An indirect comparison of acalabrutinib with and without obinutuzumab vs zanubrutinib in treatment-naive CLL.

ABSTRACT: The efficacy and safety of acalabrutinib plus obinutuzumab and acalabrutinib monotherapy vs zanubrutinib in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma without del(17p) were compared using an unanchored matching-adjusted indirect comparison. Individual patient-level data from ELEVATE-TN (acalabrutinib plus obinutuzumab, n = 162; acalabrutinib monotherapy, n = 163) were weighted to match published aggregate baseline data from SEQUOIA cohort 1, which excluded patients with del(17p) (zanubrutinib, n = 241), using variables that were prognostic/predictive of investigator-assessed progression-free survival (INV-PFS) in an exploratory Cox regression analysis of ELEVATE-TN. After matching, INV-PFS was longer with acalabrutinib plus obinutuzumab (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23-0.74) and comparable with acalabrutinib monotherapy (HR, 0.91; 95% CI, 0.53-1.56) vs zanubrutinib. Acalabrutinib monotherapy had significantly lower odds of any grade hypertension vs zanubrutinib (odds ratio [OR], 0.44; 95% CI, 0.20-0.99), whereas acalabrutinib plus obinutuzumab had significantly higher odds of neutropenia (OR, 2.19; 95% CI, 1.33-3.60) and arthralgia (OR, 2.33; 95% CI, 1.37-3.96) vs zanubrutinib. No other significant differences in safety were observed. In summary, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia than zanubrutinib, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension. These trials were registered at www.ClinicalTrials.gov as #NCT02475681 and #NCT03336333.

Effectiveness of vaccination against SARS-CoV-2 and the need for alternative preventative approaches in immunocompromised individuals: a narrative review of systematic reviews.

INTRODUCTION: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including administration of booster doses, continues to be the most effective method for controlling COVID-19-related complications including progression to severe illness and death. However, there is mounting evidence that more needs to be done to protect individuals with compromised immune function. AREAS COVERED: Here, we review the effectiveness of COVID-19 vaccination in immunocompromised patients, including those with primary immunodeficiencies, HIV, cancer (including hematological malignancies), solid organ transplant recipients, and chronic kidney disease, as reported in systematic reviews/meta-analyses published over a 12-month period in PubMed. Given the varied responses to vaccination in patients with compromised immune function, a major goal of this analysis was to try to identify specific risk-factors related to vaccine failure. EXPERT OPINION: COVID-19 remains a global problem, with new variants of concern emerging at regular intervals. There is an ongoing need for optimal vaccine strategies to combat the pandemic. In addition, alternative treatment approaches are needed for immunocompromised patients who may not mount an adequate immune response to current COVID-19 vaccines. Identification of high-risk patients and the introduction of newer antiviral approaches such as monoclonal antibodies will offer physicians therapeutic options for such vulnerable individuals.

Efficacy of I- gel™ for airway management of neonates with Pierre Robin sequence undergoing glossopexy: A prospective study.

This paper aims to review the utility of I- gel as a successful airway management device for infants with Pierre robin sequence (PRS) undergoing glossopexy. A prospective study was conducted on PRS neonates. The algorithm followed was putting a 'Tongue traction stitch' followed by the following sequence - two trials with direct laryngoscope intubation, two attempts with fiberoptic endoscope intubation followed by insertion of I-gel™ to manage difficult airway during glossopexy procedure. 6 patients were intubated with direct laryngoscope, 12 patients were intubated with fibreoptic endoscope and the rest 13 patients were intubated using I-gel™. Successful management of difficult airway was achieved with this airway management protocol during glossopexy and nil postoperative complications were encountered. Within the limitations of the study it seems that, I-gel™ is a relevant alternative toprovide a reliable and secure airway access to carry out glossopexy procedure in such patients.

Spindle cell rhabdomyosarcoma in the adult: A rare case report.

Spindle cell/sclerosing rhabdomyosarcoma (RMS) is an uncommon type of RMS and has been classified as a separate entity by the WHO in 2013. It affects both children and adults with a greater incidence in males. These tumors can pose a diagnostic challenge and can be difficult to differentiate from other spindle cell malignant tumors in the head and neck. Here, we report a case of spindle cell/sclerosing RMS in a young woman presenting with a swelling on the left side of the face of 3 months duration. A careful correlation with the radiographic images, histopathological findings and immunohistochemistry helped to arrive at a diagnosis.

Does the Timing of 1-Stage Palatoplasty With Radical Muscle Dissection Effect Long-Term Midface Growth? A Single-Center Retrospective Analysis.

