Clinicodemographic profile, management, and treatment outcomes in advanced retinoblastoma at a tertiary care center in North India.

PURPOSE: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center. METHODS: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality. RESULTS: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma ( n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period. CONCLUSION: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study.

Induction of epithelial-mesenchymal transition in thyroid follicular cells is associated with cell adhesion alterations and low-dose hyper-radiosensitivity.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with altered cellular adhesion. We previously demonstrated that cellular adhesion influences Low-dose Hyper-Radiosensitivity (HRS) in a variety of tumor cells. However, the relationship of low-dose HRS with the phenotypic plasticity incurred by EMT during the neoplastic transformation remains to be elucidated. OBJECTIVE: To investigate whether acquisition of EMT phenotype during progressive neoplastic transformation may affect low-dose radiation sensitivity. METHODS: Primary thyroid cells obtained from a human cystic thyroid nodule were first subjected to nutritional stress. This yielded immortalized INM-Thy1 cell strain, which was further treated with either multiple γ-radiation fractions (1.5 Gy each) or repetitive cycles of 3-methylcholanthrene and phorbol-12-myristate-13-acetate, yielding two progressive transformants, viz., INM-Thy1R and INM-Thy1C. Morphological alterations, chromosomal double-minutes, cell adhesion proteins, anchorage dependency, tumorigenicity in nude mice and cellular radiosensitivity were studied in these strains. RESULTS: Both transformants (INM-Thy1R, INM-Thy1C) displayed progressive tumorigenic features, viz., soft agar colony growth and solid tumor growth in nude mice, coupled with features of epithelial-mesenchymal transition and activated Wnt pathway. Incidentally, the chemical-induced transformant (INM-Thy1C) displayed a prominent HRS (αs/αr = 29.35) which remained unaffected at high cell density. However, the parental (INM-Thy1) cell line as well as radiation-induced transformant (INM-Thy1R) failed to show this hypersensitivity. CONCLUSION: The study shows that induction of EMT in thyroid follicular cells may accompany increased susceptibility to low-dose ionizing radiation, which was attenuated by adaptive resistance acquired during radiation-induced transformation.

Esculetin releases maturation arrest and induces terminal differentiation in leukemic blast cells by altering the Wnt signaling axes.

BACKGROUND: The "Differentiation therapy" has been emerging as a promising and more effective strategy against acute leukemia relapses. OBJECTIVE: In extension to the revolutionising therapeutic outcomes of All Trans Retinoic Acid (ATRA) to induce terminal differentiation of Acute Promyelocytic Leukemic (APL) blast cells, we decipher the potential effect of a natural compound "Esculetin" to serve as a differentiating agent in Acute Myeloid Leukemia (AML). Underlaying role of Wnt signaling pathways in esculetin mediated blast cell differentiation was also evaluated. METHODS: Human acute myeloid leukemic cells (Kasumi-1) with t(8;21/AML-ETO) translocation were used as a model system. Growth inhibitory and cytotoxic activity of esculetin were analysed using growth kinetics and MTT assay. Morphological alterations, cell scatter characteristics, NBT reduction assay and cell surface marker expression patterns were analysed to detect terminally differentiated phenotypes. We employed RT2profiler PCR array system for the analysis of transcriptome profile of Wnt signaling components. Calcium inhibitors (TMB8 and Amlodipine) and Transforming growth factor beta (TGF-ß) were used to modulate the Wnt signaling axes. RESULTS: We illustrate cytotoxic as well as blast cell differentiation potential of esculetin on Kasumi-1 cells. Morphological alterations akin to neutrophilic differentiation as well as the corresponding acquisition of myeloid lineage markers indicate terminal differentiation potential of esculetin in leukemic blast cells. Exposure to esculetin also resulted in downregulation of canonical Wnt axis while upto ~ 21 fold upregulation of non-canonical axis associated genes. CONCLUSIONS: Our study highlights the importance of selective use of calcium pools as well as "axis shift" of the canonical to non-canonical Wnt signaling upon esculetin treatment which might abrogate the inherent proliferation to release maturation arrest and induce the differentiation in leukemic blast cells. The current findings provide further therapeutic interventions to consider esculetin as a potent differentiating agent to counteract AML relapses.

