Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis.

BACKGROUND: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. AIMS: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. METHODS: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. RESULTS: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin's lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin's lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). CONCLUSION: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease.

Lessons we learned during the past four challenging years in the COVID-19 era: pharmacotherapy, long COVID complications, and vaccine development.

About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the "long COVID" syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the "long COVID" and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail.

Intracranial angioleiomyoma: a case series of seven patients and review of the literature.

PURPOSE: Angioleiomyoma, predominantly arising from the extremities, is a benign soft tissue tumor. Reports on its intracranial location are rare. We assessed clinical, radiological, and pathological features of intracranial angioleiomyoma (iALM) treated at our neurosurgical institution. METHODS: We consecutively enrolled all patients with neuropathologically confirmed iALM treated at a single neurosurgical institution between 2013 and 2021. Clinical and imaging data were collected, and histological tissue sections were analyzed. A review of the literature on iALM was conducted. RESULTS: Seven patients with iALM (four female) with a median age of 45 years (range: 32-76 years) were identified. In three cases, the lesion was found incidentally. In magnetic resonance imaging (MRI), all tumors were hypo- to isointense on T1-weighted, hyperintense on T2-weighted sequences, and gadolinium-enhancing. A strong FLAIR signal was seen in six patients. Surgery consisted of gross total resection in all cases without perioperative complications. Neuropathological staining was positive for smooth muscle actin (SMA) in all lesions. Mature smooth muscle cells arranged around blood vessels were typically observed. The Ki-67 index was ≤ 3%. The patients were discharged after a median of 6 days (range: 4-9 days). During a median follow-up time of 14 months (range: 4-41 months), no tumor recurrence occurred. In the current literature, 42 additional cases of iALM were identified. CONCLUSION: Intracranial angioleiomyoma is a benign soft tissue tumor treated by gross total resection. Tumor morphology and positive staining for SMA lead to the neuropathological diagnosis.

Cytomorphological patterns and clinical features of presumptive tubercular lymphadenitis patients and their comparison with bacteriological detection methods: a cross-sectional study.

INTRODUCTION: Tuberculous lymphadenitis (TBLN) is an infection of the lymph node caused by Mycobacterium tuberculosis. Histological diagnoses of presumptive patients are often accompanied by cytomorphological features. However, the sensitivities of these features are often precluded by the variable degrees of narrative similarities compared to other diagnostic modalities. OBJECTIVE: The aim of this study was to investigate and compare the cytomorphological and clinical features of presumptive TBLN patients with bacteriological detection methods. METHODS: A similar cohort of TBLN patients from our previous study who were enrolled prospectively from the ALERT Specialized Hospital, Addis Ababa, Ethiopia, was considered for this analysis. SPSS version 26 was used for data analysis. Descriptive analysis was conducted to characterize the study population using the independent variable and presented with frequency tables. The chi-square test was used to measure the association. A P-value of < 0.05 was considered statistically significant. RESULTS: Using FNAC, 60/126 (47.6%) of the participants were reported to have features consistent with TB. Of the total FNAC-positive cases, many (30/60 and 27/60) showed pattern B (caseous necrosis only) and pattern C (epithelioid granuloma with caseous necrosis), respectively. Strong concordance was observed in Pattern A (abundant caseous necrosis with few epithelioid macrophages) followed by patterns B and C with GeneXpert and MGIT culture (P value < 0.001). Night sweats and alcohol intake were shown to correlate with positive cases as reported by FNAC (P value = 0.008 respectively), GeneXpert (P value = 0.02 & 0.001), and culture methods (P-value = < 0.001 & 0.002). CONCLUSION: Cytomorphological features, particularly patterns A, B, and C, could be considered in the diagnosis of TBLN given their comparable outcomes with bacteriological detection methods. On another note, we recommend that due care and attention be given when treating TBLN patients based solely on clinical presentation, as these diagnostics may be prone to false results, leading to inappropriate administration of anti-TB drugs and other consequences.

Recent increase in atypical presentations of invasive meningococcal disease in France.

