Worsening Of Lesions Research Articles

Drug-Resistant Bone, Joint and Spine Tuberculosis: Evolution of Diagnosis and Treatment.

Drug resistant (DR) osteoarticular TB (OATB) is a challenge in view of it being deep seated lesion and paucibacillary disease. Case definition, investigation protocol, treatment of proven DR and those cases where DR could not be demonstrated lacks clarity and evidence. Hence, a series of studies were conducted to develop an algorithm to investigate and treat therapeutically refractory disease (TRD) or presumptive drug resistance (PDR) cases of OATB. 6 studies were conducted. Study one and two evaluated criteria to label TRD/PDR. Three subsequent studies were conducted where TDR/PDR or fresh cases of OATB cases were investigated by AFB smear, Bactec/liquid culture, histology and genotypic DST by CBNAAT & LPA. Sixth study was a retrospective evaluation of all DR cases treated for proven or clinical drug resistance (CDR). Patient of bone/spine TB on ATT for 5 months or more show poor clinico-radiological treatment response as worsening of lesion, increased spinal deformity, persistent discharging sinus/ulcer, appearance of fresh lesion, recurrence of previous lesion, wound dehiscence of post-operative surgical scar cab labelled as PDR cases. These cases on histology ascertained TB and were proven DR on genotypic and phenotypic DST and are treated successfully. The patients of histologically ascertained TB and no/indeterminate phenotypic and genotypic DST were successfully treated as clinical drug resistance on MDR protocol. We described an algorithm. We must suspect PDR(TRD) based on criteria described. The tissue must be procured and submitted for AFB smear, histology and phenotypic and genotypic DST for diagnosis of TB. Genotypic and phenotypic DST will be useful to prove (90% instances) type of drug resistance. Remaining on strong clinical suspicion of DR and yet inconclusive on phenotypic/genotypic DST (<10%), may be treated as CDR as MDR. The adverse drug reactions and hepatic side-effects should be monitored diligently and these cases to be treated till healed status is demonstrated.

Role of polymerase chain reaction from aqueous humor in a suspected case of ocular toxocariasis – A report of a case

An 8-year-old girl presented with unilateral panuveitis with a retinochoroidal lesion superior to disc with overlying vitritis. Laboratory workup was done, and a clinical diagnosis of toxoplasma retinochoroiditis was considered. Based on this initial diagnosis of toxoplasma retinochoroiditis empirically the patient was started on tablet clindamycin along with sulfamethoxazole and trimethoprim and oral steroids. On subsequent follow up, patient developed worsening of lesion. Intraocular fluid was collected from anterior chamber and sample revealed a positive polymerase chain reaction for toxocara canis. The diagnosis of ocular toxocariasis was made. This case highlights the use of aqueous fluid from polymerase chain reaction (PCR) to diagnose ocular toxocariasis.

Cardiac Involvement in Pediatric Mucopolysaccharidoses Patients and their Genetic Profile: A Retrospective Single-center Study

Abstract Background: Mucopolysaccharidoses (MPS) are rare metabolic disorders of monogenic inheritance, with varying degrees of cardiac involvement due to undegraded glycosaminoglycans getting aggregated in the spongiosa of the cardiac valves, the myocardium, and myointima of the coronary arteries. This study is an effort to understand the cardiac involvement and genetic pattern of pediatric MPS patients at a tertiary care center in South India. Methods: This descriptive study was done by examining records in our hospital database for MPS patients in the age group of 0–15 years, diagnosed between January 2014 and January 2023. Of these patients, 37 patients with echocardiographic loops available in the hospital system were reevaluated by a single pediatric cardiologist to avoid observer bias. The underlying genetic spectrum was also reviewed. Results: The cohort comprised 67.5% of males and a median age of 9.8 years (interquartile range: 6.5–14.9 years) with a distribution of 37.8% MPS I, 32.4% MPS II, 13.5% MPS IV, and 10.8% MPS VI. Early cardiac involvement in the form of valvar thickening, predominantly left sided (mitral [92%] &gt;aortic [38%]), was seen across all MPS subtypes. We also noted an increased involvement of the tricuspid valve (38%) in our cohort. Moderate–severe valvar involvement was seen in 16% of the cohort, mostly MPS I, II, and VI patients, and more in the second half of the age group (&gt;6 years), suggesting an age-associated worsening of cardiac lesions. Genetic analysis done in 68% of the cohort detected 61% of pathogenic variants, with a predominance of missense mutation (43%). However, no genotype–cardiac phenotype correlation could be ascertained. Conclusions: We identified a high proportion of cardiac abnormalities in our pediatric MPS cohort, which ranged from isolated valvar thickening to a more severe clinical picture, including moderate-to-severe valvular insufficiency and/or stenosis and left ventricular hypertrophy. Cardiac pathology is an early manifestation and a known cause of mortality in many MPS subtypes. Echocardiography is a key diagnostic technique for early detection, careful monitoring, and guidance in the initiation of a timely intervention that will help curb its progression. Hence, the need arises to raise awareness among the primary caretakers of this subset of patients on the need for early cardiac evaluation with a detailed echocardiography.