Experience from an immunohematology reference testing center.

Blood Centres in India lack infrastructure to investigate immunohematology problems. Reference Testing Center (RTC) was established in 2014 to investigate Immunohematological problem as it is not possible for small blood centers to go for complete immunohematology work up due to lack of financial and technical resources in remote and rural areas. Objective of this study is to share our experience as RTC of past 6 years so that more RTC are established across Indian subcontinent. 1456 Discrepant samples received from various hospitals of South India for Immunohematology problems were analysed in 6 years. Maximum requisitions obtained in 2014 were more than 40 years of age and then 21-40 years of age group in 2015 and same was observed till 2020.75% of total samples received were for antibody identification followed by blood group discrepancy resolution, investigation of positive DAT, red cell phenotype and pre-natal evaluation & antibody titration. Single allo-antibodies were identified in 773 cases whereas multiple allo-antibodies were found in 118 cases. Most common single and multiple antibody found was anti D and Anti-D+C. Weak D subgroup was the most common blood group discrepancy.22 cases & 4 cases of Bombay and para-bombay were also investigated.

Missile embolisation to the right common femoral artery following thoracic injury, without any conspicuous source of entry.

Embolisation of a projectile metallic body in the arterial system is not an unusual entity and has been reported off and on, in literature. We report the successful treatment and survival of a patient with thoracic injury, with a metallic projectile embolisation to the right common femoral artery and acute limb ischemia. Curiously, there was no identifiable entry point, on multiple imaging. The patient remained functionally independent, and without any complication on discharge. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-021-01291-1.

New-onset seizure at high altitude among healthy males.

OBJECTIVES: The risk of developing new-onset seizure following ascent to high-altitude areas is currently unknown. We undertook a prospective study to quantify this risk. METHODS: The study was conducted at a tertiary care hospital in India between July 2015 and December 2017. It included apparently healthy males of age ≥18 years who ascended to an altitude of ≥ 2500 m and stayed there for > 30 continuous days. Individuals with a history of seizure in the past two years, those who had not undergone acclimatization protocol, and those who had a history of any chronic systemic illness were excluded. RESULTS: The 39,213 individuals included in the study together had 39,848.6 person-years of high-altitude exposure. New-onset seizure after ascent occurred in 41 of them, indicating a seizure incidence rate of 102.9 per 100,000 person-years (95% CI = 75.8-139.7). The incidence per 100,000 person-years (95% CI) at altitudes of 2,500-3,500 m, 3,500-5,800 m, and > 5,800 m was 82.3 (53.6-126.1), 134.6 (84.9-213.6), and 210.8 (52.8-841.4), respectively. Seizure was secondary to cerebral venous thrombosis in 12 (29.3%) individuals. No etiology could be determined in the remaining 29 (70.7%) individuals. CONCLUSIONS: Our findings suggest that when subjects living at sea level are exposed to high altitudes, they will be at a higher risk for new-onset seizure in the immediate few months of exposure, and that this risk increases with increasing altitude.

A scalable, secure, and interoperable platform for deep data-driven health management.

The large amount of biomedical data derived from wearable sensors, electronic health records, and molecular profiling (e.g., genomics data) is rapidly transforming our healthcare systems. The increasing scale and scope of biomedical data not only is generating enormous opportunities for improving health outcomes but also raises new challenges ranging from data acquisition and storage to data analysis and utilization. To meet these challenges, we developed the Personal Health Dashboard (PHD), which utilizes state-of-the-art security and scalability technologies to provide an end-to-end solution for big biomedical data analytics. The PHD platform is an open-source software framework that can be easily configured and deployed to any big data health project to store, organize, and process complex biomedical data sets, support real-time data analysis at both the individual level and the cohort level, and ensure participant privacy at every step. In addition to presenting the system, we illustrate the use of the PHD framework for large-scale applications in emerging multi-omics disease studies, such as collecting and visualization of diverse data types (wearable, clinical, omics) at a personal level, investigation of insulin resistance, and an infrastructure for the detection of presymptomatic COVID-19.

