Category: Nevin Manimala

J Glaucoma. 2023 Jul 21. doi: 10.1097/IJG.0000000000002273. Online ahead of print.

ABSTRACT

PURPOSE: To characterize treatment patterns for newly-diagnosed glaucoma in sub-Saharan Africa (SSA).

METHODS: This was a multicenter cross-sectional study of adults newly diagnosed with glaucoma at 27 eye care centers in 10 African countries. In addition to demographic and clinical data, physician treatment recommendations (medication, laser, surgery, or no treatment) were recorded. Statistical analyses were performed using STATA version 14.0.

RESULTS: Data from 1201 patients were analyzed. Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma (69.4%), with laser (13.2%), surgery (14.9%), and no treatment (2.5%) recommended to the remaining patients. All sites had medical therapy available and most (25/27, 92.6%) could provide surgical treatment; only 16/27 (59.3%) sites offered laser, and at these sites, 30.8% of eyes were recommended to undergo primary laser procedures. As glaucoma severity increased, laser was recommended less, surgery more, and medications unchanged. Patient acceptance of medical therapy was 99.1%, laser 88.3%, and surgery 69.3%.

CONCLUSIONS: Medical therapy for first-line glaucoma management is preferred by most physicians in SSA (69%). Laser therapy may be underutilized at centers where it is available. These findings underscore the need for comparative studies of glaucoma treatments in SSA to inform the development of evidence-based treatment guidelines and of programs to reduce glaucoma blindness in SSA. Strategic approaches to glaucoma therapy in SSA must address the question of whether medical therapy is the most optimal first line approach in this setting.

PMID:37523638 | DOI:10.1097/IJG.0000000000002273

J Glaucoma. 2023 Jul 20. doi: 10.1097/IJG.0000000000002271. Online ahead of print.

ABSTRACT

PRECIS: This retrospective study found a statistically significant reduction in mean intraocular pressure and number of medications after intracameral Bimatoprost SR injection in patients with glaucoma. A history of selective laser trabeculoplasty did not impact treatment outcomes.

PURPOSE: To determine outcomes of Bimatoprost sustained release (Bimatoprost SR) on intraocular pressure (IOP) and number of topical IOP lowering medications in patients with glaucoma. A secondary objective was to determine the outcomes of Bimatoprost SR in patients with a prior history of selective laser trabeculoplasty (SLT).

METHODS: Retrospective case series. One hundred and eighteen eyes from 84 patients that received Bimatoprost SR by 6 glaucoma specialists at Wills Eye Hospital from March 2020 to September 2021 were examined. The intervention was a single injection of intracameral Bimatoprost SR. Main outcome measures included IOP and number of medications.

RESULTS: The mean most recent follow-up time for all eyes was 27.8±18.6 weeks. Mean post-treatment IOP at most recent follow-up of 16.6±5.3 mmHg was significantly lower than mean under therapy pre-treatment IOP of 18.5±5.7 mmHg for all eyes (P<0.01). Mean post-treatment number of medications at most recent follow-up of 1.3±1.3 decreased compared to number of pre-treatment medications of 2.1±1.4 for all eyes (P<0.01). Analysis of multilevel models controlling for demographic variables demonstrated a statistically significant reduction in IOP and number of medications post-treatment (P<0.01). A prior history of SLT (n=54) had no impact on treatment for both IOP and number of medications (P>0.1 for both).

CONCLUSIONS: Intracameral Bimatoprost SR reduced IOP and decreased the number of medications. Prior history of SLT did not impact Bimatoprost SR treatment outcomes.

PMID:37523637 | DOI:10.1097/IJG.0000000000002271

J Glaucoma. 2023 Jul 20. doi: 10.1097/IJG.0000000000002262. Online ahead of print.

ABSTRACT

PRCIS: Our results demonstrate that, among randomized clinical trials examining the use of surgical treatments for glaucoma, the majority were not registered. Publication bias was less likely. More than one third of registered trials presented outcome reporting bias.

PURPOSE: Despite the optimum of quality evidence provided by randomized controlled trials (RCTs), biases may be introduced and hinder their application. The primary objective of this study was to investigate outcome reporting bias (ORB) and publication bias (PB) in RCTs assessing surgical treatments of glaucoma, as well as their registration status.

