Nevin Manimala

Head Neck. 2024 Jul 20. doi: 10.1002/hed.27884. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether objective measures of oral health and salivary gland irradiation correlates with subjective measures of eating, drinking, and salivation in patients following head and neck radiation therapy (HNRT).

METHODS: This cross-sectional study included 112 patients following HNRT with a completed patient-reported outcome (PRO) scale. Objective measures at post-HNRT visit included decayed-missing-filled teeth (DMFT) scores, periodontal disease condition, oral hygiene status, dental prosthesis use, and prescribed radiation dose to salivary glands. Data were collected and statistical analysis was performed.

RESULTS: There was no significant association between PRO scales and dental prosthesis use, periodontal disease, and oral hygiene. Although some significant findings were seen with DMFT and prescribed radiation dose to salivary glands, this explained only very small amounts of the variation in eating, drinking, and salivation measures in these patients.

CONCLUSION: PRO measures should be integrated in the routine care of patients with head and neck cancer.

PMID:39032116 | DOI:10.1002/hed.27884

Am J Hum Biol. 2024 Jul 20:e24136. doi: 10.1002/ajhb.24136. Online ahead of print.

ABSTRACT

Changes in the immune status and the content of blood transport components reflect adaptations in the human body in response to adverse factors, showcasing the organism’s adaptive capabilities and functional state. In this study, we aimed to determine the features of the immune system and levels of transport components of the blood system in residents of the Arctic of the Russian Federation.

METHODS: The peripheral venous blood of 191 residents of the Arctic of the Russian Federation (Murmansk Oblast) aged 21-55 analyzed comprehensively. Blood was sampled from the ulnar vein on an empty stomach in the morning. The hemogram, phagocytic activity of neutrophils, lymphocyte content with CD3, CD4, CD8, CD10, CD19, CD16, CD71, CD25, HLA-DR and CD95 phenotypes, concentrations of cytokines: TNF-α, IFN-γ, IL-6, IL-10, extracellular receptor pool: sCD71, sCD62L, sApo-1/Fas, sFasL, circulating immune complexes (CIC) and blood transport components: haptoglobin (Hp), transferrin, IgM, IgG, IgA, IgE (immunoglobulins M, G, A and E) low-density lipoproteins (LDL), and high density lipoprotein (HDL) were evaluated. The results were analyzed using descriptive statistics and comparative, factorial, and regression analyses.

RESULTS: Residents of the Murmansk Oblast exhibit a high prevalence of erythrocytosis (62.3%), thrombocytosis (25.0%), leukocytosis (20.1%), and increased hemoglobin (Hb) concentrations (42.5%), coupled with a significantly decreased level of active phagocytes (47.6%). A significantly decreased level of lymphocytes with phenotypes CD3 (92.4%), CD4 (40.4%), CD71 (62.3%) was revealed, coupled with the activation of lymphocytes with phenotypes CD16 (50.1%), CD8 (37.5%), CD19 (15.9%) and increased concentrations of pro-inflammatory IFN-γ (47.9%), IL-6 (33.3%), and TNF-α (20.1%). Elevated levels of sCD71 (56.6%), sCD62L (32.1%), sApo-1/Fas (22.1%), sFasL (10.2%), and autoantibodies to double-stranded DNA (57.1%), RNA (10.4%), and oLDL (oxidized-modified LDL) (16.3%) were recorded in residents of the Murmansk Oblast. Arctic residents showed elevated concentrations of Hp (63.3%), IgM (63.9%), IgA (42.4%), IgE (18.8%), LDL (24.9%), and a decreased level of HDL (21.1%) owing to an ApoA-I ligand deficiency (58.1%). Elevated levels of Hp in the blood are associated with increased erythrocyte aggregation frequency, T-lymphocyte activation, and increased concentration of free receptors of the extracellular pool. Increased IgM and IgA levels in the blood are attributed to the need to bind components of the extracellular receptor pool sCD71, sCD62L, sApo-1/Fas, sFasL and are associated with decreased levels lymphocyte with CD8 and CD16 phenotypes. The humoral immune response in Arctic residents is triggered when the cellular component of immunity is under strain which compounded by ineffective clearance of metabolic byproducts owing to imbalanced LDL and HDL lipid transport complexes.

CONCLUSIONS: The immune system of Arctic residents is characterized by excessive cytotoxic activity of lymphocytes and increased concentrations of pro-inflammatory cytokines, free forms of receptors of the extracellular pool, and autoantibodies. The change in the content of transport components of the blood system is directed at maintaining homeostasis by exhibiting antioxidant, anti-inflammatory, and immunoregulatory properties.