Early outcomes after the on pump bidirectional Glenn procedure: A single center experience.

OBJECTIVE: Bidirectional Glenn procedure is a staged palliative procedure for patients with the univentricular hearts or complex congenital heart disease. We in our study, attempted to evaluate the preoperative characteristics, operative data and the early postoperative outcomes in the patients who underwent Bidirectional Glenn procedure at our center. METHODS: In our single center retrospective experience, 115 patients underwent Bidirectional Glenn procedure from January 2015 to December 2019. RESULTS: The mean age of the patients was 6.55 ± 6.5 years (range from 9 months to 48 years) and a median of 5 years. The most common anatomic diagnosis was double outlet right ventricle (n = 49, 42.6%). The primary diagnosis and the additional cardiac anamolies were not associated with the adverse outcomes. The increased cardiopulmonary bypass and operative time affect the postoperative outcomes. The median oxygen saturation in the patients postoperatively was 82%. The median postoperative stay was 8 days. The early postoperative complications were seen in 29 patients (25.2%). There were 12 early deaths (10.4%) in our study. The late age of presentation and poor preoperative nutrition, increased the risk of the postoperative morbidity and mortality. CONCLUSION: Bidirectional Glenn procedure is an effective procedure to improve efficacy of the gas exchange and reduce volume overload on the single ventricle at early as well as late stages. However, the late age of presentation increases the risk of the postoperative outcomes.

Coil assisted glue embolization to improve safety and accuracy in endovascular management of Vein of Galen patients.

BACKGROUND: Vein of Galen malformation (VOGM) patients present in neonatal age with cardiac failure or significant neurologic consequences. The most established method of treatment has been transarterial embolization with high concentration glue (N-Butyl Cyano Acrylate) which may be difficult to control due to very high flow rates and may migrate to the venous side with undesirable consequences. We describe our experience in four patients in whom initial coil placement in prominent feeding arteries helped inflow reduction thereby facilitating controlled glue injection with a good result and no incidence of non-target embolization. MATERIALS AND METHODS: Four neonates who had presented during the last three years with cardiac failure were included in the study. Prominent feeders identified on imaging or DSA were treated with transarterial helical coil placement in the terminal segment just before the VOGM sac followed by controlled glue injection. The outcome was assessed by detailed clinical and imaging follow-up. RESULTS: A total of 10 most prominent feeders were embolized in four patients. Complete embolization of the VOGM was achieved in two patients in a single session. One patient with residual small feeders showed subsequent thrombosis of these feeders, possibly secondary to flow reduction in the sac. One patient still shows thin residual feeders but good clinical improvement and is being planned for follow-up and a second session at one year of age. No complications were observed. All patients showed immediate improvement in cardiac failure and good neurological development on follow-up. On imaging, the VOGM sac regressed completely (3 patients) or significantly in size (1 patient). CONCLUSION: Planned coil placement in the terminal part of prominent feeding arteries reduced the flow and provided lattice on which glue deposits in a controlled manner without any incidence of non-target embolization in our study. This relatively less described technique increases the safety and accuracy of the endovascular treatment in VOGM patients.

Genomic Landscape and Targeted Treatment of Gallbladder Cancer: Results of a First Ongoing Prospective Study.