METHODS: A literature review was conducted in MEDLINE, EMBASE and CENTRAL databases. Inclusion criteria were RCTs published in English between 2007 and 2021 that focused on surgical treatments of patients of all ages with glaucoma or elevated intraocular pressure. Exclusion criteria included cadaveric and animal studies. Registration status was correlated with entries from clinical trial registries. PB was determined by the proportion of trials presenting statistically significant results. ORB was evaluated by comparing the study’s primary outcome with that listed in the trial registry. Trials quality was assessed using the Jadad score.

RESULTS: After deleting duplicates, 7,561 citations were screened. 161 RCTs were eligible and included between 13 and 556 participants. Ninety one percent studied an adult population and 71% included patients suffering from primary open-angle glaucoma. Among included studies, 63% were not registered and 47% had statistically significant results. An upward trend in registration was observed with time. However, 37% of the studies showed discrepancies between objectives in cited clinical trial registries and the published results.

CONCLUSION: Publication bias in surgical glaucoma trials was not obvious. Among the minority of trials that were registered, more than a third presented outcome reporting bias. Unregistered trials had lower quality. RCT registration is crucial for transparent interpretation of studies, improved patient care in surgery and informed decision-making.

PMID:37523630 | DOI:10.1097/IJG.0000000000002262

J Glaucoma. 2023 Jul 19. doi: 10.1097/IJG.0000000000002269. Online ahead of print.

ABSTRACT

PRCIS: The change in glaucoma surgical volumes due to the COVID-19 pandemic was not uniform across procedure types and unequal between rural and urban practice locations.

PURPOSE: To quantify the impact of the COVID-19 pandemic on surgical volumes performed by fellowship-trained glaucoma subspecialists.

METHODS: This retrospective cohort analysis of the CMS Medicare Public Use File extracted all glaucoma surgeries including micro-invasive glaucoma surgeries, trabeculectomy, goniotomy, lasers, and cataract surgery performed by fellowship-trained glaucoma surgeons in rural and urban areas between 2016 and 2020. Predicted estimates of 2020 surgical volumes were created utilizing linear squares regression. Percent change between predicted and observed 2020 surgical volume estimates was analyzed. Statistical significance was achieved at P<0.05.

RESULTS: In 2020, fellowship trained glaucoma surgeons operated mostly in urban areas (N=810, 95%). A 29% and 31% decrease in predicted cataract surgery volumes in urban and rural areas was observed. Glaucoma surgeries experienced a 36% decrease from predicted estimates (N=56,781). MIGS experienced a 86% and 75% decrease in rural and urban areas respectively. Trabeculectomy in rural areas experienced a 16% increase relative to predicted estimates while urban areas experienced a decrease of 3% (P>0.05). The number of goniotomies decreased by 10% more in rural areas than in urban areas (-22% and -12%, respectively). Laser procedures decreased by 8% more in urban areas than in rural areas (-18% and -10%, respectively).

CONCLUSIONS: Among glaucoma-trained surgeons, glaucoma surgeries experienced a greater volume loss than cataract surgeries. In urban US areas, relative reductions in MIGS and goniotomy volumes in urban areas may have been compensated by greater laser and trabeculectomy volumes. Trabeculectomies in rural areas was the only group exceeding predicted estimates. Glaucoma subspecialists may utilize these findings when planning for future events and in overcoming any remaining unmet need in terms of glaucoma care.

PMID:37523625 | DOI:10.1097/IJG.0000000000002269

J Clin Oncol. 2023 Jul 31:JCO2300045. doi: 10.1200/JCO.23.00045. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.ARST1321 was a phase II study designed to compare the near complete pathologic response rate after preoperative chemoradiation with/without pazopanib in children and adults with intermediate-/high-risk chemotherapy-sensitive body wall/extremity non-Rhabdomyosarcoma Soft Tissue Sarcoma (ClinicalTrials.gov identifier: NCT02180867). Enrollment was stopped early following a predetermined interim analysis that found the rate of near complete pathologic response to be significantly greater with the addition of pazopanib. As a planned secondary aim of the study, the outcome data for this cohort were analyzed. Eight-five eligible patients were randomly assigned to receive (regimen A) or not receive (regimen B) pazopanib in combination with ifosfamide and doxorubicin + preoperative radiotherapy followed by primary resection at week 13 and then further chemotherapy at week 25. As of December 31, 2021, at a median survivor follow-up of 3.3 years (range, 0.1-5.8 years), the 3-year event-free survival for all patients in the intent-to-treat analysis was 52.5% (95% CI, 34.8 to 70.2) for regimen A and 50.6% (95% CI, 32 to 69.2) for regimen B (P = .8677, log-rank test); the 3-year overall survival was 75.7% (95% CI, 59.7 to 91.7) for regimen A and 65.4% (95% CI, 48.1 to 82.7) for regimen B (P = .1919, log-rank test). Although the rate of near complete pathologic response was significantly greater with the addition of pazopanib, outcomes were not statistically significantly different between the two regimens.