OBJECTIVE: To evaluate the long-term effect of timing of 1-stage palatoplasty on midfacial growth in patients with cleft lip and palate (CLP). DESIGN: Retrospective observational cohort study. STUDY SETTING: Institutional hospital. PATIENTS: One hundred twelve patients with CLP who underwent palatoplasty and were divided into 3 groups: group I: operated between 9 and 11 months; group II: operated between 18 and 20 months; and group III: operated between 21 and 24 months. INTERVENTIONS: All patients underwent von Langenbeck palatoplasty technique, which was converted to a Bardach 2-flap technique in case of any technical difficulties. The patients were followed up between 8 and 9 years when they reported for secondary alveolar bone grafting. Postsurgical cephalometric and dental casts measurements were taken for midfacial growth analysis. MAIN OUTCOME MEASURES: The cephalometric measures were analyzed for midfacial growth and compared within the groups. RESULTS: Statistically significant difference (P < .01) was found on comparing the cephalometric parameters such as sella-nasion-A point angle (SNA), A point-nasion-B point angle (ANB), n toperpendicular to point A (N-perpA), condylon to point A (Co-A), anterior nasal spine to posterior nasal spine (ANS-PNS), nasion to Anterior nasal spine (N-ANS), nasion to menton (N Me), and witts appraisal (Witt (AO-BO)) in group I when compared to both group II and group III patients, implying deficient midfacial growth in group I. No statistical difference was found in the cephalometric values between group II and group III. Group II had better cephalometric measurements than group III, showing better growth in group II than group III. Overall, there was less incidence of midfacial hypoplasia in patients treated between 18 and 20 months (group II). CONCLUSION: We conclude that palatal closure carried out at 18 to 20 months and 21 to 24 months is associated with better midfacial growth when compared to closure at 9 to 11 months. The best time to operate would be between 18 and 20 months to avoid speech disturbances. Midfacial growth can be greatly influenced by the timing of 1-stage palatoplasty.

Phenotypic and Molecular Heterogeneity in Mandibulofacial Dysostoses: A Case Series From India.

OBJECTIVE: Facial dysostosis is a group of rare craniofacial congenital disabilities requiring multidisciplinary long-term care. This report presents the phenotypic and genotypic information from South India. DESIGN: The study is a case series. SETTING: This was an international collaborative study involving a tertiary craniofacial clinic and medical genetics unit. PATIENTS, PARTICIPANTS: The participants were 9 families with 17 affected individuals of facial dysostosis. INTERVENTION: Exome analysis focused on known genes associated with acrofacial and mandibulofacial syndromes. MAIN OUTCOME MEASURE: The outcome measure was to report phenotyptic and genetic heterogeneity in affected individuals. RESULTS: A Tessier cleft was seen in 7 (41%), lower eyelid coloboma in 12 (65%), ear anomalies in 10 (59%), uniolateral or bilateral aural atresia in 4 (24%), and deafness in 6 (35%). The facial gestalt of Treacher Collins syndrome (TCS) showed extensive phenotypic variations. Pathogenic variants in TCOF1 (Treacher Collins syndrome) were seen in six families, POLR1A (acrofacial dysostosis, Cincinnati type) and EFTUD2 (mandibulofacial dysostosis with microcephaly) in one each. One family (11.1%) had no detectable variation. Five out of six probands with Treacher Collins syndrome had other affected family members (83.3%), including a non-penetrant mother, identified after sequencing. CONCLUSION: Our report illustrates the molecular heterogeneity of mandibulofacial dysostosis in India.

Correlation between surgical protocols for palatoplasty and midfacial growth in cleft lip and palate patients: A long-term, single centre study.

To evaluate and compare the outcomes of two different surgical protocols for palatoplasty for midfacial growth in patients with cleft lip and palate. A retrospective observational cohort study was conducted in 80 patients with cleft lip and palate, who were divided into two groups. Group 1 comprised patients who underwent operation between 9 and 11 months of age using the Bardach two-flap technique without a palatal pushback. Group 2 comprised patients who had undergone operation between 18 and 20 months of age using either a Bardach two-flap technique with a palatal pushback or a von Langenbeck technique. Patient follow-up was done between 8 and 9 years of age when they reported to the centre for secondary alveolar bone grafting. Post-surgical cephalometric measurements were taken for midfacial growth analysis. Group 1 underwent palatoplasty at significantly younger ages than Group 2 (p < 0.01). A statistically significant difference(p < 0.01) was found between the two groups of patients on comparison of cephalometric parameters such as SNA, ANB, CoA, NperpA ANS-PNS, N-ANS, N-Me, Witt's (AO-BO). Group 2 had more positive cephalometric values as compared to Group 1, thereby implying that there was less incidence of midfacial hypoplasia in patients treated at the age of 18-20 months. Between the types of palatoplasty techniques within Group 2, i.e., Bardach two-flap and von Langenbeck, there was no statistical difference found in the post-opertative cephalometric values, i.e., SNA, ANB, CoA, ANS-PNS, N-ANS, N-Me, Witt's (AO-BO) except for Nperp-A, which showed a statistical difference (p = 0.03). Within the limitations of the study which is only a single center experience it seems that palatal closure should be carried out at 18-20 months of age for better midfacial growth, leading to decreased incidence of maxillary hypoplasia at a later stage in life. Repair at less than 18 months of age is also associated with mid-facial hypoplasia.