Background Prognosis of gallbladder cancer (GBC) has not changed in the past 20 years. Comprehensive genomic profiling (CGP) carries potential to determine the actionability for multiple targets, including ERBB2 , ERBB3 , MET , ROSI , FGFR , and PIK3 . This study evaluates the role of CGP and targeted therapies. Methods This is a multicenter, prospective, single-arm study. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture-based CGP was performed by Foundation Medicine CDx. All patients received first-line chemotherapy with gemcitabine-cisplatin regimen. Patients with ERBB2/3 amplification received trastuzumab with capecitabine or nab-paclitaxel, and patients with MET amplification were treated with crizotinib. For ERBB2/3 mutations, lapatinib plus capecitabine regimen was used. Results Fifty patients were studied with a median age of 56 years (range 26-83) and a male-to-female ratio of 1:1.6. ERBB2 and ERBB3 amplification was seen in 9 (18%) and 2 (4%) patients, respectively. Four patients with ERBB2 amplification received trastuzumab and/or lapatinib, showed partial response, and maintained response beyond 12 weeks. One patient had mixed response, whereas two patients progressed on trastuzumab and lapatinib. Three patients with ERBB3 mutations showed response to lapatinib-capecitabine. One patient with MET amplification responded to crizotinib for 4 weeks. PIK3 mutations were present in 14% of cases and were independent of ERBB aberrations. Conclusion GBC is enriched in 28% of patients with ERBB2 and ERBB3 amplifications and/or mutations. Responses are seen with lapatinib in concurrent ERBB2 mutation and amplification. ERBB3 mutation showed response to lapatinib. MET and PIK3 are new findings in GBC, which may be targeted.

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.

Deciphering a delayed hemolytic transfusion reactions nightmare - Case of Chido/Roger antibodies.

Antibodies against Rh (CEce) and Kidd (Jka and Jkb) system antigens are mostly implicated in delayed hemolytic transfusion reactions (DHTR), which is a potentially life-threatening complication observed in patients receiving chronic transfusions. Here, we are describing a case of Chido/Roger antibody which presented to our laboratory as DHTR. The clinical presentation and laboratory findings including the immunohematological workups with regard to the reaction are discussed, with a special emphasis on the benefit of identifying such an antibody and obtaining blood unit for transfusion supports the patient with respect to providing a compatible unit.

Bronchial artery embolization in treatment of hemoptysis: Treatment efficacy and complications at a tertiary care chest centre.

BACKGROUND: Hemoptysis is one of the most alarming condition to both the patients suffering from it and the treating physicians. It is caused due to varied etiologies. One of the emergent and at times life-saving treatment option is by minimally invasive interventional radiological technique of Bronchial Atery Embolization (BAE). The authors aimed to carry out a retrospective analysis of short term efficacy and safety of all patients treated by this technique at a tertiary care thoracic centre. METHODS: A total of 52 patients were included in the study who had a median follow up of 35 days. All these patients were referred for hemoptysis, intractable hemoptysis not controlled by conservative management or massive hemoptysis. An analysis of the underlying etiology, immediate and short term outcomes and complications was made. RESULTS: The study showed Tuberculosis and its sequel (bronchiectasis and chronic fibrotic changes) as the commonest etiology (65%). The BAE showed high short term efficacy (92%) in stopping the hemoptysis with a relatively low complication rate especially of major complications such as spinal cord ischemia (1.9%). The study strengthens the limited Indian data available on the subject and based on its outcome, BAE should be tried in all patients presenting with uncontrollable or massive hemoptysis not getting relief by conservative management alone. CONCLUSION: BAE is a very effective procedure with very less complications for management of massive or uncontrollable hemoptysis.

In vitro mesenchymal-epithelial transition in NIH3T3 fibroblasts results in onset of low-dose radiation hypersensitivity coupled with attenuated connexin-43 response.

