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INTRODUCTION: Osteomyelitis is an inflammatory condition of the bone with a multifactorial etiology, including trauma and odontogenic infections. Despite being a common condition in clinical practice, limited research exists on the clinical and pathological profile of Osteomyelitis of the Jaws (OJ). This 51-year retrospective study aimed to describe the clinical, radiographic, and histopathological features of OJ diagnosed at a single oral pathology referral center. MATERIAL AND METHODS: Clinical, radiographic, and histopathological data of cases diagnosed as OJ were collected and categorized using Zurich Classification System. RESULTS: Among 17,991 cases diagnosed at the service, 75 (0.004 %) were identified as OJ. Patients were predominantly female (n = 67; 89.3 %), with a mean age of 42.68 years (±21.10) at diagnosis. OJ commonly presented as slow-growing, symptomatic lesions (n = 69; 92.0 %) with a predilection for the mandible. Secondary chronic osteomyelitis (SCO) was the most common subtype (n = 44; 84.0 %). Odontogenic infections were identified as the most common etiological factor associated with OJ (n = 41; 54.7 %). Radiographic analysis frequently revealed generalized, moderate bone loss, while histopathological examination often showed a discrete mononuclear inflammatory infiltrate (n = 29; 38.7 %). Bacterial colonies were observed in 26 cases (34.7 %) and were significantly associated with SCO (p = 0.04). CONCLUSION: The findings indicate that OJ is a rare condition in oral pathology centers, predominantly affecting white females in their fifth decade at life, with a predilection for the mandible. Dental infections were the primary causative factor. SCO is the most common OJ subtype in cases requiring surgical management.

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INTRODUCTION: Leukemia and lymphoma mimicking periapical conditions can lead to significant diagnostic pitfalls. Guidance for endodontists in managing such cases is barely explored. This systematic review aimed to summarize the clinicopathologic, imaging, and management aspects of leukemia/lymphoma that mimicked periapical conditions and resulted in endodontic treatment. METHODS: Searches were conducted in PubMed, Embase, Scopus, Web of Science, and LILACS, supplemented by manual scrutiny and gray literature. Case reports and/or case series were included. Critical appraisal of the studies was performed using the Joanna Briggs Institute tool. RESULTS: Among 3,617 identified records, 32 studies involving 37 individuals (mean age 43.6 years; male-to-female ratio 1.2:1) were included. Diffuse large B-cell lymphoma was diagnosed in 21 (56.8%) individuals. The anterior maxilla and posterior mandible were the most frequently affected sites (29.7% each). Radiographically, 97.3% of the lesions exhibited radiolucency in the periapical region. Endodontic treatment preceded the diagnosis of leukemia/lymphoma in 94.6% of cases, while retreatment occurred in 5.4%. The mean time to final diagnosis was 4.9 months. CONCLUSION: Leukemia and lymphoma can be misdiagnosed as periapical conditions, leading to inappropriate endodontic treatments and delayed diagnoses. Endodontists should become familiar with the broad clinicoradiographic spectrum of these rare, but potentially life-threatening hematolymphoid malignancies.

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OBJECTIVE: The epidemiology of cysts and odontogenic tumors is important for differential diagnosis and treatment strategies. We aimed to describe the epidemiological features of cysts and odontogenic tumors in the Chilean population using the current WHO classification. MATERIALS AND METHODS: We reviewed 22,914 biopsy requests received between January 1984 and September 2023 at the oral pathology department, School of Dentistry, Universidad Mayor, Santiago, Chile. Patients diagnosed with cysts of the jaws and odontogenic tumors were selected and information regarding age, sex, and location was recorded. RESULTS: 4226 (18.4%) were cysts, and 551 (2.4%) were odontogenic tumors, ranging from 2 to 97 years old. Males represented 54.4% and females 45.7% of the total sample. The most prevalent cysts were radicular cysts (58.6%), dentigerous cysts (17.9%), and odontogenic keratocysts (13.3%). The most prevalent odontogenic tumors were odontomas (40.1%) and conventional ameloblastoma (17.6%). CONCLUSIONS: Our study was the first retrospective analysis to determine the epidemiological features of both cysts and odontogenic tumors together, based on the 2022 WHO classification. This is relevant as it offers a potential basis for comprehensive comparisons of the epidemiological features of these entities, which could contribute to an accurate differential diagnosis, therefore, leading to more effective therapeutic interventions.