BACKGROUND: Invasive meningococcal disease (IMD) cases declined upon the implementation of non-pharmaceutical interventions (NPI) (social distancing and mask wearing) to control the COVID-19 pandemic but rebounded in 2022 in numbers with genotypical changes of the strains. We explored here associated modifications in the clinical presentations of IMD. METHODS: We conducted a retrospective descriptive study using the Database of the French National Reference Centre for meningococci and Haemophilus influnezae for IMD cases between 2015 and 2022. We scored serogroups, sex, age groups, clinical presentations and clonal complexes of the corresponding patients and isolates. FINDINGS: Non-meningeal forms of IMD increased significantly upon easing of NPI, such as bacteremic meningococcal pneumonia and bacteremic abdominal forms. They represented 6% and 8% of all IMD forms and were significantly linked to serogroups Y and W respectively, to older adults for bacteremic pneumonia and to young adults for bacteremic abdominal presentations. These forms were significantly associated with more early mortality and clonal complexes 23, 11 and 9316. INTERPRETATION: The increase in atypical IMD forms may lead to higher burden of IMD due to delayed diagnosis and management. Updating prevention may be needed through by adapting the current vaccination strategies to epidemiological changes.

Genetic variants of ABCC8 and clinical manifestations in eight Chinese children with hyperinsulinemic hypoglycemia.

BACKGROUND: ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH). METHODS: We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations. RESULTS: The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation. CONCLUSIONS: Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.

COVID-19 in hospitalized infants aged under 3 months: multi-center experiences across Turkey.

To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions.  Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: • COVID-19 in infants and older children has been seen more mildly than in adults. • The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: • Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. • Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.

Sex-related differences in the clinical presentation of multiple system atrophy.

PURPOSE: To investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort. METHODS: The PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis. RESULTS: The literature search yielded 46 publications with sex-related information in MSA. Most studies found comparable survival rates between the sexes, while some recent reports suggested a potential survival benefit for women, possibly due to initial motor onset and overall less severe autonomic failure compared to men. The retrospective Innsbruck MSA cohort comprised 56 female and 60 male individuals with a comparable median follow-up of 27 months. At baseline, female sex was independently associated with depression (odds ratio [OR] 4.7; p = 0.007) and male sex with severe orthostatic hypotension (OR 5.5; p = 0.016). In addition, at last follow-up, female sex was associated with the intake of central nervous system-active drugs (OR 4.1; p = 0.029), whereas male sex was associated with the presence of supine hypertension (OR 3.0; p = 0.020) and the intake of antihypertensive medications (OR 8.7; p = 0.001). Male sex was also associated with initiation of antihypertensive medications over the observation period (OR 12.4; p = 0.004). CONCLUSION: The available literature and findings of the present study indicate sex-related differences in the clinical presentation of MSA and its evolution over time, highlighting the importance of considering sex in symptom exploration, therapeutic decision-making, and future clinical trial design.

Temporal trends in the clinical presentation of Graves' orbitopathy: a single-center retrospective study.

PURPOSE: Graves' ophthalmopathy (GO) is an autoimmune disease that affects orbital soft tissues and represents the most common extrathyroidal manifestation of Graves' disease (GD). The European Group of Graves' Ophthalmopathy (EUGOGO) has attempted to shed light on the European epidemiological picture of GO, suggesting that GO in newly diagnosed patients in recent years has a trend towards a less severe clinical presentation. There are no studies that focus this issue on the population of our area; we aimed to evaluate the trend of GO clinical presentation in our outpatient clinic through an observation period of 10 years. METHODS: We compared 55 consecutive patients, 11 males (F) and 44 females (M), who came to our observation from January 2005 to December 2006 [Group 1 (G1)], with 56 patients, 15 males, and 41 females, who were referred to us from 2015 to 2016 [Group 2 (G2)]. We studied the following putative predictors of GO presentation and severity: thyroid function, smoking, diabetes, hypercholesterolemia, time from GO diagnosis to referral to our thyroid centre (TGOD), sex and age. RESULTS: GO severity was significantly reduced in G2 vs. G1 (p = 0.04). TGOD ≥ 3 months was related to clinical characteristics of GO (severity and Clinical Activity Score ≥ 4) and was an independent predictor of GO severity (p = 0.01). The other variables evaluated had no independent effects. CONCLUSIONS: We found that GO severity at presentation was significantly reduced over a ten-year observation period (2005-2006 vs. 2015-2016) in GO patients referred to our tertiary thyroid centre. TGOD ≥ 3 months was an independent predictor of GO severity.