Paradoxical reactions in the form of Optochiasmatic arachnoiditis and stroke in An immunocompetent girl with tuberculous Meningitis- a case report

The paradoxical response is characterized by clinical or radiologic worsening of pre-existing lesions or the appearance of new lesions following initiation of treatment for tuberculosis (TB). The paradoxical response has raised questions about the accuracy of the diagnosis, the potential for treatment failure, and the presence of an underlying disease, making it an important topic of care for clinicians. In this case report, we present the paradox reaction of a 14 year old girl diagnosed and treated for TB meningitis. This healthy immune girl is successfully treated with steroids, and we discuss the importance of treating the paradox of tuberculosis progression despite the use of effective anti-TB drugs. Bangladesh J Medicine 2023; 34(3): 245-251

Efficacy of heat-inactivated Mycobacterium bovis vaccine delivered to European badgers (Meles meles) through edible bait

Badgers (Meles meles) are a major tuberculosis (TB) reservoir in Europe, with the potential to transmit infection to cattle. Here we assessed whether a recently described oral tuberculosis vaccine based on heat-inactivated Mycobacterium bovis (HIMB), delivered as edible baits, can protect badgers from infection. Eight badgers were given individually five baits, each one consisting of a ball of peanut butter, natural peanut and oat flakes including a dose of the vaccine containing 5 × 107 colony-forming units. In parallel, a control group of seven badgers did not receive the vaccine. One month and a half later a second dose of the vaccine was offered to the vaccinated group. Ninety-four days after the second dose, all badgers were challenged with M. bovis (103 colony-forming units per animal) delivered endobronchially to the right middle lung lobe. Clinical, immunological, pathological and bacteriological variables were measured throughout the whole study to assess the efficacy of the vaccine. Two vaccinated animals showed high bacterial load of M. bovis and worsening of pathological lesions of TB. Conversely, the other six vaccinated animals showed slight improvement in bacterial load and pathology with respect to the control group. These results suggest that delivering the TB vaccine via food bait can partially protect wild badger populations, although vaccination can lead to either protection or tolerization, likely depending on the animal's immune status and general condition at the time of vaccination. Further optimization of the vaccination trial/strategy is needed to reduce the rate of tolerization, such as altering vaccine dose, number of doses, type of bait, use of adjuvants or route of administration.

Effects of doxycycline dose rate and pre-adulticide wait period on heartworm-associated pathology and adult worm mass