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OBJECTIVE: To summarize published information about the desmoplastic fibroma of the gnathic bones into a descriptive analysis of the main features of this condition. MATERIAL AND METHODS: A systematic review according to the PRISMA guidelines was conducted. Electronic search was performed in four databases and in the gray literature. Case reports and case series were included. Frequencies were obtained for descriptive analysis. RESULTS: We identified 66 articles, for a total of 96 cases. Female patients (55.8%) in the first decade of life (40.6%) with a mean age of 18.2 years were more affected. The mandible was the most affected bone with 81.2% of the cases. The main clinical feature was painless swelling (54.2%). Most of the imaging examinations (radiological, computed tomography, and magnetic resonance) showed well-defined radiolucencies (65.4%) lesions. The treatment was surgical removal in all cases. The recurrence rate was 10.8% and all in the posterior mandible. Spindle cell fibroblasts in a collagenized stroma were often described in the histopathological features. Vimentin, smooth muscle actin, and ß-catenin were common immunohistochemical markers. CONCLUSION: Desmoplastic fibroma is a locally aggressive lesion that commonly affects the jaws in children. Histopathology is essential for diagnosis, and the pathogenesis of this tumor should be further investigated.

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Actinomycosis is a rare infection that involves soft and bone tissues caused by gram-positive, anaerobic filamentous bacteria, usually Actinomyces israelii. About 3% of all cases affect children. Not uncommonly, actinomycosis is initially diagnosed as neoplasm or other granulomatous diseases. Paediatric actinomycosis affecting the jaws is rare. To date, 20 and 1 case affecting the mandible and maxilla, respectively, have been reported. A 4-year-old girl was referred presenting an extensive symptomatic ulcerative lesion with bone exposure in the posterior region of the right maxilla two months ago. One month before, she has been diagnosed with scarlet fever. The lesion progressed, damaging the supporting periodontal tissue. After surgical removal of necrotic bone and deciduous molar, the microscopy revealed actinomycosis, which showed excellent healing after local treatment with hydrogen peroxide solution and adequate oral hygiene. Although actinomycosis of the jaws affecting pediatric patients is rare, paediatric dentists must be aware of their clinicopathological characteristics, with therapeutic and prognostic impact.

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Convergent evolution of similar phenotypes suggests some predictability in the evolutionary trajectories of organisms, due to strong and repeated selective pressures, and/or developmental constraints. In adaptive radiations, particularly in cichlid fish radiations, convergent phenotypes are commonly found within and across geographical settings. Cichlids show major repeated axes of morphological diversification. Recurrent changes in body patterns reveal adaption to alternative habitats, and modifications of the trophic apparatus respond to the exploitation of different food resources. Here we compare morphologically and genetically two Neotropical cichlid assemblages, the Mexican desert cichlid and the Nicaraguan Midas cichlid, with similar polymorphic body and trophic adaptations despite their independent evolution. We found a common morphological axis of differentiation in trophic structures in both cichlid radiations, but two different axes of differentiation in body shape, defining two alternative limnetic body patterns. Adaptation to limnetic habitats implied regulation of immune functions in the Midas cichlid, while morphogenesis and metabolic functions in the desert cichlid. Convergent phenotypic adaptions could be associated to divergent gene regulation.

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OBJECTIVES: To document the case of a patient who underwent several endodontic treatments due to a glandular odontogenic cyst misdiagnosed as an inflammatory periapical lesion. BACKGROUND: Glandular odontogenic cysts behave more aggressively, while others have an indolent course. There is limited information on this cyst in the gerodontologic literature. MATERIALS AND METHODS: A 76-year-old male patient presented with an asymptomatic expansive lesion in the anterior mandible resistant to several endodontic treatments. Cone-beam computed tomography revealed a multilocular osteolytic lesion measuring 6.0 × 4.0 cm, with cortical bone perforation. RESULTS: Histopathological analysis of a biopsy specimen was consistent with glandular odontogenic cyst. The patient underwent marginal mandibulectomy with preservation of the base of the mandible. CONCLUSION: A strict diagnostic process is important to avoid unwanted consequences, particularly in the geriatric population.