BACKGROUND: Mesenchymal-to-epithelial transition (MET) is associated with altered cell adhesion patterns. Independent studies showed that cellular adhesion regulates low-dose hyper-radiosensitivity (HRS), a phenomenon reported widely in tumour cells. Therefore, present study aimed to investigate whether MET and associated cellular adhesion alterations affect cellular radiosensitivity. METHODS: We established multiple stages of MET by in vitro transformation of NIH3T3 mouse embryonic fibroblasts. Nutritional deprivation followed by repetitive treatment cycles of 3-methylcholanthrene and phorbol-12-myristate-13-acetate with frequent isolation of foci established three progressive strains (NIH3T3.1, NIH3T3x3, NIH3T3x8x3) depicting MET, and one strain (NIH3T3x12) with partial reversion. Alterations in morphology, cell adhesion properties, expression/intracellular localization of cell adhesion proteins, microRNA expression and cellular radiosensitivity were studied in these stably transformed cell strains. RESULTS: All four transformants had increased proliferation rate, saturation density, bipolarity, E-cadherin expression; coupled with reduced cell size/spreading, pseudopodia/migration, and fibroblast marker protein and vimentin. The most aggressive trans-differentiated (phenotypically epithelial) cell strain, NIH3T3x8x3 acquired ~30% higher growth potential associated with more than two-fold reduction in cell size and migration. These phenotypic changes accompanied ~40% reduction in endogenous or radiation-induced connexin-43 expression/mitochondrial translocation. Incidentally, all three progressive strains displayed prominent HRS (αs/αr: 7.95-37.29) whereas parental (NIH3T3) and reverting (NIH3T3x12) strains lacked HRS and had distinct radiation-induced Cx43 translocation into mitochondria. CONCLUSION: Our study shows that trans-differentiating fibroblasts progressively acquiring epithelial features during MET process, display low-dose hyper-radiosensitivity associated with altered Cx43 behaviour. GENERAL SIGNIFICANCE: This study demonstrates that MET progression triggers low-dose hyper-radiosensitivity in trans-differentiating cells, which has significant therapeutic implications.

Adding to platelet safety and life: Platelet additive solutions.

BACKGROUND: Platelet additive solutions (PAS) are crystalloid nutrient media used in place of plasma for platelet storage. They replace 60%-70% of plasma in platelet components, so the amount of storage plasma can be decreased. Platelets in PAS have lower risk for allergic transfusion reactions with equivalent clinical efficacy for controlling bleeding. AIM: The aim of this study is to evaluate the clinical and laboratory efficacy of PAS-platelets. MATERIALS AND METHODS: A total of 1674 single donor platelet (SDP) were collected in PAS in the month of June to September 2016 by different apheresis systems. The quality control tests were done on 356 units in 4 months. Total number of SDP were processed with Amicus device (n = 232), Trima Accel (n = 84), and MCS+ (n = 40). The parameters analyzed were antibody titer of anti-A and anti-B, volume, platelet count, pH, bacterial contamination, and reporting of adverse transfusion reaction. Antibody titers were checked by tube technique, and platelet counts were checked by hematology analyzer Sysmex poch 100i. The swirling was checked manually, and pH was checked with pH strips. RESULTS: Out of 356, 164 units were O group, 113 units were B group, 68 units were of A group, and the remaining 11 units were of AB Group. Anti-A and anti-B titer was significantly reduced in PAS-SDP and found 1:32 or less for all the units. All the units found negative for bacterial contamination. No transfusion reaction was reported of the units transfused. All other quality parameters for platelets also found satisfactory after implementing the additive solution. CONCLUSION: The ABO antibody titers were significantly reduced after addition of PAS. This facilitates the ABO incompatible SDP transfusion and helps in inventory management. The risk of allergic transfusion reaction decreases after reducing the amount of plasma from SDP units. Using PAS-SDP certainly improve the inventory management for platelets with no compromise on clinical and laboratory efficacy.

Anterior Corneal, Posterior Corneal, and Lenticular Contributions to Ocular Aberrations.