Carcinoma ex Pleomorphic Adenoma in the Floor of the Mouth: An Unusual Diagnosis in a Rare Location.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor, mostly involving the parotid and submandibular glands. Minor salivary gland involvement is even rarer, palate being the most common site. Other reported sites are upper lip, sinonasal tract, and buccal mucosa. Here, we report a case of CXPA in an unusual location, the floor of the mouth.

Do Regional Nerve Blocks Before Bimaxillary Surgery Reduce Postoperative Pain?

PURPOSE: Any elective surgery should be as atraumatic to the patient as possible to allow for a comfortable postoperative recovery. The present study was performed to evaluate the efficacy of preoperative regional blocks in reducing pain, discomfort, and analgesic use in patients scheduled to undergo bimaxillary surgery. PATIENTS AND METHODS: A prospective, double-blind, randomized controlled trial was conducted to include all patients aged 16 to 30 years requiring bimaxillary surgery. We excluded patients with syndromes and systemic conditions. The primary predictor variable was the maxillary and mandibular nerve blocks (extraoral lateral pterygoid method) administered preoperatively in the operating room using 0.25% bupivacaine hydrochloride. Standard anesthetic and postoperative protocols were followed. The primary outcome variable was postoperative pain. The secondary outcome variables were postoperative discomfort, analgesic consumption, duration of surgery, and blood loss. The unpaired t test and Mann-Whitney U test were used for statistical analyses, with P < .05 considered to indicate statistical significance. RESULTS: A total of 110 patients were included in the study (55 in the control group and 55 in the test group), of whom 61 were female and 49 were male. Postoperative pain, recorded using a visual analog scale was significantly lower (P < .001) in the test group compared with the control group. Secondary outcome variables such as postoperative discomfort and analgesic consumption were also significantly lower in the test group. A significant positive correlation was present between the duration of surgery and pain measured at 6, 12, 24, and 48 hours postoperatively in both groups. CONCLUSIONS: From our results, it can be established that the administration of preoperative regional blocks using 0.25% bupivacaine immediately before bimaxillary surgery can effectively minimize patients' postoperative pain, discomfort, and consumption of analgesics.

Retrospective analysis of a TMJ ankylosis protocol with a 9 year follow up.

OBJECTIVE: Temporomandibular joint ankylosis (TMJa) is a debilitating condition that causes difficulty in mastication, speech and mouth opening. Its treatment poses surgical and rehabilitative challenges along with a high incidence of reankylosis. This study was designed to assess the long-term outcomes with a new two phase physiotherapy protocol following conservative resection of the ankylotic mass. MATERIALS AND METHODS: 143 patients who were treated for TMJa were initially recruited, among whom 98 were inducted into the study and retrospectively evaluated using clinical records and 3-dimensional computed tomography. All the patients underwent a minimal pre auricular incision and conservative interpositional gap arthroplasty with collagen membrane. This was followed by the new two phase physiotherapy protocol with the use of a bite block. The primary outcome measures were the maximum interincisal distance, vertical ramus height and complications. The patients were followed up at monthly intervals during the first year, quarterly intervals during the second year, and at intervals of 6 months during subsequent follow-up years. The mean follow up period was 6.38 ± 2.36 years after ankylotic release. Paired student t test was used for statistical analysis. RESULTS: The mean scores for mouth opening at T1, T2 and T3 were statistically significantly different at all intervals (p < 0.0005). The mean scores for ramal length were statistically significantly different at T1 and T2 interval (p < 0.0005) and insignificant at T2 and T3 interval. No reankylosis was observed in patients who followed the physiotherapy protocol. CONCLUSIONS: In the management of TMJa, the success of the conservative surgical technique with interpositional arthroplasty is less dependent on the longevity and rigidity of the interpositional material but more indebted to the patient compliance in following the proposed physiotherapy protocol.