PMID:39032081 | DOI:10.1002/ajhb.24136

Clin Oral Implants Res. 2024 Jul 20. doi: 10.1111/clr.14318. Online ahead of print.

ABSTRACT

PURPOSE: To histometrically compare the osseointegration and crestal bone healing of a novel tapered, self-cutting tissue-level test implant with a standard tissue-level control implant in a submerged healing regimen.

MATERIALS AND METHODS: In a mandibular minipig model, implants were inserted and evaluated histometrically after a healing period of 3, 6, and 12 weeks. The primary outcome was the evaluation of bone-to-implant contact (BIC) and secondary outcomes were primary stability as per insertion torque and first BIC (fBIC). Outcomes for the test and control implants were compared using Wilcoxon signed-rank tests and mixed linear regression models.

RESULTS: Insertion torque values were significantly higher for the test (50.0 ± 26.4 Ncm) compared to the control implants (35.2 ± 19.7 Ncm, p = .0071). BIC values of test implants were non-inferior to those of control implants over the investigated study period. After 12 weeks, the corresponding values measured were 81.62 ± 11.12% and 90.41 ± 4.81% (p = .1763) for test and control implants, respectively. Similarly, no statistical difference was found for fBIC values, except for the 12 weeks outcome that showed statistically lower values for the test (-675.58 ± 590.88 μm) compared to control implants (-182.75 ± 197.40 μm, p = .0068).

CONCLUSIONS: Novel self-cutting tissue-level implants demonstrated noninferior osseointegration and crestal bone height maintenance to the tissue-level implants. Histometric outcomes between both implants demonstrated test implants were statistically noninferior to control implants, despite substantial differences in the bone engagement mechanism and resulting differences in insertion torque and qualitative bone healing patterns.

PMID:39032079 | DOI:10.1111/clr.14318

Cancer. 2024 Aug 1;130(15):2568. doi: 10.1002/cncr.35444.

NO ABSTRACT

PMID:39032060 | DOI:10.1002/cncr.35444

Aust Vet J. 2024 Jul 20. doi: 10.1111/avj.13361. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the prevalence, type, site and breed predisposition of thoracic congenital vertebral malformations (CVM) in neurologically normal brachycephalic ‘screw-tail’ dog breeds.

STUDY DESIGN: Retrospective case series.

ANIMALS: Neurologically normal French Bulldogs (n = 63), British Bulldogs (n = 42), Boston Terriers (n = 4) and Pugs (n = 86) presenting for brachycephalic obstructive airway syndrome treatment.

METHODS: Either a plain computer tomography scan of the thorax or lateral and dorso-ventral digital radiographs of the thoracic vertebral column of each dog were assessed for any vertebral malformations and classed according to the Modified McMaster vertebral abnormality classification scheme proposed by Guiterrez et al. RESULTS: The prevalence of dogs with one or more abnormal vertebrae was 96.82% in French Bulldogs, 90.47% in British Bulldogs, and 76.74% in Pugs. Pugs had significantly lower instances of CVMs than French Bulldogs. The four Boston Terriers all had vertebral malformations, but the results were not considered to be statistically significant due to their small sample size. In French Bulldogs and British Bulldogs, ventral hypoplasia (Type 3) occurred at greater rates than all other types, followed by ventral and median hypoplasia (Types 7) and symmetrical hypoplasia (Type 8). In Pugs, symmetrical hypoplasia (Type 8) was the most common and then ventral hypoplasia (Type 3). The most affected vertebrae were T6-T9 in Pugs and T5-T10 in French Bulldogs and British Bulldogs.

CONCLUSIONS: The majority of neurologically normal brachycephalic ‘screw-tail’ dogs assessed in this paper possessed one or more congenital thoracic vertebral malformations. Dogs with vertebral malformations were found to be more likely to have more than one affected vertebra. Sex had no effect on the prevalence of CVM.

CLINICAL RELEVANCE: A substantial number of neurologically normal brachycephalic ‘screw-tail’ dogs suffer from congenital vertebral malformations. Thus, the need for selective breeding programmes to eliminate this hereditary condition is crucial.

PMID:39032038 | DOI:10.1111/avj.13361

Int J Cancer. 2024 Jul 20. doi: 10.1002/ijc.35106. Online ahead of print.