PURPOSE: To determine the corneal surfaces and lens contributions to ocular aberrations. METHODS: There were 61 healthy participants with ages ranging from 20 to 55 years and refractions -8.25 diopters (D) to +3.25 D. Anterior and posterior corneal topographies were obtained with an Oculus Pentacam, and ocular aberrations were obtained with an iTrace aberrometer. Raytracing through models of corneas provided total corneal and surface component aberrations for 5-mm-diameter pupils. Lenticular contributions were given as differences between ocular and corneal aberrations. Theoretical raytracing investigated influence of object distance on aberrations. RESULTS: Apart from defocus, the highest aberration coefficients were horizontal astigmatism, horizontal coma, and spherical aberration. Most correlations between lenticular and ocular parameters were positive and significant, with compensation of total corneal aberrations by lenticular aberrations for 5/12 coefficients. Anterior corneal aberrations were approximately three times higher than posterior corneal aberrations and usually had opposite signs. Corneal topographic centers were displaced from aberrometer pupil centers by 0.32 ± 0.19 mm nasally and 0.02 ± 0.16 mm inferiorly; disregarding corneal decentration relative to pupil center was significant for oblique astigmatism, horizontal coma, and horizontal trefoil. An object at infinity, rather than at the image in the anterior cornea, gave incorrect aberration estimates of the posterior cornea. CONCLUSIONS: Corneal and lenticular aberration magnitudes are similar, and aberrations of the anterior corneal surface are approximately three times those of the posterior surface. Corneal decentration relative to pupil center has significant effects on oblique astigmatism, horizontal coma, and horizontal trefoil. When estimating component aberrations, it is important to use correct object/image conjugates and heights at surfaces.

Cortical Reorganisation during a 30-Week Tinnitus Treatment Program.

Subjective tinnitus is characterised by the conscious perception of a phantom sound. Previous studies have shown that individuals with chronic tinnitus have disrupted sound-evoked cortical tonotopic maps, time-shifted evoked auditory responses, and altered oscillatory cortical activity. The main objectives of this study were to: (i) compare sound-evoked brain responses and cortical tonotopic maps in individuals with bilateral tinnitus and those without tinnitus; and (ii) investigate whether changes in these sound-evoked responses occur with amelioration of the tinnitus percept during a 30-week tinnitus treatment program. Magnetoencephalography (MEG) recordings of 12 bilateral tinnitus participants and 10 control normal-hearing subjects reporting no tinnitus were recorded at baseline, using 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz tones presented monaurally at 70 dBSPL through insert tube phones. For the tinnitus participants, MEG recordings were obtained at 5-, 10-, 20- and 30- week time points during tinnitus treatment. Results for the 500 Hz and 1000 Hz sources (where hearing thresholds were within normal limits for all participants) showed that the tinnitus participants had a significantly larger and more anteriorly located source strengths when compared to the non-tinnitus participants. During the 30-week tinnitus treatment, the participants' 500 Hz and 1000 Hz source strengths remained higher than the non-tinnitus participants; however, the source locations shifted towards the direction recorded from the non-tinnitus control group. Further, in the left hemisphere, there was a time-shifted association between the trajectory of change of the individual's objective (source strength and anterior-posterior source location) and subjective measures (using tinnitus reaction questionnaire, TRQ). The differences in source strength between the two groups suggest that individuals with tinnitus have enhanced central gain which is not significantly influenced by the tinnitus treatment, and may result from the hearing loss per se. On the other hand, the shifts in the tonotopic map towards the non-tinnitus participants' source location suggests that the tinnitus treatment might reduce the disruptions in the map, presumably produced by the tinnitus percept directly or indirectly. Further, the similarity in the trajectory of change across the objective and subjective parameters after time-shifting the perceptual changes by 5 weeks suggests that during or following treatment, perceptual changes in the tinnitus percept may precede neurophysiological changes. Subgroup analyses conducted by magnitude of hearing loss suggest that there were no differences in the 500 Hz and 1000 Hz source strength amplitudes for the mild-moderate compared with the mild-severe hearing loss subgroup, although the mean source strength was consistently higher for the mild-severe subgroup. Further, the mild-severe subgroup had 500 Hz and 1000 Hz source locations located more anteriorly (i.e., more disrupted compared to the control group) compared to the mild-moderate group, although this was trending towards significance only for the 500Hz left hemisphere source. While the small numbers of participants within the subgroup analyses reduce the statistical power, this study suggests that those with greater magnitudes of hearing loss show greater cortical disruptions with tinnitus and that tinnitus treatment appears to reduce the tonotopic map disruptions but not the source strength (or central gain).