BackgroundThe American Heartworm Society canine guidelines recommend treatment with doxycycline prior to adulticide administration to reduce levels of Wolbachia and its associated metabolites, which are known to be a leading cause of pulmonary pathology. Studies have determined that doxycycline administered at 10 mg/kg BID for 28 days is an effective dose for eliminating Wolbachia, but what has not been determined is the clinical relevance of this elimination. The current guidelines also recommend a 30-day wait period following administration of doxycycline to allow for clearance of metabolites, such as Wolbachia surface protein, and for further reduction in heartworm biomass before administration of adulticide. Reducing the doxycycline dose and eliminating the wait period may carry practical benefits for the animal, client, and practitioner.MethodsTo investigate these treatment practices, Dirofilaria immitis adults were surgically transplanted into each of 45 dogs, which were divided into nine study groups of five dogs each. Seventy-five days after transplantation, two groups each were administered 5, 7.5, or 10 mg/kg BID doxycycline orally for 28 days and 6 µg/kg ivermectin monthly, with three untreated groups serving as controls. Study animals were necropsied and examined prior to treatment as well as 30 and 60 days post-treatment.ResultsMean worm weight was unaffected by dosage but exhibited a significant increase at 30 days and significant decrease at 60 days post-treatment, including in control groups. Histopathology lesion scores did not significantly differ among groups, with the exception of the lung composite score for one untreated group. Liver enzymes, the levels of which are a concern in doxycycline treatment, were also examined, with no abnormalities in alanine aminotransferase or alkaline phosphatase observed.ConclusionsNo consistent worsening of tissue lesions was observed with or without the AHS-recommended 30-day wait period, nor did reduced dosages of doxycycline lead to worsening of pathology or any change in efficacy in depleting worm weight. Mean worm weight did significantly increase prior to, and decrease following, the wait period. Future work that also includes adulticide treatment (i.e. melarsomine) will study treatment recommendations that may improve both animal health and owner compliance.Graphical abstract

Contribution of HLA-G and FOXP3 genes and proteins in the severity of cervical intraepithelial neoplasia during HPV infection

Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection.Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry.53 women were HPV+ against 127 women HPV−. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries.In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.

Histological findings of diabetic kidneys transplanted in non-diabetic recipients: a case series.

Diabetic donors are recognized as a reliable source of organs, although the discard rate of kidneys is still high. Few data are available on the histological evolution of these organs especially on kidneys transplanted into non-diabetic patients who remain euglycemic. We describe the histological evolution of ten kidney biopsies performed on non-diabetic recipients of diabetic donors. Mean donor age was 69 ± 7years, 60% were males. Two donors were treated with insulin, eight with oral antidiabetic drugs. Mean recipient age was 59.9 ± 7years, 70% were males. The pre-existing diabetic lesions identified in the pre-implantation biopsies, encompassed all histological classes, and were associated with mild IF/TA and vascular damages. The median follow-up was 59.5 [IQR 32.5-99.0] months; at follow-up, 40% of cases did not change histologic classification, two patients with class IIb downgraded to IIa or I and one with class III downgraded to IIb. Conversely, three cases showed a worsening, from class 0 to I, I to IIb or from IIa to IIb. We also observed a moderate evolution of IF/TA and vascular damages. At follow-up visit, estimated GFR was stable (50.7mL/min vs. 54.8 at baseline) and proteinuria was mild (51.1 ± 78.6mg/day). Kidneys from diabetic donors show variable evolution of the histologic features of diabetic nephropathy after transplant. This variability may be associated to recipients characteristics such as euglycemic milieu, in case of improvement, or obesity and hypertension, in case of worsening of histologic lesions.

Safety and efficacy of nadifloxacin versus clindamycin observed in a tertiary care teaching hospital of Deccan Plateau

Acne vulgaris is characterised by excess sebum production and inflammatory reaction in sebaceous glands. As propionibacterium is involved in aggravation of acne, antimicrobials like nadifloxacin and clindamycin were found to be effective in treatment.Comparison of nadifloxacin with clindamycin in terms of inflammatory and non-inflammatory lesion count and global improvement rating, when given in combination with benzoyl peroxide in patients in acne vulgarisNadifloxacin 1%, benzoyl peroxide 2.5% and clindamycin 1% were used as topical treatment option. Study cohort was randomly divided into two groups: Nadifloxacin group and Clindamycin group. All subjects who were included in the study were instructed to apply a thin layer of medication over acne lesions; benzoyl peroxide 2.5% gel once daily at bedtime and clindamycin 1% gel or Nadifloxacin 1% gel twice daily. Efficacy is analysed by comparing changes in total, inflammatory and non-inflammatory lesion counts, In addition, global improvement was rated by patients using a six-point scale (worsening, no improvement, slight improvement, moderate improvement, good improvement, clearance) at end of treatment.There is progressive decline in number of inflammatory and non-inflammatory lesions in both groups. Analysis of lesion counts not showed any significant difference in between two groups. In global improvement rating scale, more number of patients using nadifloxacin with benzoyl peroxide reported good improvement compared to patients using Clindamycin with benzoyl peroxide. No patient in any group reported worsening of lesions. None of patients in study groups reported clearance. Two adverse events were reported during study, they were, burning sensation and dryness. There was no significant difference in incidence of adverse events in both treatment groups.Topical Nadifloxacin, a new fluoroquinolone is effective, tolerable and safe for mild or moderate facial acne. Its clinical effectiveness is equivalent to clindamycin when used as add-on therapy to benzoyl peroxide.