Clinical analysis of 37 Chinese patients with ocular amyloidosis: a single center study.

OBJECTIVE: To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population. METHODS: A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed. RESULTS: The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up. CONCLUSION: Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary.

Necrotizing enterocolitis: current understanding of the prevention and management.

Necrotizing enterocolitis (NEC) is one of the diseases in neonates, with a high morbidity and mortality rate, especially in preterm infants. This review aimed to briefly introduce the latest epidemiology, susceptibility factors, and clinical diagnosis and presentation of NEC. We also organized new prevention strategies by risk factors according to different pathogeneses and then discussed new treatment methods based on Bell's staging and complications, and the classification of mild to high severity based on clinical and imaging manifestations. Such a generalization will help clinicians and researchers to gain a deeper understanding of the disease and to conduct more targeted classification, grading prevention, and exploration. We focused on prevention and treatment of the early and suspected stages of NEC, including the discovery of novel biomarkers and drugs to control disease progression. At the same time, we discussed its clinical application, future development, and shortcomings.

Differences in stroke clinical presentation among sexes.

INTRODUCTION: There are sex-based differences in stroke epidemiology, treatment, and outcomes. In this manuscript, we discuss the differences that exist in the clinical presentation of acute stroke among sexes. DISCUSSION: We present the differences in stroke presentation among sexes including age at the time of presentation, severity of stroke on presentation, and stroke type and location. We discuss the atypical clinical presentations, explore the radiographic findings on presentation (including location, infarct core volume, the impact of collateral circulation, hematoma location in intracranial hemorrhage), and discuss differences in time elapsed between symptom onset and management amongst sexes. CONCLUSION: Differences exist in stroke clinical presentation amongst sexes. These disparities have public health implications, and as they become better understood, impact awareness campaigns in both the public and healthcare communities.

GBA1-Associated Parkinson's Disease Is a Distinct Entity.

GBA1-associated Parkinson's disease (GBA1-PD) is increasingly recognized as a distinct entity within the spectrum of parkinsonian disorders. This review explores the unique pathophysiological features, clinical progression, and genetic underpinnings that differentiate GBA1-PD from idiopathic Parkinson's disease (iPD). GBA1-PD typically presents with earlier onset and more rapid progression, with a poor response to standard PD medications. It is marked by pronounced cognitive impairment and a higher burden of non-motor symptoms compared to iPD. Additionally, patients with GBA1-PD often exhibit a broader distribution of Lewy bodies within the brain, accentuating neurodegenerative processes. The pathogenesis of GBA1-PD is closely associated with mutations in the GBA1 gene, which encodes the lysosomal enzyme beta-glucocerebrosidase (GCase). In this review, we discuss two mechanisms by which GBA1 mutations contribute to disease development: 'haploinsufficiency,' where a single functional gene copy fails to produce a sufficient amount of GCase, and 'gain of function,' where the mutated GCase acquires harmful properties that directly impact cellular mechanisms for alpha-synuclein degradation, leading to alpha-synuclein aggregation and neuronal cell damage. Continued research is advancing our understanding of how these mechanisms contribute to the development and progression of GBA1-PD, with the 'gain of function' mechanism appearing to be the most plausible. This review also explores the implications of GBA1 mutations for therapeutic strategies, highlighting the need for early diagnosis and targeted interventions. Currently, small molecular chaperones have shown the most promising clinical results compared to other agents. This synthesis of clinical, pathological, and molecular aspects underscores the assertion that GBA1-PD is a distinct clinical and pathobiological PD phenotype, necessitating specific management and research approaches to better understand and treat this debilitating condition.