Management of iatrogenic dislodgment of a mandibular third molar into the pterygomandibular space.

Although the surgical extraction of the mandibular third molar is routinely performed in dental clinics, the precise management of complications associated with it requires thorough knowledge and experience in the field of oral and maxillofacial surgery. Iatrogenic dislodgment of a tooth or its fragment is a rare complication and usually occurs when excessive, uncontrolled forces are applied via elevators. It also is possible that this rare complication may be underreported. This case report describes the retrieval, under local anesthesia, of a mandibular left third molar crown from the posterosuperior region of the pterygomandibular space after iatrogenic dislodgment.

Development and Application of a Novel Patient-Reported Outcome Measure on QoL and Facial Aesthetics-A Study on South Indian Population.

BACKGROUND: The goal of cleft therapy has progressed from simply correcting the deformity to uplifting the patient's quality of life (QoL). At the end of comprehensive treatment, a patient with cleft lip and palate (CLP) should report with satisfactory QoL scores in all domains such as aesthetics, speech, function, and psychology. OBJECTIVE: To develop and validate a novel, disease-specific questionnaire designed in 2 regional languages to assess the QoL in young adult patients with CLP of South India following comprehensive treatment. METHODS: A preliminary questionnaire was created from the literature review and patient interviews, considering regional sociodemographic conditions. The questionnaire was then validated by subject experts and pilot tested. The resultant tool was implemented on patients at treatment completion. Data collected were assimilated for statistical evaluation. RESULTS: The questionnaire was deemed reliable (Cronbach α = .854 and test-retest reliability, κ = 0.8) and was administered to 100 young adult patients with CLP (mean age: 22 years). A large majority (83%) of the population felt more confident about themselves, with positive responses to familial relations, social interaction, and self-image. About 25% of the patients faced problems with speech regularly, while a majority of patients did not face problems with chewing and swallowing. Nearly 60% of patients were fully satisfied with their facial appearance, while others had concerns about their lip and nose aesthetics. The results were descriptive of the local population. CONCLUSIONS: Most patients achieved satisfactory QoL in all domains following comprehensive multispeciality therapy. The novel tool is simple, reliable, and can be adapted to homogenous population groups.

Evaluation of Four Incisions Used For Radical Neck Dissection- A Comparative Study

Objective: To evaluate the four commonly used incisions for Radical Neck Dissection on the basis of certain defined parameters. Patients and Methods: The investigators designed and implemented a prospective comparative study composed of patients with oral squamous cell carcinoma. The predictor variable was time taken to raise and close the flaps, accessibility to the neck lymph nodes, injury to vital structures and scar cosmesis followed up to a period of three months. Descriptive statistics were computed. Results: The sample was composed of 40 patients grouped as follows: Macfee Incision (=10 patients), Modified Macfee Incision (=10 patients), Modified Schobinger Incision (=10 patients) and Reverse Hockey Stick Incision (=10 patients). Group A, consisiting of the patients with Macfee Incision, took the least time to close among all the groups ( Mean= 32.60 minutes) while Group C (patients with Modified Schobinger Incision) required the most time for closure ( Mean= 51.90 minutes). The Modified Schobinger Incision provided best exposure to neck node levels. The Macfee Incision was found to have the best scar cosmesis among the four incisions. Conclusion: The results of this study suggest that Modified Schobinger Incision is the preferred incision for adequate access to neck lymphatics while Macfee Incision was found to provide the best scar cosmesis.

Long-term use of Le Fort I osteotomy for the management of nasopharyngeal rhinosporidiosis: A case series.

Rhinosporidiosis is a rare, chronic, granulomatous infection of the mucous membranes that mainly involves the nose and nasopharynx; it occasionally involves the pharynx, conjunctiva, larynx, trachea and, rarely, the skin. The characteristic clinical features of this disease include the formation of painless polyps in the nasal mucosa or the nasopharynx that bleed easily on touch. At our center, excision of the lesion with a Le Fort I osteotomy is carried out in patients (1) in whom two or more previous attempts at excision of biopsy-proven rhinosporidiosis arising from the nasal mucosa was carried out or (2) in whom the rhinosporidiosis arises from the nasophayrngeal mucosa and/or extranasal sites. In this article we retrospectively present 7 cases in which, according to our inclusion criteria, complete excision of the lesion was carried out with a Le Fort I osteotomy. Excellent visualization of the entire maxillary and ethmoidal air cells after the down-fracture of the maxilla helped in the total removal of the lesions. Most of these lesions had multiple points of origin through the nasal, maxillary, and ethmoidal mucosa; the excellent visualization enabled direct cauterization of all these points of origin. The mean follow-up period was 7.96 years, and all patients were disease-free by the time the study was prepared. This article presents details of the treatment protocol and technique followed at our center for the treatment of nasopharyngeal rhinosporidiosis and the details of long-term follow-up. Through this study we hope to prove the efficacy of Le Fort I osteotomy in the definitive management of nasopharyngeal rhinosporidiosis.

