days. He was discharged from the hospital on day 34 with a daily dose of 15 mg hydrocortisone. LESSONS: Clinicians should be aware of late onset of adrenal insufficiency after adrenalectomy. In such cases, clinicians should not overlook the latent nonclassical 21-OHD.

Acquired erythropoietic uroporphyria secondary to myelodysplastic syndrome with chromosome 3 alterations: a case report.

Congenital erythropoietic porphyria is a rare autosomal recessive disease caused by a deficiency of uroporphyrinogen III synthase, owing to mutations in UROS in chromosome 10. Occasionally, patients show a mild, late-onset disease, without germline UROS mutations, associated with haematological malignancies. We report a 65-year-old patient with photosensitivity, overexcretion of porphyrins and thrombocytopenia. Bone marrow analysis gave a diagnosis of myelodysplastic syndrome (MDS) with the presence of a derivative chromosome 3, possibly due to an inversion including 3q21 and 3q26 break points. After allogeneic stem-cell transplantation, complete remission of MDS and uroporphyria was achieved. To our knowledge, this is the first reported case of acquired erythropoietic uroporphyria associated with MDS, with chromosome 3 alterations.

Anemia at older age: etiologies, clinical implications, and management.

Anemia is quite frequently diagnosed in older individuals and is a key indicator of various reactive and clonal conditions. Many underlying diseases, like myelodysplastic syndrome (MDS), develop preferentially in elderly individuals. The prevalence of anemia at older age is increasing, and this is mainly attributable to more frequently applied diagnostics and demographic changes in our societies. The etiology of anemia at older age is complex and ranges from bone marrow failure syndromes to chronic kidney disease, and from nutritional deficiencies to inflammatory processes including inflammaging in immunosenescence. In a smaller number of cases, no clear-cut etiology is identified. These patients are referred to as unexplained anemia or idiopathic cytopenia of unknown significance. In others, somatic mutations in leukocytes are found, but diagnostic criteria for MDS or other hematologic diseases are not fulfilled, a condition termed clonal cytopenia of undetermined significance. Management of anemias at older age depends on (1) the severity of the anemia, (2) underlying condition(s), and (3) patient-related factors, including comorbidities. Even a mild anemia may substantially affect physical and cognitive capacities and quality of life. An underestimated aspect is that because of age-related changes, organ function such as erythropoietin production in the kidney may become suboptimal. Management and treatment of anemia in older patients often require a multidisciplinary approach and detailed investigations of organ function. In this article, we review current concepts around anemias at older age, with special emphasis on etiologies, clinical implications, and innovative concepts in the management of these patients.

Sialocutaneous fistula to the external auditory canal repaired with superficial parotidectomy and temporoparietal flap: A case report.

RATIONALE: Gustatory otorrhea can lead to cutaneous changes, recurrent infection, and social disruption. We present a case of a late, evolving sialocutaneous fistula to the external auditory canal, managed surgically after failing conservative therapies. This case is unique by late evolution, whereby the symptoms presented with significance 27 years after her operation and 19 years after mild symptoms initially arose. PATIENT CONCERNS: Gustatory, left-sided clear otorrhea with acutely increased volume over 8 months causing social disruption. DIAGNOSES: Sialocutaneous fistula to the external auditory canal. INTERVENTIONS: Superficial parotidectomy and temporoparietal flap for closure of fistula. OUTCOMES: No postoperative complications and resolution of gustatory otorrhea at one-year follow-up. LESSONS: This rare, but important, postoperative complication can present late with evolving symptoms, causing significant social disruption. It can be treated with conservative medical management and several surgical approaches.

Very-late-onset cytomegalovirus disease: a case-report and review of the literature.

BACKGROUND: Cytomegalovirus (CMV) infection remains one of the most common and feared complications of transplantation, justifying prophylaxis or preemptive strategies guided by donor and recipient CMV serostatus. In case of seronegative donor and recipient (D-/R-), no prophylaxis is recommended. Late-onset CMV disease is usually defined as occurring after prophylaxis discontinuation in D+/R- transplant patients. CASE PRESENTATION: We are reporting the case of a D-/R- kidney Caucasian transplant recipient presenting with CMV primoinfection 12 years after renal transplant, and discuss the role of a secondary prophylaxis so late after transplantation. CONCLUSIONS: Primary infections leading to late-onset CMV disease in transplant patients remain rare. Recurrent disease has been described in as many as one-third of these patients. A systematic secondary prophylaxis in this particular group of patients is questionable.

Fatal case of cutaneous-sparing orolaryngeal zoster in a renal transplant recipient.