First and Second Waves of Covid-19: A Comparative Study of the Clinical Presentation and Outcome among Hospitalized Patients in Lagos Nigeria.

OBJECTIVE: Nigeria experienced many waves of the COVID-19 pandemic. This study compared the clinical presentations and mortality among hospitalized patients during the first and second waves of the pandemic in Lagos State, Nigeria. METHODS: A retrospective cohort study was conducted. Deidentified medical records of laboratory-confirmed COVID-19 patients admitted into 15 isolation centers in Lagos, Nigeria between February 27, 2020, and September 30, 2020 (first wave) and October 1, 2020, and April 30, 2021 (second wave) were reviewed. IBM Statistics version 25 was used for data analysis. RESULTS: More patients were hospitalized during the first wave of the pandemic. The mean age of patients was higher during the second wave (54.5±15.8 years vs. 42.2±15.5 years, p <0.001). More patients admitted during the second wave had comorbidities (56.0% vs 28.6%, p <0.001), were symptomatic (90.8% vs 52.0%, p <0.001), had severe COVID-19 disease (58.9% vs 25%, p <0.001) and died (14.9% vs 6.4%, p<0.001) compared with the first wave. The odds of death increased with age and severity of COVID-19 disease during the first and second waves. CONCLUSION: A higher proportion of the patients admitted in Lagos, Nigeria during the second wave were older, had comorbidities, and had severe COVID-19 disease than the first wave. Despite the fewer hospitalized patients, there were more deaths during the second wave.

OBJECTIF: Le Nigeria a connu plusieurs vagues de la pandémie de la COVID-19. Cette étude a comparé les présentations cliniques et la mortalité chez les patients hospitalisés lors des première et deuxième vagues de la pandémie dans l'État de Lagos, Nigeria. MÉTHODES: Une étude de cohorte rétrospective a été réalisée. Les dossiers médicaux déidentifiés des patients atteints de la COVID-19 confirmée par laboratoire, admis dans 15 centres d'isolement à Lagos, Nigeria, entre le 27 février 2020 et le 30 septembre 2020 (première vague) et entre le 1er octobre 2020 et le 30 avril 2021 (deuxième vague), ont été examinés. IBM Statistics version 25 a été utilisé pour l'analyse des données. RÉSULTATS: Un plus grand nombre de patients ont été hospitalisés lors de la première vague de la pandémie. L'âge moyen des patients était plus élevé lors de la deuxième vague (54,5±15,8 ans vs. 42,2±15,5 ans, p <0,001). Un plus grand nombre de patients admis lors de la deuxième vague avaient des comorbidités (56,0% vs. 28,6%, p <0,001), étaient symptomatiques (90,8% vs. 52,0%, p <0,001), avaient une forme grave de la maladie à la COVID-19 (58,9% vs. 25%, p <0,001) et sont décédés (14,9% vs. 6,4%, p<0,001) par rapport à la première vague. Les chances de décès ont augmenté avec l'âge et la gravité de la maladie à la COVID-19 lors des première et deuxième vagues. CONCLUSION: Une proportion plus élevée des patients admis à Lagos, Nigeria, lors de la deuxième vague étaient plus âgés, avaient des comorbidités et présentaient une forme grave de la maladie à la COVID-19 par rapport à la première vague. Malgré un nombre moindre de patients hospitalisés, il y a eu plus de décès lors de la deuxième vague. MOTS-CLÉS: Présentation Clinique, Covid-19, Première Vague, Mortalité, Nigeria, Deuxième Vague.

The Spectrum of Influenza in Children.