80 Case series of juvenile scleroderma at Aga Khan University Hospital, Nairobi

BackgroundJuvenile scleroderma includes a range of conditions presenting with skin fibrosis. It’s classified into two major categories, localized and systemic. Juvenile localized scleroderma (morphea) is limited to the skin and forms majority of pediatric presentations (>95%). Though rare, juvenile systemic sclerosis involves the skin and other internal organs and is associated with a poorer prognosis.ObjectiveTo characterize the clinical profile of two cases of scleroderma at Aga Khan university hospital, Nairobi.MethodsRetrospective review of medical records of two patients with Juvenile scleroderma managed at Aga Khan university hospital, Nairobi.ResultsThe first patient was a 7-year-old boy presenting with joint pains for 2 months, restricted activities and limping. He also had a non-itchy lesion on the right thigh for about 6 years. On examination, there was an 8 by 18 cm, flat, shiny skin lesion with ill-defined margins and skin thickening around it. There were 2 punched out scars from previous skin biopsy sites with latest biopsy showing atrophic epidermis, dermal collagen homogenization with thick sclerosed fibers in keeping with morphea. Pulmonary function tests revealed mild restrictive lung disease. There were no other systems involved on further evaluation. He was started on weekly methotrexate, daily prednisone, daily folic acid and omeprazole to be followed up in clinic.The second case is a 5-year-old girl who presented with 3-year history of inability to walk. Physical examination revealed areas of skin hypopigmentation and hyperpigmentation on the neck and back with active lesions on the left flank and posterior right leg. She had left lower limb atrophy and extreme wasting of thigh and calf muscles, a contracture of the left knee, ankle and limb length discrepancy. Her investigations revealed positive rheumatoid factor, positive antinuclear antibody (ANA), microcytic hypochromic anaemia and skin biopsy with features of morphea. She received six courses of high dose methyl prednisone over six months, weekly methotrexate, daily folic acid, daily prednisone that was tapered off gradually, calcium supplementation and iron supplementation. In addition, she received isoniazid for tuberculosis prophylaxis with pyridoxine. Her management was multidisciplinary involving orthopedics, physiotherapy, occupational therapy, and dieticians. She developed a new skin lesion on the left forearm about five months after initiation of treatment but no worsening of symptoms or other new lesions thereafter.ConclusionJuvenile scleroderma though rare has a high risk of misdiagnosis with delay in initiation of treatment. It is associated with significant morbidity and early diagnosis, treatment and follow up is imperative for good outcomes.

Churg Strauss Syndrome after Leech Therapy: A Case Report

Churg Strauss Syndrome (CSS) is a necrotizing vasculitis affecting small vessels. Although there are many accompanying findings, this syndrome has distinctive clinical findings such as asthma, nasal polyposis, and hypereosinophilia. Here, we describe a case report of a 48-year-old male patient with known asthma and nasal polyposis, who applied to the emergency department with a sudden worsening of consciousness and bullous lesions on the ankle after undergoing leech therapy (hirudotherapy), accompanied by mononeuritis multiplex and other clinical findings. Clinical findings, laboratory, electromyography, lumbar puncture, radiological imaging methods, histopathological examination and transthoracic echocardiography were used to diagnose CSS. In addition, it was desired to draw attention to the fact that leech therapy may trigger hyperosinophilia in vasculitis group diseases and cause serious complications in the individual.