PMID:37523624 | DOI:10.1200/JCO.23.00045

Surg Laparosc Endosc Percutan Tech. 2023 Jul 14. doi: 10.1097/SLE.0000000000001203. Online ahead of print.

ABSTRACT

BACKGROUND: Parastomal hernia repairs (PHRs) are often complex and challenging, even for experienced abdominal wall surgeons. Although the ideal therapeutic option in the setting of a parastomal hernia is to restore intestinal continuity, this is often not feasible, and numerous techniques have been described for PHR. Current guidelines recommend using mesh for elective PHR, but there is a scarcity of evidence comparing different PHR techniques. We aimed to report a meta-analysis comparing the outcomes of the “Sugarbaker” and “Keyhole” mesh configuration in PHR.

METHODS: A literature search of PubMed, Embase, Scopus, and Cochrane Library databases was performed to identify studies comparing Sugarbaker and Keyhole mesh configuration in PHR. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics.

RESULTS: A total of 3247 studies were screened, and 27 were fully reviewed. Ten studies and 632 patients were included in the meta-analysis. Three hundred five patients (48.3%) with Keyhole and 327 patients (51.7%) with Sugarbaker mesh configuration. Four hundred thirty-three patients (68.5%) underwent laparoscopic PHR with intraperitoneal onlay mesh. Sugarbaker mesh configuration was associated with lower hernia recurrence compared with Keyhole (odds ratio: 0.39; 95% CI: 0.19-0.83; P = 0.01; I2 = 46%). No differences were seen in overall complications, reoperations, stoma outlet obstruction, mesh infection, and postoperative bleeding.

CONCLUSION: PHR with Sugarbaker mesh configuration is associated with decreased hernia recurrence compared with Keyhole and had similar rates of overall complications, reoperations, stoma outlet obstruction, mesh infection, and postoperative bleeding.

PMID:37523583 | DOI:10.1097/SLE.0000000000001203

Surg Laparosc Endosc Percutan Tech. 2023 Jul 24. doi: 10.1097/SLE.0000000000001202. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive technique widely used to diagnose and treat pancreatic and biliary diseases; however, it is linked with imminent hyperamylasemia and post-ERCP pancreatitis (PEP). Somatostatin and indomethacin are the classic recommended drugs used for PEP prevention.

OBJECTIVE: To elucidate the effects of somatostatin and indomethacin mono or in combination to prevent hyperamylasemia and PEP in high-risk individuals.

METHODS: Altogether 1458 patients who underwent ERCP in our hospital from January 2016 to May 2022 were included in this investigation and categorized into 4 groups based on the treatment regimen: placebo, indomethacin, somatostatin, and indomethacin + somatostatin. The pre operation and post operation (at 6, 12, and 24 h) hospitalization cost, length of stay, the occurrence of hyperamylasemia and PEP, levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and VAS pain score were determined in the 4 groups. In all the groups, VAS and IL-6, TNF-α, and IL-8 levels substantially increased in the pretreatment and decreased sequentially from 6 to 24 h post operation. The individuals in the indomethacin revealed substantially reduced hyperamylasemia, VAS, and levels of IL-6, TNF-α, and IL-8, 6 h post operation, whereas the hospitalization fee, length of stay, PEP incidence, VAS, levels of IL-6, TNF-α, and IL-8, 12 and 24 h post operation were not statistically important in comparison with the individuals who received placebo therapy. The somatostatin and the indomethacin + somatostatin groups indicated markedly alleviated hospitalization fee, length of stay, the occurrence of hyperamylasemia and PEP, VAS, and the levels of IL-6, TNF-α, and IL-8 at 6, 12, and 24 h post operation compared with the placebo cohort. Furthermore, compared with the indomethacin group, the above-determined factors notably reduced at 6, 12, and 24 h post operation in somatostatin and indomethacin + somatostatin groups. It was also observed that the indomethacin + somatostatin group has substantially decreased the occurrence of hyperamylasemia, VAS score, and levels of IL-6, TNF-α, and IL-8, 6 hours post operation, while at 12 and 24 h post operation, the hospitalization fee, length of stay and incidence of PEP, VAS, levels of IL-6, TNF-α, and IL-8 were not statistically important compared with the somatostatin group. It is also worth noting that the side effects of both drugs are rare and mild.