BACKGROUND: Children constitute an important component of the influenza burden and community transmission, but the frequency of asymptomatic infection and post-influenza sequelae at the community level is poorly understood. METHODS: Two community-based prospective cohort studies (2011-2020, 2017-2020) and 1 case-ascertained study (2012-2017) were conducted in Managua, Nicaragua. Non-immunocompromised children aged 0-14 years with ≥1 influenza infections, determined by polymerase chain reaction and hemagglutination inhibition assay, were included. RESULTS: A total of 1272 influenza infections occurred in the household-based portion of the study. Influenza infection was asymptomatic in 84 (6.6%) infections, and the asymptomatic fraction increased with age (1.7%, 3.5%, and 9.1% for ages 0-1, 2-4, and 5-14, respectively; P < .001). Of asymptomatic children, 43 (51.2%) shed virus, compared to 1099 (92.5%) symptomatic children (P < .001). Also, 2140 cases of influenza occurred in the primary care portion of the study. Sequelae of influenza were rare, with the most common being pneumonia (52, 2.4%) and acute otitis media (71, 3.3%). A/H1N1 had higher age-adjusted odds of acute otitis media (odds ratio [OR] 1.99, 95% confidence interval [CI]: 1.14-3.48; P = .015) and hospitalization (OR 3.73, 95% CI: 1.68-8.67; P = .002) than A/H3N2. B/Victoria had higher age-adjusted odds of pneumonia (OR 10.99, 95% CI: 1.34-90.28; P = .026) than B/Yamagata. CONCLUSIONS: Asymptomatic influenza infection is much less common in children than adults, although viral shedding still occurs in asymptomatic children. Post-influenza sequelae are rare in children in the community setting, and virus strain may be important in understanding the risk of sequelae.

Renal AA amyloidosis: presentation, diagnosis, and current therapeutic options: a review.

Amyloid A amyloidosis is thought to be the second most common form of systemic amyloidosis behind amyloidosis secondary to monoclonal Ig. It is the result of deposition of insoluble fibrils in the extracellular space of tissues and organs derived from the precursor protein serum amyloid A, an acute phase reactant synthesized excessively in the setting of chronic inflammation. The kidney is the most frequent organ involved. Most patients present with proteinuria and kidney failure. The diagnosis is made through tissue biopsy with involvement of the glomeruli in most cases, but also often of the vessels and the tubulointerstitial compartment. The treatment usually targets the underlying etiology and consists increasingly of blocking the inflammatory cascade of cytokines with interleukin-1 inhibitors, interleukin-6 inhibitors, and tumor necrosis factor-α inhibitors to reduce serum amyloid A protein formation. This strategy has also shown efficacy in cases where an underlying etiology cannot be readily identified and has significantly improved the prognosis of this entity. In addition, there has been increased interest at developing effective therapies able to clear amyloid deposits from tissues, albeit with mitigated results so far.

Clinical presentation, viral kinetics, and management of human monkeypox cases from New Delhi, India 2022.

We describe the clinical and demographic characteristics, virological follow-up, and management of five confirmed monkeypox cases from New Delhi, India without any international travel history. The viral load kinetics and viral clearance were estimated in oropharyngeal swabs (OPS), nasopharyngeal swabs (NPS), EDTA blood, serum, urine, and various lesion specimens on every fourth day of follow-up ranging from 5 to 24 post onset day (POD) of illness. All five cases presented with mild to moderate-grade intermittent fever, myalgia, and lesions on the genitals, groins, lower limb, trunk, and upper limb. Four cases had non-tender firm lymphadenopathy. No secondary complications or sexually transmitted infections were recorded in these cases except for the presence of viral hepatitis B infection marker hepatitis B virus surface antigen (HBsAg) in one case. All the cases were mild and had a good recovery. A higher viral load was detected in lesion fluid (POD 9), followed by lesion roof (POD 9), urine (POD 5), lesion base (POD 5), and OPS/NPS (POD 5). The monkeypox virus (MPXV) DNA was detected in clinical samples from 5th to 24th POD. These monkeypox cases without international travel history suggest the underdiagnosed monkeypox infection in the community. This emphasizes the need for active surveillance of MPXV in the high-risk population such as men having sex with men and female sex workers.

Lupus, antiphospholipid syndrome, and stroke: An attempt to crossmatch.