Chromosomal Abnormalities in Syndromic Orofacial Clefts: Report of Three Children.

This case series of three children reports clinical features and chromosomal abnormalities seen in a craniofacial clinic. All presented with orofacial cleft, developmental or intellectual disability, and dysmorphism. Emanuel syndrome or supernumerary der (22)t(11; 22), the prototype of complex small supernumerary marker disorders, was seen in one child. Duplication 4q27q35.2 with concomitant deletion 21q22.2q22.3 and duplication 12p13.33p13.32 with concomitant deletion 18q22.3q23 seen in the remaining two children are not reported in literature. Maternal balanced translocation was established in both of these children.

Does C-Arm Guidance Improve Reduction of Zygomatic Arch Fractures?-A Randomized Controlled Trial.

PURPOSE: Traditionally, in the assessment of the reduction of zygomatic arch fractures, the surgeon uses subjective measures such as palpation of a bony step deformity, the anecdotal "pop" sounds, and visual confirmation of symmetry. In the present study, we sought to objectively assess the accuracy of reduction and improvement in form and function after C-arm-guided reduction of isolated zygomatic arch fractures (IZAFs) and to compare these results with those obtained conventionally. PATIENTS AND METHODS: A prospective, randomization of patients scheduled for surgical closed reduction of IZAF was performed. The test group underwent C-arm-guided reduction of the fracture until the arch contour was re-established and visualized on fluoroscopic images. In the control group, palpation, auditory cues, and visualization of symmetry determined the adequacy of the reduction. The patients and evaluator were both unaware of the treatment technique used. The primary outcome measures were the maximum interincisal distance (IID), standardized measurements on computed tomography (CT), and measures of symmetry on facial photographs. Variables such as intragroup differences and patient-evaluator agreement were also studied. The data were analyzed using SPSS software, version 21. RESULTS: The study sample consisted of 20 patients (10 each in the test and control groups). Significant improvement in facial symmetry was observed in all 20 patients (P < .001) from preoperatively to 30 days postoperatively. The CT measurements confirmed acceptable symmetry, with insignificant differences between the 2 groups (C-arm group, P < .001; vs control group, P = .004 for intragroup improvement in symmetry). The IID had improved significantly (P < .001) at the end of follow-up in both groups. CONCLUSIONS: Although significantly superior outcomes were not inferred in the symmetry-related and CT measurements, C-arm-guided reduction provided an opportunity to instantaneously confirm the accuracy of bony reduction. Thus, the need for postoperative imaging and secondary surgery can be overcome, enabling even inexperienced surgeons to attain precise and reproducible results.

Torque Control During Intrusion on Upper Central Incisor in Labial and Lingual bracket System - A 3D Finite Element Study.

BACKGROUND: The aim of present study was to investigate the difference of torque control during intrusive force on upper central incisors with normal, under and high torque in lingual and labial orthodontic systems through 3D finite element analysis. MATERIAL AND METHODS: Six 3D models of an upper right central incisor with different torque were designed in Solid Works 2006. Software ANSYS Version 16.0 was used to evaluate intrusive force on upper central incisor model . An intrusive force of 0.15 N was applied to the bracket slot in different torque models and the displacements along a path of nodes in the upper central incisor was assessed. RESULTS: On application of Intrusive force on under torqued upper central incisor in Labial system produce labial crown movement but in Lingual system caused lingual movement in the apical and incisal parts. The same intrusive force in normal-torqued central incisor led to a palatal movement in apical and labial displacement of incisal edge in Lingual system and a palatal displacement in apical area and a labial movement in the incisal edge in Labial systemin. In overtorqued upper central incisor, the labial crown displacement in Labial system is more than Lingual system. CONCLUSIONS: In labial and lingual system on application of the same forces in upper central incisor with different inclinations showed different responses. The magnitudes of torque Loss during intrusive loads in incisors with normal, under and over-torque were higher in Labial system than Lingual orthodontic appliances. Key words:FEM, lingual orthodontics, intrusion, torque control, labial bracket systems.