Herpesvirus infections in solid organ transplant (SOT) recipients are a significant cause of morbidity and mortality. We report a case of herpes zoster (HZ) in a kidney transplant recipient while receiving belatacept, a CTLA-4 inhibitor that prevents acute rejection. The patient presented with oropharyngolaryngeal mucosal lesions that subsequently disseminated resulting in pneumonitis and meningo-encephalitis. Very late-onset HZ can occur and can present atypically in SOT recipients. Delayed recognition and treatment may result in poor outcomes, as illustrated by this case.

Cannabis and Neuropsychiatry, 2: The Longitudinal Risk of Psychosis as an Adverse Outcome.

Psychosis is one of the most serious among the adverse effects associated with cannabis use. The association between cannabis use and psychosis has been variously explored in a series of recent meta-analyses. The results of these meta-analyses show that persons who develop psychosis experience onset of psychosis about 2-3 years earlier if they are cannabis users; this effect is not observed with alcohol or other substance use. Higher levels of cannabis use are associated with greater risk of psychosis. Current cannabis abuse or dependence (but not past use or lower levels of current use) increases the risk of transition into psychosis in persons at ultrahigh risk of psychosis. About a third of patients with first-episode psychosis are cannabis users, and, at follow-up, about half of these users are found to continue their cannabis use. Continued cannabis use (in those who are treated after developing psychosis) is associated with higher risk of relapse into psychosis, and discontinuation of cannabis use reduces the risk of relapse to that in cannabis nonusers. Finally, persons with psychosis who continue to use cannabis have more severe positive symptoms and poorer levels of functioning. Because experimental studies in humans show that cannabinoids and cannabis can induce psychotic symptoms, it is reasonable to assume that the epidemiologic data indicate a causal effect of cannabis in anticipating, triggering, or exacerbating psychosis in vulnerable individuals and in worsening the course and outcome of the illness in those who continue to use the substance. Given the public health implications of these findings, the trend to legalize medical marijuana must be viewed with concern, and efforts are necessary to educate patients and the public about the serious mental and physical health risks associated with cannabis use and abuse.

Onset of psychosis at age 81? With regard to frontal lobe syndromes / Psicose inaugural aos 81 anos? A propósito das síndromes do lobo frontal

When the frontal lobe of the brain is affected important behavioral changes may occur mainly at the level of executive functioning, i.e., planning, decision-making, judgment and self-perception. However, the behavioral changes may be of different nature with marked indifference and apathy. We report a clinical case of an 81-year-old patient with sudden onset of behavioral changes that were initially interpreted as an acute confusional episode of infectious etiology, but actually they were due to an ischemic lesion in the frontal lobe.

O lobo frontal, quando afetado, pode provocar alterações importantes do comportamento, principalmente na função executiva: planejamento, tomada de decisões, juízo e autopercepção. Contudo, as alterações podem ser de outra natureza, caracterizando-se por marcada indiferença e apatia. É relatado aqui o caso de uma paciente de 81 anos, com alterações súbitas do comportamento, que foram interpretadas inicialmente como um quadro confusional agudo de natureza infecciosa, mas que se mostraram provocadas por uma lesão isquêmica na região frontal.

Onset of psychosis at age 81? With regard to frontal lobe syndromes.

When the frontal lobe of the brain is affected important behavioral changes may occur mainly at the level of executive functioning, i.e., planning, decision-making, judgment and self-perception. However, the behavioral changes may be of different nature with marked indifference and apathy. We report a clinical case of an 81-year-old patient with sudden onset of behavioral changes that were initially interpreted as an acute confusional episode of infectious etiology, but actually they were due to an ischemic lesion in the frontal lobe.

Late complication of a renal calculus: fistulisation to the psoas muscle, skin and bronchi.

Kidney disease presenting with cutaneous fistula is a rare condition. We present a case of a 90-year-old woman with dementia who had no prior urological problems and had a cutaneous fistula in the left lumbar region. A fistulogram and computer tomography examination revealed a large staghorn calculus with signs of xanthogranulomatous pyelonephritis in the left kidney and renal fistulisation to the psoas muscle, skin and bronchi. To our knowledge this is the first report in the literature of coexisting renal fistulisation to the psoas major muscle, skin and bronchi. This report illustrates how computed tomography in combination with fistulography can resolve the diagnostic dilemma that pertains to the complex spread of the disease in cases involving nephrocutaneous fistula. Furthermore, the report shows how a renal calculus, even asymptomatic, can cause a serious medical condition, and highlights the importance of early medical intervention.