Cerebrovascular accidents (CVAs) or strokes are part of the common thrombotic manifestations of Systemic Lupus Erythematosus (SLEs) and Antiphospholipid syndrome (APS). Such neurological thrombotic events tend to occur in patients with SLE at a higher frequency when Antiphospholipid antibodies (aPLs) are present, and tend to involve the large cerebral vessels. The mechanism of stroke in SLE can be driven by complement deposition and neuroinflammation involving the blood-brain barrier although the traditional cardiovascular risk factors remain major contributing factors. Primary prevention with antiplatelet therapy and disease activity controlling agent is the basis of the management. Anticoagulation via warfarin had been a tool for secondary prevention, especially in stroke recurrence, although the debate continues regarding the target international normalized ratio (INR). The presence of either of the three criteria antiphospholipid antibodies (aPLs) and certain non-criteria aPL can be an independent risk factor for stroke. The exact mechanism for the involvement of the large cerebral arteries, especially in lupus anticoagulant (LAC) positive cases, is still to be deciphered. The data on the role of non-criteria aPL remain very limited and heterogenous, but IgA antibodies against ß2GPI and the D4/5 subunit as well as aPS/PT IgG might have a contribution. Anticoagulation with warfarin has been recommended although the optimal dosing or the utility of combination with antiplatelet agents is still unknown. Minimal data is available for direct oral anticoagulants (DOACs).

Clinical presentation of 13 children with alkaptonuria.

Until now, only a few studies have focused on the early onset of symptoms of alkaptonuria (AKU) in the pediatric population. This prospective, longitudinal study is a comprehensive approach to the assessment of children with recognized AKU during childhood. The study includes data from 32 visits of 13 patients (five males, eight females; age 4-17 years) with AKU. A clinical evaluation was performed with particular attention to eye, ear, and skin pigmentation, musculoskeletal complaints, magnetic resonance imaging (MRI), and ultrasound (US) imaging abnormalities. The cognitive functioning and adaptive abilities were examined. Molecular genetic analyses were performed. The most common symptoms observed were dark urine (13/13), followed by joint pain (6/13), and dark ear wax (6/13). In 4 of 13 patients the values obtained in the KOOS-child questionnaire were below the reference values. MRI and US did not show degenerative changes in knee cartilages. One child had nephrolithiasis. Almost half of the children with AKU (5/13) presented deficits in cognitive functioning and/or adaptive abilities. The most frequent HGD variants observed in the patients were c.481G>A (p.Gly161Arg) mutation and the c.240A>T (p.His80Gln) polymorphism. The newly described allele of the HGD gene (c.948G>T, p.Val316Phe) which is potentially pathogenic was identified.

EBV associated T- and NK-cell lymphoproliferative diseases: A comprehensive overview of clinical manifestations and novel therapeutic insights.

EBV is a ubiquitous virus that infects nearly all people around the world. Most infected people are asymptomatic and do not show serious sequelae, while others may develop Epstein-Barr virus (EBV)-positive T and NK-cell lymphoproliferations characterised by EBV-infected T or NK cells. These disorders are more common in Asian and Latin American people, suggesting genetic predisposition as a contributing factor. The revised WHO classification classifies the lymphoproliferative diseases as: extranodal NK/T-cell lymphoma nasal type (ENKTL), aggressive NK-cell leukemia (ANKL), primary EBV-positive nodal T or NK cell lymphoma (NNKTL), systemic EBV-positive T-cell lymphoproliferative disease of childhood (STCLC), systemic chronic active EBV infection (sys CAEBV), hydroa-vacciniforme (HV) and severe mosquito bite allergy (SMBA). Recent advances in the molecular pathogenesis of these diseases have led to the development of new therapeutic strategies. Due to the infrequency of the diseases and broad clinicopathological overlap, the diagnosis and classification are challenging for both clinicians and pathologists. In this article, we aim to review the recent pathological findings which can be helpful for designing new drugs, clinical presentations and differential diagnoses, and suggested therapeutic interventions to provide a better understanding of these rare disorders.