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Osteonecrosis of the jaws is a complex and debilitating condition, whose characteristic is the gradual destruction of the jaws in patients exposed to predisposing factors, such as tooth extraction. The clinical manifestations vary according to the severity of the lesion, which may culminate in the exposure of necrotic bone. The objective of this study is to discuss therapeutic options in the management of osteonecrosis associated with the use of cancer medication (MRONJ) through a case report, in addition to discourse the topic, discussing the importance of the role of Dentistry in the prevention and management of the condition. A 45-year-old female patient, melanoderma, with malignant left breast neoplasm associated with metastasis in the bone and peritoneum, and using the bisphosphonate Zometa®, was diagnosed with MRONJ after teeth 26 extraction'. Multimodal therapy through the use of topical antimicrobials, Antimicrobial Photodynamic Therapy, systemic antibiotic and ozone therapy were adopted to regression of the case. The patient was follow-up for 46 months. In order to update the information regarding MRONJ, cases in maxilla, their repercussions, challenges and therapeutic options, It was carried out aditional search in eletronic databases. MRONJ is a challenging condition that deserves to be discussed in order to contribute to a better understanding of the disease, prevention and management. That way, the positive result of adjuvant therapies demonstrated in this report may contribute to the structuring of effective protocols for the management of MRONJ, in addition to enabling the development of new questions and, therefore, new studies related to the condition. (AU)

A osteonecrose dos maxilares é uma condição complexa e debilitante, que tem como característica a destruição gradativa dos maxilares em pacientes expostos a fatores predisponentes, como uma extração dentária. As manifestações clínicas variam de acordo com a gravidade da lesão, podendo culminar na exposição de osso necrótico. Este trabalho tem como objetivo discutir opções terapêuticas no manejo da osteonecrose associada ao uso de medicamento (OMAM) oncológico por meio de um relato de caso, além de discorrer acerca do tema, discutindo a importância da atuação da Odontologia na prevenção e manejo da condição. Paciente 45 anos, sexo feminino, melanoderma, portadora de neoplasia maligna em mama esquerda, com metástase em osso e peritônio e sob uso do bisfosfonato Zometa® foi diagnosticada com OMAM após exodontia de unidade 26. Terapia multimodal através do uso de antimicrobiano tópico, Terapia Fotodinâmica antimicrobiana, antibioticoterapia sistêmica e ozonioterapia foram adotadas com vistas à regressão do caso e a paciente foi acompanhada por 46 meses. No intuito de atualizar informações referentes à OMAM, sobretudo casos em maxila, suas repercussões, desafios e opções terapêuticas, foi realizada uma busca adicional em bases eletrônicas. A OMAM é uma condição desafiadora que merece ser discutida a fim de contribuir com um melhor conhecimento, prevenção e manejo. Dessa forma, o resultado positivo das terapias adjuvantes demonstrado no presente relato pode contribuir com a estruturação de protocolos efetivos para o manejo da OMAM, além de possibilitar a elaboração de novos questionamentos e, portanto, novos estudos relacionados à condição. (AU)

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Aneurysmal bone cyst is a rare osteolytic lesion of uncertain etiology, commonly observed in the lower limbs, with only 1-2% of reports in gnathic bones. We present the case of a 27-year-old male patient referred to the oral and maxillofacial surgery and traumatology service due to complaints of paresthesia in the mental region and increased mandibular volume. Physical examination revealed midline shift and hard consistency. Imaging examinations demonstrated a radiolucent/hypodense lesion with disruption of the mandibular cortices. The histopathological examination of incisional biopsy material led to the diagnosis of a central giant cell lesion. The patient underwent surgical resection, and the histopathological analysis of the specimen revealed a predominantly solid lesion, characterized by blood-filled spaces of varying size, not covered by epithelium or endothelium, with the presence of spindle cells, multinucleated giant cells, and basophilic osteoid material, concluding the diagnosis of mixed-type aneurysmal bone cyst. Despite being uncommon, aneurysmal bone cysts should be considered in the differential diagnosis of volumetric increase in the gnathic bones of young patients.