P271 A masquerading case of Cryptococcus neoformans

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMIntroductionCryptococcal infections are commonly seen in immunocompromised hosts, especially HIV-infected patients and patients on immunosuppressive therapy. Cryptococcus shows a strong tropism for the central nervous system however cutaneous tropism is not uncommon. Here we describe an HIV-negative immunocompromised patient who developed disseminated cryptococcosis with the predominant presentation being painful thigh lesions.Case DetailsA 56-year-old lady presented with skin lesions and burning pain over both thighs for 1 month and a high-grade fever for 15 days. Her thigh lesions were initially treated elsewhere as tinea corporis. Her previous medical history was significant for poorly controlled diabetes, and chronic liver disease (secondary to autoimmune hepatitis or AIH). Her ongoing medications included prednisolone, anti-diabetics, and tenofovir. At presentation, the only significant physical findings were large irregular areas of central hypo-pigmentation with peripheral hyper-pigmentation and superficial small blisters over both thighs. These areas showed signs of inflammation. The empiric antimicrobial therapy included piperacillin-tazobactam and fluconazole (in view of prior urine culture growing Candida species). Over the next 48 h, fever continued, thigh pain worsened and the lesions on thighs blistered with violaceous discoloration. Her blood cultures sent at admission grew Candida kruzei, resistant to fluconazole, sensitive to voriconazole, amphotericin and echinocandins. Beta-D Glucan was also elevated. Fluconazole was discontinued, and anidulafungin was initiated. A repeat culture (prior to the start of anidulafungin) was still positive for C. krusei, but a subsequent blood culture (after the start of anidulafungin) was negative. Echocardiography did not show features of endocarditis. After a transient improvement, she worsened again with breakthrough fever, hypotension, and worsening of thigh lesions with eschar formation. Wound debridement was done, and antibiotics were escalated to carbapenem and polymyxins. Tissue cultures (sent during wound debridement) grew carbapenem-resistant klebsiella pneumonia. With these, the fever and her wounds were better; but the fever still persisted and she described a persisting severe burning pain over both the thigh wounds which did not respond to several analgesics.A few days later, the fever worsened, and she had hypotension and disorientation. Blood and urine cultures were repeated. Repeat Serum beta D glucan levels were elevated. CSF examination was not possible in view of severe coagulopathy. The blood and wound cultures both grew C. neoformans (confirmed on MaldiTOFF). Antibiotics and anidulafungin were discontinued; liposomal amphotericin and flucytosine were started. Patient had significant improvement in sensorium, fever, and thigh pains within the next 72 h. Later, liposomal amphotericin was switched to conventional amphotericin because of financial constraints. This was followed by acute kidney injury and a flare of AIH. Amphotericin and flucytosine were withheld for a few days; a pulse of methylprednisolone was needed for AIH. Following resolution of acute kidney injury and AIH flare, conventional amphotericin B and flucytosine were restarted (and given for cumulative 3 weeks). This was followed by fluconazole consolidation. At hospital discharge, although there were raw areas over the thighs, these were healthy and she was otherwise well. A total of 3 months later, skin grafting was successfully performed.Conclusions Cryptococcus can be a great masquerader, and can mimic a variety of conditions. A high index of suspicion is required to clinch the diagnosis.

Four cases of dermatomyositis with abnormally high anti-MDA-5 antibody titres and not high levels of serum ferritin.

Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis is a fatal disease presenting with rapidly progressive interstitial lung disease. High ferritin levels are a well-known poor prognostic factor. A high anti-MDA-5 antibody titre was also recently identified as a poor prognostic factor. We encountered four cases that had extremely high anti-MDA-5 antibody titres without high levels of ferritin in the initial examination. All cases were female with ages ranging between 29 and 54 years (mean age, 44 years). In the initial examination, anti-MDA-5 antibody titres were 2060-3040 (normal range, <32 index), ferritin levels were 87-480 ng/ml (normal range, 2.6-129.4 ng/ml), KL-6 level was 186-1806 U/ml (normal range, <500 U/ml), and creatine kinase level was normal in all patients. One patient had respiratory distress on exertion. Computed Tomography (CT) images showed mild ground-glass attenuation/reticular shadows near the pleura in all patients. Three patients were treated with a combination of high-dose glucocorticoids, intermittent intravenous cyclophosphamide, and calcineurin inhibitors, and two required plasma exchange due to the worsening of lung lesion. In these patients, ferritin and KL-6 levels tended to elevate after the beginning of treatment. Very mild pulmonary lesions disappeared in one patient treated with moderate doses of a glucocorticoid and calcineurin inhibitor. All patients survived, and one required oxygen on exertion at discharge. The condition of patients with abnormally high anti-MDA-5 antibody titres may deteriorate even though ferritin levels were not high and lung shadows are minimal at presentation. Therefore, intensive treatment needs to be considered early in the course of the disease regardless of the serum ferritin level.