ABSTRACT

Identifying Lynch syndrome significantly impacts cancer risk management, treatment, and prognosis. Validation of mutation risk predictive models for mismatch repair (MMR) genes is crucial for guiding genetic counseling and testing, particularly in the understudied Asian population. We evaluated the performance of four MMR mutation risk predictive models in a Chinese cohort of 604 patients with colorectal cancer (CRC), endometrial cancer (EC), or ovarian cancer (OC) in Taiwan. All patients underwent germline genetic testing and 36 (6.0%) carried a mutation in the MMR genes (MLH1, MSH2, MSH6, and PMS2). All models demonstrated good performance, with area under the receiver operating characteristic curves comparable to Western cohorts: PREMM₅ 0.80 (95% confidence interval [CI], 0.73-0.88), MMRPro 0.88 (95% CI, 0.82-0.94), MMRPredict 0.82 (95% CI, 0.74-0.90), and Myriad 0.76 (95% CI, 0.67-0.84). Notably, MMRPro exhibited exceptional performance across all subgroups regardless of family history (FH+ 0.88, FH- 0.83), cancer type (CRC 0.84, EC 0.85, OC 1.00), or sex (male 0.83, female 0.90). PREMM₅ and MMRPredict had good accuracy in the FH+ subgroup (0.85 and 0.82, respectively) and in CRC patients (0.76 and 0.82, respectively). Using the ratio of observed and predicted mutation rates, MMRPro and PREMM₅ had good overall fit, while MMRPredict and Myriad overestimated mutation rates. Risk threshold settings in different models led to different positive predictive values. We suggest a lower threshold (5%) for recommending genetic testing when using MMRPro, and a higher threshold (20%) when using PREMM₅ and MMRPredict. Our findings have important implications for personalized mutation risk assessment and counseling on genetic testing.

PMID:39032036 | DOI:10.1002/ijc.35106

Int J Cancer. 2024 Jul 20. doi: 10.1002/ijc.35103. Online ahead of print.

ABSTRACT

It is known, that different metastatic organ systems respond differently to immune checkpoint inhibitors (ICIs). In this study, we aimed to investigate the extent to which skin/subcutaneous metastases respond to ICI or targeted therapies (TTs) and whether the response rate differs from that of distant metastases in the same patient. Patients with melanoma diagnosed between January 2021 and September 2023 with at least one skin/subcutaneous metastasis who had received therapy with ICI or TT in an advanced setting were included in the analysis. Best overall response (BOR) was classified according to the revised response evaluation criteria in solid tumors (RECIST). The BOR of skin metastases and visceral metastases to ICI and TT was compared using the chi-square test. Skin metastases treated with ICI a first-line setting showed an overall response rate (ORR) of 44.1%. In contrast, visceral metastases had a higher ORR of 51.1%. However, the difference was not statistically significant (p = .77). Regarding TT, the ORR for skin metastases was 57.1%, compared to 38.5% for visceral metastases (p = .59). Interestingly, the ORR for skin/subcutaneous metastases was notably lower with ICI compared to visceral metastases, in contrast to patients who underwent TT. Skin metastases showed a poorer response to ICI than visceral metastases. Therefore, careful monitoring is recommended to detect non-response early in patients with skin metastases as skin metastases may have a worse response than TT. A larger cohort is needed for a comprehensive analysis and confirmation of our results.

PMID:39032035 | DOI:10.1002/ijc.35103

Arch Immunol Ther Exp (Warsz). 2024 Jul 20;72(1). doi: 10.2478/aite-2024-0015. eCollection 2024 Jan 1.

ABSTRACT

Elevated immunoglobulin G4 (IgG4) serum antibodies are an important feature of IgG4-related disease. However, IgG4 antibodies can play a role in autoimmune thyroid disorders. In this study, we aimed to evaluate the impact of serum IgG4 levels on clinical features of Graves’ disease (GD). We recruited 60 patients with GD (48 patients without thyroid eye disease, 12 patients with moderate-to-severe Graves’ orbitopathy [GO], and 25 healthy control subjects). The prevalence of high IgG4 serum concentration was 4.2% among GD patients without GO and 33.33% in patients with moderate-to-severe GO. The group with GO had significantly higher median IgG4 levels (87.9 mg/dL) than the control group (41.2 mg/dL, P = 0.034) and the GD without GO group (30.75 mg/dL, P < 0.001). Patients with thyroid nodules had lower IgG4 levels than patients without thyroid nodules, but the difference was not statistically significant (35.7 [24.8; 41.53] mg/dL vs. 43 [30.1; 92.7] mg/dL, P = 0.064). IgG4 as a diagnostic tool for moderate-to-severe GO had the following parameters: area under the curve (AUC): 0.851 (P < 0.001), at the cut-off value of 49 mg/dL, negative predictive value: 100%, positive predictive value: 48%, sensitivity: 100%, specificity: 73%. There were no significant differences between the high and normal IgG4 groups in thyroid hormones, antithyroid antibodies, and ultrasound features. Serum IgG4 levels are associated with some of the clinical features of GD and can help in the diagnostic process of the disease. More research is needed to better understand the pathophysiology of IgG4 involvement in GD.