RESULTS: For high-risk PEP patients, indomethacin and somatostatin can efficiently alleviate post-operative hyperamylasemia and improve their life standard within 6 hours and 24 hours, respectively. Indomethacin is suitable for individuals who underwent simple, short-duration ERCP with expected mild post-operative abdominal pain, whereas somatostatin is given to patients with complicated, long-duration ERCP and expected severe post-operative abdominal pain. Their combinational therapy produces a synergistic effect and can reduce the incidence of hyperamylasemia, thereby improving patients’ quality of life within 6 h and is also effective against individuals who received a more complicated, longer-duration ERCP and were expected to have severer and longer post-operative abdominal pain.

PMID:37523580 | DOI:10.1097/SLE.0000000000001202

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2308935120. doi: 10.1073/pnas.2308935120. Epub 2023 Jul 31.

ABSTRACT

The instability of Stokes waves, steady propagating waves on the surface of an ideal fluid of infinite depth, is a fundamental problem in the field of nonlinear science. The dominant instability of these waves depends on their steepness. For small amplitude waves, it is well known that the Benjamin-Feir or modulational instability dominates the dynamics of a wave train. We demonstrate that for steeper waves, an instability caused by disturbances localized at the wave crest vastly surpasses the growth rate of the modulational instability. These dominant localized disturbances are either coperiodic with the Stokes wave or have twice its period. In either case, the nonlinear evolution of the instability leads to the formation of plunging breakers. This phenomenon explains why long propagating ocean swell consists of small-amplitude waves.

PMID:37523557 | DOI:10.1073/pnas.2308935120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2300828120. doi: 10.1073/pnas.2300828120. Epub 2023 Jul 31.

ABSTRACT

Traditionally, nuclear spin is not considered to affect biological processes. Recently, this has changed as isotopic fractionation that deviates from classical mass dependence was reported both in vitro and in vivo. In these cases, the isotopic effect correlates with the nuclear magnetic spin. Here, we show nuclear spin effects using stable oxygen isotopes (¹⁶O, ¹⁷O, and ¹⁸O) in two separate setups: an artificial dioxygen production system and biological aquaporin channels in cells. We observe that oxygen dynamics in chiral environments (in particular its transport) depend on nuclear spin, suggesting future applications for controlled isotope separation to be used, for instance, in NMR. To demonstrate the mechanism behind our findings, we formulate theoretical models based on a nuclear-spin-enhanced switch between electronic spin states. Accounting for the role of nuclear spin in biology can provide insights into the role of quantum effects in living systems and help inspire the development of future biotechnology solutions.

PMID:37523549 | DOI:10.1073/pnas.2300828120

Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2303402120. doi: 10.1073/pnas.2303402120. Epub 2023 Jul 31.

ABSTRACT

The endoplasmic reticulum (ER) and mitochondria form a unique subcellular compartment called mitochondria-associated ER membranes (MAMs). Disruption of MAMs impairs Ca²⁺ homeostasis, triggering pleiotropic effects in the neuronal system. Genome-wide kinase-MAM interactome screening identifies casein kinase 2 alpha 1 (CK2A1) as a regulator of composition and Ca²⁺ transport of MAMs. CK2A1-mediated phosphorylation of PACS2 at Ser207/208/213 facilitates MAM localization of the CK2A1-PACS2-PKD2 complex, regulating PKD2-dependent mitochondrial Ca²⁺ influx. We further reveal that mutations of PACS2 (E209K and E211K) associated with developmental and epileptic encephalopathy-66 (DEE66) impair MAM integrity through the disturbance of PACS2 phosphorylation at Ser207/208/213. This, in turn, causes the reduction of mitochondrial Ca²⁺ uptake and the dramatic increase of the cytosolic Ca²⁺ level, thereby, inducing neurotransmitter release at the axon boutons of glutamatergic neurons. In conclusion, our findings suggest a molecular mechanism that MAM alterations induced by pathological PACS2 mutations modulate Ca²⁺-dependent neurotransmitter release.

PMID:37523531 | DOI:10.1073/pnas.2303402120