Pretreatment visceral metastases in castration resistant metastatic prostate cancer: role in prediction versus actual site of disease progression

BackgroundTo evaluate the anatomic site(s) of initial disease progression in patients with castration resistant metastatic prostate cancer (mCRPC) in the presence or absence of pre-treatment visceral metastases while on systemic therapy. MethodsThis is a retrospective cohort study of mCRPC patients who have baseline and at least one follow up bone scan and CT chest, abdomen and pelvis (CAP). Disease progression was determined by RECIST and/or ≥ 30% increase in automated bone scan lesion area score. Kaplan–Meier plot was used to estimate the median progression free survival and log-rank tests were used to compare anatomic sites.ResultsOf 203 patients, 61 (30%) had pre-treatment visceral metastases. Patients with baseline visceral disease were 1.5 times more likely to develop disease progression (HR = 1.53; 95% CI, 1.03–2.26). Disease progression was a result of worsening bone scan disease (42% (16/38)) versus visceral (32% (12/38)) or lymph node disease (3% (1/38)) by CT or a combination thereof (23% (9/38)). Median time to progression (TTP) did not differ by anatomic location of initial progression (p = 0.86). Development of new lesions occurred in 50% of those visceral patients with soft tissue only progression and was associated with a significantly longer TTP (3.1 months (2.8–4.3 months) than those with worsening of pre-existing lesions (1.8 months (1.6–2.7 months); p = 0.04.ConclusionsPatients with pre-treatment visceral metastases in mCRPC are more likely to experience disease progression of bone disease with the initial anatomic site of progression similar to those without baseline visceral involvement.

1401. Infliximab for Immune Reconstitution Inflammatory Syndrome (IRIS) in Tuberculous Meningitis; A Treatment Paradox

BackgroundTumor necrosis factor (TNF)-α inhibitors are known for the reactivation of latent tuberculosis (TB). As a paradox, it has been reported to have a role in the treatment of immune reconstitution inflammatory syndrome (IRIS) from anti-TB therapy.MethodsWe report a case of paradoxical worsening of central nervous system TB after initiation of anti-TB medications, which was treated successfully with infliximab (TNF-α inhibitor).ResultsA 34-year-old man from Nepal with a history of untreated latent TB presented with complaints of occipital headache, slurred speech, and witnessed seizure. His physical exam was consistent with hyperreflexia. MRI of the brain revealed multiple small contrast-enhancing lesions in cerebral hemispheres. CT Chest showed bilateral centrilobular nodules suggestive of miliary TB. Cerebrospinal fluid (CSF) analysis showed pleocytosis, high protein, and low glucose. He was started on isoniazid, rifampin, ethambutol, and pyrazinamide along with high-dose dexamethasone for TB meningitis. Later, MTB DNA probe from bronchioalveolar lavage and CSF detected Mycobacterium Tuberculosis which was pan-susceptible. Repeat MRI of the brain 6 months into therapy revealed worsening of brain lesions. Moxifloxacin and linezolid were added to the regimen given clinical progression on first-line therapy. 6-months into this enhanced regimen he started experiencing blurring of vision. Visual field mapping showed left homonymous hemianopia. Repeat MRI of the brain confirmed extensive changes of basilar meningitis completely enveloping the optic chiasm. IRIS from TB was suspected. His prednisone dose was increased, and 3-doses of infliximab infusion were, 2-weeks apart were administered which showed clinical and radiological improvement.MRI Brain MRI Brain (axial T2/flair sequence) shows hyperintensities in multiple locations including the involvement of the left optic nerve and the left occipital region.ConclusionExacerbation of pre-existing clinical symptoms, formation of new lesions, or cavitation of prior pulmonary infiltrates is known as tuberculosis IRIS or paradoxical reaction. Despite the clinical and radiological exacerbation, mycobacterial cultures usually stay negative. Continuation of anti-TB medications and high-dose corticosteroids are the backbone of treatment but in refractory cases, immune modulation is needed with anti-TNF-α agents.Disclosures All Authors: No reported disclosures

Clinical Effects of Oral Bacteriotherapy on Anal HPV Infection and Related Dysplasia in HIV-Positive MSM: Results from the "HPVinHIV" Trial.