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BACKGROUND: Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report. RESULTS: A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases. CONCLUSION: MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.

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Introduction: Osteoradionecrosis (ORN) is a secondary complication from radiotherapy, which is difficult to manage and significantly reduces the life quality of the affected patients. Case Report: A 59-year-old female patient, diagnosed with infiltration by squamous cell carcinoma in the left cervical region, underwent adjuvant cervical-facial radiotherapy with a total dose of 66.6 Gy of radiation. Eight years after the diagnosis, the patient underwent multiple extractions and, subsequently, the installation of osseointegrated implants, evolving to extensive intraoral bone exposure associated with oral cutaneous fistula. The patient was initially exposed to photobiomodulation therapy (PBMT), with a low-power laser at wavelengths of 660 nm and 808 nm, and thereafter to antimicrobial photodynamic therapy (aPDT). After an improvement in the clinical condition and resolution of the oral cutaneous fistula, a surgical procedure with the Er: YAG laser was performed to remove the remaining necrotic bone. Once the ORN condition was completely treated, the patient's oral rehabilitation was implemented by the installation of an upper mucous-supported total prosthesis and a lower implant-supported prosthesis. Conclusion: The patient is in a clinical follow-up and has no signs of bone necrosis recurrence, suggesting that low and high-power laser treatment can be an effective therapeutic alternative to resolve this condition.

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BACKGROUND: This study aimed to investigate the clinicopathological features of metastases in the oral and maxillofacial regions. METHODS: In this retrospective study, biopsy records were obtained from referral centers for oral and maxillofacial diagnosis in Brazil, Guatemala, Mexico, and South Africa. RESULTS: A total of 120 cases were evaluated. Of these, 53.78% affected female patients, with a mean age of 57.64 years. Intraosseous lesions were more frequent, particularly in the posterior region of the mandible (49.58%). Clinically, most cases presented with symptomatic swelling, with an average evolution time of 25 months. The clinical diagnostic hypothesis in most instances was that of a malignant lesion. Breast cancer was the most common primary tumor location in females, while lung origin was most common in males. In most cases, the primary cancer was an adenocarcinoma (44.73%). The follow-up period was available for 29 cases, and out of these, 20 had died due to the disease. CONCLUSION: Although this is a rare condition, clinicians should be aware that any oral lesions have the possibility of being metastatic, particularly in individuals with a previous history of cancer. The findings from this study could assist clinicians in prompt diagnosing these lesions and subsequent conducting oncologic assessments and treatment.

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BACKGROUND: The Mexican tetra, Astyanax mexicanus, includes interfertile surface-dwelling and cave-dwelling morphs, enabling powerful studies aimed at uncovering genes involved in the evolution of cave-associated traits. Compared to surface fish, cavefish harbor several extreme traits within their skull, such as a protruding lower jaw, a wider gape, and an increase in tooth number. These features are highly variable between individual cavefish and even across different cavefish populations. RESULTS: To investigate these traits, we created a novel feeding behavior assay wherein bite impressions could be obtained. We determined that fish with an underbite leave larger bite impressions with an increase in the number of tooth marks. Capitalizing on the ability to produce hybrids from surface and cavefish crosses, we investigated genes underlying these segregating orofacial traits by performing Quantitative Trait Loci (QTL) analysis with F2 hybrids. We discovered significant QTL for bite (underbite vs. overbite) that mapped to a single region of the Astyanax genome. Within this genomic region, multiple genes exhibit coding region mutations, some with known roles in bone development. Further, we determined that there is evidence that this genomic region is under natural selection. CONCLUSIONS: This work highlights cavefish as a valuable genetic model for orofacial patterning and will provide insight into the genetic regulators of jaw and tooth development.