PMID:39032009 | DOI:10.2478/aite-2024-0015

Microsurgery. 2024 Sep;44(6):e31214. doi: 10.1002/micr.31214.

ABSTRACT

BACKGROUND: In breast reconstruction, arterial coupling has been reported to be more favorable in the thoracodorsal artery (TDA) than the internal mammary artery (IMA). This technique may help overcome anastomosis in a small, deep space. Understanding the arteries’ mechanical properties is crucial for breast reconstruction’s safety and success.

METHODS: Abdominal-based free flap breast reconstructions performed by a single surgeon between 2020 and 2022 were retrospectively analyzed. The patients were classified by microanastomosis technique (handsewn and coupler device) to compare the rate of vascular revision. Histomorphometric analysis of arterial coupling in TDA and IMA was performed in 10 fresh cadavers for comparing wall thickness and composition, including densities of elastic fiber, smooth muscle, and collagen.

RESULTS: A total of 309 patients (339 reconstructed breasts) were included. There were 29 patients in the TDA handsewn group (A), 38 patients in the TDA coupler group (B), and 242 patients in the IMA handsewn group (C). The rates of arterial revision in groups A, B, and C were 0.00% (95%CI: 0.00%-11.03%), 2.5% (95%CI: 0.44%-12.88%), and 1.49% (95%CI: 0.58%-3.77%), respectively, with no statistically significant differences (p-value = .694). Histologically, the thickness of the tunica media and adventitia between IMA and TDA showed no significant difference. The density of elastic fiber was significantly higher in IMA (16.70%) than in TDA (0.79%) (p-value <.001).

CONCLUSION: The histologic characteristics of TDA are more favorable for arterial coupling than those of IMA. Arterial coupling is a safe option in situations where TDA anastomosis must be performed through a narrow and deep incision.

PMID:39031998 | DOI:10.1002/micr.31214

Am J Health Syst Pharm. 2024 Jul 20:zxae211. doi: 10.1093/ajhp/zxae211. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: The purpose of this study was to evaluate pharmacist prescribing of nirmatrelvir/ritonavir to ensure this method of increasing access to treatment is safe and effective.

METHODS: This multicenter, retrospective observational study included patients receiving a prescription for nirmatrelvir/ritonavir by a physician, nurse practitioner (NP), physician assistant (PA), or pharmacist at an Indiana University (IU) Health West Central Region site over a 3-month period. Patients were divided into two groups: those who received nirmatrelvir/ritonavir prescribed by a pharmacist (the pharmacist prescribed group) and those who received nirmatrelvir/ritonavir prescribed by other providers (the physician/NP/PA prescribed group). Electronic health record (EHR) reviews were performed to assess the appropriateness of prescriptions based on the presence of risk factors and symptoms, day of symptom onset, and dosing. The primary endpoint was the overall appropriateness of nirmatrelvir/ritonavir prescriptions in the two study groups based on emergency use authorization inclusion and exclusion requirements. Secondary endpoints included appropriateness of nirmatrelvir/ritonavir dosing and medically attended visits or mortality within 30 days. Statistical analysis of the endpoints occurred post hoc utilizing the Fisher’s exact test.

RESULTS: A total of 259 patients were included in the pharmacist prescribed group and 265 patients in the physician/NP/PA prescribed group. Overall appropriate nirmatrelvir/ritonavir prescribing occurred in 258 patients (99.6%) and 232 patients (87.5%) in the pharmacist and physician/NP/PA prescribed groups, respectively (P < 0.0001). Nirmatrelvir/ritonavir dosing was appropriate in 256 patients (98.8%) and 240 patients (90.6%) in the pharmacist and physician/NP/PA prescribed groups, respectively (P < 0.0001). The 30-day rates of medically attended visits were similar between groups. No patients died within 30 days of treatment in either group.

CONCLUSION: Pharmacist prescribing of nirmatrelvir/ritonavir may result in a higher likelihood of prescriptions meeting overall appropriateness criteria. Pharmacists represent an important healthcare professional resource to improve nirmatrelvir/ritonavir prescribing and utilization.

PMID:39030731 | DOI:10.1093/ajhp/zxae211