Background. Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. Methods. In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. Results. 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). Conclusion. Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

Leptomeningeal Metastasis in ER + HER2- Advanced Breast Cancer Patients: A Review of the Cases in a Single Institute Over a 15-year Period.

While leptomeningeal metastasis (LM) from estrogen receptor-positive, HER2-negative advanced breast cancer (ER + HER2-ABC) has a poor prognosis, the details of ER + HER2-LM are unclear. We therefore retrospectively investigated patients with LM from ER + HER2-ABC. ER + HER2-ABC patients who received any therapy at Shizuoka Cancer Center between October 2002 and December 2017 were retrospectively analyzed. Patients with central nervous system (CNS) metastases were divided into three groups: brain metastasis (BM) only (B group); BM with LM (BL group); and LM only (L group). Among 369 patients, 102 developed CNS metastases: 70 (68.6%), 13 (12.8%), and 19 (18.6%) in the B, BL, and L groups, respectively. The L group showed a later onset, poorer performance status, more symptoms, and more skull metastasis than the other groups. Radiotherapy as the initial treatment was introduced to 13/13 (100%) and 15/19 (78.9%) in the BL and L groups, respectively. Subsequent systemic therapy excluding best supportive care was introduced to 5/13 (38.5%) and 5/19 (26.3%) in the BL and L groups, respectively. The median overall survival from the diagnosis of CNS lesions was 295.0, 146.0, and 99.0 days in the B, BL, and L groups, respectively, and worsening of CNS lesions was the major cause of death in the BL and L groups. Multivariate analyses showed that concurrent soft tissue metastasis (hazard ratio, 4.620) and subsequent systemic therapy (hazard ratio, 0.063) were prognostic for the L group. Management of LM from ER + HER2-ABC remains challenging, so a multimodal approach with novel systemic therapy is warranted.

A Randomized Controlled Trial on Efficacy of Surgical Excision of Nondysplastic Leukoplakia to Prevent Oral Cancer.

The aim of this study was to evaluate the effectiveness of surgical excision to prevent cancer in patients with nondysplastic oral leukoplakia (OL). This study was the first randomized controlled clinical trial comparing surgical treatment with standard care in this group of patients. Patients were divided into two groups. The first group underwent standard care, that is smoking counseling, follow-up visits every 6 months, and control biopsy when indicated. The second group underwent surgical excision, together with standard care. Oral cancer onset was the primary outcome; secondary outcomes included healing, recurrence after surgery, onset of new lesions, and worsening of the primary lesions. The differences in distribution of the patients' and lesions' characteristics were investigated through nonparametrical tests (Wilcoxon rank-sum and Fisher exact). Univariate and multivariate logistic regressions have been performed to estimate the odds ratio of the treatment on the recurrence or worsening of the lesions. A total of 260 patients took part in the study of which 132 were women (50.8%); during the follow-up period, two subjects developed oral cancer, one for each arm. Surgical treatment, when compared with standard care, was associated with a lower probability of the treated zone to remain healed during the follow up period (OR = 7.43; 95% confidence interval, 2.96-22.66). In conclusion, it is possible to assumed that regular clinical follow-up could be considered a reliable standard of care among patients with nondysplastic OLs.Prevention Relevance: Oral white patches can transform into cancer and none has provided clinical guidelines to prevent it. For the first time ever, we have showed that the clinical follow up of non dysplastic lesions was able to provide benefits if compared with surgical excision.