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Introduction: Surface osteosarcomas represent around 3-6% of all osteosarcomas, which include the parosteal (low-grade), periosteal (intermediate-grade) and high-grade surface osteosarcomas. The classical location is the femur, followed by tibia and humerus. Parosteal osteosarcoma is the most common type of surface osteosarcoma. To date, 26 cases of parosteal osteosarcoma affecting the jaws have been reported, with most cases following an evolution time of several months to years, clinically favoring a benign osseous or fibro-osseous lesion. Methods: Here, we report a 39-year-old female who was referred presenting a maxillary tumoral mass 5 years ago, clinically diagnosed as osteoma. After clinical, imaginological and histopathological analysis, a diagnosis of parosteal osteosarcoma was made. Conclusion: Thus, parosteal osteosarcoma should also be considered in the differential diagnosis of benign-appearance, bone-forming nodular lesions affecting the jaws.

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The value of birds' ability to move the upper beak relative to the braincase has been shown in vital tasks like feeding and singing. In woodpeckers, such cranial kinesis has been thought to hinder pecking as delivering forceful blows calls for a head functioning as a rigid unit. Here, we tested whether cranial kinesis is constrained in woodpeckers by comparing upper beak rotation during their daily activities such as food handling, calling and gaping with those from closely related species that also have a largely insectivorous diet but do not peck at wood. Both woodpeckers and non-woodpecker insectivores displayed upper beak rotations of up to 8 degrees. However, the direction of upper beak rotation differed significantly between the two groups, with woodpeckers displaying primarily depressions and non-woodpeckers displaying elevations. The divergent upper beak rotation of woodpeckers may be caused either by anatomical modifications to the craniofacial hinge that reduce elevation, by the caudal orientation of the mandible depressor muscle forcing beak depressions, or by both. Our results suggest that pecking does not result in plain rigidification at the upper beak's basis of woodpeckers, but it nevertheless significantly influences the way cranial kinesis is manifested.

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The microscopical diagnosis of radicular cyst (RC) is straightforward; nonetheless, in some cases with unusual histopathological features, strict clinicopathological correlation is necessary to achieve the correct diagnosis. We report a case of a 5-year-old girl was referred presenting extensive carious lesion in the tooth #55, associated with vestibular sinus tract. Medical history revealed allergic asthma diagnosis. After clinical and imagi-nological exams, the deciduous tooth was extracted. Microscopically, the soft tissue lesion attached to the root showed typical RC features; however, in the cystic capsule, lymphoid follicles and vascular networks (lined by epithelioid endothelial cells) surrounded by nu-merous eosinophils, were observed. Immunohistochemistry, through CD3, CD20, CD34 and alpha-smooth muscle actin antibodies, highlighted these findings. Moreover, CD1a and CD207 were negative. To the best of our knowledge, this is the first report of RC showing angiolymphoid hyperplasia with eosinophilia (ALHE)-like features. (AU)

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The mandibular apparatus of batoids (skates, electric rays, guitarfishes, stingrays, and sawfishes) is composed of a few skeletal elements to which the muscular bundles, responsible for all movements involved in the feeding mechanism, are inserted. The description of the different mandibular morphologies can help to understand the different feeding guilds in this group. In this study, we examined the cranio-mandibular myology of adult Rostroraja velezi, Narcine entemedor, and Zapteryx exasperata, three species of rays that coexist in the Southern Gulf of California, Mexico. This study described the muscles on the ventral and the dorsal surfaces for each species, identified the origins and insertions of these muscles, as well as the general characteristics of muscle morphology. There were 17 and 18 muscle bundles attached to the feeding apparatus, including five on the dorsal surface. Only the levator rostri, which elevates the rostrum during feeding, showed considerable differences in shape and size among species. The muscles of the adductor complex showed the greatest differences in size among the three species. N. entemedor presented the exclusive muscle X in the lower mandibular area and the extreme reduction of the coracohyoideus in the pharyngeal area derived from the absence of the basihyal cartilage. The information generated in our study supports the morphological specialization of electric rays (N. entemedor) for an almost exclusive suction feeding strategy.

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OBJECTIVE: To define which are and how the radiomics features of jawbone pathologies are extracted for diagnosis, predicting prognosis and therapeutic response. METHODS: A comprehensive literature search was conducted using eight databases and gray literature. Two independent observers rated these articles according to exclusion and inclusion criteria. 23 papers were included to assess the radiomics features related to jawbone pathologies. Included studies were evaluated by using JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies. RESULTS: Agnostic features were mined from periapical, dental panoramic radiographs, cone beam CT, CT and MRI images of six different jawbone alterations. The most frequent features mined were texture-, shape- and intensity-based features. Only 13 studies described the machine learning step, and the best results were obtained with Support Vector Machine and random forest classifier. For osteoporosis diagnosis and classification, filtering, shape-based and Tamura texture features showed the best performance. For temporomandibular joint pathology, gray-level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), first-order statistics analysis and shape-based analysis showed the best results. Considering odontogenic and non-odontogenic cysts and tumors, contourlet and SPHARM features, first-order statistical features, GLRLM, GLCM had better indexes. For odontogenic cysts and granulomas, first-order statistical analysis showed better classification results. CONCLUSIONS: GLCM was the most frequent feature, followed by first-order statistics, and GLRLM features. No study reported predicting response, prognosis or therapeutic response, but instead diseases diagnosis or classification. Although the lack of standardization in the radiomics workflow of the included studies, texture analysis showed potential to contribute to radiologists' reports, decreasing the subjectivity and leading to personalized healthcare.

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BACKGROUND: Rhabdomyosarcoma (RMS) harboring EWSR1/FUS-TFCP2 fusions has been recently described as a distinct form of RMS with an aggressive course and predilection for the craniofacial bones, especially the jaws. METHODS: We report three new cases of this rare entity, two from Brazil and one from Guatemala, with detailed clinicopathologic, immunohistochemical, and molecular descriptions. Additionally, we explored the English-language literature searching RMS with TFCP2 rearrangement or typical immunophenotype with co-expression of AE1/AE3 and ALK in the head and neck region. RESULTS: Case 1 is a 58-year-old male with a 3-month history of painful swelling in the anterior maxilla. Case 2 is a 22-year-old male presenting with right facial swelling and proptosis. Case 3 is a 43-year-old female with a rapidly growing tumor located in the zygomatic region. Imaging examinations revealed highly destructive intraosseous masses in the first two cases, and a soft tissue tumor with bone invasion in case 3. Microscopically, all cases showed a hybrid spindle and epithelioid phenotype of tumor cells which expressed desmin, myogenin and/or Myo-D1, AE1/AE3, and ALK. FISH confirmed molecular alterations related to TFCP2 rearrangement in Cases 1-2. In case 3, there was no available material for molecular analysis. The patients were subsequently referred to oncologic treatment. Additionally, we summarized the clinicopathologic, immunohistochemical, and molecular features of 27 cases of this rare RMS variant in the head and neck region reported in the English-language literature. CONCLUSION: RMS with TFCP2 rearrangement is a rare and aggressive tumor with a particular predilection for craniofacial bones, especially the jaws. Knowing its clinicopathologic and immunohistochemical profile can avoid misdiagnosis.

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AIMS: To report the case of chronic osteomyelitis of a maxilla in a woman with uncontrolled diabetes mellitus (DM), glucose-6-phosphate dehydrogenase (G6PD) deficiency and mental illness, in an attempt to clarify its pathogenesis and treatment. METHODS AND RESULTS: A case of a woman with moderate G6PD deficiency (Class III) who developed bilateral and asynchronous chronic suppurative osteomyelitis (CSO) of her maxilla with extensive bone sequestra, fistulae and whose management was performed by local surgery for bony sequestra and fistulae removal; closure communication under 4 weeks antibiotic cover. CONCLUSIONS: CSO of the jaw may be a complication of the G6PD deficiency and DM and its severity depends on patient's medical status.