Analysis of Systemic and Cutaneous Inflammatory Immune Response in Canine Atopic Dermatitis

Background: Canine atopic dermatitis (CAD) is a chronic and inflammatory disease present in veterinary dermatological practice. The inflammation in CAD is triggered by environmental allergens and skin microorganisms, which are responsible for the worsening of cutaneous lesions. This continuous activation of skin inflammatory process can induce the production of free radicals that also contribute to cellular damage and ultimately leads to changes in blood parameters in dogs with CAD. Although there are reports of inflammatory parameters in CAD, there are a lack of studies correlating skin lesions, blood leukocytes and oxidative stress. Based on that,this study aimed to evaluate the integumentary and systemic inflammatory response in dogs with atopic dermatitis. Materials, Methods &amp; Results: Dogs with confirmed diagnosis of canine atopic dermatitis (n = 10) were divided in two groups according to CADESI-IV: AI, with CADESI between 0-10, AII, with CADESI between 10-34, and control group (n = 5). Blood-biochemical and histological analysis were performed to access systemic and cutaneous inflammatory response. AII group tended to higher neutrophil and eosinophil counts, as well as neutrophil/lymphocyte ratio (NLR) when compared to AI. The albumin was lower in AII compared to AI and control (P &lt; 0.05), while total bilirubin and malondialdehyde (MDA) did not differ between groups. NLR (r = 0.64 and P = 0.04) and MDA (r = 0.54 and P = 0.1) were positively correlated with CADESI, while albumin was negatively correlated with CADESI (r = -0.79 and P = 0.005). Histopathological analysis revealed a larger number of neutrophils, macrophages and mast cells in AI and AII than in control group (P &lt; 0.05). Discussion: In this study it was possible to evaluate the systemic and cutaneous leukocyte dynamics in CAD. Skin inflammation induces the production of chemotactic molecules contribute to neutrophil outflow from blood vessel toward the affected tissue, which can be visualized as perivascular inflammatory infiltrate and exocytosis. At systemic level, there was a tendency to increase in total leukocytes and circulating neutrophil count in group AII, as well as in neutrophil/lymphocyte ratio (NLR), when compared to AI. The NLR is a widely available and inexpensive laboratory biomarker that quantifies systemic inflammation, being used in human medicine to evaluate prognosis in different types of cancer. In our study, dogs in AII group showed an increased NLR compared to AI and control, which demonstrates the influence of skin injury in systemic parameters. Furthermore, AII group is composed of dogs with greater lesion state, which reflects in higher NLR values. Since this disease is known by its chronicity and may remain stable for years, NLR may be a novel biomarker to evaluate acute exacerbation in CAD and could potentially explain why some patients have longer crisis duration and frequent flares. The maintenance of the inflammatory state also induces the production of oxidizing substances, which possibly exceed the total antioxidant capacity, generating a situation of oxidative stress, which can result in damage to membrane lipids and release of their products. MDA is reliable and is the most commonly used marker of the overall lipid peroxidation level and the presence of oxidative stress. This result may be related with the antioxidant system, such as albumin and bilirubin, which was able to promote an efficient control of oxidant substances. In conclusion, the presented data demonstrated an inflammatory process progression as well as introduced NLR as a potential marker of disease exacerbation in CAD.

Estratégias terapêuticas do esteticista frente ao paciente portador de hidradenite supurativa

A Hidradenite Supurativa (HS), também chamada de Hidrosadenite, Acne Inversa ou Doença de Verneuil é uma doença inflamatória crônica, recorrente, estigmatizante e debilitante. Sua etiopatogênese envolve oclusão folicular e fatores genéticos, ambientais e imunológicos, podendo ocorrer isolada ou simultaneamente em diversas regiões do corpo. As características iniciais da HS são comumente equivocadas com furunculoses, carbúnculos e foliculites, levando a um atraso no diagnóstico e no agravamento das lesões, na necessidade de intensificar a terapêutica medicamentosa e muitas vezes, o afastamento das atividades laborais. O objetivo deste trabalho é inserir o Esteticista Cosmetólogo em equipe multidisciplinar para o tratamento aos portadores de HS, oferecendo técnicas terapêuticas alternativas complementares às medicamentosas e de controle evolutivo da doença. Para tanto, intensificar a abordagem do tema nos cursos de formação do Técnico em Estética e nas graduações de Esteticista Cosmetólogo. Por ser uma doença ainda sem cura, e os tratamentos disponíveis são muitas vezes ineficazes, portanto é de fundamental importância novas estratégias terapêuticas que possam contribuir significativamente para o aumento da qualidade de vida dos portadores de HS.